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Kirkpatrick, John P.

Overview:

Malignant and benign tumors of the brain, spine and base of skull. Mathematical modelling of tumor metabolism, mass transfer and the response to ionizing radiation. Enhancing clinical outcome in stereotactic radiosurgery, fractionated stereotactic radiotherapy and stereotactic body radiotherapy.

Positions:

Associate Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Associate Professor in Surgery

Neurosurgery
School of Medicine

Associate Professor in Neurosurgery

Neurosurgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1978

Ph.D. — Rice University

M.D. 1999

M.D. — University of Texas Medical School at Houston

Grants:

Developing knowledge models to enable rapid learning in radiation therapy

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
June 01, 2016
End Date
May 31, 2020

Decision support for dose prescription in radiation treatment planning

Administered By
Radiation Oncology
AwardedBy
University of North Carolina - Charlotte
Role
Co Investigator
Start Date
March 13, 2013
End Date
June 30, 2015

Robotic SPECT for Biological Imaging Onboard Radiation Therapy Machines

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
September 22, 2011
End Date
November 30, 2013

Cross-disciplinary Training in Medical Physics

Administered By
Duke University Medical Physics Graduate Program
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 2007
End Date
June 30, 2013
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Publications:

Biopsy of enlarging lesions after stereotactic radiosurgery for brain metastases frequently reveals radiation necrosis.

Stereotactic radiosurgery (SRS) offers excellent local control for brain metastases (BM) with low rates of toxicity. Radiation necrosis (RN) may occur after treatment and is challenging to distinguish from local recurrence (LR). We evaluated enlarging brain lesions following SRS that were subsequently biopsied to differentiate RN versus LR.This study reviewed patients receiving SRS for BM between 2008 and 2012 who underwent a biopsy for suspicion of RN versus LR on MRI. Data collection included demographics, radiation parameters, imaging findings, and post-biopsy pathology. Kaplan-Meier methods determined overall survival. Fisher's exact test assessed for association between lesion biopsy result and variables of interest.Thirty-four patients with 35 biopsied BM were included. Lesions were biopsied a median of 8.8 months after SRS. Most patients had primary lung cancer (11; 31.4%). Eleven (31.4%) biopsies were positive for LR and 24 (68.6%) showed RN only. Median overall survival was longer for patients with RN (31.0 mo) than for patients with LR (14.5 mo; P = 0.135). Time from SRS to biopsy was significantly different between RN and LR groups; 10 lesions (52.5%) biopsied ≤9 months after SRS showed LR, whereas 1 lesion (6.3%) biopsied >9 months after SRS showed LR (P = 0.004). For 16 (65.7%) lesions, management was changed or directed by the biopsy results.Stereotactic biopsy for accessible enlarging lesions after SRS appears diagnostically valuable in patients with few lesions and changes clinical management. RN should be suspected in patients with an enlarging lesion more than 9 months post-SRS.

Authors
Narloch, JL; Farber, SH; Sammons, S; McSherry, F; Herndon, JE; Hoang, JK; Yin, F-F; Sampson, JH; Fecci, PE; Blackwell, KL; Kirkpatrick, JP; Kim, GJ
MLA Citation
Narloch, JL, Farber, SH, Sammons, S, McSherry, F, Herndon, JE, Hoang, JK, Yin, F-F, Sampson, JH, Fecci, PE, Blackwell, KL, Kirkpatrick, JP, and Kim, GJ. "Biopsy of enlarging lesions after stereotactic radiosurgery for brain metastases frequently reveals radiation necrosis." Neuro-oncology 19.10 (October 2017): 1391-1397.
PMID
28472527
Source
epmc
Published In
Neuro-Oncology
Volume
19
Issue
10
Publish Date
2017
Start Page
1391
End Page
1397
DOI
10.1093/neuonc/nox090

Accelerated Brain DCE-MRI Using Iterative Reconstruction With Total Generalized Variation Penalty for Quantitative Pharmacokinetic Analysis: A Feasibility Study.

To investigate the feasibility of using undersampled k-space data and an iterative image reconstruction method with total generalized variation penalty in the quantitative pharmacokinetic analysis for clinical brain dynamic contrast-enhanced magnetic resonance imaging.Eight brain dynamic contrast-enhanced magnetic resonance imaging scans were retrospectively studied. Two k-space sparse sampling strategies were designed to achieve a simulated image acquisition acceleration factor of 4. They are (1) a golden ratio-optimized 32-ray radial sampling profile and (2) a Cartesian-based random sampling profile with spatiotemporal-regularized sampling density constraints. The undersampled data were reconstructed to yield images using the investigated reconstruction technique. In quantitative pharmacokinetic analysis on a voxel-by-voxel basis, the rate constant Ktrans in the extended Tofts model and blood flow FB and blood volume VB from the 2-compartment exchange model were analyzed. Finally, the quantitative pharmacokinetic parameters calculated from the undersampled data were compared with the corresponding calculated values from the fully sampled data. To quantify each parameter's accuracy calculated using the undersampled data, error in volume mean, total relative error, and cross-correlation were calculated.The pharmacokinetic parameter maps generated from the undersampled data appeared comparable to the ones generated from the original full sampling data. Within the region of interest, most derived error in volume mean values in the region of interest was about 5% or lower, and the average error in volume mean of all parameter maps generated through either sampling strategy was about 3.54%. The average total relative error value of all parameter maps in region of interest was about 0.115, and the average cross-correlation of all parameter maps in region of interest was about 0.962. All investigated pharmacokinetic parameters had no significant differences between the result from original data and the reduced sampling data.With sparsely sampled k-space data in simulation of accelerated acquisition by a factor of 4, the investigated dynamic contrast-enhanced magnetic resonance imaging pharmacokinetic parameters can accurately estimate the total generalized variation-based iterative image reconstruction method for reliable clinical application.

Authors
Wang, C; Yin, F-F; Kirkpatrick, JP; Chang, Z
MLA Citation
Wang, C, Yin, F-F, Kirkpatrick, JP, and Chang, Z. "Accelerated Brain DCE-MRI Using Iterative Reconstruction With Total Generalized Variation Penalty for Quantitative Pharmacokinetic Analysis: A Feasibility Study." Technology in cancer research & treatment 16.4 (August 2017): 446-460.
PMID
27215931
Source
epmc
Published In
Technology in cancer research & treatment
Volume
16
Issue
4
Publish Date
2017
Start Page
446
End Page
460
DOI
10.1177/1533034616649294

Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer.

Breast cancer is the most common malignancy diagnosed among women and represents a heterogeneous group of subtypes. Radiation therapy is a critical component of treatment for breast cancer patients. However, little is known about radiation response among these intrinsic subtypes. In previous studies, we identified a significant induction of FAS after irradiation in biologically favorable breast cancer patients and breast cancer cell lines. Here, we expanded our study and investigated radiation response in a mouse model of breast cancer. MCF7 (luminal), HCC1954 (HER2+) or SUM159 (basal) cells were implanted orthotopically into the dorsal mammary fat pad of nude mice. These mice were then treated with different doses of radiation to assess tumor growth control. We further investigated the therapeutic effect of FAS modulation by silencing FAS in radiation-responsive tumors and injecting FAS agonist antibody into radiation-resistant tumors. Exposure to radiation inhibited MCF7, and to a lesser extent HCC1954 tumor growth in a dose-dependent manner. In contrast, SUM159 tumors were resistant to radiation. The estimated TCD50 values were 19.3 Gy for MCF7 and 44.9 Gy for SUM159. Radiation induced FAS expression in MCF7 tumors, but not SUM159 tumors. We found that silencing of FAS did not negatively impact radiation response in MCF7 tumors, possibly due to compensation by other apoptotic pathways. On the other hand, FAS activating antibody in combination with radiation treatment delayed SUM159 and HCC1954 tumor growth. However, it did not reach statistical significance compared to radiation treatment alone. Our results suggest that there is intrinsic variation in radiation response among breast cancer subtypes. FAS activation concurrent with radiation slows tumor growth in the radiation-resistant subtypes, but the effect was not significant. Alternative subtype-specific modulators of radiation response are under investigation.

Authors
Lee, C-T; Zhou, Y; Roy-Choudhury, K; Siamakpour-Reihani, S; Young, K; Hoang, P; Kirkpatrick, JP; Chi, J-TA; Dewhirst, MW; Horton, JK
MLA Citation
Lee, C-T, Zhou, Y, Roy-Choudhury, K, Siamakpour-Reihani, S, Young, K, Hoang, P, Kirkpatrick, JP, Chi, J-TA, Dewhirst, MW, and Horton, JK. "Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer." Radiation research 188.2 (August 2017): 169-180.
PMID
28598289
Source
epmc
Published In
Radiation Research
Volume
188
Issue
2
Publish Date
2017
Start Page
169
End Page
180
DOI
10.1667/rr14664.1

Hippocampal dose from stereotactic radiosurgery for 4 to 10 brain metastases: Risk factors, feasibility of dose reduction via re-optimization, and patient outcomes.

This study aimed to report hippocampal dose from single-fraction stereotactic radiosurgery (SRS) for 4 to 10 brain metastases and determine feasibility of hippocampal-sparing SRS. Patients with 4 to 10 brain metastases receiving single-isocenter, multi-target single-fraction SRS were identified. Hippocampi were contoured using the Radiation Therapy Oncology Group (RTOG) 0933 atlas. RTOG 0933 dose constraints were converted to a biologically effective dose using an alpha/beta of 2 (D100 421 cGy, Dmax 665 cGy). Number of metastases, total target volume, prescribed dose, and distance of nearest metastasis (dmin) were analyzed as risk factors for exceeding hippocampal constraints. If hippocampi exceeded constraints, the SRS plan was re-optimized. Key dosimetric parameters were compared between original and re-optimized plans. To determine if a single target can exceed constraints, all targets but the closest metastasis were removed from the plan, and dosimetry was compared. Forty plans were identified. Fifteen hippocampi (19%) exceeded constraints in 12 SRS plans. Hippocampal sparing was achieved in 10 of 12 replanned cases (83%). Risk factors associated with exceeding hippocampal constraints were decreasing dmin (24.0 vs 8.0 mm, p = 0.002; odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04 to 1.26) and total target volume (5.46 cm(3)vs 1.98 cm(3), p = 0.03; OR 1.14, 95% CI 1.00 to 1.32). There was no difference in exceeding constraints for 4 to 5 vs 6 to 10 metastases (27% vs 21%, p = 0.409) or prescribed dose (18 Gy, p = 0.58). For re-optimized plans, there were no significant differences in planning target volume (PTV) coverage (99.6% vs 99.0%, p = 0.17) or conformality index (1.47 vs 1.4, p = 0.78). Six (50%) plans exceeded constraints with a single target. A substantial minority of hippocampi receive high radiation dose from SRS for 4 to 10 brain metastases. Decreasing distance of the closest metastasis and total target volume are associated with exceeding hippocampal constraints. Re-optimizing these plans yielded hippocampal-sparing SRS plans with acceptable dosimetry. Prospective evaluation of the impact of hippocampal dose from SRS on neurocognition merits consideration.

Authors
Birer, SR; Olson, AC; Adamson, J; Hood, R; Susen, M; Kim, G; Salama, JK; Kirkpatrick, JP
MLA Citation
Birer, SR, Olson, AC, Adamson, J, Hood, R, Susen, M, Kim, G, Salama, JK, and Kirkpatrick, JP. "Hippocampal dose from stereotactic radiosurgery for 4 to 10 brain metastases: Risk factors, feasibility of dose reduction via re-optimization, and patient outcomes." July 28, 2017.
PMID
28760560
Source
epmc
Published In
Medical Dosimetry
Publish Date
2017
DOI
10.1016/j.meddos.2017.06.007

Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA).

Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. As systemic therapies improve, patients with lung cancer live longer and thus are at increased risk for brain metastases. Understanding how prognosis varies across this heterogeneous patient population is essential to individualize care and design future clinical trials.To update the current Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with non-small-cell lung cancer (NSCLC) and brain metastases. The DS-GPA is based on data from patients diagnosed between 1985 and 2005, and we set out to update it by incorporating more recently reported gene and molecular alteration data for patients with NSCLC and brain metastases. This new index is called the Lung-molGPA.This is a multi-institutional retrospective database analysis of 2186 patients diagnosed between 2006 and 2014 with NSCLC and newly diagnosed brain metastases. The multivariable analyses took place between December 2015 and May 2016, and all prognostic factors were weighted for significance by hazard ratios. Significant factors were included in the updated Lung-molGPA prognostic index.The main outcome was survival. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. Log rank tests were used to compare adjacent classes and to compare overall survival for adenocarcinoma vs nonadenocarcinoma groups.The original DS-GPA was based on 4 factors found in 1833 patients with NSCLC and brain metastases diagnosed between 1985 and 2005: patient age, Karnofsky Performance Status, extracranial metastases, and number of brain metastases. The patients studied for the creation of the DS-GPA had a median survival of 7 months from the time of initial treatment of brain metastases. To design the updated Lung-molGPA, we analyzed data from 2186 patients from 2006 through 2014 with NSCLC and newly diagnosed brain metastases (1521 adenocarcinoma and 665 nonadenocarcinoma). Significant prognostic factors included the original 4 factors used in the DS-GPA index plus 2 new factors: EGFR and ALK alterations in patients with adenocarcinoma (mutation status was not routinely tested for nonadenocarcinoma). The overall median survival for the cohort in the present study was 12 months, and those with NSCLC-adenocarcinoma and Lung-molGPA scores of 3.5 to 4.0 had a median survival of nearly 4 years.In recent years, patient survival and physicians' ability to predict survival in NSCLC with brain metastases has improved significantly. The updated Lung-molGPA incorporating gene alteration data into the DS-GPA is a user-friendly tool that may facilitate clinical decision making and appropriate stratification of future clinical trials.

Authors
Sperduto, PW; Yang, TJ; Beal, K; Pan, H; Brown, PD; Bangdiwala, A; Shanley, R; Yeh, N; Gaspar, LE; Braunstein, S; Sneed, P; Boyle, J; Kirkpatrick, JP; Mak, KS; Shih, HA; Engelman, A; Roberge, D; Arvold, ND; Alexander, B; Awad, MM; Contessa, J; Chiang, V; Hardie, J; Ma, D; Lou, E; Sperduto, W; Mehta, MP
MLA Citation
Sperduto, PW, Yang, TJ, Beal, K, Pan, H, Brown, PD, Bangdiwala, A, Shanley, R, Yeh, N, Gaspar, LE, Braunstein, S, Sneed, P, Boyle, J, Kirkpatrick, JP, Mak, KS, Shih, HA, Engelman, A, Roberge, D, Arvold, ND, Alexander, B, Awad, MM, Contessa, J, Chiang, V, Hardie, J, Ma, D, Lou, E, Sperduto, W, and Mehta, MP. "Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA)." JAMA oncology 3.6 (June 2017): 827-831.
PMID
27892978
Source
epmc
Published In
JAMA oncology
Volume
3
Issue
6
Publish Date
2017
Start Page
827
End Page
831
DOI
10.1001/jamaoncol.2016.3834

Management of GBM: a problem of local recurrence.

Forty years ago, adjuvant treatment of patients with GBM using fractionated radiotherapy following surgery was shown to substantially improve survival compared to surgery alone. However, even with the addition of temozolomide to radiotherapy, overall survival is quite limited and local failure remains a fundamental problem, despite multiple attempts to increase dose to the tumor target. This review presents the historical background and clinical rationale leading to the current standard of care consisting of 60 Gy total dose in 2 Gy fractions to the MRI-defined targets in younger, high performance status patients and more hypofractionated regimens in elderly and/or debilitated patients. Particle therapies offer the potential to increase local control while reducing dose and, potentially, long-term neurocognitive toxicity. However, improvements in systemic therapies for GBM will need to be implemented before the full benefits of improved local control can be realized.

Authors
Kirkpatrick, JP; Laack, NN; Shih, HA; Gondi, V
MLA Citation
Kirkpatrick, JP, Laack, NN, Shih, HA, and Gondi, V. "Management of GBM: a problem of local recurrence." Journal of neuro-oncology (April 4, 2017). (Review)
PMID
28378194
Source
epmc
Published In
Journal of Neuro-Oncology
Publish Date
2017
DOI
10.1007/s11060-016-2347-y

The radiosurgery fractionation quandary: single fraction or hypofractionation?

Stereotactic radiosurgery (SRS), typically administered in a single session, is widely employed to safely, efficiently, and effectively treat small intracranial lesions. However, for large lesions or those in close proximity to critical structures, it can be difficult to obtain an acceptable balance of tumor control while avoiding damage to normal tissue when single-fraction SRS is utilized. Treating a lesion in 2 to 5 fractions of SRS (termed "hypofractionated SRS" [HF-SRS]) potentially provides the ability to treat a lesion with a total dose of radiation that provides both adequate tumor control and acceptable toxicity. Indeed, studies of HF-SRS in large brain metastases, vestibular schwannomas, meningiomas, and gliomas suggest that a superior balance of tumor control and toxicity is observed compared with single-fraction SRS. Nonetheless, a great deal of effort remains to understand radiobiologic mechanisms for HF-SRS driving the dose-volume response relationship for tumors and normal tissues and to utilize this fundamental knowledge and the results of clinic studies to optimize HF-SRS. In particular, the application of HF-SRS in the setting of immunomodulatory cancer therapies offers special challenges and opportunities.

Authors
Kirkpatrick, JP; Soltys, SG; Lo, SS; Beal, K; Shrieve, DC; Brown, PD
MLA Citation
Kirkpatrick, JP, Soltys, SG, Lo, SS, Beal, K, Shrieve, DC, and Brown, PD. "The radiosurgery fractionation quandary: single fraction or hypofractionation?." Neuro-oncology 19.suppl_2 (April 2017): ii38-ii49.
PMID
28380634
Source
epmc
Published In
Neuro-Oncology
Volume
19
Issue
suppl_2
Publish Date
2017
Start Page
ii38
End Page
ii49
DOI
10.1093/neuonc/now301

Is a single isocenter sufficient for volumetric modulated arc therapy radiosurgery when multiple itracranial metastases are spatially dispersed?

Previous work demonstrated improved dosimetry of single isocenter volumetric modulated arc therapy (VMAT) of multiple intracranial targets when they are located ≤ 4cm from isocenter because of narrower multileaf collimators (MLCs). In follow-up, we sought to determine if decreasing isocenter-target distance (diso) by using 2 to 3 isocenters would improve dosimetry for spatially dispersed targets. We also investigated the effect of a maximum dose constraint during VMAT optimization, and the dosimetric effect of the number of VMAT arcs used for a larger number of targets (i.e., 7 to 9). We identified radiosurgery cases that had multiple intracranial targets with diso of at least 1 target > 5cm. A single isocenter VMAT plan was created using a standardized 4-arc technique with 18Gy per target. Each case was then replanned (1) using 2 to 3 isocenters, (2) including a maximum dose constraint per target, and in the case of 7 to 9 targets, (3) using 3 to 6 arcs. Dose evaluation included brain V6Gy and V12Gy, and conformity index (CI), gradient index (GI), and heterogeneity index (HI) per target. Two isocenters were sufficient to limit diso to ≤ 4cm and ≤ 5cm for 11/15 and 13/15 cases, respectively; after replanning with 2 to 3 isocenters, diso decreased from 5.8 ± 2.8cm (2.3 14.9) to 2.5 ± 1.4cm (0 5.2). All dose statistics improved on average, albeit modestly: V6Gy = 6.9 ± 7.1%, V12Gy = 0.9% ± 4.4%, CI = 2.6% ± 4.6%, GI = 0.9% ± 12.7%, and HI = 2.6% ± 5.2%; however, the number of arcs doubled and monitor units increase by nearly 2-fold. A maximum dose constraint had a negative effect on all dose indices, increasing V12Gy by 9.7 ± 6.9%. For ≥ 7 targets, increasing number of arcs to > 3 improved CI, V12Gy, and V6Gy. A single isocenter is likely sufficient for VMAT radiosurgery of multiple intracranial metastases. Optimal treatment plan quality is achieved when no constraint is placed on the maximum target dose; for cases with many targets at least 4 arcs are needed for optimal plan quality.

Authors
Morrison, J; Hood, R; Yin, F-F; Salama, JK; Kirkpatrick, J; Adamson, J
MLA Citation
Morrison, J, Hood, R, Yin, F-F, Salama, JK, Kirkpatrick, J, and Adamson, J. "Is a single isocenter sufficient for volumetric modulated arc therapy radiosurgery when multiple itracranial metastases are spatially dispersed?." Medical dosimetry : official journal of the American Association of Medical Dosimetrists 41.4 (December 2016): 285-289.
PMID
27614790
Source
epmc
Published In
Medical Dosimetry
Volume
41
Issue
4
Publish Date
2016
Start Page
285
End Page
289
DOI
10.1016/j.meddos.2016.06.007

Long-Term Outcomes for Patients With Atypical or Malignant Meningiomas Treated With Radiation Therapy: A Single-Institution Retrospective Analysis

Authors
Kent, CL; Mowery, YM; Wright, AO; Kim, GJ; Desjardins, A; Peters, KB; Vlahovic, G; Friedman, HS; Cummings, TJ; McLendon, RE; Friedman, AH; Sampson, JH; Kirkpatrick, JP
MLA Citation
Kent, CL, Mowery, YM, Wright, AO, Kim, GJ, Desjardins, A, Peters, KB, Vlahovic, G, Friedman, HS, Cummings, TJ, McLendon, RE, Friedman, AH, Sampson, JH, and Kirkpatrick, JP. "Long-Term Outcomes for Patients With Atypical or Malignant Meningiomas Treated With Radiation Therapy: A Single-Institution Retrospective Analysis." October 1, 2016.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
E83
End Page
E84

Single-Fraction Radiosurgery for 4 or More Brain Metastases

Authors
Limon, D; Kim, GJ; McSherry, F; Herndon, J; Fecci, PE; Adamson, J; Sampson, JH; Floyd, SR; Wang, Z; Vlahovic, G; Yin, FF; Kirkpatrick, JP
MLA Citation
Limon, D, Kim, GJ, McSherry, F, Herndon, J, Fecci, PE, Adamson, J, Sampson, JH, Floyd, SR, Wang, Z, Vlahovic, G, Yin, FF, and Kirkpatrick, JP. "Single-Fraction Radiosurgery for 4 or More Brain Metastases." October 1, 2016.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
E84
End Page
E85

The Effect of Gene Mutations on Survival in Patients With Melanoma Following the Development of Brain Metastases

Authors
Sperduto, PW; Jiang, W; Brown, PD; Braunstein, SE; Sneed, PK; Wattson, DA; Shih, HA; Bangdiwala, A; Shanley, R; Lockney, NA; Beal, K; Lou, E; Amatruda, T; Sperduto, WA; Kirkpatrick, JP; Yeh, N; Gaspar, LE; Molitoris, JK; Masucci, L; Roberge, D; Yu, JB; Chiang, VL; Mehta, MP
MLA Citation
Sperduto, PW, Jiang, W, Brown, PD, Braunstein, SE, Sneed, PK, Wattson, DA, Shih, HA, Bangdiwala, A, Shanley, R, Lockney, NA, Beal, K, Lou, E, Amatruda, T, Sperduto, WA, Kirkpatrick, JP, Yeh, N, Gaspar, LE, Molitoris, JK, Masucci, L, Roberge, D, Yu, JB, Chiang, VL, and Mehta, MP. "The Effect of Gene Mutations on Survival in Patients With Melanoma Following the Development of Brain Metastases." October 1, 2016.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
S178
End Page
S178

Anti-PD-1 Therapy and Stereotactic Radiation for Melanoma and Non-Small Cell Lung Cancer Patients with Brain Metastases: A 2-Institution Series

Authors
Olson, AC; Patel, K; Mowery, YM; Wynne, J; Ready, N; Kirkpatrick, JP; Salama, AK; Khan, MK
MLA Citation
Olson, AC, Patel, K, Mowery, YM, Wynne, J, Ready, N, Kirkpatrick, JP, Salama, AK, and Khan, MK. "Anti-PD-1 Therapy and Stereotactic Radiation for Melanoma and Non-Small Cell Lung Cancer Patients with Brain Metastases: A 2-Institution Series." October 1, 2016.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
E97
End Page
E98

The Effect of Gene Mutations on Survival in Patients With Melanoma Following the Development of Brain Metastases

Authors
Sperduto, PW; Jiang, W; Brown, PD; Braunstein, SE; Sneed, PK; Wattson, DA; Shih, HA; Bangdiwala, A; Shanley, R; Lockney, NA; Beal, K; Lou, E; Amatruda, T; Sperduto, WA; Kirkpatrick, JP; Yeh, N; Gaspar, LE; Molitoris, JK; Masucci, L; Roberge, D; Yu, JB; Chiang, VL; Mehta, MP
MLA Citation
Sperduto, PW, Jiang, W, Brown, PD, Braunstein, SE, Sneed, PK, Wattson, DA, Shih, HA, Bangdiwala, A, Shanley, R, Lockney, NA, Beal, K, Lou, E, Amatruda, T, Sperduto, WA, Kirkpatrick, JP, Yeh, N, Gaspar, LE, Molitoris, JK, Masucci, L, Roberge, D, Yu, JB, Chiang, VL, and Mehta, MP. "The Effect of Gene Mutations on Survival in Patients With Melanoma Following the Development of Brain Metastases." October 1, 2016.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
S178
End Page
S178

Hippocampal Dose From Stereotactic Radiosurgery for 4 to 10 Brain Metastases: Risk Factors and Feasibility of Dose Reduction Via Reoptimization

Authors
Birer, SR; Olson, AC; Adamson, J; Kim, GJ; Salama, JK; Kirkpatrick, JP
MLA Citation
Birer, SR, Olson, AC, Adamson, J, Kim, GJ, Salama, JK, and Kirkpatrick, JP. "Hippocampal Dose From Stereotactic Radiosurgery for 4 to 10 Brain Metastases: Risk Factors and Feasibility of Dose Reduction Via Reoptimization." October 1, 2016.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
E608
End Page
E609

The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases.

Lung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno).A multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials.Of 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR-/+ was 10/15 months (P=.02) and for ALK-/+ was 10/20 months (P<.01), respectively. The MS for the group overall (n=1521) was 15 months. The MS from first treatment for BM for EGFR and ALK-, EGFR+, ALK+ were 14, 23 (P<.01), and 45 (P<.0001) months, respectively. The MS after BM for EGFR+ patients who did/did not receive TKI before BM was 17/30 months (P<.01), respectively, but the risk of death was not statistically different between TKI-naïve patients who did/did not receive TKI after the diagnosis of BM (EGFR/ALK hazard ratios: 1.06 [P=.84]/1.60 [P=.45], respectively). The CoD was nonneurologic in 82% of patients with known CoD.EGFR and ALK gene alterations are associated with delayed onset of BM and longer MS relative to patients without these alterations. The CoD was overwhelmingly nonneurologic in patients with known CoD.

Authors
Sperduto, PW; Yang, TJ; Beal, K; Pan, H; Brown, PD; Bangdiwala, A; Shanley, R; Yeh, N; Gaspar, LE; Braunstein, S; Sneed, P; Boyle, J; Kirkpatrick, JP; Mak, KS; Shih, HA; Engelman, A; Roberge, D; Arvold, ND; Alexander, B; Awad, MM; Contessa, J; Chiang, V; Hardie, J; Ma, D; Lou, E; Sperduto, W; Mehta, MP
MLA Citation
Sperduto, PW, Yang, TJ, Beal, K, Pan, H, Brown, PD, Bangdiwala, A, Shanley, R, Yeh, N, Gaspar, LE, Braunstein, S, Sneed, P, Boyle, J, Kirkpatrick, JP, Mak, KS, Shih, HA, Engelman, A, Roberge, D, Arvold, ND, Alexander, B, Awad, MM, Contessa, J, Chiang, V, Hardie, J, Ma, D, Lou, E, Sperduto, W, and Mehta, MP. "The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases." International journal of radiation oncology, biology, physics 96.2 (October 2016): 406-413.
PMID
27598807
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
406
End Page
413
DOI
10.1016/j.ijrobp.2016.06.006

The Effect of Gene Mutations on Survival in Patients With Melanoma Following the Development of Brain Metastases.

Authors
Sperduto, PW; Jiang, W; Brown, PD; Braunstein, SE; Sneed, PK; Wattson, DA; Shih, HA; Bangdiwala, A; Shanley, R; Lockney, NA; Beal, K; Lou, E; Amatruda, T; Sperduto, WA; Kirkpatrick, JP; Yeh, N; Gaspar, LE; Molitoris, JK; Masucci, L; Roberge, D; Yu, JB; Chiang, VL; Mehta, MP
MLA Citation
Sperduto, PW, Jiang, W, Brown, PD, Braunstein, SE, Sneed, PK, Wattson, DA, Shih, HA, Bangdiwala, A, Shanley, R, Lockney, NA, Beal, K, Lou, E, Amatruda, T, Sperduto, WA, Kirkpatrick, JP, Yeh, N, Gaspar, LE, Molitoris, JK, Masucci, L, Roberge, D, Yu, JB, Chiang, VL, and Mehta, MP. "The Effect of Gene Mutations on Survival in Patients With Melanoma Following the Development of Brain Metastases." International journal of radiation oncology, biology, physics 96.2S (October 2016): S178-.
PMID
27675718
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
S178
DOI
10.1016/j.ijrobp.2016.06.447

Single-Fraction Radiosurgery for 4 or More Brain Metastases.

Authors
Limon, D; Kim, GJ; McSherry, F; Herndon, J; Fecci, PE; Adamson, J; Sampson, JH; Floyd, SR; Wang, Z; Vlahovic, G; Yin, FF; Kirkpatrick, JP
MLA Citation
Limon, D, Kim, GJ, McSherry, F, Herndon, J, Fecci, PE, Adamson, J, Sampson, JH, Floyd, SR, Wang, Z, Vlahovic, G, Yin, FF, and Kirkpatrick, JP. "Single-Fraction Radiosurgery for 4 or More Brain Metastases." International journal of radiation oncology, biology, physics 96.2S (October 2016): E84-E85.
PMID
27675479
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
E84
End Page
E85
DOI
10.1016/j.ijrobp.2016.06.804

Anti-PD-1 Therapy and Stereotactic Radiation for Melanoma and Non-Small Cell Lung Cancer Patients with Brain Metastases: A 2-Institution Series.

Authors
Olson, AC; Patel, K; Mowery, YM; Wynne, J; Ready, N; Kirkpatrick, JP; Salama, AK; Khan, MK
MLA Citation
Olson, AC, Patel, K, Mowery, YM, Wynne, J, Ready, N, Kirkpatrick, JP, Salama, AK, and Khan, MK. "Anti-PD-1 Therapy and Stereotactic Radiation for Melanoma and Non-Small Cell Lung Cancer Patients with Brain Metastases: A 2-Institution Series." International journal of radiation oncology, biology, physics 96.2S (October 2016): E97-E98.
PMID
27675516
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
E97
End Page
E98
DOI
10.1016/j.ijrobp.2016.06.837

Long-Term Outcomes for Patients With Atypical or Malignant Meningiomas Treated With Radiation Therapy: A Single-Institution Retrospective Analysis.

Authors
Kent, CL; Mowery, YM; Wright, AO; Kim, GJ; Desjardins, A; Peters, KB; Vlahovic, G; Friedman, HS; Cummings, TJ; McLendon, RE; Friedman, AH; Sampson, JH; Kirkpatrick, JP
MLA Citation
Kent, CL, Mowery, YM, Wright, AO, Kim, GJ, Desjardins, A, Peters, KB, Vlahovic, G, Friedman, HS, Cummings, TJ, McLendon, RE, Friedman, AH, Sampson, JH, and Kirkpatrick, JP. "Long-Term Outcomes for Patients With Atypical or Malignant Meningiomas Treated With Radiation Therapy: A Single-Institution Retrospective Analysis." International journal of radiation oncology, biology, physics 96.2S (October 2016): E83-E84.
PMID
27675478
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
E83
End Page
E84
DOI
10.1016/j.ijrobp.2016.06.802

Hippocampal Dose From Stereotactic Radiosurgery for 4 to 10 Brain Metastases: Risk Factors and Feasibility of Dose Reduction Via Reoptimization.

Authors
Birer, SR; Olson, AC; Adamson, J; Kim, GJ; Salama, JK; Kirkpatrick, JP
MLA Citation
Birer, SR, Olson, AC, Adamson, J, Kim, GJ, Salama, JK, and Kirkpatrick, JP. "Hippocampal Dose From Stereotactic Radiosurgery for 4 to 10 Brain Metastases: Risk Factors and Feasibility of Dose Reduction Via Reoptimization." International journal of radiation oncology, biology, physics 96.2S (October 2016): E608-E609.
PMID
27675151
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
E608
End Page
E609
DOI
10.1016/j.ijrobp.2016.06.2153

Re-examining TG-142 recommendations in light of modern techniques for linear accelerator based radiosurgery.

The recent development of multifocal stereotactic radiosurgery (SRS) using a single isocenter volumetric modulated arc theory (VMAT) technique warrants a re-examination of the quality assurance (QA) tolerances for routine mechanical QA recommended by the American Association of Physicists in Medicine Task Group Report Number 142. Multifocal SRS can result in targets with small volumes being at a large off-axis distance from the treatment isocenter. Consequently, angular errors in the collimator, patient support assembly (PSA), or gantry could have an increased impact on target coverage.The authors performed a retrospective analysis of dose deviations caused by systematic errors in PSA, collimator, and gantry angle at the tolerance level for routine linear accelerator QA as recommended by TG-142. Dosimetric deviations from multifocal SRS plans (N = 10) were compared to traditional single target SRS using dynamic conformal arcs (N = 10). The chief dosimetric quantities used in determining clinical impact were V100% and D99% of the individual planning target volumes and V12Gy of the healthy brain.Induced errors at tolerance levels showed the greatest change in multifocal SRS target coverage for collimator rotations (±1.0°) with the average changes to V100% and D99% being 5% and 6%, respectively, with maximum changes of 33% and 20%. A reduction in the induced error to half the TG-142 tolerance (±0.5°) demonstrated similar changes in coverage loss to traditional single target SRS assessed at the recommended tolerance level. The observed change in coverage for multifocal SRS was reduced for gantry errors (±1.0°) at 2% and 4.5% for V100% and D99%, respectively, with maximum changes of 18% and 12%. Minimal change in coverage was noted for errors in PSA rotation.This study indicates that institutions utilizing a single isocenter VMAT technique for multifocal disease should pay careful attention to the angular mechanical tolerances in designing a robust and complete QA program.

Authors
Faught, AM; Trager, M; Yin, F-F; Kirkpatrick, J; Adamson, J
MLA Citation
Faught, AM, Trager, M, Yin, F-F, Kirkpatrick, J, and Adamson, J. "Re-examining TG-142 recommendations in light of modern techniques for linear accelerator based radiosurgery." Medical physics 43.10 (October 2016): 5437-.
PMID
27782700
Source
epmc
Published In
Medical physics
Volume
43
Issue
10
Publish Date
2016
Start Page
5437
DOI
10.1118/1.4962471

Phase II study to evaluate the safety and efficacy of intravenous palonosetron (PAL) in primary malignant glioma (MG) patients receiving standard radiotherapy (RT) and concomitant temozolomide (TMZ).

In malignant glioma (MG) patients undergoing radiation therapy (RT) with concomitant temozolomide, chemoradiation-induced nausea and vomiting (cRINV) degrades quality of life (QoL) and reduces treatment adherence, which thereby potentially compromises cancer control.We conducted a 6-week phase II single-arm trial of PAL, a second-generation 5-HT3RA antiemetic, for cRINV prevention in MG patients receiving radiation therapy (RT; 54-60 Gy) and concomitant daily temozolomide (TMZ; 75 mg/m(2)/dX42d). Each week before radiation, patients received single-dose palonosetron (PAL) 0.25 mg IV (total = 6 doses). With safety/tolerability as the primary endpoint, the study was designed to differentiate between toxicity rates of 25 % (unacceptable) and 10 % (acceptable) toxicity rates. Secondary endpoints included the percentage of patients achieving cRINV complete response (CR: no emesis or rescue antiemetic) and QoL. Patients reported adverse effects in Common Toxicity Criteria for Adverse Events diaries; recorded vomiting, nausea, and rescue medication use in diaries (which were used to assess cRINV-CR); and reported QoL 4 days/week using the Modified Functional Living Index-Emesis (M-FLIE) and Osoba nausea and vomiting/retching modules.We enrolled 38 patients (mean age 59 years, 55 % female, 95 % white, 68 % used oral corticosteroids, 76 % reported low alcohol use). Four patients (10.5 %) experienced unacceptable treatment-related toxicity, defined as any grade 3, 4, or 5 non-hematologic toxicity. M-FLIE and Osoba scores showed no evidence of treatment impact on QoL. Overall, cRINV-CR rates for 6 weeks ranged from 67-79 %.Single-dose weekly PAL is a safe and tolerable antiemetic for cRINV prevention in MG patients receiving standard RT and concomitant TMZ.

Authors
Affronti, ML; Woodring, S; Allen, K; Kirkpatrick, J; Peters, KB; Herndon, JE; McSherry, F; Healy, PN; Desjardins, A; Vredenburgh, JJ; Friedman, HS
MLA Citation
Affronti, ML, Woodring, S, Allen, K, Kirkpatrick, J, Peters, KB, Herndon, JE, McSherry, F, Healy, PN, Desjardins, A, Vredenburgh, JJ, and Friedman, HS. "Phase II study to evaluate the safety and efficacy of intravenous palonosetron (PAL) in primary malignant glioma (MG) patients receiving standard radiotherapy (RT) and concomitant temozolomide (TMZ)." October 2016.
PMID
27271867
Source
epmc
Published In
Supportive Care in Cancer
Volume
24
Issue
10
Publish Date
2016
Start Page
4365
End Page
4375
DOI
10.1007/s00520-016-3276-1

Radiation therapy for glioblastoma: Executive summary of an American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline.

To present evidence-based guidelines for radiation therapy in treating glioblastoma not arising from the brainstem.The American Society for Radiation Oncology (ASTRO) convened the Glioblastoma Guideline Panel to perform a systematic literature review investigating the following: (1) Is radiation therapy indicated after biopsy/resection of glioblastoma and how does systemic therapy modify its effects? (2) What is the optimal dose-fractionation schedule for external beam radiation therapy after biopsy/resection of glioblastoma and how might treatment vary based on pretreatment characteristics such as age or performance status? (3) What are ideal target volumes for curative-intent external beam radiation therapy of glioblastoma? (4) What is the role of reirradiation among glioblastoma patients whose disease recurs following completion of standard first-line therapy? Guideline recommendations were created using predefined consensus-building methodology supported by ASTRO-approved tools for grading evidence quality and recommendation strength.Following biopsy or resection, glioblastoma patients with reasonable performance status up to 70 years of age should receive conventionally fractionated radiation therapy (eg, 60 Gy in 2-Gy fractions) with concurrent and adjuvant temozolomide. Routine addition of bevacizumab to this regimen is not recommended. Elderly patients (≥70 years of age) with reasonable performance status should receive hypofractionated radiation therapy (eg, 40 Gy in 2.66-Gy fractions); preliminary evidence may support adding concurrent and adjuvant temozolomide to this regimen. Partial brain irradiation is the standard paradigm for radiation delivery. A variety of acceptable strategies exist for target volume definition, generally involving 2 phases (primary and boost volumes) or 1 phase (single volume). For recurrent glioblastoma, focal reirradiation can be considered in younger patients with good performance status.Radiation therapy occupies an integral role in treating glioblastoma. Whether and how radiation therapy should be applied depends on characteristics specific to tumor and patient, including age and performance status.

Authors
Cabrera, AR; Kirkpatrick, JP; Fiveash, JB; Shih, HA; Koay, EJ; Lutz, S; Petit, J; Chao, ST; Brown, PD; Vogelbaum, M; Reardon, DA; Chakravarti, A; Wen, PY; Chang, E
MLA Citation
Cabrera, AR, Kirkpatrick, JP, Fiveash, JB, Shih, HA, Koay, EJ, Lutz, S, Petit, J, Chao, ST, Brown, PD, Vogelbaum, M, Reardon, DA, Chakravarti, A, Wen, PY, and Chang, E. "Radiation therapy for glioblastoma: Executive summary of an American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline." Practical radiation oncology 6.4 (July 2016): 217-225.
PMID
27211230
Source
epmc
Published In
Practical Radiation Oncology
Volume
6
Issue
4
Publish Date
2016
Start Page
217
End Page
225
DOI
10.1016/j.prro.2016.03.007

Embracing rejection: Immunologic trends in brain metastasis.

Brain metastases represent the most common type of brain tumor. These tumors offer a dismal prognosis and significantly impact quality of life for patients. Their capacity for central nervous system (CNS) invasion is dependent upon induced disruptions to the blood-brain barrier (BBB), alterations to the brain microenvironment, and mechanisms for escaping CNS immunosurveillance. In the emerging era of immunotherapy, understanding how metastases are influenced by the immunologic peculiarities of the CNS will be crucial to forging therapeutic advances. In this review, the immunology of brain metastasis is explored.

Authors
Farber, SH; Tsvankin, V; Narloch, JL; Kim, GJ; Salama, AKS; Vlahovic, G; Blackwell, KL; Kirkpatrick, JP; Fecci, PE
MLA Citation
Farber, SH, Tsvankin, V, Narloch, JL, Kim, GJ, Salama, AKS, Vlahovic, G, Blackwell, KL, Kirkpatrick, JP, and Fecci, PE. "Embracing rejection: Immunologic trends in brain metastasis." Oncoimmunology 5.7 (July 2016): e1172153-. (Review)
PMID
27622023
Source
epmc
Published In
OncoImmunology
Volume
5
Issue
7
Publish Date
2016
Start Page
e1172153
DOI
10.1080/2162402x.2016.1172153

Physics considerations for single-isocenter, volumetric modulated arc radiosurgery for treatment of multiple intracranial targets.

Our purpose was to address challenges associated with single-isocenter radiosurgery for multiple intracranial targets (SIRMIT) including increased sensitivity to rotational uncertainties (resulting from distance of the targets from isocenter) as well as potential for decreased plan quality from larger multileaf collimator width >4 cm from isocenter.We evaluated the effect that a 6 degrees-of-freedom couch correction had on localization uncertainty for SIRMIT using thermoplastic mask immobilization. Required setup margin was determined from rotation of the skull and mask (setup kV cone beam computed tomography relative to planning computed tomography). Intraoperational margin was determined from skull rotation within the mask (difference between pre- and posttreatment cone beam computed tomography). We also investigated 4 isocenter placement strategies: volume centroid, centroid of equally weighted points (1 per target), centroid of points weighted by inverse of volume, and Eclipse's built-in method.When no 6 degrees-of-freedom couch correction is performed after initial setup, a 0.35-mm margin is required per centimeter of target-isocenter separation to account for 95% of rotational uncertainties at initial setup. This margin is reduced to 0.10 mm/cm of target-isocenter separation to account for intraoperative rotational uncertainties when the initial setup uncertainty is eliminated via image guided 6 degrees-of-freedom couch correction. Analysis of 11 multitarget plans (37 targets) showed that conformity index and gradient index improved with decreasing distance from isocenter, this trend being more pronounced for targets <1 mL. Alternative isocenters aimed at decreasing distance of small targets improved their gradient index, but resulted in poorer dose indices for large targets. Mean distance from isocenter was smallest for the centroid of equally weighted points (4.1 ± 1.6cm vs 4.2-4.5cm).Rotational corrections via image guidance are necessary for SIRMIT with a thermoplastic mask for immobilization. There is a clear tradeoff between dosimetric quality of small and large targets that should be considered carefully when placing the isocenter.

Authors
Stanhope, C; Chang, Z; Wang, Z; Yin, F-F; Kim, G; Salama, JK; Kirkpatrick, J; Adamson, J
MLA Citation
Stanhope, C, Chang, Z, Wang, Z, Yin, F-F, Kim, G, Salama, JK, Kirkpatrick, J, and Adamson, J. "Physics considerations for single-isocenter, volumetric modulated arc radiosurgery for treatment of multiple intracranial targets." May 2016.
PMID
26723551
Source
epmc
Published In
Practical Radiation Oncology
Volume
6
Issue
3
Publish Date
2016
Start Page
207
End Page
213
DOI
10.1016/j.prro.2015.10.010

Stereotactic Radiosurgery for Recurrent High Grade Gliomas: Patterns of Failure

Authors
Boyle, JM; Chino, JP; Sampson, JH; Desjardins, A; Kirkpatrick, JP
MLA Citation
Boyle, JM, Chino, JP, Sampson, JH, Desjardins, A, and Kirkpatrick, JP. "Stereotactic Radiosurgery for Recurrent High Grade Gliomas: Patterns of Failure." November 1, 2015.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
E92
End Page
E92

Outcomes for Patients With Intracranial Meningiomas Treated With Radiation therapy and Bevacizumab: A Single-Institution Retrospective Analysis

Authors
Mowery, YM; Kim, GJ; Wright, A; Desjardins, A; Peters, KB; Vlahovic, G; Friedman, HS; Sampson, JH; Kirkpatrick, JP
MLA Citation
Mowery, YM, Kim, GJ, Wright, A, Desjardins, A, Peters, KB, Vlahovic, G, Friedman, HS, Sampson, JH, and Kirkpatrick, JP. "Outcomes for Patients With Intracranial Meningiomas Treated With Radiation therapy and Bevacizumab: A Single-Institution Retrospective Analysis." November 1, 2015.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
E104
End Page
E104

Rotational Corrections for Stereotactic Radiosurgery (SRS) of Multiple Brain Metastases Treated With Single Isocenter Technique

Authors
Wang, Z; Kirkpatrick, JP; Kim, GJ; Kelsey, CR; Yin, FF
MLA Citation
Wang, Z, Kirkpatrick, JP, Kim, GJ, Kelsey, CR, and Yin, FF. "Rotational Corrections for Stereotactic Radiosurgery (SRS) of Multiple Brain Metastases Treated With Single Isocenter Technique." November 1, 2015.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
E602
End Page
E602

A Simple Kinetic Model Provides an Early Prediction of Thrombocytopenia in Malignant Glioma Patients Treated With Radiation and Temozolomide

Authors
Brownstein, J; Randazzo, D; Kim, GJ; Peters, K; Kirkpatrick, JP
MLA Citation
Brownstein, J, Randazzo, D, Kim, GJ, Peters, K, and Kirkpatrick, JP. "A Simple Kinetic Model Provides an Early Prediction of Thrombocytopenia in Malignant Glioma Patients Treated With Radiation and Temozolomide." November 1, 2015.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
E92
End Page
E92

The Effect of Gene Mutations on Survival in Patients With Adenocarcinoma of the Lung Following the Development of Brain Metastases

Authors
Sperduto, PW; Yang, TJ; Beal, K; Pan, HY; Brown, PD; Ho, YY; Yeh, N; Gaspar, LE; Braunstein, SE; Sneed, PK; Boyle, JM; Kirkpatrick, JP; Mak, KS; Shih, HA; Engelman, A; Roberge, D; Arvold, ND; Yu, JB; Hardie, JG; Mehta, MP
MLA Citation
Sperduto, PW, Yang, TJ, Beal, K, Pan, HY, Brown, PD, Ho, YY, Yeh, N, Gaspar, LE, Braunstein, SE, Sneed, PK, Boyle, JM, Kirkpatrick, JP, Mak, KS, Shih, HA, Engelman, A, Roberge, D, Arvold, ND, Yu, JB, Hardie, JG, and Mehta, MP. "The Effect of Gene Mutations on Survival in Patients With Adenocarcinoma of the Lung Following the Development of Brain Metastases." November 1, 2015.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
S37
End Page
S38

Pathologic Evaluation of Radiographically Enlarging Lesions After Stereotactic Radiosurgery for Brain Metastases

Authors
Kim, GJ; Barkdoll, T; Sampson, JH; Wang, Z; Hoang, J; Fecci, PE; Yin, FF; Kirkpatrick, JP
MLA Citation
Kim, GJ, Barkdoll, T, Sampson, JH, Wang, Z, Hoang, J, Fecci, PE, Yin, FF, and Kirkpatrick, JP. "Pathologic Evaluation of Radiographically Enlarging Lesions After Stereotactic Radiosurgery for Brain Metastases." November 1, 2015.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
E93
End Page
E93

Radiosurgery for Brain Metastases in Melanoma Patients Receiving Ipilimumab

Authors
Olson, AC; Qin, R; Singh, B; Bhavsar, N; Wolf, S; Salama, JK; Kirkpatrick, JP; Salama, AK
MLA Citation
Olson, AC, Qin, R, Singh, B, Bhavsar, N, Wolf, S, Salama, JK, Kirkpatrick, JP, and Salama, AK. "Radiosurgery for Brain Metastases in Melanoma Patients Receiving Ipilimumab." November 1, 2015.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
E88
End Page
E88

Is Less, More? The Evolving Role of Radiation Therapy for Brain Metastases

Authors
Soltys, SG; Kirkpatrick, JP; Laack, NN; Kavanagh, BD; Breneman, JC; Shih, HA
MLA Citation
Soltys, SG, Kirkpatrick, JP, Laack, NN, Kavanagh, BD, Breneman, JC, and Shih, HA. "Is Less, More? The Evolving Role of Radiation Therapy for Brain Metastases." International Journal of Radiation Oncology*Biology*Physics 92.5 (August 2015): 963-966.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
92
Issue
5
Publish Date
2015
Start Page
963
End Page
966
DOI
10.1016/j.ijrobp.2015.03.003

Radiation-induced malignant gliomas: a current review.

Radiation-induced malignant gliomas (RIMGs) are known uncommon risks of brain irradiation. We describe 4 cases of RIMG that occurred at our institution and conduct the largest comprehensive review of the literature to characterize RIMGs better.Patients were identified through the PubMed database. Pearson R linear correlation test was used to evaluate the correlation between radiotherapy (RT) dose and age and latency period. Student t test was used to evaluate differences between latency periods for original tumor lesions. A normalized biologic equivalent dose analysis was performed to indicate the minimum and maximum radiation threshold for neoplasia. A Kaplan-Meier analysis was used to illustrate the overall survival curves.The analysis included 172 cases from the PubMed database and 4 cases occurring at our institution. The median RT dose administered was 35.6 Gy, with the most common dosage ranges being 21-30 Gy (31%) and 41-50 Gy (21.5%). Median latency period was 9 years until diagnosis of RIMG, and RIMG occurred within 15 years in 82% of the patients. There was no correlation between the age of the patient at the time RT was administered (R(2) = 0.00081) or amount of RT (R(2) = 0.00005) and latency period for RIMG. The mean biologic equivalent dose for neoplasia of a RIMG was 63.3 Gy. The median survival of patients with RIMG improved over time (P = 0.004), with median survival of 9 months before 2007 and 11.5 months after 2007.The risk of RIMG appears to be the same for all age groups, histologies, and RT dosages. Although the risk is low, patients should be aware of RIMG as a possible complication of brain irradiation.

Authors
Elsamadicy, AA; Babu, R; Kirkpatrick, JP; Adamson, DC
MLA Citation
Elsamadicy, AA, Babu, R, Kirkpatrick, JP, and Adamson, DC. "Radiation-induced malignant gliomas: a current review." World neurosurgery 83.4 (April 2015): 530-542. (Review)
PMID
25524065
Source
epmc
Published In
World Neurosurgery
Volume
83
Issue
4
Publish Date
2015
Start Page
530
End Page
542
DOI
10.1016/j.wneu.2014.12.009

From active shape model to active optical flow model: a shape-based approach to predicting voxel-level dose distributions in spine SBRT.

Prediction of achievable dose distribution in spine stereotactic body radiation therapy (SBRT) can help in designing high-quality treatment plans to maximally protect spinal cords and to effectively control tumours. Dose distributions at spinal cords are primarily affected by the shapes of adjacent planning target volume (PTV) contours. In this work, we estimate such contour effects and predict dose distributions by exploring active optical flow model (AOFM) and active shape model (ASM). We first collect a sequence of dose sub-images and PTV contours near spinal cords from fifteen SBRT plans in the training dataset. The data collection is then classified into five groups according to the PTV locations in relation to spinal cords. In each group, we randomly choose a dose sub-image as the reference and register all other sub-images to the reference using an optical flow method. AOFM is then constructed by importing optical flow vectors and dose values into the principal component analysis (PCA). Similarly, we build ASM by using PCA on PTV contour points. The correlation between ASM and AOFM is estimated via a stepwise multiple regression model. When predicting dose distribution of a new case, the group is first determined based on the PTV contour. The prediction model of the selected group is used to estimate dose distributions by mapping the PTV contours from the ASM space to the AOFM space. This method was validated on fifteen SBRT plans in the testing dataset. Analysis of dose-volume histograms revealed that the important D2%, D5%, D10% and D0.1cc dosimetric parameters of spinal cords between the prediction and the clinical plans were 11.7 ± 1.7 Gy versus 11.8 ± 1.7 Gy (p = 0.95), 10.9 ± 1.7 Gy versus 11.1 ± 1.9 Gy (p = 0.8295), 10.2 ± 1.6 Gy versus 10.1 ± 1.7 (p = 0.9036) and 11.2 ± 2.0 Gy versus 11.1 ± 2.2 Gy (p = 0.5208), respectively. Here, the ‘cord’ is the spinal cord proper (not the thecal sac) extended 5 mm inferior and superior to the involved vertebral bodies, and the ‘PTV’ is the involved segment of the vertebral body expanded uniformly by 2 mm but excluding the spinal cord volume expanded by 2 mm (Ref. RTOG 0631). These results suggested that the AOFM-based approach is a promising tool for predicting accurate spinal cord dose in clinical practice. In this work, we demonstrated the feasibility of using AOFM and ASM models derived from previously treated patients to estimate the achievable dose distributions for new patients.

Authors
Liu, J; Wu, QJ; Kirkpatrick, JP; Yin, F-F; Yuan, L; Ge, Y
MLA Citation
Liu, J, Wu, QJ, Kirkpatrick, JP, Yin, F-F, Yuan, L, and Ge, Y. "From active shape model to active optical flow model: a shape-based approach to predicting voxel-level dose distributions in spine SBRT." Physics in medicine and biology 60.5 (March 2015): N83-N92.
PMID
25675394
Source
epmc
Published In
Physics in Medicine and Biology
Volume
60
Issue
5
Publish Date
2015
Start Page
N83
End Page
N92
DOI
10.1088/0031-9155/60/5/n83

An active optical flow model for dose prediction in spinal SBRT plans

© Springer International Publishing Switzerland 2015. Accurate dose predication is critical to spinal stereotactic body radiation therapy (SBRT). It enables radiation oncologists and planners to design treatment plans that maximally protect spinal cord while effectively controlling surrounding tumors. Spinal cord dose distribution is primarily affected by the shapes of tumor boundaries near the organ. In this work, we estimate such boundary effects and predict dose distribution by exploring an active optical flow model (AOFM). To establish AOFM, we collect a sequence of dose sub-images and tumor contours near spinal cords from a database of clinically accepted spine SBRT plans. The data are classified into five groups according to the tumor location in relation to the spinal cords. In each group, we randomly choose a dose sub-image as the reference and register all other dose images to the reference using an optical flow method. AOFM is then constructed by importing optical flow vectors and dose values into the principal component analysis. To develop the predictive model for a group, we also build active shape model (ASM) of tumor contours near the spinal cords. The correlation between ASM and AOFM is estimated via the multiple regression model. When predicting dose distribution of a new case, the group was first determined based on the case's tumor contour. Then the corresponding model for the group is used to map from the ASM space to the AOFM space. Finally, the parameters in the AOFM space are used to estimate dose distribution. This method was validated on 30 SBRT plans. Analysis of dose-volume histograms revealed that at the important 2 % volume mark, the dose difference between prediction and clinical plan is less than 4 %. These results suggest that the AOFM-based approach is a promising tool for predicting accurate spinal cord dose in clinical practice.

Authors
Liu, J; Wu, QJ; Yin, FF; Kirkpatrick, JP; Cabrera, A; Ge, Y
MLA Citation
Liu, J, Wu, QJ, Yin, FF, Kirkpatrick, JP, Cabrera, A, and Ge, Y. "An active optical flow model for dose prediction in spinal SBRT plans." January 1, 2015.
Source
scopus
Published In
Lecture Notes in Engineering and Computer Science
Volume
20
Publish Date
2015
Start Page
27
End Page
35
DOI
10.1007/978-3-319-14148-0-3

An active optical flow model for dose prediction in spinal sbrt plans

© Springer International Publishing Switzerland 2015. Accurate dose predication is critical to spinal stereotactic body radiation therapy (SBRT). It enables radiation oncologists and planners to design treatment plans that maximally protect spinal cord while effectively controlling surrounding tumors. Spinal cord dose distribution is primarily affected by the shapes of tumor boundaries near the organ. In this work, we estimate such boundary effects and predict dose distribution by exploring an active optical flow model (AOFM). To establish AOFM, we collect a sequence of dose sub-images and tumor contours near spinal cords from a database of clinically accepted spine SBRT plans. The data are classified into five groups according to the tumor location in relation to the spinal cords. In each group, we randomly choose a dose sub-image as the reference and register all other dose images to the reference using an optical flowmethod. AOFM is then constructed by importing optical flow vectors and dose values into the principal component analysis. To develop the predictivemodel for a group, we also build active shape model (ASM) of tumor contours near the spinal cords. The correlation between ASM and AOFM is estimated via the multiple regression model. When predicting dose distribution of a new case, the group was first determined based on the case’stumor contour. Then the corresponding model for the group is used to map from the ASM space to the AOFM space. Finally, the parameters in the AOFM space are used to estimate dose distribution. This method was validated on 30 SBRT plans. Analysis of dose-volume histograms revealed that at the important 2%volume mark, the dose difference between prediction and clinical plan is less than 4%. These results suggest that theAOFM-based approach is a promising tool for predicting accurate spinal cord dose in clinical practice.

Authors
Liu, J; Jackie Wu, Q; Yin, FF; Kirkpatrick, JP; Cabrera, A; Ge, Y
MLA Citation
Liu, J, Jackie Wu, Q, Yin, FF, Kirkpatrick, JP, Cabrera, A, and Ge, Y. "An active optical flow model for dose prediction in spinal sbrt plans." Lecture Notes in Computational Vision and Biomechanics 20 (January 1, 2015): 27-35.
Source
scopus
Published In
Lecture Notes in Computational Vision and Biomechanics
Volume
20
Publish Date
2015
Start Page
27
End Page
35
DOI
10.1007/978-3-319-14148-0_3

Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: results of a randomized trial.

PURPOSE: To identify an optimal margin about the gross target volume (GTV) for stereotactic radiosurgery (SRS) of brain metastases, minimizing toxicity and local recurrence. METHODS AND MATERIALS: Adult patients with 1 to 3 brain metastases less than 4 cm in greatest dimension, no previous brain radiation therapy, and Karnofsky performance status (KPS) above 70 were eligible for this institutional review board-approved trial. Individual lesions were randomized to 1- or 3- mm uniform expansion of the GTV defined on contrast-enhanced magnetic resonance imaging (MRI). The resulting planning target volume (PTV) was treated to 24, 18, or 15 Gy marginal dose for maximum PTV diameters less than 2, 2 to 2.9, and 3 to 3.9 cm, respectively, using a linear accelerator-based image-guided system. The primary endpoint was local recurrence (LR). Secondary endpoints included neurocognition Mini-Mental State Examination, Trail Making Test Parts A and B, quality of life (Functional Assessment of Cancer Therapy-Brain), radionecrosis (RN), need for salvage radiation therapy, distant failure (DF) in the brain, and overall survival (OS). RESULTS: Between February 2010 and November 2012, 49 patients with 80 brain metastases were treated. The median age was 61 years, the median KPS was 90, and the predominant histologies were non-small cell lung cancer (25 patients) and melanoma (8). Fifty-five, 19, and 6 lesions were treated to 24, 18, and 15 Gy, respectively. The PTV/GTV ratio, volume receiving 12 Gy or more, and minimum dose to PTV were significantly higher in the 3-mm group (all P<.01), and GTV was similar (P=.76). At a median follow-up time of 32.2 months, 11 patients were alive, with median OS 10.6 months. LR was observed in only 3 lesions (2 in the 1 mm group, P=.51), with 6.7% LR 12 months after SRS. Biopsy-proven RN alone was observed in 6 lesions (5 in the 3-mm group, P=.10). The 12-month DF rate was 45.7%. Three months after SRS, no significant change in neurocognition or quality of life was observed. CONCLUSIONS: SRS was well tolerated, with low rates of LR and RN in both cohorts. However, given the higher potential risk of RN with a 3-mm margin, a 1-mm GTV expansion is more appropriate.

Authors
Kirkpatrick, JP; Wang, Z; Sampson, JH; McSherry, F; Herndon, JE; Allen, KJ; Duffy, E; Hoang, JK; Chang, Z; Yoo, DS; Kelsey, CR; Yin, F-F
MLA Citation
Kirkpatrick, JP, Wang, Z, Sampson, JH, McSherry, F, Herndon, JE, Allen, KJ, Duffy, E, Hoang, JK, Chang, Z, Yoo, DS, Kelsey, CR, and Yin, F-F. "Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: results of a randomized trial." International journal of radiation oncology, biology, physics 91.1 (January 2015): 100-108.
PMID
25442342
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
91
Issue
1
Publish Date
2015
Start Page
100
End Page
108
DOI
10.1016/j.ijrobp.2014.09.004

A hypothesis: indirect cell death in the radiosurgery era.

Authors
Sperduto, PW; Song, CW; Kirkpatrick, JP; Glatstein, E
MLA Citation
Sperduto, PW, Song, CW, Kirkpatrick, JP, and Glatstein, E. "A hypothesis: indirect cell death in the radiosurgery era." International journal of radiation oncology, biology, physics 91.1 (January 2015): 11-13.
PMID
25835617
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
91
Issue
1
Publish Date
2015
Start Page
11
End Page
13
DOI
10.1016/j.ijrobp.2014.08.355

Abstract 3774: Hyperthermia treatment overcomes temozolomide resistance in glioma cells by downregulating MGMT expression and increasing temozolomide uptake

Authors
Lee, C-T; Blackley, A; Landon, C; Spasojevic, I; Kirkpatrick, JP; Dewhirst, MW
MLA Citation
Lee, C-T, Blackley, A, Landon, C, Spasojevic, I, Kirkpatrick, JP, and Dewhirst, MW. "Abstract 3774: Hyperthermia treatment overcomes temozolomide resistance in glioma cells by downregulating MGMT expression and increasing temozolomide uptake." October 1, 2014.
Source
crossref
Published In
Cancer Research
Volume
74
Issue
19 Supplement
Publish Date
2014
Start Page
3774
End Page
3774
DOI
10.1158/1538-7445.AM2014-3774

Recurrent malignant gliomas.

In almost all patients, malignant glioma recurs following initial treatment with maximal safe resection, conformal radiotherapy, and temozolomide. This review describes the many options for treatment of recurrent malignant gliomas, including reoperation, alternating electric field therapy, chemotherapy, stereotactic radiotherapy or radiosurgery, or some combination of these modalities, presenting the evidence for each approach. No standard of care has been established, though the antiangiogenic agent, bevacizumab; stereotactic radiotherapy or radiosurgery; and, perhaps, combined treatment with these 2 modalities appear to offer modest benefits over other approaches. Clearly, randomized trials of these options would be advantageous, and novel, more efficacious approaches are urgently needed.

Authors
Kirkpatrick, JP; Sampson, JH
MLA Citation
Kirkpatrick, JP, and Sampson, JH. "Recurrent malignant gliomas." Seminars in radiation oncology 24.4 (October 2014): 289-298. (Review)
PMID
25219814
Source
epmc
Published In
Seminars in Radiation Oncology
Volume
24
Issue
4
Publish Date
2014
Start Page
289
End Page
298
DOI
10.1016/j.semradonc.2014.06.006

Predicting Dose Distributions in Spinal SBRT Plans Using An Active Appearance Model (AAM)

Authors
Liu, J; Wu, Q; Yin, F; Kirkpatrick, JP; Cabrera, AR; Ge, Y
MLA Citation
Liu, J, Wu, Q, Yin, F, Kirkpatrick, JP, Cabrera, AR, and Ge, Y. "Predicting Dose Distributions in Spinal SBRT Plans Using An Active Appearance Model (AAM)." September 1, 2014.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
90
Publish Date
2014
Start Page
S17
End Page
S18

Evaluating radiation-induced white matter changes in patients treated with stereotactic radiosurgery using diffusion tensor imaging: a pilot study.

Stereotactic radiosurgery (SRS) has been an effective treatment method for brain tumors; however, few data are available regarding radiation-induced white matter (WM) damage by SRS. In this work, diffusion tensor imaging (DTI) was used to investigate WM changes following SRS. Fifteen patients with gliomas were enrolled, with prescription doses ranging 18-25 Gy. Patients were scanned with magnetic resonance imaging (MRI) including DTI before and after SRS. Diffusion tensors were calculated and fiber tracking was performed. Non-irradiated WM volumes and irradiated WM volumes receiving ≥ 12 Gy and ≥ Gy were contoured as volumes of interest (VOI). Apparent diffusion coefficient (〈D〉), fractional anisotropy (FA) and number of fibers (NF) were calculated and assessed using the Wilcoxon signed-rank test. Compared with those of non-irradiated VOIs, FA and NF decreased considerably after two months of SRS in the irradiated WM VOIs. The variation in (〈D〉 was however small and was not statistically significant. The preliminary results suggested that FA and NF might potentially be more sensitive indicators than (〈D〉 in measuring radiation-induced WM changes and DTI could be a valuable tool to assess radiation-induced WM changes in SRS. Although it is still preliminary, this pilot study may be useful to provide insights for future studies.

Authors
Chang, Z; Kirkpatrick, JP; Wang, Z; Cai, J; Adamson, J; Yin, F-F
MLA Citation
Chang, Z, Kirkpatrick, JP, Wang, Z, Cai, J, Adamson, J, and Yin, F-F. "Evaluating radiation-induced white matter changes in patients treated with stereotactic radiosurgery using diffusion tensor imaging: a pilot study." Technol Cancer Res Treat 13.1 (February 2014): 21-28.
PMID
23862743
Source
pubmed
Published In
Technology in cancer research & treatment
Volume
13
Issue
1
Publish Date
2014
Start Page
21
End Page
28
DOI
10.7785/tcrt.2012.500358

Stereotactic body radiotherapy: A critical review for nonradiation oncologists

Stereotactic body radiotherapy (SBRT) involves the treatment of extracranial primary tumors or metastases with a few, high doses of ionizing radiation. In SBRT, tumor kill is maximized and dose to surrounding tissue is minimized, by precise and accurate delivery of multiple radiation beams to the target. This is particularly challenging, because extracranial lesions often move with respiration and are irregular in shape, requiring careful treatment planning and continual management of this motion and patient position during irradiation. This review presents the rationale, process workflow, and technology for the safe and effective administration of SBRT, as well as the indications, outcome, and limitations for this technique in the treatment of lung cancer, liver cancer, and metastatic disease. © 2013 American Cancer Society.

Authors
Kirkpatrick, JP; Kelsey, CR; Palta, M; Cabrera, AR; Salama, JK; Patel, P; Perez, BA; Lee, J; Yin, FF
MLA Citation
Kirkpatrick, JP, Kelsey, CR, Palta, M, Cabrera, AR, Salama, JK, Patel, P, Perez, BA, Lee, J, and Yin, FF. "Stereotactic body radiotherapy: A critical review for nonradiation oncologists." Cancer 120.7 (January 1, 2014): 942-954. (Review)
Source
scopus
Published In
Cancer
Volume
120
Issue
7
Publish Date
2014
Start Page
942
End Page
954
DOI
10.1002/cncr.28515

Stereotactic body radiotherapy: A critical review for non-radiation oncologists

Authors
Kirkpatrick, JP; Kelsey, CR; Palta, M; Cabrera, AR; Salama, JK; Patel, P; Perez, BA; Lee, J; Yin, F-F
MLA Citation
Kirkpatrick, JP, Kelsey, CR, Palta, M, Cabrera, AR, Salama, JK, Patel, P, Perez, BA, Lee, J, and Yin, F-F. "Stereotactic body radiotherapy: A critical review for non-radiation oncologists." Cancer (2014).
PMID
24382744
Source
scopus
Published In
Cancer
Publish Date
2014

Early Results of a Randomized Trial to Identify an Optimal PTV in Stereotactic Radiosurgery of Brain Metastases

Authors
Kirkpatrick, JP; Wang, Z; Sampson, J; Kelsey, C; Allen, K; Duffy, E; Green, S; Cabrera, A; Palta, M; Yin, F
MLA Citation
Kirkpatrick, JP, Wang, Z, Sampson, J, Kelsey, C, Allen, K, Duffy, E, Green, S, Cabrera, A, Palta, M, and Yin, F. "Early Results of a Randomized Trial to Identify an Optimal PTV in Stereotactic Radiosurgery of Brain Metastases." October 1, 2013.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
2
Publish Date
2013
Start Page
S50
End Page
S50

Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: a prospective trial.

PURPOSE: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. METHODS AND MATERIALS: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. RESULTS: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. CONCLUSIONS: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach.

Authors
Cabrera, AR; Cuneo, KC; Desjardins, A; Sampson, JH; McSherry, F; Herndon, JE; Peters, KB; Allen, K; Hoang, JK; Chang, Z; Craciunescu, O; Vredenburgh, JJ; Friedman, HS; Kirkpatrick, JP
MLA Citation
Cabrera, AR, Cuneo, KC, Desjardins, A, Sampson, JH, McSherry, F, Herndon, JE, Peters, KB, Allen, K, Hoang, JK, Chang, Z, Craciunescu, O, Vredenburgh, JJ, Friedman, HS, and Kirkpatrick, JP. "Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: a prospective trial." Int J Radiat Oncol Biol Phys 86.5 (August 1, 2013): 873-879.
PMID
23725997
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
86
Issue
5
Publish Date
2013
Start Page
873
End Page
879
DOI
10.1016/j.ijrobp.2013.04.029

MO-F-108-11: 3D Verification for Multifocal Single Isocenter SRS.

Recent trends in SRS use multifocal VMAT plans to simultaneously treat several, distinct targets. Conventional verification often involves low resolution measurements in a single plane, cylinder, or intersecting planes of diodes or ion chambers. This work presents an investigation into the accuracy, consistency and reproducibility of this treatment technique using a high-resolution 3D dosimetry system (PRESAGE/Optical-CT).A complex VMAT plan consisting of a single isocenter but 5 separate targets was created in Eclipse for a head phantom containing a cylindrical PRESAGE dosimetry insert of 10cm diameter and height. The plan contained 5 arcs delivering doses from 12-20 Gy. The treatment was delivered to four separate dosimeters positioned in the head-phantom. Each delivery was performed after IGRT positioning using 2D and 3D kilovoltage images. A final delivery was given to a modified insert containing a pin-point ion chamber enabling calibration of Presage data to dose. Dosimetric data was read out in an optical-CT scanner. Consistency and reproducibility of the treatment technique (including IGRT set-up) was investigated by comparing the dose distributions in the 4 inserts, and with the predicted TPS distribution.Dose distributions from the 4 dosimeters were registered to find the mean and standard deviation at all points throughout the dosimeters. They showed less than 3% standard deviation within voxels of similar dose regions. 3D gamma maps show the calculated delivered dose matched output to within expected tolerances and errors - passing rate was 98.0% (3%, 2mm).The deliveries of the irradiation were found to be consistent and matched the treatment plan, demonstrating high accuracy and reproducibility of the treatment machine, the IGRT procedure, and the 3D measurement. The complexity of the treatment (multiple arcs) and dosimetry (multiple strong gradients) pose a substantial challenge for comprehensive verification. 3D dosimetry can be uniquely effective in this scenario.

Authors
Thomas, A; Niebanck, M; Wang, Z; Kirkpatrick, J; Oldham, M
MLA Citation
Thomas, A, Niebanck, M, Wang, Z, Kirkpatrick, J, and Oldham, M. "MO-F-108-11: 3D Verification for Multifocal Single Isocenter SRS." Medical physics 40.6Part24 (June 2013): 409-.
PMID
28518457
Source
epmc
Published In
Medical physics
Volume
40
Issue
6Part24
Publish Date
2013
Start Page
409
DOI
10.1118/1.4815287

Oncology scan - Low-grade gliomas: Predicting and changing outcome

Authors
Kirkpatrick, JP
MLA Citation
Kirkpatrick, JP. "Oncology scan - Low-grade gliomas: Predicting and changing outcome." International Journal of Radiation Oncology Biology Physics 87.2 (2013): 234-236.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
2
Publish Date
2013
Start Page
234
End Page
236
DOI
10.1016/j.ijrobp.2013.05.009

Implementing and integrating a clinically driven electronic medical record for radiation oncology in a large medical enterprise.

PURPOSE/OBJECTIVE: While our department is heavily invested in computer-based treatment planning, we historically relied on paper-based charts for management of Radiation Oncology patients. In early 2009, we initiated the process of conversion to an electronic medical record (EMR) eliminating the need for paper charts. Key goals included the ability to readily access information wherever and whenever needed, without compromising safety, treatment quality, confidentiality, or productivity. METHODOLOGY: In February, 2009, we formed a multi-disciplinary team of Radiation Oncology physicians, nurses, therapists, administrators, physicists/dosimetrists, and information technology (IT) specialists, along with staff from the Duke Health System IT department. The team identified all existing processes and associated information/reports, established the framework for the EMR system and generated, tested and implemented specific EMR processes. RESULTS: Two broad classes of information were identified: information which must be readily accessed by anyone in the health system versus that used solely within the Radiation Oncology department. Examples of the former are consultation reports, weekly treatment check notes, and treatment summaries; the latter includes treatment plans, daily therapy records, and quality assurance reports. To manage the former, we utilized the enterprise-wide system, which required an intensive effort to design and implement procedures to export information from Radiation Oncology into that system. To manage "Radiation Oncology" data, we used our existing system (ARIA, Varian Medical Systems.) The ability to access both systems simultaneously from a single workstation (WS) was essential, requiring new WS and modified software. As of January, 2010, all new treatments were managed solely with an EMR. We find that an EMR makes information more widely accessible and does not compromise patient safety, treatment quality, or confidentiality. However, compared to paper charts, time required by clinicians to access/enter patient information has substantially increased. While productivity is improving with experience, substantial growth will require better integration of the system components, decreased access times, and improved user interfaces. $127K was spent on new hardware and software; elimination of paper yields projected savings of $21K/year. One year after conversion to an EMR, more than 90% of department staff favored the EMR over the previous paper charts. CONCLUSION: Successful implementation of a Radiation Oncology EMR required not only the effort and commitment of all functions of the department, but support from senior health system management, corporate IT, and vendors. Realization of the full benefits of an EMR will require experience, faster/better integrated software, and continual improvement in underlying clinical processes.

Authors
Kirkpatrick, JP; Light, KL; Walker, RM; Georgas, DL; Antoine, PA; Clough, RW; Cozart, HB; Yin, F-F; Yoo, S; Willett, CG
MLA Citation
Kirkpatrick, JP, Light, KL, Walker, RM, Georgas, DL, Antoine, PA, Clough, RW, Cozart, HB, Yin, F-F, Yoo, S, and Willett, CG. "Implementing and integrating a clinically driven electronic medical record for radiation oncology in a large medical enterprise. (Published online)" Front Oncol 3 (2013): 69-.
PMID
23616946
Source
pubmed
Published In
Frontiers in Oncology
Volume
3
Publish Date
2013
Start Page
69
DOI
10.3389/fonc.2013.00069

Radiotherapy and Radiosurgery for Tumors of the Central Nervous System

In this article, the application of radiotherapy, alone and in combination with surgery and chemotherapy, in the treatment of metastases to the brain (the most common malignant brain lesion), primary malignant gliomas (the most common malignant primary brain tumor), and metastases to the osseous spine is reviewed. Brain metastases may be treated with surgical resection, whole-brain radiotherapy, stereotactic radiosurgery, or some combination of these treatments. The optimum treatment of brain metastases is a matter of controversy, and patient and disease factors favoring one treatment scheme over another are presented. © 2013 Elsevier Inc. All rights reserved.

Authors
Kirkpatrick, JP; Yin, F-F; Sampson, JH
MLA Citation
Kirkpatrick, JP, Yin, F-F, and Sampson, JH. "Radiotherapy and Radiosurgery for Tumors of the Central Nervous System." Surgical Oncology Clinics of North America (2013).
PMID
23622073
Source
scival
Published In
Surgical Oncology Clinics of North America
Publish Date
2013
DOI
10.1016/j.soc.2013.02.008

The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer

Our group has previously published the Diagnosis-Specific Graded Prognostic Assessment (GPA) showing the prognostic factors associated with survival in patients with brain metastases (BM). The purpose of this study is to investigate the relationship of breast cancer subtype to the time interval from primary diagnosis (PD) to development of BM (TPDBM), number of BM at initial BM presentation and survival. We analyzed our previously described multi-institutional retrospective database of 865 breast cancer patients treated for newly-diagnosed BM from 1993 to 2010. Several factors found to be associated with survival were incorporated into the Breast-GPA, including tumor subtype. The GPA database was further analyzed to determine if the subtype correlated with the TPDBM, number of BM, and survival from PD. After exclusions for incomplete data, 383 patients remained eligible for analysis. The subtypes were approximated as follows: Luminal B: triple positive; HER2: HER2 positive/ER/PR negative; Luminal A; ER/PR positive/HER2 negative; Basal: triple negative. Patients with Basal (90), HER2 (119), Luminal B (98) and Luminal A (76) tumor subtypes had a median TPDBM of 27.5, 35.8, 47.4 and 54.4 months (p < 0.01), median survival from PD of 39.6, 66.4, 90.3 and 72.7 months (p < 0.01) and median survival from BM of 7.3, 17.9, 22.9 and 10.0 months (p < 0.01), respectively. Tumor subtype is an important prognostic factor for survival in patients with breast cancer and BM. Although TPDBM is not an independent prognostic factor for survival (and thus not part of the Breast-GPA), the TPDBM does correlate with tumor subtype but does not correlate with the number of BM. Patients with Basal and HER2 tumor subtypes have short TPDBM. Prospective studies are needed to determine if screening brain MRIs are indicated in patients with Basal or HER2 subtypes. © 2013 Springer Science+Business Media New York.

Authors
Sperduto, PW; Kased, N; Roberge, D; Chao, ST; Shanley, R; Luo, X; Sneed, PK; Suh, J; Weil, RJ; Jensen, AW; al, E
MLA Citation
Sperduto, PW, Kased, N, Roberge, D, Chao, ST, Shanley, R, Luo, X, Sneed, PK, Suh, J, Weil, RJ, Jensen, AW, and al, E. "The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer." Journal of Neuro-Oncology (2013): 1-6.
PMID
23462853
Source
scival
Published In
Journal of Neuro-Oncology
Publish Date
2013
Start Page
1
End Page
6
DOI
10.1007/s11060-013-1083-9

Radiotherapy and Radiosurgery for Tumors of the Central Nervous System

In this article, the application of radiotherapy, alone and in combination with surgery and chemotherapy, in the treatment of metastases to the brain (the most common malignant brain lesion), primary malignant gliomas (the most common malignant primary brain tumor), and metastases to the osseous spine is reviewed. Brain metastases may be treated with surgical resection, whole-brain radiotherapy, stereotactic radiosurgery, or some combination of these treatments. The optimum treatment of brain metastases is a matter of controversy, and patient and disease factors favoring one approach over another are presented. © 2013 Elsevier Inc.

Authors
Kirkpatrick, JP; Yin, F-F; Sampson, JH
MLA Citation
Kirkpatrick, JP, Yin, F-F, and Sampson, JH. "Radiotherapy and Radiosurgery for Tumors of the Central Nervous System." Surgical Oncology Clinics of North America 22.3 (2013): 445-461.
Source
scival
Published In
Surgical Oncology Clinics of North America
Volume
22
Issue
3
Publish Date
2013
Start Page
445
End Page
461
DOI
10.1016/j.soc.2013.02.008

Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: A prospective trial

Purpose: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. Methods and Materials: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. Results: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. Conclusions: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach. © 2013 Elsevier Inc.

Authors
Cabrera, AR; Cuneo, KC; Desjardins, A; Sampson, JH; McSherry, F; II, JEH; Peters, KB; Allen, K; Hoang, JK; Chang, Z; Craciunescu, O; Vredenburgh, JJ; Friedman, HS; Kirkpatrick, JP
MLA Citation
Cabrera, AR, Cuneo, KC, Desjardins, A, Sampson, JH, McSherry, F, II, JEH, Peters, KB, Allen, K, Hoang, JK, Chang, Z, Craciunescu, O, Vredenburgh, JJ, Friedman, HS, and Kirkpatrick, JP. "Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: A prospective trial." International Journal of Radiation Oncology Biology Physics 86.5 (2013): 873-879.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
86
Issue
5
Publish Date
2013
Start Page
873
End Page
879
DOI
10.1016/j.ijrobp.2013.04.029

The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer

Our group has previously published the Diagnosis-Specific Graded Prognostic Assessment (GPA) showing the prognostic factors associated with survival in patients with brain metastases (BM). The purpose of this study is to investigate the relationship of breast cancer subtype to the time interval from primary diagnosis (PD) to development of BM (TPDBM), number of BM at initial BM presentation and survival. We analyzed our previously described multi-institutional retrospective database of 865 breast cancer patients treated for newly-diagnosed BM from 1993 to 2010. Several factors found to be associated with survival were incorporated into the Breast-GPA, including tumor subtype. The GPA database was further analyzed to determine if the subtype correlated with the TPDBM, number of BM, and survival from PD. After exclusions for incomplete data, 383 patients remained eligible for analysis. The subtypes were approximated as follows: Luminal B: triple positive; HER2: HER2 positive/ER/PR negative; Luminal A; ER/PR positive/HER2 negative; Basal: triple negative. Patients with Basal (90), HER2 (119), Luminal B (98) and Luminal A (76) tumor subtypes had a median TPDBM of 27.5, 35.8, 47.4 and 54.4 months (p < 0.01), median survival from PD of 39.6, 66.4, 90.3 and 72.7 months (p < 0.01) and median survival from BM of 7.3, 17.9, 22.9 and 10.0 months (p < 0.01), respectively. Tumor subtype is an important prognostic factor for survival in patients with breast cancer and BM. Although TPDBM is not an independent prognostic factor for survival (and thus not part of the Breast-GPA), the TPDBM does correlate with tumor subtype but does not correlate with the number of BM. Patients with Basal and HER2 tumor subtypes have short TPDBM. Prospective studies are needed to determine if screening brain MRIs are indicated in patients with Basal or HER2 subtypes. © 2013 Springer Science+Business Media New York.

Authors
Sperduto, PW; Kased, N; Roberge, D; Chao, ST; Shanley, R; Luo, X; Sneed, PK; Suh, J; Weil, RJ; Jensen, AW; Brown, PD; Shih, HA; Kirkpatrick, J; Gaspar, LE; Fiveash, JB; Chiang, V; Knisely, JPS; Sperduto, CM; Lin, N; Mehta, M
MLA Citation
Sperduto, PW, Kased, N, Roberge, D, Chao, ST, Shanley, R, Luo, X, Sneed, PK, Suh, J, Weil, RJ, Jensen, AW, Brown, PD, Shih, HA, Kirkpatrick, J, Gaspar, LE, Fiveash, JB, Chiang, V, Knisely, JPS, Sperduto, CM, Lin, N, and Mehta, M. "The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer." Journal of Neuro-Oncology 112.3 (2013): 467-472.
Source
scival
Published In
Journal of Neuro-Oncology
Volume
112
Issue
3
Publish Date
2013
Start Page
467
End Page
472
DOI
10.1007/s11060-013-1083-9

Targeted radiotherapy for malignant gliomas.

Malignant glioma remains a disease with poor prognosis despite recent advances in the multidisciplinary care of this disease. Herein we review the evolution of and recent advances in radiation therapy for malignant glioma that have allowed for more targeted therapy, potentially improving efficacy while decreasing normal tissue toxicity. Current and emerging techniques are presented, including stereotactic radiotherapy and radiosurgery, brachytherapy, radioimmunotherapy, and charged particle therapy, as well as the combination of these modalities with novel targeted biochemotherapies.

Authors
Oh, DS; Adamson, DC; Kirkpatrick, JP
MLA Citation
Oh, DS, Adamson, DC, and Kirkpatrick, JP. "Targeted radiotherapy for malignant gliomas." Curr Drug Discov Technol 9.4 (December 2012): 268-279. (Review)
PMID
22339072
Source
pubmed
Published In
Current drug discovery technologies
Volume
9
Issue
4
Publish Date
2012
Start Page
268
End Page
279

Patterns of Failure as a Function of Clinical Target Volumes in Patients With GBM Treated With Radiation Therapy (RT), Temozolomide, and Bevacizumab

Authors
Lewis, S; Vredenburgh, J; Desjardins, A; Peters, K; Green, S; Hood, R; Yang, Y; Sampson, J; Wang, Z; Kirkpatrick, JP
MLA Citation
Lewis, S, Vredenburgh, J, Desjardins, A, Peters, K, Green, S, Hood, R, Yang, Y, Sampson, J, Wang, Z, and Kirkpatrick, JP. "Patterns of Failure as a Function of Clinical Target Volumes in Patients With GBM Treated With Radiation Therapy (RT), Temozolomide, and Bevacizumab." November 1, 2012.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
84
Issue
3
Publish Date
2012
Start Page
S266
End Page
S267

Impact of Concurrent and Adjuvant Bevacizumab on the Risk of Radiation Necrosis Following Radiosurgery for Recurrent Glioma

Authors
Cuneo, KC; Vredenburgh, J; Desjardins, A; Peters, K; Sampson, J; Allen, K; Chang, Z; Duffy, E; Peterson, B; Kirkpatrick, JP
MLA Citation
Cuneo, KC, Vredenburgh, J, Desjardins, A, Peters, K, Sampson, J, Allen, K, Chang, Z, Duffy, E, Peterson, B, and Kirkpatrick, JP. "Impact of Concurrent and Adjuvant Bevacizumab on the Risk of Radiation Necrosis Following Radiosurgery for Recurrent Glioma." November 1, 2012.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
84
Issue
3
Publish Date
2012
Start Page
S7
End Page
S7

Quantitative analysis of the factors which affect the interpatient organ-at-risk dose sparing variation in IMRT plans.

PURPOSE: The authors present an evidence-based approach to quantify the effects of an array of patient anatomical features of the planning target volumes (PTVs) and organs-at-risk (OARs) and their spatial relationships on the interpatient OAR dose sparing variation in intensity modulated radiation therapy (IMRT) plans by learning from a database of high-quality prior plans. METHODS: The authors formulized the dependence of OAR dose volume histograms (DVHs) on patient anatomical factors into feature models which were learned from prior plans by a stepwise multiple regression method. IMRT plans for 64 prostate, 82 head-and-neck (HN) treatments were used to train the models. Two major groups of anatomical features were considered in this study: the volumetric information and the spatial information. The geometry of OARs relative to PTV is represented by the distance-to-target histogram, DTH. Important anatomical and dosimetric features were extracted from DTH and DVH by principal component analysis. The final models were tested by additional 24 prostate and 24 HN plans. RESULTS: Significant patient anatomical factors contributing to OAR dose sparing in prostate and HN IMRT plans have been analyzed and identified. They are: the median distance between OAR and PTV, the portion of OAR volume within an OAR specific distance range, and the volumetric factors: the fraction of OAR volume which overlaps with PTV and the portion of OAR volume outside the primary treatment field. Overall, the determination coefficients R(2) for predicting the first principal component score (PCS1) of the OAR DVH by the above factors are above 0.68 for all the OARs and they are more than 0.53 for predicting the second principal component score (PCS2) of the OAR DVHs except brainstem and spinal cord. Thus, the above set of anatomical features combined has captured significant portions of the DVH variations for the OARs in prostate and HN plans. To test how well these features capture the interpatient organ dose sparing variations in general, the DVHs and specific dose-volume indices calculated from the regression models were compared with the actual DVHs and dose-volume indices from each patient's plan in the validation dataset. The dose-volume indices compared were V99%, V85%, and V50% for bladder and rectum in prostate plans and parotids median dose in HN plans. The authors found that for the bladder and rectum models, 17 out of 24 plans (71%) were within 6% OAR volume error and 21 plans (85%) were within 10% error; For the parotids model, the median dose values for 30 parotids out of 48 (63%) were within 6% prescription dose error and the values in 40 parotids (83%) were within 10% error. CONCLUSIONS: Quantitative analysis of patient anatomical features and their correlation with OAR dose sparing has identified a number of important factors that explain significant amount of interpatient DVH variations in OARs. These factors can be incorporated into evidence-based learning models as effective features to provide patient-specific OAR dose sparing goals.

Authors
Yuan, L; Ge, Y; Lee, WR; Yin, FF; Kirkpatrick, JP; Wu, QJ
MLA Citation
Yuan, L, Ge, Y, Lee, WR, Yin, FF, Kirkpatrick, JP, and Wu, QJ. "Quantitative analysis of the factors which affect the interpatient organ-at-risk dose sparing variation in IMRT plans." Med Phys 39.11 (November 2012): 6868-6878.
PMID
23127079
Source
pubmed
Published In
Medical physics
Volume
39
Issue
11
Publish Date
2012
Start Page
6868
End Page
6878
DOI
10.1118/1.4757927

Stereotactic body radiotherapy treatment of extracranial metastases.

Radiotherapy is an integral treatment for patients with metastatic cancer, although it is usually reserved for palliation of pain, dyspnoea, oedema, bleeding and neurological symptoms. However, the administration of high-precision radiotherapy, termed stereotactic body radiotherapy (SBRT), has the potential to significantly affect the disease course for some patients with metastatic cancer by delivering high doses of radiation to the secondary tumours with limited high-dose delivery to adjacent healthy tissues. Indeed, such accurate delivery has been firmly established as a therapy for medically inoperable early-stage non-small-cell lung cancer. To date, the technique has demonstrated improvements in controlling metastasis and, in some cases, improved palliation compared with conventionally fractionated radiotherapy. Active areas of research in SBRT include patient selection for curative intent, optimization of SBRT planning techniques, dosing schema and integration of SBRT into systemic therapies. Given the improvements in cytotoxic and targeted therapies over the past decade, studies testing the careful integration of SBRT into standard systemic therapy regimens are needed. Further investigations are also needed to understand the basic biological mechanisms underlying SBRT because they are likely to be different to those mechanisms in conventional radiotherapy.

Authors
Salama, JK; Kirkpatrick, JP; Yin, F-F
MLA Citation
Salama, JK, Kirkpatrick, JP, and Yin, F-F. "Stereotactic body radiotherapy treatment of extracranial metastases." Nat Rev Clin Oncol 9.11 (November 2012): 654-665. (Review)
PMID
23007273
Source
pubmed
Published In
Nature Reviews Clinical Oncology
Volume
9
Issue
11
Publish Date
2012
Start Page
654
End Page
665
DOI
10.1038/nrclinonc.2012.166

A quality assurance method that utilizes 3D dosimetry and facilitates clinical interpretation.

PURPOSE: To demonstrate a new three-dimensional (3D) quality assurance (QA) method that provides comprehensive dosimetry verification and facilitates evaluation of the clinical significance of QA data acquired in a phantom. Also to apply the method to investigate the dosimetric efficacy of base-of-skull (BOS) intensity-modulated radiotherapy (IMRT) treatment. METHODS AND MATERIALS: Two types of IMRT QA verification plans were created for 6 patients who received BOS IMRT. The first plan enabled conventional 2D planar IMRT QA using the Varian portal dosimetry system. The second plan enabled 3D verification using an anthropomorphic head phantom. In the latter, the 3D dose distribution was measured using the DLOS/Presage dosimetry system (DLOS = Duke Large-field-of-view Optical-CT System, Presage Heuris Pharma, Skillman, NJ), which yielded isotropic 2-mm data throughout the treated volume. In a novel step, measured 3D dose distributions were transformed back to the patient's CT to enable calculation of dose-volume histograms (DVH) and dose overlays. Measured and planned patient DVHs were compared to investigate clinical significance. RESULTS: Close agreement between measured and calculated dose distributions was observed for all 6 cases. For gamma criteria of 3%, 2 mm, the mean passing rate for portal dosimetry was 96.8% (range, 92.0%-98.9%), compared to 94.9% (range, 90.1%-98.9%) for 3D. There was no clear correlation between 2D and 3D passing rates. Planned and measured dose distributions were evaluated on the patient's anatomy, using DVH and dose overlays. Minor deviations were detected, and the clinical significance of these are presented and discussed. CONCLUSIONS: Two advantages accrue to the methods presented here. First, treatment accuracy is evaluated throughout the whole treated volume, yielding comprehensive verification. Second, the clinical significance of any deviations can be assessed through the generation of DVH curves and dose overlays on the patient's anatomy. The latter step represents an important development that advances the clinical relevance of complex treatment QA.

Authors
Oldham, M; Thomas, A; O'Daniel, J; Juang, T; Ibbott, G; Adamovics, J; Kirkpatrick, JP
MLA Citation
Oldham, M, Thomas, A, O'Daniel, J, Juang, T, Ibbott, G, Adamovics, J, and Kirkpatrick, JP. "A quality assurance method that utilizes 3D dosimetry and facilitates clinical interpretation." Int J Radiat Oncol Biol Phys 84.2 (October 1, 2012): 540-546.
PMID
22361085
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
84
Issue
2
Publish Date
2012
Start Page
540
End Page
546
DOI
10.1016/j.ijrobp.2011.12.015

Stereotactic radiosurgery and bevacizumab for recurrent glioblastoma multiforme.

Despite contemporary surgery, image-guided radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) persists or relapses in nearly all patients, and tumors almost always recur locally. Management of recurrent GBM is variable, but approaches include best supportive care, reoperation, reirradiation, and/or systemic therapy. Promising novel therapies include antiangiogenic agents and stereotactic radiosurgery, which have cytotoxic effects on tumor microvasculature. Emerging data suggest the safety and efficacy of bevacizumab and radiosurgery either alone or in combination. This report presents the case of a man with locally recurrent GBM treated with stereotactic radiosurgery and concurrent bevacizumab, and reviews the preclinical and clinical data supporting this approach.

Authors
Cabrera, AR; Cuneo, KC; Vredenburgh, JJ; Sampson, JH; Kirkpatrick, JP
MLA Citation
Cabrera, AR, Cuneo, KC, Vredenburgh, JJ, Sampson, JH, and Kirkpatrick, JP. "Stereotactic radiosurgery and bevacizumab for recurrent glioblastoma multiforme." J Natl Compr Canc Netw 10.6 (June 1, 2012): 695-699.
PMID
22679114
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
10
Issue
6
Publish Date
2012
Start Page
695
End Page
699

TU-E-BRB-09: Validation of Multi-Focal Stereotactic Radiosurgery with Volumetric Modulated Arc Therapy with High-Resolution 3D Dosimetry.

Volumetric modulated arc therapy (VMAT) enables stereotactic radiosurgery (SRS) treatment for multiple lesions with a single isocenter setup. Dosimetry verification is highly challenging however, and the purpose of this study is to validate this new treatment using novel 3D dosimetry techniques, with potential for dramatically more comprehensive verification than possible with conventional approaches.A cylindrical PRESAGE dosimeter was inserted into an RPC type head phantom for treatment validation. The phantom was immobilized with an SRS U-frame system and a set of simulation CT images was acquired with a SRS localizer. A 5-arc VMAT multi-focal SRS plan was created to treat 5 intracranial lesions simultaneously. A set of cone-beam CT (CBCT) images was then acquired to localize the isocenter, and the VMAT plan delivered to the combined phantom. The PRESAGE dosimeter was then removed and scanned by optical-computed-tomography (optical-CT). The 3D PRESAGE dose measurement was reconstructed with 1 mm resolution. Another PRESAGE insert with a pre-drilled ion chamber channel was placed in the phantom and an SRS ion chamber was mounted for an absolute dose measurement. The phantom was again localized with CBCT and the VMAT plan was delivered. The dose measured with the ion chamber was compared with calculated dose.The mean planned and PRESAGE measured doses to target 1 were 12.1Gy and 12.2 Gy, 18.7 Gy and 18.5 Gy for target 2, 18.6 Gy and 18.4 Gy for target 3, 15.5 Gy and 15.4 Gy for target 4, 18.7 Gy and 19.0 Gy for target 5. The 3D gamma passing rate was 95.6% for 3% and 1mm. The ion chamber measured dose was within 1% of the planned dose.Our 3D PRESAGE dose measurement shows that multi-focal VMAT is a valid technique for single isocenter SRS treatment of multiple lesions. This research is partially supported by NCI R01CA100835. This research is partially supported by NCI R01CA100835.

Authors
Wang, Z; Newton, J; Niebanck, M; Juang, T; Kirkpatrick, J; Oldham, M
MLA Citation
Wang, Z, Newton, J, Niebanck, M, Juang, T, Kirkpatrick, J, and Oldham, M. "TU-E-BRB-09: Validation of Multi-Focal Stereotactic Radiosurgery with Volumetric Modulated Arc Therapy with High-Resolution 3D Dosimetry." Medical physics 39.6Part24 (June 2012): 3910-.
PMID
28518712
Source
epmc
Published In
Medical physics
Volume
39
Issue
6Part24
Publish Date
2012
Start Page
3910
DOI
10.1118/1.4735958

SU-E-T-645: Treatment of Multiple Brain Metastases Using Stereotactic Radiosurgery with Single-Isocenter Volumetric Modulated Arc Therapy: Comparison with Conventional Dynamic Conformal Arc and Static Beam Stereotactic Radiosurgery.

To investigate the treatment of multiple brain metastases using stereotactic radiosurgery with single-isocenter volumetric modulated arc therapy (VMAT) compared with conventional multi-isocenter dynamic conformal arc therapy (DCAT) and three-dimensional conformal radiation therapy (3D-CRT).Seventeen patients with 2 to 5 brain metastatic lesions were studied. The number of patients with 5, 4, 3, and 2 lesions were 4, 5, 4, and 4, respectively. For patients treated with DCAT/3D-CRT plans, VMAT plans were retrospectively generated, and vice versa. Single-isocenter set up was employed in VMAT plans while the number of isocenters was proportional to the number of lesions in DCAT/3D-CRT plans. The DCAT/3D-CRT and VMAT plans were generated using iPlan® RT Dose Version 4.1.1 (BrainLAB, Germany) and Eclipse™ Version 8.6 (Varian, USA) treatment planning system, respectively. All plans were designed to be delivered on Novalis Tx™ system (Varian, USA and BrainLAB, Germany), in which the accelerator equipped with a high definition multileaf collimator (HDMLC).Conformity index for VMAT plans were equivalent to or better than that for DCAT/3D-CRT plans. While VMAT and DCAT/3D-CRT plans were similar in target coverage, quality of coverage for VMAT plans was better. However, the volume receiving 5Gy was 46% larger for VMAT plans. In addition, the distance from individual lesion to the VMAT isocenter has no impact on VMAT plans. Compared with DCAT/3D-CRT plans, the mean monitor units (MU) decreased by 42% and the estimated treatment time decreased by 49% for VMAT plans.This work suggests that single-isocenter VMAT is promising for stereotactic radiosurgery in the treatment of multiple brain metastases. Single-isocenter VMAT is able to achieve comparable conformity, target coverage and quality of coverage with significantly superior delivery efficiency.

Authors
Huang, C; Ren, L; Kirkpatrick, J; Wang, Z
MLA Citation
Huang, C, Ren, L, Kirkpatrick, J, and Wang, Z. "SU-E-T-645: Treatment of Multiple Brain Metastases Using Stereotactic Radiosurgery with Single-Isocenter Volumetric Modulated Arc Therapy: Comparison with Conventional Dynamic Conformal Arc and Static Beam Stereotactic Radiosurgery." Medical physics 39.6Part20 (June 2012): 3854-.
PMID
28517544
Source
epmc
Published In
Medical physics
Volume
39
Issue
6Part20
Publish Date
2012
Start Page
3854
DOI
10.1118/1.4735734

WE-A-217A-09: Evaluating Radiation-Induced White Matter Changes in Patients with Recurrent Malignant Gliomas under Treatment of Stereotactic Radiosurgery Using Diffusion Tensor Imaging

Authors
Chang, Z; Kirkpatrick, J; Cai, J; Wang, Z; Yin, F
MLA Citation
Chang, Z, Kirkpatrick, J, Cai, J, Wang, Z, and Yin, F. "WE-A-217A-09: Evaluating Radiation-Induced White Matter Changes in Patients with Recurrent Malignant Gliomas under Treatment of Stereotactic Radiosurgery Using Diffusion Tensor Imaging." June 2012.
Source
crossref
Published In
Medical physics
Volume
39
Issue
6Part26
Publish Date
2012
Start Page
3937
End Page
3937
DOI
10.1118/1.4736067

Stereotactic radiotherapy for malignancies involving the trigeminal and facial nerves.

Involvement of a cranial nerve caries a poor prognosis for many malignancies. Recurrent or residual disease in the trigeminal or facial nerve after primary therapy poses a challenge due to the location of the nerve in the skull base, the proximity to the brain, brainstem, cavernous sinus, and optic apparatus and the resulting complex geometry. Surgical resection caries a high risk of morbidity and is often not an option for these patients. Stereotactic radiosurgery and radiotherapy are potential treatment options for patients with cancer involving the trigeminal or facial nerve. These techniques can deliver high doses of radiation to complex volumes while sparing adjacent critical structures. In the current study, seven cases of cancer involving the trigeminal or facial nerve are presented. These patients had unresectable recurrent or residual disease after definitive local therapy. Each patient was treated with stereotactic radiation therapy using a linear accelerator based system. A multidisciplinary approach including neuroradiology and surgical oncology was used to delineate target volumes. Treatment was well tolerated with no acute grade 3 or higher toxicity. One patient who was reirradiated experienced cerebral radionecrosis with mild symptoms. Four of the seven patients treated had no evidence of disease after a median follow up of 12 months (range 2-24 months). A dosimetric analysis was performed to compare intensity modulated fractionated stereotactic radiation therapy (IM-FSRT) to a 3D conformal technique. The dose to 90% (D90) of the brainstem was lower with the IM-FSRT plan by a mean of 13.5 Gy. The D95 to the ipsilateral optic nerve was also reduced with IM-FSRT by 12.2 Gy and the D95 for the optic chiasm was lower with FSRT by 16.3 Gy. Treatment of malignancies involving a cranial nerve requires a multidisciplinary approach. Use of an IM-FSRT technique with a micro-multileaf collimator resulted in a lower dose to the brainstem, optic nerves and chiasm for each case examined.

Authors
Cuneo, KC; Zagar, TM; Brizel, DM; Yoo, DS; Hoang, JK; Chang, Z; Wang, Z; Yin, FF; Das, SK; Green, S; Ready, N; Bhatti, MT; Kaylie, DM; Becker, A; Sampson, JH; Kirkpatrick, JP
MLA Citation
Cuneo, KC, Zagar, TM, Brizel, DM, Yoo, DS, Hoang, JK, Chang, Z, Wang, Z, Yin, FF, Das, SK, Green, S, Ready, N, Bhatti, MT, Kaylie, DM, Becker, A, Sampson, JH, and Kirkpatrick, JP. "Stereotactic radiotherapy for malignancies involving the trigeminal and facial nerves." Technol Cancer Res Treat 11.3 (June 2012): 221-228.
PMID
22468993
Source
pubmed
Published In
Technology in cancer research & treatment
Volume
11
Issue
3
Publish Date
2012
Start Page
221
End Page
228
DOI
10.7785/tcrt.2012.500290

Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas.

PURPOSE: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity. METHODS AND MATERIALS: A retrospective analysis was performed on patients with recurrent malignant gliomas treated with salvage SRS from September 2002 to March 2010. All patients had experienced progression after treatment with temozolomide and radiotherapy. Salvage SRS was typically administered only after multiple postchemoradiation salvage systemic therapies had failed. RESULTS: 63 patients were treated with SRS for recurrent high-grade glioma; 49 patients had World Health Organization (WHO) Grade 4 disease. Median follow-up was 31 months from primary diagnosis and 7 months from SRS. Median overall survival from primary diagnosis was 41 months for all patients. Median progression-free survival (PFS) and overall survival from SRS (OS-SRS) were 6 and 10 months for all patients, respectively. The 1-year OS-SRS for patients with Grade 4 glioma who received adjuvant (concurrent with or after SRS) bevacizumab was 50% vs. 22% for patients not receiving adjuvant bevacizumab (p = 0.005). Median PFS for patients with a WHO Grade 4 glioma who received adjuvant bevacizumab was 5.2 months vs. 2.1 months for patients who did not receive adjuvant bevacizumab (p = 0.014). Karnofsky performance status (KPS) and age were not significantly different between treatment groups. Treatment-related Grade 3/4 toxicity for patients receiving and not receiving adjuvant BVZ was 10% and 14%, respectively (p = 0.58).On multivariate analysis, the relative risk of death and progression with adjuvant bevacizumab was 0.37 (confidence interval [CI] 0.17-0.82) and 0.45 (CI 0.21-0.97). KPS >70 and age <50 years were significantly associated with improved survival. CONCLUSIONS: The combination of salvage radiosurgery and bevacizumab to treat recurrent malignant gliomas is well tolerated and seems to be associated with improved outcomes. Prospective multiinstitutional studies are required to determine efficacy and long-term toxicity with this approach.

Authors
Cuneo, KC; Vredenburgh, JJ; Sampson, JH; Reardon, DA; Desjardins, A; Peters, KB; Friedman, HS; Willett, CG; Kirkpatrick, JP
MLA Citation
Cuneo, KC, Vredenburgh, JJ, Sampson, JH, Reardon, DA, Desjardins, A, Peters, KB, Friedman, HS, Willett, CG, and Kirkpatrick, JP. "Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas." Int J Radiat Oncol Biol Phys 82.5 (April 1, 2012): 2018-2024.
PMID
21489708
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
82
Issue
5
Publish Date
2012
Start Page
2018
End Page
2024
DOI
10.1016/j.ijrobp.2010.12.074

Prospective trial of synchronous bevacizumab, erlotinib, and concurrent chemoradiation in locally advanced head and neck cancer.

PURPOSE: We assessed the safety and efficacy of synchronous VEGF and epidermal growth factor receptor (EGFR) blockade with concurrent chemoradiation (CRT) in locally advanced head and neck cancer (HNC). EXPERIMENTAL DESIGN: Newly diagnosed patients with stage III/IV HNC received a 2-week lead-in of bevacizumab and/or erlotinib, followed by both agents with concurrent cisplatin and twice daily radiotherapy. Safety was assessed using Common Toxicity Criteria version 3.0. The primary efficacy endpoint was clinical complete response (CR) rate after CRT. RESULTS: Twenty-nine patients enrolled on study, with 27 completing therapy. Common grade III toxicities were mucositis (n = 14), dysphagia (n = 8), dehydration (n = 7), osteoradionecrosis (n = 3), and soft tissue necrosis (n = 2). Feeding tube placement was required in 79% but no patient remained dependent at 12-month posttreatment. Clinical CR after CRT was 96% [95% confidence interval (CI), 82%-100%]. Median follow-up was 46 months in survivors, with 3-year locoregional control and distant metastasis-free survival rates of 85% and 93%. Three-year estimated progression-free survival, disease-specific survival, and overall survival rates were 82%, 89%, and 86%, respectively. Dynamic contrast enhanced MRI (DCE-MRI) analysis showed that patients who had failed had lower baseline pretreatment median K(trans) values, with subsequent increases after lead-in therapy and 1 week of CRT. Patients who did not fail had higher median K(trans) values that decreased during therapy. CONCLUSIONS: Dual VEGF/EGFR inhibition can be integrated with CRT in locally advanced HNC, with efficacy that compares favorably with historical controls albeit with an increased risk of osteoradionecrosis. Pretreatment and early DCE-MRI may prospectively identify patients at high risk of failure.

Authors
Yoo, DS; Kirkpatrick, JP; Craciunescu, O; Broadwater, G; Peterson, BL; Carroll, MD; Clough, R; MacFall, JR; Hoang, J; Scher, RL; Esclamado, RM; Dunphy, FR; Ready, NE; Brizel, DM
MLA Citation
Yoo, DS, Kirkpatrick, JP, Craciunescu, O, Broadwater, G, Peterson, BL, Carroll, MD, Clough, R, MacFall, JR, Hoang, J, Scher, RL, Esclamado, RM, Dunphy, FR, Ready, NE, and Brizel, DM. "Prospective trial of synchronous bevacizumab, erlotinib, and concurrent chemoradiation in locally advanced head and neck cancer." Clin Cancer Res 18.5 (March 1, 2012): 1404-1414.
PMID
22253412
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
18
Issue
5
Publish Date
2012
Start Page
1404
End Page
1414
DOI
10.1158/1078-0432.CCR-11-1982

Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme.

PURPOSE: To determine the safety of the addition of bevacizumab to standard radiation therapy and daily temozolomide for newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS: A total of 125 patients with newly diagnosed GBM were enrolled in the study, and received standard radiation therapy and daily temozolomide. All patients underwent a craniotomy and were at least 2 weeks postoperative. Radiation therapy was administered in 1.8-Gy fractions, with the clinical target volume for the primary course treated to a dose of 45 to 50.4 Gy, followed by a boost of 9 to 14.4 Gy, to a total dose of 59.4 Gy. Patients received temozolomide at 75 mg/m(2) daily throughout the course of radiation therapy. Bevacizumab was given at 10 mg/kg intravenously every 14 days, beginning a minimum of 4 weeks postoperatively. RESULTS: Of the 125 patients, 120 (96%) completed the protocol-specified radiation therapy. Five patients had to stop the protocol therapy, 2 patients with pulmonary emboli, and 1 patient each with a Grade 2 central nervous system hemorrhage, Grade 4 pancytopenia, and wound dehiscence requiring surgical intervention. All 5 patients ultimately finished the radiation therapy. After radiation therapy, 3 patients had progressive disease, 2 had severe fatigue and decreased performance status, 1 patient had a colonic perforation, and 1 had a rectal fissure; these 7 patients therefore did not proceed with the protocol-specified adjuvant temozolomide, bevacizumab, and irinotecan. However, 113 patients (90%) were able to continue on study. CONCLUSIONS: The addition of bevacizumab to standard radiation therapy and daily temozolomide was found to be associated with minimal toxicity in patients newly diagnosed with GBM.

Authors
Vredenburgh, JJ; Desjardins, A; Kirkpatrick, JP; Reardon, DA; Peters, KB; Herndon, JE; Marcello, J; Bailey, L; Threatt, S; Sampson, J; Friedman, A; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Kirkpatrick, JP, Reardon, DA, Peters, KB, Herndon, JE, Marcello, J, Bailey, L, Threatt, S, Sampson, J, Friedman, A, and Friedman, HS. "Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme." Int J Radiat Oncol Biol Phys 82.1 (January 1, 2012): 58-66.
PMID
21036490
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
82
Issue
1
Publish Date
2012
Start Page
58
End Page
66
DOI
10.1016/j.ijrobp.2010.08.058

Reply to M.C. Chamberlain et al

Authors
Sperduto, PW; Kased, N; Roberge, D; Xu, Z; Shanley, R; Luo, X; Sneed, PK; Chao, ST; Weil, RJ; Suh, J; Bhatt, A; Jensen, AW; Brown, PD; Shih, HA; Kirkpatrick, J; Gaspar, LE; Fiveash, JB; Chiang, V; Knisely, JPS; Sperduto, CM; Lin, N; Mehta, M
MLA Citation
Sperduto, PW, Kased, N, Roberge, D, Xu, Z, Shanley, R, Luo, X, Sneed, PK, Chao, ST, Weil, RJ, Suh, J, Bhatt, A, Jensen, AW, Brown, PD, Shih, HA, Kirkpatrick, J, Gaspar, LE, Fiveash, JB, Chiang, V, Knisely, JPS, Sperduto, CM, Lin, N, and Mehta, M. "Reply to M.C. Chamberlain et al." Journal of Clinical Oncology 30.26 (2012): 3316-3317.
Source
scival
Published In
Journal of Clinical Oncology
Volume
30
Issue
26
Publish Date
2012
Start Page
3316
End Page
3317
DOI
10.1200/JCO.2012.43.0256

Effect of tumor subtype on survival and the graded prognostic assessment for patients with breast cancer and brain metastases

Purpose: The diagnosis-specific Graded Prognostic Assessment (GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast-GPA by analyzing a larger cohort and tumor subtype. Methods and Materials: A multi-institutional retrospective database of 400 breast cancer patients treated for newly diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression and recursive partitioning analysis (RPA). Factors were weighted by the magnitude of their regression coefficients to define the GPA index. Results: Significant prognostic factors by multivariate Cox regression and RPA were Karnofsky performance status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60 to 80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 3.4 (n = 23), 7.7 (n = 104), 15.1 (n = 140), and 25.3 (n = 133) months, respectively (p < 0.0001). Among HER2-negative patients, being ER/PR positive improved MST from 6.4 to 9.7 months, whereas in HER2-positive patients, being ER/PR positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA vs. 55 for tumor subtype. Conclusions: The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision making and stratification in clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone. © 2012 Elsevier Inc.

Authors
Sperduto, PW; Kased, N; Roberge, D; Xu, Z; Shanley, R; Luo, X; Sneed, PK; Chao, ST; Weil, RJ; Suh, J; Bhatt, A; Jensen, AW; Brown, PD; Shih, HA; Kirkpatrick, J; Gaspar, LE; Fiveash, JB; Chiang, V; Knisely, JPS; Sperduto, CM; Lin, N; Mehta, M
MLA Citation
Sperduto, PW, Kased, N, Roberge, D, Xu, Z, Shanley, R, Luo, X, Sneed, PK, Chao, ST, Weil, RJ, Suh, J, Bhatt, A, Jensen, AW, Brown, PD, Shih, HA, Kirkpatrick, J, Gaspar, LE, Fiveash, JB, Chiang, V, Knisely, JPS, Sperduto, CM, Lin, N, and Mehta, M. "Effect of tumor subtype on survival and the graded prognostic assessment for patients with breast cancer and brain metastases." International Journal of Radiation Oncology Biology Physics 82.5 (2012): 2111-2117.
PMID
21497451
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
82
Issue
5
Publish Date
2012
Start Page
2111
End Page
2117
DOI
10.1016/j.ijrobp.2011.02.027

Summary report on the graded prognostic assessment: An accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases

Purpose: Our group has previously published the Graded Prognostic Assessment (GPA), a prognostic index for patients with brain metastases. Updates have been published with refinements to create diagnosis-specific Graded Prognostic Assessment indices. The purpose of this report is to present the updated diagnosis-specific GPA indices in a single, unified, user-friendly report to allow ease of access and use by treating physicians. Methods: A multi-institutional retrospective (1985 to 2007) database of 3,940 patients with newly diagnosed brain metastases underwent univariate and multivariate analyses of prognostic factors associated with outcomes by primary site and treatment. Significant prognostic factors were used to define the diagnosis-specific GPA prognostic indices. A GPA of 4.0 correlates with the best prognosis, whereas a GPA of 0.0 corresponds with the worst prognosis. Results: Significant prognostic factors varied by diagnosis. For lung cancer, prognostic factors were Karnofsky performance score, age, presence of extracranial metastases, and number of brain metastases, confirming the original Lung-GPA. For melanoma and renal cell cancer, prognostic factors were Karnofsky performance score and the number of brain metastases. For breast cancer, prognostic factors were tumor subtype, Karnofsky performance score, and age. For GI cancer, the only prognostic factor was the Karnofsky performance score. The median survival times by GPA score and diagnosis were determined. Conclusion: Prognostic factors for patients with brain metastases vary by diagnosis, and for each diagnosis, a robust separation into different GPA scores was discerned, implying considerable heterogeneity in outcome, even within a single tumor type. In summary, these indices and related worksheet provide an accurate and facile diagnosis-specific tool to estimate survival, potentially select appropriate treatment, and stratify clinical trials for patients with brain metastases. © 2011 by American Society of Clinical Oncology.

Authors
Sperduto, PW; Kased, N; Roberge, D; Xu, Z; Shanley, R; Luo, X; Sneed, PK; Chao, ST; Weil, RJ; Suh, J; Bhatt, A; Jensen, AW; Brown, PD; Shih, HA; Kirkpatrick, J; Gaspar, LE; Fiveash, JB; Chiang, V; Knisely, JPS; Sperduto, CM; Lin, N; Mehta, M
MLA Citation
Sperduto, PW, Kased, N, Roberge, D, Xu, Z, Shanley, R, Luo, X, Sneed, PK, Chao, ST, Weil, RJ, Suh, J, Bhatt, A, Jensen, AW, Brown, PD, Shih, HA, Kirkpatrick, J, Gaspar, LE, Fiveash, JB, Chiang, V, Knisely, JPS, Sperduto, CM, Lin, N, and Mehta, M. "Summary report on the graded prognostic assessment: An accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases." Journal of Clinical Oncology 30.4 (2012): 419-425.
PMID
22203767
Source
scival
Published In
Journal of Clinical Oncology
Volume
30
Issue
4
Publish Date
2012
Start Page
419
End Page
425
DOI
10.1200/JCO.2011.38.0527

In Regard to Yamamoto et al

Authors
Sperduto, PW; Sneed, PK; Roberge, D; Shanley, R; Luo, X; Weil, RJ; Suh, J; Bhatt, A; Jensen, AW; Brown, PD; Shih, HA; Kirkpatrick, J; Gaspar, LE; Fiveash, JB; Knisely, JPS; Lin, N; Mehta, M
MLA Citation
Sperduto, PW, Sneed, PK, Roberge, D, Shanley, R, Luo, X, Weil, RJ, Suh, J, Bhatt, A, Jensen, AW, Brown, PD, Shih, HA, Kirkpatrick, J, Gaspar, LE, Fiveash, JB, Knisely, JPS, Lin, N, and Mehta, M. "In Regard to Yamamoto et al." International Journal of Radiation Oncology Biology Physics 84.4 (2012): 875-876.
PMID
23078894
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
84
Issue
4
Publish Date
2012
Start Page
875
End Page
876
DOI
10.1016/j.ijrobp.2012.03.050

THE ADDITION OF BEVACIZUMAB TO TEMOZOLOMIDE AND RADIATION THERAPY FOLLOWED BY BEVACIZUMAB, TEMOZOLOMIDE, AND ORAL TOPOTECAN FOR NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME

Authors
Vredenburgh, JJ; Desjardins, A; Reardon, DA; Peters, KB; Kirkpatrick, JP; II, HJE; Coan, AD; Bailey, L; Janney, D; Lu, C; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Reardon, DA, Peters, KB, Kirkpatrick, JP, II, HJE, Coan, AD, Bailey, L, Janney, D, Lu, C, and Friedman, HS. "THE ADDITION OF BEVACIZUMAB TO TEMOZOLOMIDE AND RADIATION THERAPY FOLLOWED BY BEVACIZUMAB, TEMOZOLOMIDE, AND ORAL TOPOTECAN FOR NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME." NEURO-ONCOLOGY 13 (November 2011): 89-90.
Source
wos-lite
Published In
Neuro-Oncology
Volume
13
Publish Date
2011
Start Page
89
End Page
90

The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma.

PURPOSE: To determine if the addition of bevacizumab to radiation therapy and temozolomide, followed by bevacizumab, temozolomide, and irinotecan, for newly diagnosed glioblastoma patients is safe and effective. EXPERIMENTAL DESIGN: A total of 75 patients with newly diagnosed glioblastoma were enrolled in the phase II trial that investigated the addition of bevacizumab to standard radiation therapy and daily temozolomide followed by the addition of bevacizumab and irinotecan to adjuvant temozolomide. The bevacizumab was given at 10 mg/kg every 14 days beginning a minimum of 4 weeks postcraniotomy. Two weeks after radiation therapy, the patients began 6 to 12 cycles of 5-day temozolomide with bevacizumab and irinotecan every 14 days. The primary endpoint was the proportion of patients alive 16 months after informed consent. RESULTS: The therapy had moderate toxicity. Three patients, one of whom had a grade 2 central nervous system hemorrhage, came off study during radiation therapy. Seventy patients started the postradiation therapy, and 16 (23%) terminated this adjuvant therapy early because of toxicity. The median overall survival was 21.2 months (95% CI: 17.2-25.4), and 65% of the patients were alive at 16 months (95% CI: 53.4-74.9). The median progression-free survival was 14.2 months (95% CI: 12-16). CONCLUSION: The addition of bevacizumab to standard radiation therapy and temozolomide, followed by bevacizumab, irinotecan, and temozolomide, for the treatment of newly diagnosed glioblastoma has moderate toxicity and may improve efficacy compared with historical controls. The results from phase III trials are required before the role of bevacizumab for newly diagnosed glioblastoma is established.

Authors
Vredenburgh, JJ; Desjardins, A; Reardon, DA; Peters, KB; Herndon, JE; Marcello, J; Kirkpatrick, JP; Sampson, JH; Bailey, L; Threatt, S; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Reardon, DA, Peters, KB, Herndon, JE, Marcello, J, Kirkpatrick, JP, Sampson, JH, Bailey, L, Threatt, S, Friedman, AH, Bigner, DD, and Friedman, HS. "The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma." Clin Cancer Res 17.12 (June 15, 2011): 4119-4124.
PMID
21531816
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
17
Issue
12
Publish Date
2011
Start Page
4119
End Page
4124
DOI
10.1158/1078-0432.CCR-11-0120

SU-E-T-23: Ontological Representation of Radiation Treatment Guidelines

Authors
Ge, Y; Minta, T; Kirkpatrick, J; Yuan, L; Wu, Q
MLA Citation
Ge, Y, Minta, T, Kirkpatrick, J, Yuan, L, and Wu, Q. "SU-E-T-23: Ontological Representation of Radiation Treatment Guidelines." June 2011.
Source
crossref
Published In
Medical physics
Volume
38
Issue
6Part10
Publish Date
2011
Start Page
3490
End Page
3490
DOI
10.1118/1.3611973

A review of VEGF/VEGFR-targeted therapeutics for recurrent glioblastoma.

Glioblastoma, the most common primary malignant brain tumor among adults, is a highly angiogenic and deadly tumor. Angiogenesis in glioblastoma, driven by hypoxia-dependent and independent mechanisms, is primarily mediated by vascular endothelial growth factor (VEGF), and generates blood vessels with distinctive features. The outcome for patients with recurrent glioblastoma is poor because of ineffective therapies. However, recent encouraging rates of radiographic response and progression-free survival, and adequate safety, led the FDA to grant accelerated approval of bevacizumab, a humanized monoclonal antibody against VEGF, for the treatment of recurrent glioblastoma in May 2009. These results have triggered significant interest in additional antiangiogenic agents and therapeutic strategies for patients with both recurrent and newly diagnosed glioblastoma. Given the potent antipermeability effect of VEGF inhibitors, the Radiologic Assessment in Neuro-Oncology (RANO) criteria were recently implemented to better assess response among patients with glioblastoma. Although bevacizumab improves survival and quality of life, eventual tumor progression is the norm. Better understanding of resistance mechanisms to VEGF inhibitors and identification of effective therapy after bevacizumab progression are currently a critical need for patients with glioblastoma.

Authors
Reardon, DA; Turner, S; Peters, KB; Desjardins, A; Gururangan, S; Sampson, JH; McLendon, RE; Herndon, JE; Jones, LW; Kirkpatrick, JP; Friedman, AH; Vredenburgh, JJ; Bigner, DD; Friedman, HS
MLA Citation
Reardon, DA, Turner, S, Peters, KB, Desjardins, A, Gururangan, S, Sampson, JH, McLendon, RE, Herndon, JE, Jones, LW, Kirkpatrick, JP, Friedman, AH, Vredenburgh, JJ, Bigner, DD, and Friedman, HS. "A review of VEGF/VEGFR-targeted therapeutics for recurrent glioblastoma." J Natl Compr Canc Netw 9.4 (April 2011): 414-427. (Review)
PMID
21464146
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
9
Issue
4
Publish Date
2011
Start Page
414
End Page
427

Cellular redox modulator, ortho Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin, MnTnHex-2-PyP(5+) in the treatment of brain tumors.

Despite intensive efforts to improve multimodal treatment of brain tumor, survival remains limited. Current therapy consists of a combination of surgery, irradiation and chemotherapy with predisposition to long-term complications. Identifying novel targeted therapies is therefore at the forefront of brain tumor research. This study explores the utility of a manganese porphyrin in a brain tumor model. The compound used is ortho isomer, mangnese(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin, MnTnHex-2-PyP(5+). It is a powerful SOD mimic and peroxynitrite scavenger and a potent modulator of redox-based cellular transcriptional activity, able to suppress excessive immune and inflammatory responses and in turn proliferative pathways. It is further one of the most lipophilic compound among cationic Mn(III) N-alkylpyridylporphyrins, and thus accumulates predominantly in mitochondria relative to cytosol. In mitochondria, MnTnHex-2-PyP(5+) mimics our key antioxidant system, mitochondrial superoxide dismutase, MnSOD, whose overexpression has been widely shown to suppress tumor growth. Importantly, MnTnHex-2-PyP(5+) crosses blood brain barrier in sufficient amounts to demonstrate efficacy in treating CNS injuries. For those reasons we elected to test its effects in inhibiting brain tumor growth. This study is the first report of the antitumor properties of MnTnHex-2-PyP(5+) as a single agent in adult and pediatric glioblastoma multiforme (D-54 MG, D-245 MG, D-256 MG, D-456 MG) and pediatric medulloblastoma (D-341 MED), and is the first case where a redox-able metal complex has been used in glioma therapy. When given subcutaneously to mice bearing subcutaneous and intracranial xenografts, MnTnHex-2-PyP(5+) caused a significant (P ≤ 0.001) growth delay in D 245 MG, D-256 MG, D-341 MED, and D-456 MG tumors. Growth delay for mice bearing subcutaneous xenografts ranged from 3 days in D-54 MG to 34 days in D-341 MED. With mice bearing intracranial xenografts, MnTnHex-2-PyP(5+) increases median survival by 33% in adult glioblastoma multiforme (D-256 MG; p≤ 0.001) and 173% in pediatric medulloblastoma (D-341 MED, <0.001). The beneficial effects of MnTnHex-2-PyP(5+) are presumably achieved either (1) indirectly via elimination of signaling reactive oxygen and nitrogen species (in particular superoxide and peroxynitrite) which in turn would prevent activation of transcription factors; or (2) directly by coupling with cellular reductants and redox-sensitive signaling proteins. The former action is antioxidative while the latter action is presumably pro-oxidative in nature. Our findings suggest that the use of Mn porphyrin-based SOD mimics, and in particular lipophilic analogues such as MnTnHex-2-PyP(5+), is a promising approach for brain tumor therapy.

Authors
Keir, ST; Dewhirst, MW; Kirkpatrick, JP; Bigner, DD; Batinic-Haberle, I
MLA Citation
Keir, ST, Dewhirst, MW, Kirkpatrick, JP, Bigner, DD, and Batinic-Haberle, I. "Cellular redox modulator, ortho Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin, MnTnHex-2-PyP(5+) in the treatment of brain tumors." Anticancer Agents Med Chem 11.2 (February 2011): 202-212.
PMID
21291403
Source
pubmed
Published In
Anti-Cancer Agents in Medicinal Chemistry
Volume
11
Issue
2
Publish Date
2011
Start Page
202
End Page
212

Primary meningeal rhabdomyosarcoma.

Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI) demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13). Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC) systemic therapy.

Authors
Palta, M; Riedel, RF; Vredenburgh, JJ; Cummings, TJ; Green, S; Chang, Z; Kirkpatrick, JP
MLA Citation
Palta, M, Riedel, RF, Vredenburgh, JJ, Cummings, TJ, Green, S, Chang, Z, and Kirkpatrick, JP. "Primary meningeal rhabdomyosarcoma." Sarcoma 2011 (2011): 312802-.
PMID
21772793
Source
pubmed
Published In
Sarcoma
Volume
2011
Publish Date
2011
Start Page
312802
DOI
10.1155/2011/312802

Reply to Drs. mulvenna and holt

Authors
Sperduto, PW; Chao, ST; Suh, J; Sneed, PK; Luo, X; Roberge, D; Bhatt, A; Mehta, MP; Jensen, AW; Brown, PD; Shih, H; Kirkpatrick, J; Gaspar, LE; Fiveash, JB; Chiang, V; Knisely, J; Sperduto, CM
MLA Citation
Sperduto, PW, Chao, ST, Suh, J, Sneed, PK, Luo, X, Roberge, D, Bhatt, A, Mehta, MP, Jensen, AW, Brown, PD, Shih, H, Kirkpatrick, J, Gaspar, LE, Fiveash, JB, Chiang, V, Knisely, J, and Sperduto, CM. "Reply to Drs. mulvenna and holt." International Journal of Radiation Oncology Biology Physics 81.4 (2011): 1194-1195.
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
81
Issue
4
Publish Date
2011
Start Page
1194
End Page
1195
DOI
10.1016/j.ijrobp.2010.09.047

Imaging-Guided Localization for Stereotactic Radiosurgery of Multiple Intracranial Lesions with a Single Isocenter Setup

Authors
Wang, Z; Yin, F; Chang, Z; Sampson, J; Kirkpatrick, JP
MLA Citation
Wang, Z, Yin, F, Chang, Z, Sampson, J, and Kirkpatrick, JP. "Imaging-Guided Localization for Stereotactic Radiosurgery of Multiple Intracranial Lesions with a Single Isocenter Setup." INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 81.2 (2011): S860-S860.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
81
Issue
2
Publish Date
2011
Start Page
S860
End Page
S860

Bevacizumab and Radiosurgery for Recurrent Malignant Glioma: Toxicity Results from a Prospective Pilot Study

Authors
Cuneo, KC; Cabrera, AR; Sampson, J; Allen, K; Duffy, E; Vredenburgh, JJ; Peters, KB; Chang, Z; Desjardins, A; Kirkpatrick, JP
MLA Citation
Cuneo, KC, Cabrera, AR, Sampson, J, Allen, K, Duffy, E, Vredenburgh, JJ, Peters, KB, Chang, Z, Desjardins, A, and Kirkpatrick, JP. "Bevacizumab and Radiosurgery for Recurrent Malignant Glioma: Toxicity Results from a Prospective Pilot Study." INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 81.2 (2011): S185-S185.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
81
Issue
2
Publish Date
2011
Start Page
S185
End Page
S185

Evaluating Recurrent Gliomas with Diffusion-weighted MR Imaging Before and After Concurrent Radiosurgery and Bevacizumab

Authors
Cabrera, AR; Craciunescu, O; Cuneo, KC; Chang, Z; Kirkpatrick, JP
MLA Citation
Cabrera, AR, Craciunescu, O, Cuneo, KC, Chang, Z, and Kirkpatrick, JP. "Evaluating Recurrent Gliomas with Diffusion-weighted MR Imaging Before and After Concurrent Radiosurgery and Bevacizumab." INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 81.2 (2011): S793-S793.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
81
Issue
2
Publish Date
2011
Start Page
S793
End Page
S793

Protein Pathway Activation after Ionizing Radiation in Luminal and Basal Breast Cancer Cell Lines

Authors
Horton, JK; Fels, DR; Chi, JA; Kung, H; Kirkpatrick, JP; Dewhirst, M
MLA Citation
Horton, JK, Fels, DR, Chi, JA, Kung, H, Kirkpatrick, JP, and Dewhirst, M. "Protein Pathway Activation after Ionizing Radiation in Luminal and Basal Breast Cancer Cell Lines." INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 81.2 (2011): S160-S161.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
81
Issue
2
Publish Date
2011
Start Page
S160
End Page
S161

Balancing Tumor Kill and Normal Tissue Toxicity in Radiosurgery: Critical Impact of the Peritumoral Zone

Authors
Kirkpatrick, JP; Green, S; Zagar, T; Wang, Z
MLA Citation
Kirkpatrick, JP, Green, S, Zagar, T, and Wang, Z. "Balancing Tumor Kill and Normal Tissue Toxicity in Radiosurgery: Critical Impact of the Peritumoral Zone." INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 81.2 (2011): S866-S866.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
81
Issue
2
Publish Date
2011
Start Page
S866
End Page
S866

SURVIVAL AND TOXICITY UPDATE OF THE PHASE 2 TRIAL OF BEVACIZUMAB (BV) IN COMBINATION WITH TEMOZOLOMIDE (TMZ) AND RADIATION THERAPY (RT) FOLLOWED BY BV, TMZ, AND IRINOTECAN (CPT-11) FOR NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME (GBM) PATIENTS

Authors
Desjardins, A; Reardon, DA; Peters, KB; II, HJE; Kirkpatrick, JP; Friedman, HS; Vredenburgh, JJ
MLA Citation
Desjardins, A, Reardon, DA, Peters, KB, II, HJE, Kirkpatrick, JP, Friedman, HS, and Vredenburgh, JJ. "SURVIVAL AND TOXICITY UPDATE OF THE PHASE 2 TRIAL OF BEVACIZUMAB (BV) IN COMBINATION WITH TEMOZOLOMIDE (TMZ) AND RADIATION THERAPY (RT) FOLLOWED BY BV, TMZ, AND IRINOTECAN (CPT-11) FOR NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME (GBM) PATIENTS." November 2010.
Source
wos-lite
Published In
Neuro-Oncology
Volume
12
Publish Date
2010
Start Page
77
End Page
77

USE OF BIOCHEMOTHERAPY AND STEREOTACTIC RADIOSURGERY IN THE MANAGEMENT OF RECURRENT MALIGNANT GLIOMA

Authors
Cuneo, KC; Vredenburgh, JJ; Sampson, JH; Reardon, DA; Desjardins, A; Peters, KL; Kirkpatrick, JP
MLA Citation
Cuneo, KC, Vredenburgh, JJ, Sampson, JH, Reardon, DA, Desjardins, A, Peters, KL, and Kirkpatrick, JP. "USE OF BIOCHEMOTHERAPY AND STEREOTACTIC RADIOSURGERY IN THE MANAGEMENT OF RECURRENT MALIGNANT GLIOMA." November 2010.
Source
wos-lite
Published In
Neuro-Oncology
Volume
12
Publish Date
2010
Start Page
107
End Page
107

Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients.

PURPOSE: Controversy endures regarding the optimal treatment of patients with brain metastases (BMs). Debate persists, despite many randomized trials, perhaps because BM patients are a heterogeneous population. The purpose of the present study was to identify significant diagnosis-specific prognostic factors and indexes (Diagnosis-Specific Graded Prognostic Assessment [DS-GPA]). METHODS AND MATERIALS: A retrospective database of 5,067 patients treated for BMs between 1985 and 2007 was generated from 11 institutions. After exclusion of the patients with recurrent BMs or incomplete data, 4,259 patients with newly diagnosed BMs remained eligible for analysis. Univariate and multivariate analyses of the prognostic factors and outcomes by primary site and treatment were performed. The significant prognostic factors were determined and used to define the DS-GPA prognostic indexes. The DS-GPA scores were calculated and correlated with the outcomes, stratified by diagnosis and treatment. RESULTS: The significant prognostic factors varied by diagnosis. For non-small-cell lung cancer and small-cell lung cancer, the significant prognostic factors were Karnofsky performance status, age, presence of extracranial metastases, and number of BMs, confirming the original GPA for these diagnoses. For melanoma and renal cell cancer, the significant prognostic factors were Karnofsky performance status and the number of BMs. For breast and gastrointestinal cancer, the only significant prognostic factor was the Karnofsky performance status. Two new DS-GPA indexes were thus designed for breast/gastrointestinal cancer and melanoma/renal cell carcinoma. The median survival by GPA score, diagnosis, and treatment were determined. CONCLUSION: The prognostic factors for BM patients varied by diagnosis. The original GPA was confirmed for non-small-cell lung cancer and small-cell lung cancer. New DS-GPA indexes were determined for other histologic types and correlated with the outcome, and statistical separation between the groups was confirmed. These data should be considered in the design of future randomized trials and in clinical decision-making.

Authors
Sperduto, PW; Chao, ST; Sneed, PK; Luo, X; Suh, J; Roberge, D; Bhatt, A; Jensen, AW; Brown, PD; Shih, H; Kirkpatrick, J; Schwer, A; Gaspar, LE; Fiveash, JB; Chiang, V; Knisely, J; Sperduto, CM; Mehta, M
MLA Citation
Sperduto, PW, Chao, ST, Sneed, PK, Luo, X, Suh, J, Roberge, D, Bhatt, A, Jensen, AW, Brown, PD, Shih, H, Kirkpatrick, J, Schwer, A, Gaspar, LE, Fiveash, JB, Chiang, V, Knisely, J, Sperduto, CM, and Mehta, M. "Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients." Int J Radiat Oncol Biol Phys 77.3 (July 1, 2010): 655-661.
PMID
19942357
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
77
Issue
3
Publish Date
2010
Start Page
655
End Page
661
DOI
10.1016/j.ijrobp.2009.08.025

SU-GG-T-483: Does Breath-Hold Immobilization Affect Tumor Radioresistance in Breast?

Authors
Adamson, J; Kirkpatrick, J; Yin, F
MLA Citation
Adamson, J, Kirkpatrick, J, and Yin, F. "SU-GG-T-483: Does Breath-Hold Immobilization Affect Tumor Radioresistance in Breast?." June 2010.
Source
crossref
Published In
Medical physics
Volume
37
Issue
6Part23
Publish Date
2010
Start Page
3298
End Page
3298
DOI
10.1118/1.3468881

SU-GG-T-530: Comparison of Coplanar and Non-Coplanar Intensity Modulated Arc Techniques for Treatment of Intracranial Multi-Focal Stereotactic Radiosurgery

Authors
Wang, Z; Kirkpatrick, J; Chang, Z; Cai, J; Zhuang, T; Yin, F
MLA Citation
Wang, Z, Kirkpatrick, J, Chang, Z, Cai, J, Zhuang, T, and Yin, F. "SU-GG-T-530: Comparison of Coplanar and Non-Coplanar Intensity Modulated Arc Techniques for Treatment of Intracranial Multi-Focal Stereotactic Radiosurgery." June 2010.
Source
crossref
Published In
Medical physics
Volume
37
Issue
6Part24
Publish Date
2010
Start Page
3309
End Page
3309
DOI
10.1118/1.3468927

Stereotactic radiosurgery in the treatment of a dural carotid-cavernous fistula.

Because of the success of stereotactic radiosurgery (SRS) in the treatment of cerebral arteriovenous malformations (AVMs), SRS is being applied to the treatment of carotid-cavernous dural arteriovenous fistulas (CCDAVFs) when these lesions are not accessible endovascularly. We report a patient with a CCDAVF that could not be accessed endovascularly on 2 attempts, whose fistula was successfully closed with SRS, a less invasive modality than endovascular embolization. Further experience with SRS in this role will be necessary to determine its utility.

Authors
Chong, GT; Mukundan, S; Kirkpatrick, JP; Zomorodi, A; Sampson, JH; Bhatti, MT
MLA Citation
Chong, GT, Mukundan, S, Kirkpatrick, JP, Zomorodi, A, Sampson, JH, and Bhatti, MT. "Stereotactic radiosurgery in the treatment of a dural carotid-cavernous fistula." J Neuroophthalmol 30.2 (June 2010): 138-144.
PMID
20431489
Source
pubmed
Published In
Journal of Neuro-Ophthalmology
Volume
30
Issue
2
Publish Date
2010
Start Page
138
End Page
144
DOI
10.1097/WNO.0b013e3181ceb3e3

6D image guidance for spinal non-invasive stereotactic body radiation therapy: Comparison between ExacTrac X-ray 6D with kilo-voltage cone-beam CT.

PURPOSE: To investigate setup discrepancies measured with ExacTrac X-ray 6 degree-of-freedom (6D) and cone-beam computed tomography (CBCT) for patients under treatments of stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: In this work, phantom and patient studies were performed. In the phantom studies, an anthropomorphic phantom was placed with pre-defined positions, and imaged with ExacTrac X-ray 6D and CBCT to test the accuracy of the imaging systems. In the patient studies, 16 spinal SBRT patient cases were retrospectively analyzed. The patients were initially positioned in customized immobilization cradles and then aligned with ExacTrac X-ray 6D and CBCT. The setup discrepancies were computed and quantitatively analyzed. RESULTS: This study indicates modest discrepancies between ExacTrac X-ray 6D and CBCT with spinal SBRT. The phantom experiments showed that translational and rotational discrepancies in root-mean-square (RMS) between ExacTrac X-ray 6D and CBCT were, respectively, <1.0mm and <1 degrees . In the retrospective patient studies, translational and rotational discrepancies in RMS between ExacTrac X-ray 6D and CBCT were <2.0mm and <1.5 degrees . CONCLUSIONS: ExacTrac X-ray 6D represents a potential alternative to CBCT; however, pre-caution should be taken when only ExacTrac X-ray 6D is used to guide SBRT with small setup margins.

Authors
Chang, Z; Wang, Z; Ma, J; O'Daniel, JC; Kirkpatrick, J; Yin, F-F
MLA Citation
Chang, Z, Wang, Z, Ma, J, O'Daniel, JC, Kirkpatrick, J, and Yin, F-F. "6D image guidance for spinal non-invasive stereotactic body radiation therapy: Comparison between ExacTrac X-ray 6D with kilo-voltage cone-beam CT." Radiother Oncol 95.1 (April 2010): 116-121.
PMID
20122747
Source
pubmed
Published In
Radiotherapy and Oncology
Volume
95
Issue
1
Publish Date
2010
Start Page
116
End Page
121
DOI
10.1016/j.radonc.2009.12.036

Radiation dose-volume effects in the spinal cord.

Dose-volume data for myelopathy in humans treated with radiotherapy (RT) to the spine is reviewed, along with pertinent preclinical data. Using conventional fractionation of 1.8-2 Gy/fraction to the full-thickness cord, the estimated risk of myelopathy is <1% and <10% at 54 Gy and 61 Gy, respectively, with a calculated strong dependence on dose/fraction (alpha/beta = 0.87 Gy.) Reirradiation data in animals and humans suggest partial repair of RT-induced subclinical damage becoming evident about 6 months post-RT and increasing over the next 2 years. Reports of myelopathy from stereotactic radiosurgery to spinal lesions appear rare (<1%) when the maximum spinal cord dose is limited to the equivalent of 13 Gy in a single fraction or 20 Gy in three fractions. However, long-term data are insufficient to calculate a dose-volume relationship for myelopathy when the partial cord is treated with a hypofractionated regimen.

Authors
Kirkpatrick, JP; van der Kogel, AJ; Schultheiss, TE
MLA Citation
Kirkpatrick, JP, van der Kogel, AJ, and Schultheiss, TE. "Radiation dose-volume effects in the spinal cord." Int J Radiat Oncol Biol Phys 76.3 Suppl (March 1, 2010): S42-S49. (Review)
PMID
20171517
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
76
Issue
3 Suppl
Publish Date
2010
Start Page
S42
End Page
S49
DOI
10.1016/j.ijrobp.2009.04.095

Radiation dose-volume effects of optic nerves and chiasm.

Publications relating radiation toxicity of the optic nerves and chiasm to quantitative dose and dose-volume measures were reviewed. Few studies have adequate data for dose-volume outcome modeling. The risk of toxicity increased markedly at doses >60 Gy at approximately 1.8 Gy/fraction and at >12 Gy for single-fraction radiosurgery. The evidence is strong that radiation tolerance is increased with a reduction in the dose per fraction. Models of threshold tolerance were examined.

Authors
Mayo, C; Martel, MK; Marks, LB; Flickinger, J; Nam, J; Kirkpatrick, J
MLA Citation
Mayo, C, Martel, MK, Marks, LB, Flickinger, J, Nam, J, and Kirkpatrick, J. "Radiation dose-volume effects of optic nerves and chiasm." Int J Radiat Oncol Biol Phys 76.3 Suppl (March 1, 2010): S28-S35. (Review)
PMID
20171514
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
76
Issue
3 Suppl
Publish Date
2010
Start Page
S28
End Page
S35
DOI
10.1016/j.ijrobp.2009.07.1753

Assessing neurotoxicity from the low-dose radiation component of radiosurgery using magnetic resonance spectroscopy.

The aim of the study was to determine if biochemical changes indicative of injury, assessed using magnetic resonance spectroscopic imaging (SI), are observed after stereotactic radiosurgery (SRS). The study included patients who underwent SI immediately before and 1, 30, and 90 days following SRS. Short TE spectra (TR/TE 1000/35 ms) were acquired at the SRS isocenter with a 2D PRESS-CSI sequence on a single 1.5 T scanner. The SRS isodose lines were overlaid on the magnetic resonance imaging slice utilized for SI data acquisition. N-Acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were computed for multiple voxels located between the 25 and 50 cGy isodose lines (low dose) and the 200 and 350 cGy isodose lines (medium dose). An analysis of variance and paired t-tests compared metabolite levels at different time points. Twelve patients were enrolled, although 3 were excluded secondary to poor spectral data quality or deviations from the prescribed SI protocol. The median number of voxels analyzed from the low- and medium-dose region was 7 and 4, respectively. No significant changes in metabolite peak height ratios over time were seen in the low-dose region, for either NAA/Cr (P = .89) or Cho/Cr (P = .85). There was no difference in Cho/Cr peak height ratios in the medium-dose region (P = .62). There was an increase in the NAA/Cr peak height ratio in the medium-dose region between day -1 and day +30 (P = .003), followed by a decline to baseline between days +30 and +90 (P = .03). We did not observe a significant decline in NAA/Cr or change in Cho/Cr peak heights in uninvolved brain parenchyma after SRS.

Authors
Kelsey, CR; Mukundan, S; Wang, Z; Hahn, CA; Soher, BJ; Kirkpatrick, JP
MLA Citation
Kelsey, CR, Mukundan, S, Wang, Z, Hahn, CA, Soher, BJ, and Kirkpatrick, JP. "Assessing neurotoxicity from the low-dose radiation component of radiosurgery using magnetic resonance spectroscopy." Neuro Oncol 12.2 (February 2010): 145-152.
PMID
20150381
Source
pubmed
Published In
Neuro-Oncology
Volume
12
Issue
2
Publish Date
2010
Start Page
145
End Page
152
DOI
10.1093/neuonc/nop040

Low-dose Whole Brain Radiotherapy followed by Radiosurgery for Primary CNS Lymphoma Achieving Partial Response to Induction Chemotherapy

Authors
Oh, DS; Reardon, DA; Prosnitz, LR; Gockerman, JP; Sampson, J; Kirkpatrick, JP
MLA Citation
Oh, DS, Reardon, DA, Prosnitz, LR, Gockerman, JP, Sampson, J, and Kirkpatrick, JP. "Low-dose Whole Brain Radiotherapy followed by Radiosurgery for Primary CNS Lymphoma Achieving Partial Response to Induction Chemotherapy." 2010.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
78
Issue
3
Publish Date
2010
Start Page
S293
End Page
S293

Implementing a Clinically Driven Electronic Medical Record for Radiation Oncology in a Major Medical Center

Authors
Kirkpatrick, JP; Yoo, S; Light, K; Antoine, P; Walker, R; Clough, R; Robbins, M; Cozart, H; Tabor, J; Willett, C
MLA Citation
Kirkpatrick, JP, Yoo, S, Light, K, Antoine, P, Walker, R, Clough, R, Robbins, M, Cozart, H, Tabor, J, and Willett, C. "Implementing a Clinically Driven Electronic Medical Record for Radiation Oncology in a Major Medical Center." 2010.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
78
Issue
3
Publish Date
2010
Start Page
S493
End Page
S494

Volumetric arc intensity-modulated therapy for spine body radiotherapy: comparison with static intensity-modulated treatment.

PURPOSE: This clinical study evaluates the feasibility of using volumetric arc-modulated treatment (VMAT) for spine stereotactic body radiotherapy (SBRT) to achieve highly conformal dose distributions that spare adjacent organs at risk (OAR) with reduced treatment time. METHODS AND MATERIALS: Ten spine SBRT patients were studied retrospectively. The intensity-modulated radiotherapy (IMRT) and VMAT plans were generated using either one or two arcs. Planning target volume (PTV) dose coverage, OAR dose sparing, and normal tissue integral dose were measured and compared. Differences in treatment delivery were also analyzed. RESULTS: The PTV DVHs were comparable between VMAT and IMRT plans in the shoulder (D(99%)-D(90%)), slope (D(90%)-D(10%)), and tail (D(10%)-D(1%)) regions. Only VMAT(2arc) had a better conformity index than IMRT (1.09 vs. 1.15, p = 0.007). For cord sparing, IMRT was the best, and VMAT(1arc) was the worst. Use of IMRT achieved greater than 10% more D(1%) sparing for six of 10 cases and 7% to 15% more D(10%) sparing over the VAMT(1arc). The differences between IMRT and VAMT(2arc) were smaller and statistically nonsignificant at all dose levels. The differences were also small and statistically nonsignificant for other OAR sparing. The mean monitor units (MUs) were 8711, 7730, and 6317 for IMRT, VMAT(1arc), and VMAT(2arc) plans, respectively, with a 26% reduction from IMRT to VMAT(2arc). The mean treatment time was 15.86, 8.56, and 7.88 min for IMRT, VMAT(1arc,) and VMAT(2arc). The difference in integral dose was statistically nonsignificant. CONCLUSIONS: Although VMAT provided comparable PTV coverage for spine SBRT, 1arc showed significantly worse spinal cord sparing compared with IMRT, whereas 2arc was comparable to IMRT. Treatment efficiency is substantially improved with the VMAT.

Authors
Wu, QJ; Yoo, S; Kirkpatrick, JP; Thongphiew, D; Yin, F-F
MLA Citation
Wu, QJ, Yoo, S, Kirkpatrick, JP, Thongphiew, D, and Yin, F-F. "Volumetric arc intensity-modulated therapy for spine body radiotherapy: comparison with static intensity-modulated treatment." Int J Radiat Oncol Biol Phys 75.5 (December 1, 2009): 1596-1604.
PMID
19733447
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
75
Issue
5
Publish Date
2009
Start Page
1596
End Page
1604
DOI
10.1016/j.ijrobp.2009.05.005

ExacTrac X-ray 6 degree-of-freedom image-guidance for intracranial non-invasive stereotactic radiotherapy: comparison with kilo-voltage cone-beam CT.

BACKGROUND AND PURPOSE: To compare the residual setup errors measured with ExacTrac X-ray 6 degree-of-freedom (6D) and cone-beam computed tomography (CBCT) for a head phantom and patients receiving intracranial non-invasive fractionated stereotactic radiotherapy (SRT). MATERIALS AND METHODS: Setup data were collected on a Novalis Tx treatment unit for an anthropomorphic head phantom and 18 patients with intracranial tumors. Initial corrections were determined and corrected with the ExacTrac system only, and then the residual setup error was determined by means of three different procedures. These procedures included registrations of ExacTrac X-ray images with the corresponding digitally reconstructed radiographs (DRRs) using the ExacTrac 6D fusion, and registrations of CBCT images with the planning CT using both online 3D fusion and offline 6D fusion. The difference in residual setup errors between ExacTrac system and CBCT was computed. The impact of rotations on the difference was evaluated. RESULTS: A modest difference in residual setup errors was found between ExacTrac system and CBCT. The root-mean-square (RMS) of the differences observed for translations was typically <0.5mm for phantom, and <1.5mm for patients, respectively. The RMS of the differences for rotation(s) was however <0.2 degree for phantom, and <1.0 degree for patients, respectively. The impact of rotation on the setup difference was minor but not negligible. CONCLUSIONS: This study indicates that there is a general agreement between ExacTrac system and CBCT.

Authors
Ma, J; Chang, Z; Wang, Z; Jackie Wu, Q; Kirkpatrick, JP; Yin, F-F
MLA Citation
Ma, J, Chang, Z, Wang, Z, Jackie Wu, Q, Kirkpatrick, JP, and Yin, F-F. "ExacTrac X-ray 6 degree-of-freedom image-guidance for intracranial non-invasive stereotactic radiotherapy: comparison with kilo-voltage cone-beam CT." Radiother Oncol 93.3 (December 2009): 602-608.
PMID
19846229
Source
pubmed
Published In
Radiotherapy and Oncology
Volume
93
Issue
3
Publish Date
2009
Start Page
602
End Page
608
DOI
10.1016/j.radonc.2009.09.009

Point/Counterpoint. The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery.

Authors
Kirkpatrick, JP; Brenner, DJ; Orton, CG
MLA Citation
Kirkpatrick, JP, Brenner, DJ, and Orton, CG. "Point/Counterpoint. The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery." Med Phys 36.8 (August 2009): 3381-3384.
PMID
19746770
Source
pubmed
Published In
Medical physics
Volume
36
Issue
8
Publish Date
2009
Start Page
3381
End Page
3384
DOI
10.1118/1.3157095

SU-EE-A3-02: Imaging Guided Frameless Stereotactic RadioSurgery Using CBCT 6D Image Registration and 6D Couch On Novalis Tx™ System

Authors
Chang, Z; Wang, Z; Wu, Q; Kirkpatrick, J; Yin, F
MLA Citation
Chang, Z, Wang, Z, Wu, Q, Kirkpatrick, J, and Yin, F. "SU-EE-A3-02: Imaging Guided Frameless Stereotactic RadioSurgery Using CBCT 6D Image Registration and 6D Couch On Novalis Tx™ System." June 2009.
Source
crossref
Published In
Medical physics
Volume
36
Issue
6Part2
Publish Date
2009
Start Page
2430
End Page
2431
DOI
10.1118/1.3181106

SU-FF-T-545: Feasibility Study for Treatment of Intracranial Multi-Focal Stereotactic Radiosurgery with Multiple Intensity Modulated Arc Technique

Authors
Wang, Z; Kirkpatrick, J; Chang, Z; O'Daniel, J; Willett, C; Yin, F
MLA Citation
Wang, Z, Kirkpatrick, J, Chang, Z, O'Daniel, J, Willett, C, and Yin, F. "SU-FF-T-545: Feasibility Study for Treatment of Intracranial Multi-Focal Stereotactic Radiosurgery with Multiple Intensity Modulated Arc Technique." June 2009.
Source
crossref
Published In
Medical physics
Volume
36
Issue
6Part17
Publish Date
2009
Start Page
2649
End Page
2649
DOI
10.1118/1.3182043

SU-FF-T-548: Comparison of Cone-Beam CT and Frame-Based Localizations for Stereotactic Radiosurgery with Fixed Head Rings and Removable Frames

Authors
Wang, Z; Kirkpatrick, J; Wu, Q; Chang, Z; Willett, C; Yin, F
MLA Citation
Wang, Z, Kirkpatrick, J, Wu, Q, Chang, Z, Willett, C, and Yin, F. "SU-FF-T-548: Comparison of Cone-Beam CT and Frame-Based Localizations for Stereotactic Radiosurgery with Fixed Head Rings and Removable Frames." June 2009.
Source
crossref
Published In
Medical physics
Volume
36
Issue
6Part17
Publish Date
2009
Start Page
2650
End Page
2650
DOI
10.1118/1.3182046

SU-FF-T-673: Application of RapidArc Technique to Cervical Spine Stereotactic Treatment

Authors
Brooks, A; Yin, F; Kirkpatrick, J; Wang, Z
MLA Citation
Brooks, A, Yin, F, Kirkpatrick, J, and Wang, Z. "SU-FF-T-673: Application of RapidArc Technique to Cervical Spine Stereotactic Treatment." June 2009.
Source
crossref
Published In
Medical physics
Volume
36
Issue
6Part19
Publish Date
2009
Start Page
2680
End Page
2680
DOI
10.1118/1.3182171

SU-FF-T-567: Volumetric Modulated Arc Therapy for Spine Body Radiotherapy: Comparison with Static Intensity Modulated Treatment

Authors
Wu, Q; Yoo, S; Kirkpatrick, J; McMahon, R; Thongphiew, D; Yin, F
MLA Citation
Wu, Q, Yoo, S, Kirkpatrick, J, McMahon, R, Thongphiew, D, and Yin, F. "SU-FF-T-567: Volumetric Modulated Arc Therapy for Spine Body Radiotherapy: Comparison with Static Intensity Modulated Treatment." June 2009.
Source
crossref
Published In
Medical physics
Volume
36
Issue
6Part18
Publish Date
2009
Start Page
2655
End Page
2655
DOI
10.1118/1.3182065

Paraganglioma of the head and neck: long-term local control with radiotherapy.

OBJECTIVES: Paragangliomas are rare neuroendocrine neoplasms of the head and neck. Treatment strategies include resection, definitive external beam radiation therapy (EBRT), stereotactic radiosurgery (SRS), or observation alone. Due to their rarity and indolent clinical behavior, the optimal management for long-term control is unknown. METHODS: This Institutional Review Board-approved retrospective study identified all paragangliomas of the head and neck treated with definitive fractionated radiotherapy at Duke University Medical Center from 1963 to 2005 with minimum 2-year follow-up. Local control (LC) was calculated using the Kaplan-Meier method. RESULTS: Thirty-one patients were identified and treated with EBRT (median dose: 54 Gy, range: 38-65 Gy). Twelve patients were treated with megavoltage photon; 19 were treated with either cobalt-60 or cesium-137. Fourteen (45%) had undergone resection preceding radiation. Median follow-up was 9 years (range: 2-35 years), with 10 patients having greater than 15-year follow-up. LC at 5, 10, and 15 years was 96%, 90%, and 90%, respectively. There were no failures in the group treated with megavoltage photons, although this was not statistically significant (P = 0.28). There was no difference in LC between salvage radiation therapy (RT) used after surgical failure and definitive RT alone (10-year LC, 73% vs. 100%, respectively, P = 0.31). The incidence of acute toxicity greater than grade 2 was 3%, and there were no late toxicities greater than grade 2. CONCLUSIONS: RT is an effective and well-tolerated treatment for paragangliomas of the head and neck.

Authors
Chino, JP; Sampson, JH; Tucci, DL; Brizel, DM; Kirkpatrick, JP
MLA Citation
Chino, JP, Sampson, JH, Tucci, DL, Brizel, DM, and Kirkpatrick, JP. "Paraganglioma of the head and neck: long-term local control with radiotherapy." Am J Clin Oncol 32.3 (June 2009): 304-307.
PMID
19433962
Source
pubmed
Published In
American Journal of Clinical Oncology: Cancer Clinical Trials
Volume
32
Issue
3
Publish Date
2009
Start Page
304
End Page
307
DOI
10.1097/COC.0b013e318187dd94

Phase I study of vandetanib, imatinib mesylate, and hydroxyurea for recurrent malignant glioma

Authors
Kirkpatrick, JP; Vredenburgh, JJ; Desjardins, A; Gururangan, S; Peters, KB; Boulton, ST; Friedman, AH; Friedman, HS; Reardon, DA
MLA Citation
Kirkpatrick, JP, Vredenburgh, JJ, Desjardins, A, Gururangan, S, Peters, KB, Boulton, ST, Friedman, AH, Friedman, HS, and Reardon, DA. "Phase I study of vandetanib, imatinib mesylate, and hydroxyurea for recurrent malignant glioma." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Phase I study of vandetanib, imatinib mesylate, and hydroxyurea for recurrent malignant glioma.

e13007 Background: Malignant glioma (MG), an incurable primary CNS tumor, is characterized by frequent aberrant activation of EGFR, VEGFR, and PDGFR. This study will determine the MTD and DLT of vandetanib (V), a once-daily, oral selective inhibitor of VEGFR and EGFR when combined with imatinib mesylate (IM), an inhibitor of multiple tyrosine kinases including PDGFR and hydroxyurea (H).Adult recurrent MG patients with ≤ 3 prior recurrences, KPS ≥ 60% and adequate organ function were stratified based on concurrent enzyme-inducing anticonvulsant use (EIAC). Both strata were independently escalated using a "3+3" design. H is administered at 500 mg BID while IM is administered at 500 mg BID for patients on EIAC and 400 mg QD for those not on EIAC. V is increased by 100 mg in successive cohorts beginning at 100 mg and 200 mg for patients not on and on EIAC, respectively. Evaluations were after every other 28-day cycle. Pharmacokinetics of V and IM were obtained on days 1 and 28 of cycle 1.Twenty-six patients (grade 4 MG, n = 20; grade 3 MG, n = 6) have enrolled. Only 1 DLT (reversible grade 4 transaminase elevation; dose level 1) occurred among 22 non-EIAC patients and enrollment to this stratum is planned to continue at dose level 4. The MTD of V for patients on EIAC is 200 mg/day due to 2 of 3 patients developing grade 3 thrombocytopenia at the 300 mg/day dose level. Evidence of therapeutic benefit to date includes 1 partial response and 15 patients (58%) with stable disease for at least 4 weeks, including 4 patients for ≥4 months.Combination of V, IM, and H is well-tolerated in recurrent MG patients. Further accrual is ongoing and an update of outcome, toxicity, and pharmacokinetic analyses will be presented. No significant financial relationships to disclose.

Authors
Kirkpatrick, JP; Vredenburgh, JJ; Desjardins, A; Gururangan, S; Peters, KB; Boulton, ST; Friedman, AH; Friedman, HS; Reardon, DA
MLA Citation
Kirkpatrick, JP, Vredenburgh, JJ, Desjardins, A, Gururangan, S, Peters, KB, Boulton, ST, Friedman, AH, Friedman, HS, and Reardon, DA. "Phase I study of vandetanib, imatinib mesylate, and hydroxyurea for recurrent malignant glioma." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27.15_suppl (May 2009): e13007-.
PMID
27962760
Source
epmc
Published In
Journal of Clinical Oncology
Volume
27
Issue
15_suppl
Publish Date
2009
Start Page
e13007

Stereotactic body radiotherapy for lesions of the spine and paraspinal regions.

PURPOSE: To describe our experience and clinical strategy for stereotactic body radiotherapy (SBRT) of spinal lesions. METHODS AND MATERIALS: Thirty-two patients with 33 spinal lesions underwent computed tomography-based simulation while free breathing. Gross/clinical target volumes included involved portions of the vertebral body and paravertebral/epidural tumor. Planning target volume (PTV) expansion was 6 mm axially and 3 mm radially; the cord was excluded from the PTV. Biologic equivalent dose was calculated using the linear quadratic model with alpha/beta = 3 Gy. Treatment was linear accelerator based with on-board imaging; dose was adjusted to maintain cord dose within tolerance. Survival, local control, pain, and neurologic status were monitored. RESULTS: Twenty-one patients are alive at 1 year (median survival, 14 months). Median follow-up is 6 months for all patients (7 months for survivors). Mean previous radiotherapy dose to 22 patients was 35 Gy, and median interval was 17 months. Renal (31%), breast, and lung (19% each) were the most common histologic sites. Three SBRT fractions (range, one to four fractions) of 7 Gy (range, 5-16 Gy) were delivered. Median cord and target biologic equivalent doses were 70 Gy(3) and 34.3 Gy(10), respectively. Thirteen patients reported complete and 17 patients reported partial pain relief at 1 month. There were four failures (mean, 5.8 months) with magnetic resonance imaging evidence of in-field progression. No dosimetric parameters predictive of failure were identified. No treatment-related toxicity was seen. CONCLUSIONS: Spinal SBRT is effective in the palliative/re-treatment setting. Volume expansion must ensure optimal PTV coverage while avoiding spinal cord toxicity. The long-term safety of spinal SBRT and the applicability of the linear-quadratic model in this setting remain to be determined, particularly the time-adjusted impact of prior radiotherapy.

Authors
Nelson, JW; Yoo, DS; Sampson, JH; Isaacs, RE; Larrier, NA; Marks, LB; Yin, F-F; Wu, QJ; Wang, Z; Kirkpatrick, JP
MLA Citation
Nelson, JW, Yoo, DS, Sampson, JH, Isaacs, RE, Larrier, NA, Marks, LB, Yin, F-F, Wu, QJ, Wang, Z, and Kirkpatrick, JP. "Stereotactic body radiotherapy for lesions of the spine and paraspinal regions." Int J Radiat Oncol Biol Phys 73.5 (April 1, 2009): 1369-1375.
PMID
19004569
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
73
Issue
5
Publish Date
2009
Start Page
1369
End Page
1375
DOI
10.1016/j.ijrobp.2008.06.1949

Dose-dependent effects of radiation therapy on cerebral blood flow, metabolism, and neurocognitive dysfunction.

PURPOSE: A prospective study was performed to formally relate dose-dependent radiologically defined changes in normal brain induced by radiotherapy (RT) to neurocognitive dysfunction in subjects with primary brain tumors. METHODS AND MATERIALS: Adult patients receiving three-dimensional RT for central nervous system (CNS) tumors were enrolled. Positron emission tomography (PET) scanning and neuropsychological testing were performed before RT and 3 weeks and 6 months after treatment. Analyses were performed for correlations between changes in 2-deoxy-2-[(18)F]-fluoro-d-glucose (FDG)-PET (metabolism), (15)O-PET (relative blood flow), regional radiation dose, follow-up time, and neuropsychological test scores. RESULTS: Eleven subjects were enrolled and 6 completed follow-up studies. The PET data showed reduced FDG uptake, with average decreases of 2-6% in regions of the brain receiving greater than 40 Gy at 3 weeks' and 6 months' follow-up. The (15)O-H(2)O PET showed increases (<10%) at 3 weeks in relative regional blood flow in brain receiving greater than 30 Gy, but less at the 6-month follow-up studies. There were significant correlations between decreases in FDG uptake and increased scores from the Symptom Checklist-90-R, with an average increase in T score of 2 (p < 0.0001). The Wisconsin Card Sorting Test showed a significant correlation of decreased FDG uptake with increased errors and perseveration in test performance, with an average decrease in T score of 11 (p = 0.037). CONCLUSIONS: A dose-dependent response of CNS tissue was detected using FDG PET in this small number of patients. Decreases in CNS metabolism correlated with decreased performance on neuropsychological tests for problem solving, cognitive flexibility, and global measures of psychopathology. Additional research is needed to verify and define these findings.

Authors
Hahn, CA; Zhou, S-M; Raynor, R; Tisch, A; Light, K; Shafman, T; Wong, T; Kirkpatrick, J; Turkington, T; Hollis, D; Marks, LB
MLA Citation
Hahn, CA, Zhou, S-M, Raynor, R, Tisch, A, Light, K, Shafman, T, Wong, T, Kirkpatrick, J, Turkington, T, Hollis, D, and Marks, LB. "Dose-dependent effects of radiation therapy on cerebral blood flow, metabolism, and neurocognitive dysfunction." Int J Radiat Oncol Biol Phys 73.4 (March 15, 2009): 1082-1087.
PMID
18755558
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
73
Issue
4
Publish Date
2009
Start Page
1082
End Page
1087
DOI
10.1016/j.ijrobp.2008.05.061

Quantifying the dosimetric trade-offs when using intensity-modulated radiotherapy to treat concave targets containing normal tissues.

PURPOSE: To quantitatively assess the relationship between intensity-modulated radiotherapy (IMRT)-driven sparing of dose to normal tissues located "within" concave targets with heterogeneity in dose delivered to the target and redistribution of dose to normal tissue beyond the concavity. METHODS AND MATERIALS: A combination of idealized and real-patient volumes was considered. Multiple IMRT plans were generated with progressive dose restriction to the normal tissue within the concavity. We quantified the impact of such sparing on the heterogeneity of dose within the target tissue itself, and the dose received by normal tissues beyond the concavity. RESULTS: As the dose to the normal tissue concavity region is reduced, the heterogeneity in dose delivered to the target increases in an exponential fashion. Furthermore, there is a rapid increase in redistributed dose to other normal tissue regions, particularly to the other normal tissues immediately adjacent to the outside edges of the concavity. Increasingly restricting dose to these adjacent normal tissue regions resulted in increasing dose to the normal tissue in the concavity and increasing dose heterogeneity in the target volume. CONCLUSIONS: For targets with concavities, there are dosimetric consequences associated with reducing dose to normal tissue located within these concavities. There appears to be a trade-off between the heterogeneity in dose delivered to the target, the mean dose to the concavity, and the redistributed dose to other normal tissues. Understanding the interaction between these dosimetric factors can aid the planner in assessing the feasibility of a desired dose distribution.

Authors
Reese, AS; Das, SK; Kirkpatrick, JP; Marks, LB
MLA Citation
Reese, AS, Das, SK, Kirkpatrick, JP, and Marks, LB. "Quantifying the dosimetric trade-offs when using intensity-modulated radiotherapy to treat concave targets containing normal tissues." Int J Radiat Oncol Biol Phys 73.2 (February 1, 2009): 585-593.
PMID
19147022
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
73
Issue
2
Publish Date
2009
Start Page
585
End Page
593
DOI
10.1016/j.ijrobp.2008.09.044

Refinement of treatment setup and target localization accuracy using three-dimensional cone-beam computed tomography for stereotactic body radiotherapy.

PURPOSES: To quantitatively compare two-dimensional (2D) orthogonal kV with three-dimensional (3D) cone-beam CT (CBCT) for target localization; and to assess intrafraction motion with kV images in patients undergoing stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: A total of 50 patients with 58 lesions received 178 fractions of SBRT. After clinical setup using in-room lasers and skin/cradle marks placed at simulation, patients were imaged and repositioned according to orthogonal kV/MV registration of bony landmarks to digitally reconstructed radiographs from the planning CT. A subsequent CBCT was registered to the planning CT using soft tissue information, and the resultant "residual error" was measured and corrected before treatment. Posttreatment 2D kV and/or 3D CBCT images were compared with pretreatment images to determine any intrafractional position changes. Absolute averages, statistical means, standard deviations, and root mean square (RMS) values of observed setup error were calculated. RESULTS: After initial setup to external marks with laser guidance, 2D kV images revealed vector mean setup deviations of 0.67 cm (RMS). Cone-beam CT detected residual setup deviations of 0.41 cm (RMS). Posttreatment imaging demonstrated intrafractional variations of 0.15 cm (RMS). The individual shifts in three standard orthogonal planes showed no obvious directional biases. CONCLUSIONS: After localization based on superficial markings in patients undergoing SBRT, orthogonal kV imaging detects setup variations of approximately 3 to 4 mm in each direction. Cone-beam CT detects residual setup variations of approximately 2 to 3 mm.

Authors
Wang, Z; Nelson, JW; Yoo, S; Wu, QJ; Kirkpatrick, JP; Marks, LB; Yin, F-F
MLA Citation
Wang, Z, Nelson, JW, Yoo, S, Wu, QJ, Kirkpatrick, JP, Marks, LB, and Yin, F-F. "Refinement of treatment setup and target localization accuracy using three-dimensional cone-beam computed tomography for stereotactic body radiotherapy." Int J Radiat Oncol Biol Phys 73.2 (February 1, 2009): 571-577.
PMID
19147021
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
73
Issue
2
Publish Date
2009
Start Page
571
End Page
577
DOI
10.1016/j.ijrobp.2008.09.040

Impact of collimator leaf width and treatment technique on stereotactic radiosurgery and radiotherapy plans for intra- and extracranial lesions.

BACKGROUND: This study evaluated the dosimetric impact of various treatment techniques as well as collimator leaf width (2.5 vs 5 mm) for three groups of tumors -- spine tumors, brain tumors abutting the brainstem, and liver tumors. These lesions often present challenges in maximizing dose to target volumes without exceeding critical organ tolerance. Specifically, this study evaluated the dosimetric benefits of various techniques and collimator leaf sizes as a function of lesion size and shape. METHODS: Fifteen cases (5 for each site) were studied retrospectively. All lesions either abutted or were an integral part of critical structures (brainstem, liver or spinal cord). For brain and liver lesions, treatment plans using a 3D-conformal static technique (3D), dynamic conformal arcs (DARC) or intensity modulation (IMRT) were designed with a conventional linear accelerator with standard 5 mm leaf width multi-leaf collimator, and a linear accelerator dedicated for radiosurgery and hypofractionated therapy with a 2.5 mm leaf width collimator. For the concave spine lesions, intensity modulation was required to provide adequate conformality; hence, only IMRT plans were evaluated using either the standard or small leaf-width collimators.A total of 70 treatment plans were generated and each plan was individually optimized according to the technique employed. The Generalized Estimating Equation (GEE) was used to separate the impact of treatment technique from the MLC system on plan outcome, and t-tests were performed to evaluate statistical differences in target coverage and organ sparing between plans. RESULTS: The lesions ranged in size from 2.6 to 12.5 cc, 17.5 to 153 cc, and 20.9 to 87.7 cc for the brain, liver, and spine groups, respectively. As a group, brain lesions were smaller than spine and liver lesions. While brain and liver lesions were primarily ellipsoidal, spine lesions were more complex in shape, as they were all concave. Therefore, the brain and the liver groups were compared for volume effect, and the liver and spine groups were compared for shape. For the brain and liver groups, both the radiosurgery MLC and the IMRT technique contributed to the dose sparing of organs-at-risk(OARs), as dose in the high-dose regions of these OARs was reduced up to 15%, compared to the non-IMRT techniques employing a 5 mm leaf-width collimator. Also, the dose reduction contributed by the fine leaf-width MLC decreased, as dose savings at all levels diminished from 4 - 11% for the brain group to 1 - 5% for the liver group, as the target structures decreased in volume. The fine leaf-width collimator significantly improved spinal cord sparing, with dose reductions of 14 - 19% in high to middle dose regions, compared to the 5 mm leaf width collimator. CONCLUSION: The fine leaf-width MLC in combination with the IMRT technique can yield dosimetric benefits in radiosurgery and hypofractionated radiotherapy. Treatment of small lesions in cases involving complex target/OAR geometry will especially benefit from use of a fine leaf-width MLC and the use of IMRT.

Authors
Wu, QJ; Wang, Z; Kirkpatrick, JP; Chang, Z; Meyer, JJ; Lu, M; Huntzinger, C; Yin, F-F
MLA Citation
Wu, QJ, Wang, Z, Kirkpatrick, JP, Chang, Z, Meyer, JJ, Lu, M, Huntzinger, C, and Yin, F-F. "Impact of collimator leaf width and treatment technique on stereotactic radiosurgery and radiotherapy plans for intra- and extracranial lesions. (Published online)" Radiat Oncol 4 (January 21, 2009): 3-.
PMID
19159471
Source
pubmed
Published In
Radiation Oncology
Volume
4
Publish Date
2009
Start Page
3
DOI
10.1186/1748-717X-4-3

Impact of collimator leaf width and treatment technique on stereotactic radiosurgery and radiotherapy plans for intra- and extracranial lesions.

BACKGROUND: This study evaluated the dosimetric impact of various treatment techniques as well as collimator leaf width (2.5 vs 5 mm) for three groups of tumors -- spine tumors, brain tumors abutting the brainstem, and liver tumors. These lesions often present challenges in maximizing dose to target volumes without exceeding critical organ tolerance. Specifically, this study evaluated the dosimetric benefits of various techniques and collimator leaf sizes as a function of lesion size and shape. METHODS: Fifteen cases (5 for each site) were studied retrospectively. All lesions either abutted or were an integral part of critical structures (brainstem, liver or spinal cord). For brain and liver lesions, treatment plans using a 3D-conformal static technique (3D), dynamic conformal arcs (DARC) or intensity modulation (IMRT) were designed with a conventional linear accelerator with standard 5 mm leaf width multi-leaf collimator, and a linear accelerator dedicated for radiosurgery and hypofractionated therapy with a 2.5 mm leaf width collimator. For the concave spine lesions, intensity modulation was required to provide adequate conformality; hence, only IMRT plans were evaluated using either the standard or small leaf-width collimators.A total of 70 treatment plans were generated and each plan was individually optimized according to the technique employed. The Generalized Estimating Equation (GEE) was used to separate the impact of treatment technique from the MLC system on plan outcome, and t-tests were performed to evaluate statistical differences in target coverage and organ sparing between plans. RESULTS: The lesions ranged in size from 2.6 to 12.5 cc, 17.5 to 153 cc, and 20.9 to 87.7 cc for the brain, liver, and spine groups, respectively. As a group, brain lesions were smaller than spine and liver lesions. While brain and liver lesions were primarily ellipsoidal, spine lesions were more complex in shape, as they were all concave. Therefore, the brain and the liver groups were compared for volume effect, and the liver and spine groups were compared for shape. For the brain and liver groups, both the radiosurgery MLC and the IMRT technique contributed to the dose sparing of organs-at-risk(OARs), as dose in the high-dose regions of these OARs was reduced up to 15%, compared to the non-IMRT techniques employing a 5 mm leaf-width collimator. Also, the dose reduction contributed by the fine leaf-width MLC decreased, as dose savings at all levels diminished from 4 - 11% for the brain group to 1 - 5% for the liver group, as the target structures decreased in volume. The fine leaf-width collimator significantly improved spinal cord sparing, with dose reductions of 14 - 19% in high to middle dose regions, compared to the 5 mm leaf width collimator. CONCLUSION: The fine leaf-width MLC in combination with the IMRT technique can yield dosimetric benefits in radiosurgery and hypofractionated radiotherapy. Treatment of small lesions in cases involving complex target/OAR geometry will especially benefit from use of a fine leaf-width MLC and the use of IMRT.

Authors
Wu, QJ; Wang, Z; Kirkpatrick, JP; Chang, Z; Meyer, JJ; Lu, M; Huntzinger, C; Yin, F-F
MLA Citation
Wu, QJ, Wang, Z, Kirkpatrick, JP, Chang, Z, Meyer, JJ, Lu, M, Huntzinger, C, and Yin, F-F. "Impact of collimator leaf width and treatment technique on stereotactic radiosurgery and radiotherapy plans for intra- and extracranial lesions." Radiation oncology (London, England) 4 (2009): 3--.
Source
scival
Published In
Radiation Oncology
Volume
4
Publish Date
2009
Start Page
3-
DOI
10.1186/1748-717X-4-3

The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery

Authors
Kirkpatrick, JP; Brenner, DJ; Orton, CG
MLA Citation
Kirkpatrick, JP, Brenner, DJ, and Orton, CG. "The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery." Medical Physics 36.8 (2009): 3381-3384.
PMID
28541614
Source
scival
Published In
Medical physics
Volume
36
Issue
8
Publish Date
2009
Start Page
3381
End Page
3384
DOI
10.1118/1.3157095

Synchronous Chemoradiation and Multiple Targeted Drugs for Advanced Head and Neck Cancer

Authors
Brizel, DM; Yoo, DS; Ready, N; Kirkpatrick, JP; Dewhirst, MW; Scher, RL; Cleland, E; MacFall, J; Barboriak, D; Craciunescu, O
MLA Citation
Brizel, DM, Yoo, DS, Ready, N, Kirkpatrick, JP, Dewhirst, MW, Scher, RL, Cleland, E, MacFall, J, Barboriak, D, and Craciunescu, O. "Synchronous Chemoradiation and Multiple Targeted Drugs for Advanced Head and Neck Cancer." 2009.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
75
Issue
3
Publish Date
2009
Start Page
S175
End Page
S176

Imaging Guided Stereotactic Radiosurgery and its Accuracy Compared to Frame-based Localization

Authors
Wang, Z; Kirkpatrick, JP; Wu, QJ; Chang, Z; Willett, CG; Yin, F
MLA Citation
Wang, Z, Kirkpatrick, JP, Wu, QJ, Chang, Z, Willett, CG, and Yin, F. "Imaging Guided Stereotactic Radiosurgery and its Accuracy Compared to Frame-based Localization." 2009.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
75
Issue
3
Publish Date
2009
Start Page
S690
End Page
S690

Radiotherapy, Temozolomide and Bevacizumab followed by Irinotecan, Temozolomide and Bevacizumab Appears Well-tolerated and Efficacious in Newly Diagnosed Glioblastoma Multiforme: Results from a Phase II Trial

Authors
Kirkpatrick, JP; Desjardins, A; Reardon, DA; Friedman, AH; Friedman, HS; Vredenburgh, JJ
MLA Citation
Kirkpatrick, JP, Desjardins, A, Reardon, DA, Friedman, AH, Friedman, HS, and Vredenburgh, JJ. "Radiotherapy, Temozolomide and Bevacizumab followed by Irinotecan, Temozolomide and Bevacizumab Appears Well-tolerated and Efficacious in Newly Diagnosed Glioblastoma Multiforme: Results from a Phase II Trial." 2009.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
75
Issue
3
Publish Date
2009
Start Page
S102
End Page
S103

Bevacizumab in Patients Treated with Stereotactic Radiosurgery for Recurrent Malignant Gliomas is Associated with Improved Overall Survival

Authors
Cuneo, KC; Vredenburgh, JJ; Sampson, JH; Reardon, DA; Desjardins, A; Willett, CG; Kirkpatrick, JP
MLA Citation
Cuneo, KC, Vredenburgh, JJ, Sampson, JH, Reardon, DA, Desjardins, A, Willett, CG, and Kirkpatrick, JP. "Bevacizumab in Patients Treated with Stereotactic Radiosurgery for Recurrent Malignant Gliomas is Associated with Improved Overall Survival." 2009.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
75
Issue
3
Publish Date
2009
Start Page
S249
End Page
S250

The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery.

The linear-quadratic (LQ) model is widely used to model the effect of total dose and dose per fraction in conventionally fractionated radiotherapy. Much of the data used to generate the model are obtained in vitro at doses well below those used in radiosurgery. Clinically, the LQ model often underestimates tumor control observed at radiosurgical doses. The underlying mechanisms implied by the LQ model do not reflect the vascular and stromal damage produced at the high doses per fraction encountered in radiosurgery and ignore the impact of radioresistant subpopulations of cells. The appropriate modeling of both tumor control and normal tissue toxicity in radiosurgery requires the application of emerging understanding of molecular-, cellular-, and tissue-level effects of high-dose/fraction-ionizing radiation and the role of cancer stem cells.

Authors
Kirkpatrick, JP; Meyer, JJ; Marks, LB
MLA Citation
Kirkpatrick, JP, Meyer, JJ, and Marks, LB. "The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery." Semin Radiat Oncol 18.4 (October 2008): 240-243.
PMID
18725110
Source
pubmed
Published In
Seminars in Radiation Oncology
Volume
18
Issue
4
Publish Date
2008
Start Page
240
End Page
243
DOI
10.1016/j.semradonc.2008.04.005

SU-GG-T-454: Localization Accuracy of Cone-Beam CT Guided Radiosurgery as Investigated Utilizing a Geometric Phantom

Authors
Wang, Z; Wu, Q; Chang, Z; Kirkpatrick, J; Yin, F
MLA Citation
Wang, Z, Wu, Q, Chang, Z, Kirkpatrick, J, and Yin, F. "SU-GG-T-454: Localization Accuracy of Cone-Beam CT Guided Radiosurgery as Investigated Utilizing a Geometric Phantom." June 2008.
Source
crossref
Published In
Medical physics
Volume
35
Issue
6Part16
Publish Date
2008
Start Page
2829
End Page
2829
DOI
10.1118/1.2962202

SU-GG-T-438: Rind Radiosurgery: Investigation of a Novel Radiation Therapy Technique for the Treatment of Intracranial Lesions

Authors
Hosfeld, V; Kirkpatrick, J; Oldham, M
MLA Citation
Hosfeld, V, Kirkpatrick, J, and Oldham, M. "SU-GG-T-438: Rind Radiosurgery: Investigation of a Novel Radiation Therapy Technique for the Treatment of Intracranial Lesions." June 2008.
Source
crossref
Published In
Medical physics
Volume
35
Issue
6Part16
Publish Date
2008
Start Page
2825
End Page
2825
DOI
10.1118/1.2962186

The actuarial incidence of brain metastases in 975 patients undergoing surgery for early-stage lung cancer.

8094 Background: The risk of developing brain metastases after definitive treatment for locally-advanced non-small cell lung cancer (NSCLC) is approximately 30%-50%. The risk for patients with early-stage disease is less defined. We sought to investigate this further and study potential factors associated with an increased risk. METHODS: The records of all patients who underwent surgery for T1-2 N0-1 NSCLC at Duke University between 1995-2005 were reviewed. Patients who received preoperative therapy, had synchronous primaries, or had a prior history of lung cancer were excluded. The cumulative incidence of distant metastases and brain metastases was estimated using the Kaplan-Meier method. A univariate and multivariate analysis assessed factors associated with the development of brain metastases. RESULTS: Of 975 consecutive patients, 85% were stage I and 15% were stage II. Adjuvant chemotherapy was given to 7%. The 5-year actuarial rate of distant metastases and brain metastases was 31% (95% CI: 27-35%) and 10% (95% CI: 8-13%), respectively. Of patients developing brain metastases, the brain was the sole site of failure in 43%. On multivariate analysis, younger age (HR 1.03), larger tumor size (HR 1.26), lymphovascular space invasion (HR 1.87), and lymph node involvement (HR 1.18) were associated with an increased risk of brain metastases. CONCLUSIONS: In this large series of patients treated surgically for early-stage NSCLC, the 5-year actuarial risk of brain metastases was 10%. While prophylactic cranial irradiation is currently under investigation in locally-advanced disease, a better understanding of predictive factors and biological susceptibility is needed to identify the subset of patients with early-stage NSCLC who are at particularly high risk. No significant financial relationships to disclose.

Authors
Boyd, JA; Hubbs, JL; Hollis, DR; Kirkpatrick, JP; Kim, DW; Marks, LB; Kelsey, CR
MLA Citation
Boyd, JA, Hubbs, JL, Hollis, DR, Kirkpatrick, JP, Kim, DW, Marks, LB, and Kelsey, CR. "The actuarial incidence of brain metastases in 975 patients undergoing surgery for early-stage lung cancer." J Clin Oncol 26.15_suppl (May 20, 2008): 8094-.
PMID
27949193
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
15_suppl
Publish Date
2008
Start Page
8094

Final report: Phase I trial of imatinib mesylate, hydroxyurea, and vatalanib for patients with recurrent malignant glioma (MG)

Authors
Kirkpatrick, JP; Rich, JN; Vredenburgh, JJ; Desjardins, A; Quinn, JA; Gururangan, S; Sathornsumetee, S; Egorin, MJ; Friedman, HS; Reardon, DA
MLA Citation
Kirkpatrick, JP, Rich, JN, Vredenburgh, JJ, Desjardins, A, Quinn, JA, Gururangan, S, Sathornsumetee, S, Egorin, MJ, Friedman, HS, and Reardon, DA. "Final report: Phase I trial of imatinib mesylate, hydroxyurea, and vatalanib for patients with recurrent malignant glioma (MG)." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

The actuarial incidence of brain metastases in 975 patients undergoing surgery for early-stage lung cancer

Authors
Boyd, JA; Hubbs, JL; Hollis, DR; Kirkpatrick, JP; Kim, DW; Marks, LB; Kelsey, CR
MLA Citation
Boyd, JA, Hubbs, JL, Hollis, DR, Kirkpatrick, JP, Kim, DW, Marks, LB, and Kelsey, CR. "The actuarial incidence of brain metastases in 975 patients undergoing surgery for early-stage lung cancer." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

Final report: Phase I trial of imatinib mesylate, hydroxyurea, and vatalanib for patients with recurrent malignant glioma (MG).

2057 Background: Angiogenesis is a hallmark of MG with VEGF as a key regulator. Imatinib mesylate (IM) and hydroxyurea (H) have recently demonstrated promising anti-glioma activity. We attempt to extend the efficacy of IM and H by adding a VEGF receptor inhibitor, vatalanib (V; PTK787).We employed a "3+3" dose escalation design to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of V when administered with established doses of IM and H in adult recurrent MG patients with < 3 prior recurrences, KPS ≥ 70% and adequate organ function. Patients were stratified based on concurrent enzyme-inducing anticonvulsant (EIAC) administration, and both strata (A- not on EIAC and B- on EIAC) were independently dose-escalated. Response was evaluated after every other 28-day cycle. Pharmacokinetic (PK) studies were performed during cycle 1.Thirty-seven recurrent MG patients enrolled including 34 (92%) with glioblastoma multiforme and 3 (8%) with WHO grade 3 MG. The median age is 53 (range 26 to 76) and 51% are on EIAC. The MTD of V is 1,000 mg bid. DLTs included grade 3 thrombocytopenia, rash, fatigue, hypertension and transaminase elevation. Best responses include partial response (n=8, 22%) and stable disease (n=19, 51%). With a median follow-up of 82 weeks, 6-month progression-free survival is 27%. PK results are pending.Combination of imatinib, hydroxyurea and vatalanib is safe and well tolerated with an encouraging rate of radiographic response. MTD is 1,000 mg of V bid with standard imatinib and hydroxyurea dosing for recurrent MG patients. [Table: see text].

Authors
Kirkpatrick, JP; Rich, JN; Vredenburgh, JJ; Desjardins, A; Quinn, JA; Gururangan, S; Sathornsumetee, S; Egorin, MJ; Friedman, HS; Reardon, DA
MLA Citation
Kirkpatrick, JP, Rich, JN, Vredenburgh, JJ, Desjardins, A, Quinn, JA, Gururangan, S, Sathornsumetee, S, Egorin, MJ, Friedman, HS, and Reardon, DA. "Final report: Phase I trial of imatinib mesylate, hydroxyurea, and vatalanib for patients with recurrent malignant glioma (MG)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 26.15_suppl (May 2008): 2057-.
PMID
27948101
Source
epmc
Published In
Journal of Clinical Oncology
Volume
26
Issue
15_suppl
Publish Date
2008
Start Page
2057

Integration of cone-beam CT in stereotactic body radiation therapy.

This report describes the technique and initial experience using cone beam CT (CBCT) for localization of treatment targets in patients undergoing stereotactic body radiation therapy (SBRT). Patients selected for SBRT underwent 3-D or 4-D CT scans in a customized immobilization cradle. GTV, CTV, ITV, and PTV were defined. Intensity-modulated radiation beams, multiple 3-D conformal beams, or dynamic conformal arcs were delivered using a Varian 21EX with 120-leaf MLC. CBCT images were obtained prior to each fraction, and registered to the planning CT by using soft tissue and bony structures to assure accurate isocenter localization. Patients were repositioned for treatment based on the CBCT images. Radiographic images (kV, MV, or CBCT) were taken before and after beam delivery to further assess set-up accuracy. Ten patients with lung, liver, and spine lesions received 29 fractions of treatment using this technique. The prescription doses ranged 1250 approximately 6000 cGy in 1 approximately 5 fractions. Compared to traditional 2-D matching using bony structures, CBCT corrects target deviation from 1 mm to 15 mm, with an average of 5 mm. Comparison of pre-treatment to post-treatment radiographic images demonstrated an average 2 mm deviation (ranging from 0-4 mm). Improved immobilization may enhance positioning accuracy. Typical total "in-room" times for the patients are approximately 1 hour. CBCT-guided SBRT is feasible and enhances setup accuracy using 3-D anatomical information.

Authors
Yin, F-F; Wang, Z; Yoo, S; Wu, QJ; Kirkpatrick, J; Larrier, N; Meyer, J; Willett, CG; Marks, LB
MLA Citation
Yin, F-F, Wang, Z, Yoo, S, Wu, QJ, Kirkpatrick, J, Larrier, N, Meyer, J, Willett, CG, and Marks, LB. "Integration of cone-beam CT in stereotactic body radiation therapy." Technol Cancer Res Treat 7.2 (April 2008): 133-139.
PMID
18345702
Source
pubmed
Published In
Technology in cancer research & treatment
Volume
7
Issue
2
Publish Date
2008
Start Page
133
End Page
139
DOI
10.1177/153303460800700206

Analytic solution to steady-state radial diffusion of a substrate with first-order reaction kinetics in the tissue of a Krogh's cylinder.

It is often useful to calculate the concentration profile for a substrate undergoing reaction in the tissue surrounding a capillary. In this paper, we consider a model geometry consisting of a long straight cylinder of tissue surrounding a capillary. Substrate diffuses radially out of the capillary through the tissue, with consumption of substrate in the tissue directly proportional to substrate concentration (i.e., first-order reaction kinetics). The model is extended to include the case where a cylinder of necrotic tissue surrounds a metabolically active inner tissue cylinder. A simple analytic solution is derived, and concentration profiles are generated for various combinations of parameters. Compared to the case where substrate consumption is independent of concentration, this model predicts much more rapid depletion of substrate near the capillary interface. This can have significant implications for the calculation of the hypoxic fraction (e.g., tissue with pO(2)<0.5-5 mmHg) when tumor oxygenation is modeled. The model also permits calculation of the limiting substrate concentration for cell viability when the reaction rate constant is known and vice versa.

Authors
Kirkpatrick, JP; Dewhirst, MW
MLA Citation
Kirkpatrick, JP, and Dewhirst, MW. "Analytic solution to steady-state radial diffusion of a substrate with first-order reaction kinetics in the tissue of a Krogh's cylinder." Radiat Res 169.3 (March 2008): 350-354.
PMID
18302491
Source
pubmed
Published In
Radiation Research
Volume
169
Issue
3
Publish Date
2008
Start Page
350
End Page
354
DOI
10.1667/RR1166.1

Elevated CAIX Expression is Associated with an Increased Risk of Distant Failure in Early-Stage Cervical Cancer.

Tumor hypoxia is associated with adverse outcome in many malignancies. The goal of this study was to determine if elevated expression of carbonic anhydrase IX (CAIX), a biomarker of hypoxia, predicts for recurrence in early-stage cervical cancer. The charts of all patients with early-stage cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988-2001 were reviewed. Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remained disease-free were stained for CAIX. An immunohistochemical score (IHC) was generated from the extent/intensity of staining. Outcome, as measured by freedom from recurrence (FFR), distant metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age, IHC, lymph node status (LN) and histology. Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastases as first site of failure (5-year FFDM 50%) than patients with only +LN, elevated IHC or neither feature (70, 85 and 95%, respectively, p = 0.0004). In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p = 0.0015) though there was a strong trend with elevated CAIX expression (p = 0.069). Elevated CAIX expression is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment.

Authors
Kirkpatrick, JP; Rabbani, ZN; Bentley, RC; Hardee, ME; Karol, S; Meyer, J; Oosterwijk, E; Havrilesky, L; Secord, AA; Vujaskovic, Z; Dewhirst, MW; Jones, EL
MLA Citation
Kirkpatrick, JP, Rabbani, ZN, Bentley, RC, Hardee, ME, Karol, S, Meyer, J, Oosterwijk, E, Havrilesky, L, Secord, AA, Vujaskovic, Z, Dewhirst, MW, and Jones, EL. "Elevated CAIX Expression is Associated with an Increased Risk of Distant Failure in Early-Stage Cervical Cancer. (Published online)" Biomark Insights 3 (February 1, 2008): 45-55.
PMID
19578493
Source
pubmed
Published In
Biomarker Insights
Volume
3
Publish Date
2008
Start Page
45
End Page
55

Choroidal metastasis of follicular thyroid adenocarcinoma diagnosed by 25-gauge transretinal biopsy.

We report a case of a patient with previously treated follicular thyroid carcinoma who presented with a symptomatic amelanotic choroidal mass with low internal reflectivity and a metastatic lytic skull lesion. A 25-gauge vitrector was used to perform transretinal choroidal biopsy (TRCB), confirming the diagnosis of metastatic follicular thyroid carcinoma.

Authors
Scott, AW; Cummings, TJ; Kirkpatrick, JP; Mruthyunjaya, P
MLA Citation
Scott, AW, Cummings, TJ, Kirkpatrick, JP, and Mruthyunjaya, P. "Choroidal metastasis of follicular thyroid adenocarcinoma diagnosed by 25-gauge transretinal biopsy." Ann Ophthalmol (Skokie) 40.2 (2008): 110-112.
PMID
19013920
Source
pubmed
Published In
Annals of ophthalmology (Skokie, Ill.)
Volume
40
Issue
2
Publish Date
2008
Start Page
110
End Page
112

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to assess changes in tumor physiology caused by molecular targeted agents in locally advanced head and neck cancer (LAHNC)

Authors
Yoo, DS; Craciunescu, O; Cleland, E; Barboriak, D; Muradyan, N; Dolguikh, M; Kirkpatrick, JP; Carroll, MD; Brizel, DM
MLA Citation
Yoo, DS, Craciunescu, O, Cleland, E, Barboriak, D, Muradyan, N, Dolguikh, M, Kirkpatrick, JP, Carroll, MD, and Brizel, DM. "Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to assess changes in tumor physiology caused by molecular targeted agents in locally advanced head and neck cancer (LAHNC)." 2008.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
72
Issue
1
Publish Date
2008
Start Page
S160
End Page
S160
DOI
10.1016/j.ijrobp.2008.06.504

High-definition micro-multileaf collimator in radiosurgery treatment planning for arteriovenous malformations

Authors
Boyd, JA; Kim, DW; Meyer, JJ; Wang, Z; Britz, GW; Wu, J; Yin, F; Kirkpatrick, JP
MLA Citation
Boyd, JA, Kim, DW, Meyer, JJ, Wang, Z, Britz, GW, Wu, J, Yin, F, and Kirkpatrick, JP. "High-definition micro-multileaf collimator in radiosurgery treatment planning for arteriovenous malformations." 2008.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
72
Issue
1
Publish Date
2008
Start Page
S531
End Page
S532
DOI
10.1016/j.ijrobp.2008.06.064

Dosimetrical evaluation of SRS/SBRT techniques

Authors
Wu, QJ; Wang, Z; Kirkpatrick, JP; Chang, Z; Zhou, S; Willett, CG; Yin, F
MLA Citation
Wu, QJ, Wang, Z, Kirkpatrick, JP, Chang, Z, Zhou, S, Willett, CG, and Yin, F. "Dosimetrical evaluation of SRS/SBRT techniques." 2008.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
72
Issue
1
Publish Date
2008
Start Page
S650
End Page
S651
DOI
10.1016/j.ijrobp.2008.06.328

Can cone beam CT replace frame-based localization for stereotactic radiosurgery?

Authors
Wang, Z; Kirkpatrick, JP; Wu, QJ; Chang, Z; Willett, CG; Yin, F
MLA Citation
Wang, Z, Kirkpatrick, JP, Wu, QJ, Chang, Z, Willett, CG, and Yin, F. "Can cone beam CT replace frame-based localization for stereotactic radiosurgery?." 2008.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
72
Issue
1
Publish Date
2008
Start Page
S534
End Page
S534
DOI
10.1016/j.ijrobp.2008.06.070

Radiotherapy, temozolomide, and bevacizumab followed by irinotecan, temozolomide and bevacizumab in newly diagnosed glioblastoma multiforme: Preliminary results front an ongoing phase II trial

Authors
Kirkpatrick, JP; Desjardins, A; Reardon, DA; Vredenburgh, JJ
MLA Citation
Kirkpatrick, JP, Desjardins, A, Reardon, DA, and Vredenburgh, JJ. "Radiotherapy, temozolomide, and bevacizumab followed by irinotecan, temozolomide and bevacizumab in newly diagnosed glioblastoma multiforme: Preliminary results front an ongoing phase II trial." 2008.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
72
Issue
1
Publish Date
2008
Start Page
S209
End Page
S209
DOI
10.1016/j.ijrobp.2008.06.1537

Stereotactic body radiosurgery of the spine: The duke experience

Authors
Nelson, JW; Yoo, DS; Sampson, JH; Isaacs, RE; Larrier, NA; Marks, LB; Yin, FF; Wu, QJ; Wang, Z; Kirkpatrick, JP
MLA Citation
Nelson, JW, Yoo, DS, Sampson, JH, Isaacs, RE, Larrier, NA, Marks, LB, Yin, FF, Wu, QJ, Wang, Z, and Kirkpatrick, JP. "Stereotactic body radiosurgery of the spine: The duke experience." 2008.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
72
Issue
1
Publish Date
2008
Start Page
S489
End Page
S490
DOI
10.1016/j.ijrobp.2008.06.1438

How much radiation is the chemotherapy worth in advanced head and neck cancer?

PURPOSE: To estimate the radiotherapeutic dose equivalence of chemoradiotherapy in head and neck cancer. METHODS: The biologic equivalent dose (BED) of radiotherapy in nine trials of standard and five trials of modified fractionated radiotherapy with or without chemotherapy was calculated using the linear-quadratic formulation. Data from Radiation Therapy Oncology Group (RTOG) study 90-03 were used to calculate the relationship (S) between increase in locoregional control (LRC) and increase in BED with modified vs. standard fractionated radiotherapy. The increase in LRC with chemoradiotherapy vs. radiotherapy alone, the BED of the radiotherapy-alone arms, and the "S" value were used to calculate the BED contribution from chemotherapy and the total BED of chemoradiotherapy from each study. RESULTS: From RTOG 90-03, a 1% increase in BED yields a 1.1% increase in LRC. The mean BED of standard fractioned radiotherapy was 60.2 Gy(10) and 66 Gy(10) for modified fractionation. The mean BED of standard fractionated chemoradiotherapy was 71 Gy(10) (10.8 Gy(10) contributed by chemotherapy). The mean BED of modified fractionated chemoradiotherapy was 76 Gy(10) (10.4 Gy(10) contributed by chemotherapy). CONCLUSIONS: Chemotherapy increases BED by approximately 10 Gy(10) in standard and modified fractionated radiotherapy, equivalent to a dose escalation of 12 Gy in 2 Gy daily or 1.2 Gy twice daily. Such an escalation could not be safely achieved by increasing radiation dose alone.

Authors
Kasibhatla, M; Kirkpatrick, JP; Brizel, DM
MLA Citation
Kasibhatla, M, Kirkpatrick, JP, and Brizel, DM. "How much radiation is the chemotherapy worth in advanced head and neck cancer?." Int J Radiat Oncol Biol Phys 68.5 (August 1, 2007): 1491-1495.
PMID
17674979
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
68
Issue
5
Publish Date
2007
Start Page
1491
End Page
1495
DOI
10.1016/j.ijrobp.2007.03.025

Estimating the magnitude and field-size dependence of radiotherapy-induced mortality and tumor control after postoperative radiotherapy for non-small-cell lung cancer: calculations from clinical trials.

PURPOSE: To create, on the basis of available data, a mathematical model to describe the tumor stage- and field size-dependent risks/benefits of postoperative radiotherapy (PORT) for non-small-cell lung cancer (NSCLC), and to assess whether this simple model can accurately describe the reported changes in overall survival. METHODS AND MATERIALS: The increase in overall survival afforded by PORT is assumed equal to the increase in cancer-specific survival minus the rate of RT-induced mortality. The increase in cancer-specific survival is the product of the probabilities of (residual local disease) x (sterilization of residual disease with PORT) x (absence of metastatic disease). Data were extracted from the literature to estimate these probabilities. Different models were considered to relate the RT-induced mortality to field size. RESULTS: The rate of RT-induced mortality seems to be proportional to the cube of the field size. When these mortality rates are included in the model, the predicted changes in overall survival approximate the literature values. CONCLUSION: Clinical data can be explained by a simple model that suggests that RT-induced mortality is strongly dependent on field size and at least partly offsets the benefit afforded by PORT. Smaller RT fields, tailored to treat the areas most at risk for recurrence, provide the highest therapeutic ratio. The data used do not reflect the impact of chemotherapy, which will reduce the rate of distant metastases and enhance the efficacy of RT.

Authors
Miles, EF; Kelsey, CR; Kirkpatrick, JP; Marks, LB
MLA Citation
Miles, EF, Kelsey, CR, Kirkpatrick, JP, and Marks, LB. "Estimating the magnitude and field-size dependence of radiotherapy-induced mortality and tumor control after postoperative radiotherapy for non-small-cell lung cancer: calculations from clinical trials." Int J Radiat Oncol Biol Phys 68.4 (July 15, 2007): 1047-1052.
PMID
17507176
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
68
Issue
4
Publish Date
2007
Start Page
1047
End Page
1052
DOI
10.1016/j.ijrobp.2007.02.028

SU-FF-T-252: Improvement of Localization Accuracy by Using 3D Cone Beam CT for Stereotactic Body Radiation Therapy of Liver, Lung and Spine Lesions

Authors
Wang, Z; Nelson, J; Yoo, S; Wu, QJ; Kirkpatrick, J; Larrier, N; Meyer, J; Willett, C; Yin, F
MLA Citation
Wang, Z, Nelson, J, Yoo, S, Wu, QJ, Kirkpatrick, J, Larrier, N, Meyer, J, Willett, C, and Yin, F. "SU-FF-T-252: Improvement of Localization Accuracy by Using 3D Cone Beam CT for Stereotactic Body Radiation Therapy of Liver, Lung and Spine Lesions." June 2007.
Source
crossref
Published In
Medical physics
Volume
34
Issue
6Part11
Publish Date
2007
Start Page
2459
End Page
2459
DOI
10.1118/1.2760913

Temporal onset of hypoxia and oxidative stress after pulmonary irradiation.

PURPOSE: To investigate the temporal onset of hypoxia following irradiation, and to show how it relates to pulmonary vascular damage, macrophage accumulation, and the production of reactive oxygen species and cytokines. Our previous studies showed that tissue hypoxia in the lung after irradiation contributed to radiation-induced injury. METHODS AND MATERIALS: Female Fisher 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy. Serial studies were performed up to 20 weeks following irradiation. Radionuclide lung-perfusion studies were performed to detect changes in pulmonary vasculature. Immunohistochemical studies were conducted to study macrophages, tissue hypoxia (carbonic anhydrase-9 marker), oxidative stress (8-hydroxy-2'-deoxyguanosine), and the expression of profibrogenic (transforming growth factor-beta [TGF-beta]) and proangiogenic (vascular endothelial growth factor [VEGF]) cytokines. RESULTS: Significant changes in lung perfusion along with tissue hypoxia were observed 3 days after irradiation. Significant oxidative stress was detected 1 week after radiation, whereas macrophages started to accumulate at 4 weeks. A significant increase in TGF-beta expression was seen within 1 day after radiation, and for VEGF at 2 weeks after radiation. Levels of hypoxia, oxidative stress, and both cytokines continued to rise with time after irradiation. The steepest increase correlated with vast macrophage accumulation. CONCLUSIONS: Early changes in lung perfusion, among other factors initiate, the development of hypoxia and chronic oxidative stress after irradiation. Tissue hypoxia is associated with a significant increase in the activation of macrophages and their continuous production of reactive oxygen species, stimulating the production of fibrogenic and angiogenic cytokines, and maintaining the development of chronic radiation-induced lung injury.

Authors
Fleckenstein, K; Zgonjanin, L; Chen, L; Rabbani, Z; Jackson, IL; Thrasher, B; Kirkpatrick, J; Foster, WM; Vujaskovic, Z
MLA Citation
Fleckenstein, K, Zgonjanin, L, Chen, L, Rabbani, Z, Jackson, IL, Thrasher, B, Kirkpatrick, J, Foster, WM, and Vujaskovic, Z. "Temporal onset of hypoxia and oxidative stress after pulmonary irradiation." Int J Radiat Oncol Biol Phys 68.1 (May 1, 2007): 196-204.
PMID
17448873
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
68
Issue
1
Publish Date
2007
Start Page
196
End Page
204
DOI
10.1016/j.ijrobp.2006.12.056

High-risk gestational trophoblastic neoplasia with brain metastases: individualized multidisciplinary therapy in the management of four patients.

PURPOSE: To report our recent experience managing four patients with brain metastases of gestational trophoblastic neoplasia (GTN), coordinating systemic chemotherapy with early neurosurgical intervention or stereotactic radiosurgery and intensive supportive care during initial therapy to prevent early mortality. MATERIALS AND METHODS: A series of four consecutive patients with brain metastases from high-risk Stage IV GTN managed at our institution in 2003 and 2005. Patients were assigned FIGO stage and risk score prospectively. Because of concern for chronic toxicity resulting from concurrent moderate dose methotrexate and whole brain radiation, an individualized multidisciplinary approach was used to manage patients. RESULTS: All four women presented with brain and pulmonary metastases; one had multiple liver metastases. Neurological symptoms at presentation included grand mal seizures in 2 patients, left upper extremity hemiparesis and headache each in 1 patient, while 1 patient was asymptomatic. Index pregnancies were term pregnancies in all patients with interval from prior delivery ranging from 2 weeks to 4 years. Two had received prior chemotherapy for postmolar GTN prior to the index pregnancy with incomplete follow-up. Initial hCG values ranged from 26,400 to 137,751 mIU/ml; FIGO risk scores were > or =16 for all patients. Systemic combination chemotherapy was initiated with etoposide and cisplatin followed by moderate/high-dose (500-1000 mg/m(2)) methotrexate combinations. Craniotomy was used before or during the first chemotherapy cycle to extirpate solitary lesions in 3 patients, while stereotactic radiosurgery was administered after the first cycle to treat two brain lesions in the remaining patient. None received whole brain radiation or intrathecal methotrexate. In one patient, selective angiographic embolization was used to control hemorrhage from multiple liver metastases. Two patients required ventilator support early in treatment to allow stabilization from intrathoracic hemorrhage and neutropenic sepsis with respiratory distress syndrome, respectively. Hysterectomy was performed in one patient after completion of salvage chemotherapy. All have completed maintenance chemotherapy and are in prolonged remission (12-24 months). Neurologic sequelae include persistent left upper extremity dyskinesia and weakness in one patient, and episodic grand mal seizures and pseudoseizures in a second patient with a pre-existing seizure disorder. CONCLUSION: This case series documents the utility for a multidisciplinary approach to the treatment of brain metastases from GTN. Using early craniotomy or stereotactic radiosurgery combined with etoposide-cisplatin and moderate/high-dose methotrexate combination chemotherapy, we were able to stabilize patients early in their treatment and avoid whole brain radiation therapy or intrathecal chemotherapy.

Authors
Soper, JT; Spillman, M; Sampson, JH; Kirkpatrick, JP; Wolf, JK; Clarke-Pearson, DL
MLA Citation
Soper, JT, Spillman, M, Sampson, JH, Kirkpatrick, JP, Wolf, JK, and Clarke-Pearson, DL. "High-risk gestational trophoblastic neoplasia with brain metastases: individualized multidisciplinary therapy in the management of four patients." Gynecol Oncol 104.3 (March 2007): 691-694.
PMID
17137617
Source
pubmed
Published In
Gynecologic Oncology
Volume
104
Issue
3
Publish Date
2007
Start Page
691
End Page
694
DOI
10.1016/j.ygyno.2006.10.027

Assessing neurotoxicity from radiosurgery: Results from a prospective study using magnetic resonance spectroscopy

Authors
Kelsey, CR; Mukundan, S; Wang, Z; Fabregas, M; Kelley, K; Kirkpatrick, JP
MLA Citation
Kelsey, CR, Mukundan, S, Wang, Z, Fabregas, M, Kelley, K, and Kirkpatrick, JP. "Assessing neurotoxicity from radiosurgery: Results from a prospective study using magnetic resonance spectroscopy." 2007.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
69
Issue
3
Publish Date
2007
Start Page
S245
End Page
S245
DOI
10.1016/j.ijrobp.2007.07.1244

Localization for MRI-based radiation treatment of intracranial lesions by using three-dimensional MRI and cone-beam CT matching

Authors
Wang, Z; Wu, Q; Kirkpatrick, JP; Willett, CG; Yin, F
MLA Citation
Wang, Z, Wu, Q, Kirkpatrick, JP, Willett, CG, and Yin, F. "Localization for MRI-based radiation treatment of intracranial lesions by using three-dimensional MRI and cone-beam CT matching." 2007.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
69
Issue
3
Publish Date
2007
Start Page
S189
End Page
S189
DOI
10.1016/j.ijrobp.2007.07.341

Increasing the number of orthogonal beam pairs does not improve the biologic effect in normal tissue in a phantom model

Authors
Kirkpatrick, JP; Wang, Z
MLA Citation
Kirkpatrick, JP, and Wang, Z. "Increasing the number of orthogonal beam pairs does not improve the biologic effect in normal tissue in a phantom model." 2007.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
69
Issue
3
Publish Date
2007
Start Page
S601
End Page
S602
DOI
10.1016/j.ijrobp.2007.07.1907

Kinetic modeling of tumor growth and dissemination in the craniospinal axis: implications for craniospinal irradiation.

BACKGROUND: Medulloblastoma and other types of tumors that gain access to the cerebrospinal fluid can spread throughout the craniospinal axis. The purpose of this study was to devise a simple multi-compartment kinetic model using established tumor cell growth and treatment sensitivity parameters to model the complications of this spread as well as the impact of treatment with craniospinal radiotherapy. METHODS: A two-compartment mathematical model was constructed. Rate constants were derived from previously published work and the model used to predict outcomes for various clinical scenarios. RESULTS: The model is simple and with the use of known and estimated clinical parameters is consistent with known clinical outcomes. Treatment outcomes are critically dependent upon the duration of the treatment break and the radiosensitivity of the tumor. Cross-plot analyses serve as an estimate of likelihood of cure as a function of these and other factors. CONCLUSION: The model accurately describes known clinical outcomes for patients with medulloblastoma. It can help guide treatment decisions for radiation oncologists treating patients with this disease. Incorporation of other treatment modalities, such as chemotherapy, that enhance radiation sensitivity and/or reduce tumor burden, are predicted to significantly increase the probability of cure.

Authors
Meyer, JJ; Marks, LB; Halperin, EC; Kirkpatrick, JP
MLA Citation
Meyer, JJ, Marks, LB, Halperin, EC, and Kirkpatrick, JP. "Kinetic modeling of tumor growth and dissemination in the craniospinal axis: implications for craniospinal irradiation. (Published online)" Radiat Oncol 1 (December 22, 2006): 48-.
PMID
17187666
Source
pubmed
Published In
Radiation Oncology
Volume
1
Publish Date
2006
Start Page
48
DOI
10.1186/1748-717X-1-48

Tumor hypoxia and prognosis in human gliomas.

Authors
Kirkpatrick, JP
MLA Citation
Kirkpatrick, JP. "Tumor hypoxia and prognosis in human gliomas." Cancer J 12.6 (November 2006): 451-454.
PMID
17207312
Source
pubmed
Published In
Cancer Journal
Volume
12
Issue
6
Publish Date
2006
Start Page
451
End Page
454

Three-dimensional imaging of xenograft tumors using optical computed and emission tomography.

The physical basis and preliminary applications of optical computed tomography (optical-CT) and optical emission computed tomography (optical-ECT) are introduced, as new techniques with potential to provide unique 3D information on a variety of aspects of tumor structure and function. A particular focus here is imaging tumor micro-vasculature, and the spatial distribution of viable tumor cells, although the techniques have the potential for much wider application. The principle attractiveness of optical-CT and optical-ECT are that high resolution (<20 microm) and high contrast co-registered 3D images of structure and function can be acquired for relatively large intact samples. The unique combination of high contrast and resolution offers advantages over micro-CT and micro-MRI, and the lack of requirement for sectioning offers advantages over confocal microscopy, conventional microscopy, and histological sectioning techniques. Optical-CT/ECT are implemented using in-house custom apparatus and a commercial dissecting microscope capable of both transmission and fluorescence imaging. Basic studies to characterize imaging performance are presented. Negligible geometrical distortion and accurate reconstruction of relative attenuation coefficients was observed. Optical-CT and optical-ECT are investigated here by application to high resolution imaging of HCT116 xenograft tumors, about 1 cc in dimension, which were transfected with constitutive red fluorescent protein (RFP). Tumor microvasculature was stained in vivo by tail vein injection of either passive absorbing dyes or active fluorescent markers (FITC conjugated lectin). Prior to imaging, the tumors were removed (ex vivo) and optically cleared in a key process to make the samples amenable to light transmission. The cleared tumors were imaged in three modes (i) optical-CT to image the 3D distribution of microvasculature as indicated by absorbing dye, (ii) optical-ECT using the FITC excitation and emission filter set, to determine microvasculature as indicated by lectin-endothelial binding, and (iii) optical-ECT using the DSRed2 filter set to determine the 3D distribution of viable tumor as indicated by RFP emission. A clear correlation was observed between the independent vasculature imaging modes (i) and (ii) and postimaging histological sections, providing substantial validation of the optical-CT and optical-ECT techniques. Strong correlation was also observed between the RFP imaging of mode iii, and modes i and ii, supporting the intuitive conclusion that well-perfused regions contain significant viable tumor. In summary, optical-CT and optical-ECT, when combined with new optical clearing techniques, represent powerful new imaging modalities with potential for providing unique information on the structure and function of tumors.

Authors
Oldham, M; Sakhalkar, H; Oliver, T; Wang, YM; Kirpatrick, J; Cao, Y; Badea, C; Johnson, GA; Dewhirst, M
MLA Citation
Oldham, M, Sakhalkar, H, Oliver, T, Wang, YM, Kirpatrick, J, Cao, Y, Badea, C, Johnson, GA, and Dewhirst, M. "Three-dimensional imaging of xenograft tumors using optical computed and emission tomography." Med Phys 33.9 (September 2006): 3193-3202.
PMID
17022212
Source
pubmed
Published In
Medical physics
Volume
33
Issue
9
Publish Date
2006
Start Page
3193
End Page
3202
DOI
10.1118/1.2217109

SU-FF-T-66: A Technique for Cone-Beam CT-Guided Stereotactic Body Radiation Therapy

Authors
Yin, F; Marks, L; Wang, Z; Kirkpatrick, J; Wu, J; Yoo, S; Larrier, N; Meyer, J; Willett, C
MLA Citation
Yin, F, Marks, L, Wang, Z, Kirkpatrick, J, Wu, J, Yoo, S, Larrier, N, Meyer, J, and Willett, C. "SU-FF-T-66: A Technique for Cone-Beam CT-Guided Stereotactic Body Radiation Therapy." June 2006.
Source
crossref
Published In
Medical physics
Volume
33
Issue
6Part7
Publish Date
2006
Start Page
2063
End Page
2063
DOI
10.1118/1.2240992

Physics and imaging for targeting of oligometastases.

Oligometastases refer to metastases that are limited in number and location and are amenable to regional treatment. The majority of these metastases appear in the brain, lung, liver, and bone. Although the focus of interest in the past within radiation oncology has been on the treatment of intracranial metastases, there has been growing interest in extracranial sites such as the liver and lung. This is largely because of the rapid development of targeting techniques for oligometastases such as intensity-modulated and image-guided radiation therapy, which has made it possible to deliver single or a few fractions of high-dose radiation treatments, highly conformal to the target. The clinical decision to use radiation to treat oligometastases is based on both radiobiological and physics considerations. The radiobiological considerations involve improvement of treatment schema for time, dose, and volume. Areas of interests are hypofractionation, tumor and normal tissue tolerance, and hypoxia. The physics considerations for oligometastases treatment are focused mainly on ensuring treatment accuracy and precision. This article discusses the physics and imaging aspects involved in each step of the radiation treatment process for oligometastases, including target definition, treatment simulation, treatment planning, pretreatment target localization, radiation delivery, treatment verification, and treatment evaluation.

Authors
Yin, F-F; Das, S; Kirkpatrick, J; Oldham, M; Wang, Z; Zhou, S-M
MLA Citation
Yin, F-F, Das, S, Kirkpatrick, J, Oldham, M, Wang, Z, and Zhou, S-M. "Physics and imaging for targeting of oligometastases." Semin Radiat Oncol 16.2 (April 2006): 85-101. (Review)
PMID
16564444
Source
pubmed
Published In
Seminars in Radiation Oncology
Volume
16
Issue
2
Publish Date
2006
Start Page
85
End Page
101
DOI
10.1016/j.semradonc.2005.12.004

Combined-modality therapy versus radiotherapy alone for treatment of early-stage Hodgkin's disease: cure balanced against complications.

PURPOSE: The treatment of early-stage Hodgkin's disease (HD) has evolved from radiotherapy alone (RT) to combined-modality therapy (CMT) because of concerns about late adverse effects from high-dose subtotal nodal irradiation (STNI). However, there is little information regarding the long-term results of CMT programs that substantially reduce the dose and extent of radiation. In addition, lowering the total radiation dose may reduce the complication rate without compromising cure. This retrospective study compares the long-term results of STNI with CMT using modestly reduced RT dose in the treatment of early-stage HD. PATIENTS AND METHODS: Between 1982 and 2002, 111 patients with stage IA and IIA HD were treated definitively with RT (mean dose, 37.9 Gy); 70 patients were treated with CMT with low-dose involved-field radiotherapy (LDIFRT; mean dose, 25.5 Gy). Median follow-up was 11.7 years for RT patients and 8.1 years for the CMT group. RESULTS: There was a trend toward improved 20-year overall survival with CMT (83% v 70%; P = .405). No second cancers were observed in the CMT group; in the RT group the actuarial frequency of a second cancer was 16% at 20 years. There was no difference in the frequency of cardiac complications (9% v 6%, RT v CMT). CONCLUSION: In this retrospective review, CMT with LDIFRT was effective in curing early-stage HD and was not associated with an increase in second malignancies. For RT alone, a moderate dose seemed to reduce cardiac complications but did not lessen second malignancies compared with higher doses used historically.

Authors
Koontz, BF; Kirkpatrick, JP; Clough, RW; Prosnitz, RG; Gockerman, JP; Moore, JO; Prosnitz, LR
MLA Citation
Koontz, BF, Kirkpatrick, JP, Clough, RW, Prosnitz, RG, Gockerman, JP, Moore, JO, and Prosnitz, LR. "Combined-modality therapy versus radiotherapy alone for treatment of early-stage Hodgkin's disease: cure balanced against complications." J Clin Oncol 24.4 (February 1, 2006): 605-611.
PMID
16446333
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
4
Publish Date
2006
Start Page
605
End Page
611
DOI
10.1200/JCO.2005.02.9850

Erythropoietin inhibits apoptosis in breast cancer cells via an Akt-dependent pathway without modulating in vivo chemosensitivity.

Evidence for erythropoietin signaling has been shown in several nonhematopoietic tissues, including many tumor types. Clinically, recombinant erythropoietin treatment of malignancy-related anemia has yet to be definitively associated with any modulation of chemotherapy or radiotherapy efficacy. Preclinically, recombinant erythropoietin has been shown to increase tumor oxygenation, but the direct effects of recombinant erythropoietin on tumor cells that express erythropoietin receptor are not yet fully characterized. This study examined the effects of exogenous recombinant erythropoietin on rodent mammary adenocarcinoma cells (R3230) in vitro and in vivo, and determined the effects of systemic recombinant erythropoietin on tumor growth delay in Taxol treatment. We showed that systemic recombinant erythropoietin treatment of rats bearing R3230 mammary carcinomas induced an increase in phospho-Akt levels within tumor cells. This was associated with a decrease in the frequency of apoptotic cells in tumors from recombinant erythropoietin-treated animals, but did not noticeably affect tumor growth rate. In vitro studies revealed that not only does recombinant erythropoietin induce Akt phosphorylation, but it also stimulates phosphorylation of p44/42 mitogen-activated protein kinases, Erk1 and Erk2. Activation of erythropoietin-mediated signaling in R3230 cells was associated with dose-dependent inhibition of apoptosis in response to Taxol treatment and serum starvation, an effect that was blocked by the addition of a phosphatidylinositol-3-kinase inhibitor. Despite its cytoprotective effects in vitro, recombinant erythropoietin did not significantly affect tumor growth delay in Taxol treatment. This study shows direct recombinant erythropoietin-mediated activation of specific intracellular signaling pathways in mammary adenocarcinoma cells in vivo and in vitro. Modulation of tumor apoptosis pathways by recombinant erythropoietin may have negative consequences by decreasing the chemosensitivity and radiosensitivity of erythropoietin receptor-positive breast tumors, although it did not have any obvious effects on growth with or without chemotherapy in this model.

Authors
Hardee, ME; Rabbani, ZN; Arcasoy, MO; Kirkpatrick, JP; Vujaskovic, Z; Dewhirst, MW; Blackwell, KL
MLA Citation
Hardee, ME, Rabbani, ZN, Arcasoy, MO, Kirkpatrick, JP, Vujaskovic, Z, Dewhirst, MW, and Blackwell, KL. "Erythropoietin inhibits apoptosis in breast cancer cells via an Akt-dependent pathway without modulating in vivo chemosensitivity." Mol Cancer Ther 5.2 (February 2006): 356-361.
PMID
16505109
Source
pubmed
Published In
Molecular cancer therapeutics
Volume
5
Issue
2
Publish Date
2006
Start Page
356
End Page
361
DOI
10.1158/1535-7163.MCT-05-0196

The effect of darbepoetin alfa on growth, oxygenation and radioresponsiveness of a breast adenocarcinoma.

Tumor hypoxia is associated with poor clinical outcome in a variety of tumors, including cervical, head/neck and breast cancer. Administration of erythropoietic factors has been suggested as a means of improving tumor oxygenation (pO2). This study randomized rats to treatment with low-dose or high-dose darbepoetin alfa or a placebo to determine the effect of darbepoetin alfa on the pO2, growth and response to radiation therapy of R3230 mammary adenocarcinoma. Rats received 3 microg/kg (high dose) or 0.2 microg/kg (low dose) darbepoetin alfa or placebo for eight doses prior to either (1) pO2 measurement and pimonidazole staining or (2) irradiation or sham irradiation on post-transplant day 20. In the animals randomized to radiation treatment, placebo or darbepoetin alfa administration at a reduced dose was continued for 9 weeks or until the tumor diameter exceeded 15 mm (defined as failure for survival analysis). Treatment with high-dose and low-dose darbepoetin alfa produced hematocrits of 68 and 56% compared to 44 and 45% in their respective control groups (both P < 10(-5)). At 18 days post-transplant, tumor volume was not different for either darbepoetin alfa group compared to the placebo group. Tumor oxygenation, as measured by the fraction of pO2 measurement <10 mmHg and the intensity of pimonidazole staining, was significantly improved in the high-dose group (P = 0.046 and 0.03, respectively, compared with controls) but not in the low-dose group. Growth delay curves after irradiation did not differ significantly for high- or low-dose darbepoetin alfa compared to placebo. In this nonanemic animal model of mammary adenocarcinoma, darbepoetin alfa does not significantly alter tumor growth or radioresponsiveness, even though it improves oxygenation when administered at high doses.

Authors
Kirkpatrick, JP; Hardee, ME; Snyder, SA; Peltz, CM; Zhao, Y; Brizel, DM; Dewhirst, MW; Blackwell, KL
MLA Citation
Kirkpatrick, JP, Hardee, ME, Snyder, SA, Peltz, CM, Zhao, Y, Brizel, DM, Dewhirst, MW, and Blackwell, KL. "The effect of darbepoetin alfa on growth, oxygenation and radioresponsiveness of a breast adenocarcinoma." Radiat Res 165.2 (February 2006): 192-201.
PMID
16518899
Source
pubmed
Published In
Radiation Research
Volume
165
Issue
2
Publish Date
2006
Start Page
192
End Page
201

Erythropoietin biology in cancer.

Erythropoietin (Epo) has long been known to be the principal hematopoietic growth factor that regulates cellular proliferation and differentiation along the erythroid lineage. Recent studies have shown that Epo is a pleiotropic cytokine that is proangiogenic and exerts broad tissue-protective effects in diverse nonhematopoietic organs. Recombinant Epo (rEpo) has been widely used in the clinic to prevent or treat malignancy-associated anemia. A series of clinical trials have documented the efficacy of rEpo in reducing RBC transfusion requirements and improving quality of life in cancer patients, and a recent meta-analysis suggested a positive effect on survival. However, two randomized trials reported negative outcomes with rEpo, as patients in the rEpo arm fared worse than their placebo-treated counterparts with respect to progression-free survival. The expression of Epo receptor (EpoR) in cancer cells has raised the possibility that exogenous rEpo may exert direct effects on tumor cells associated with the potential for stimulation of proliferation, inhibition of apoptosis, or modulation of sensitivity to chemoradiation therapy. The presence of an autocrine-paracrine Epo-EpoR system in tumors and potential effects of Epo on tumor microenvironment and angiogenesis are consistent with a complex biology for Epo-EpoR signaling in cancer that requires further research. This review describes Epo and EpoR biology, focusing on the pleiotropic effects of Epo on nonhematopoietic tissues as well as the expression and function of EpoR in cancer cells.

Authors
Hardee, ME; Arcasoy, MO; Blackwell, KL; Kirkpatrick, JP; Dewhirst, MW
MLA Citation
Hardee, ME, Arcasoy, MO, Blackwell, KL, Kirkpatrick, JP, and Dewhirst, MW. "Erythropoietin biology in cancer." Clin Cancer Res 12.2 (January 15, 2006): 332-339. (Review)
PMID
16428469
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
12
Issue
2
Publish Date
2006
Start Page
332
End Page
339
DOI
10.1158/1078-0432.CCR-05-1771

Multisession CyberKnife radiosurgery for intramedullary spinal cord arteriovenous malformations: Commentary

Authors
Kirkpatrick, JP; Friedman, AH
MLA Citation
Kirkpatrick, JP, and Friedman, AH. "Multisession CyberKnife radiosurgery for intramedullary spinal cord arteriovenous malformations: Commentary." Neurosurgery 58.6 (2006): 1089--.
Source
scival
Published In
Neurosurgery
Volume
58
Issue
6
Publish Date
2006
Start Page
1089-
DOI
10.1227/01.NEU.0000215891.25153.BA

Tissue transglutaminase expression in early-stage cervical cancer

Authors
Rabbani, ZN; Kirkpatrick, JP; Salahuddin, FK; Bentley, RC; Secord, AA; Greenberg, CS; Havrilesky, LJ; Vujaskovic, Z; Jones, E; Dewhirst, MW
MLA Citation
Rabbani, ZN, Kirkpatrick, JP, Salahuddin, FK, Bentley, RC, Secord, AA, Greenberg, CS, Havrilesky, LJ, Vujaskovic, Z, Jones, E, and Dewhirst, MW. "Tissue transglutaminase expression in early-stage cervical cancer." 2006.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S167
End Page
S167
DOI
10.1016/j.ijrobp.2006.07.331

A novel water-clear, low-modulus bolus material

Authors
Kirkpatrick, JP; Irani, FR; Johnston, SE; Stalnecker, AM; Cooney, TM; Georgas, DL; Oldham, M
MLA Citation
Kirkpatrick, JP, Irani, FR, Johnston, SE, Stalnecker, AM, Cooney, TM, Georgas, DL, and Oldham, M. "A novel water-clear, low-modulus bolus material." 2006.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S704
End Page
S705
DOI
10.1016/j.ijrobp.2006.07.1294

Human recombinant erythropoietin (rEpo) has no effect on tumour growth or angiogenesis.

Tumour hypoxia has been shown to increase mutation rate, angiogenesis, and metastatic potential, and decrease response to conventional therapeutics. Improved tumour oxygenation should translate into increased treatment response. Exogenous recombinant erythropoietin (rEpo) has been recently shown to increase tumour oxygenation in a mammary carcinoma model. The mechanism of this action is not yet understood completely. The presence of Epo and its receptor (EpoR) have been demonstrated on several normal and neoplastic tissues, including blood vessels and various solid tumours. In addition, rEpo has been shown in two recent prospective, randomized clinical trials to negatively impact treatment outcome. In this study, we attempt to characterize the direct effects of rEpo on tumour growth and angiogenesis in two separate rodent carcinomas. The effect of rEpo on R3230 rat mammary adenocarcinomas, CT-26 mouse colon carcinomas, HCT-116 human colon carcinomas, and FaDu human head and neck tumours, all of which express EpoR, was examined. There were no differences in tumour growth or proliferation (measured by Ki-67) between placebo-treated and rEpo-treated tumours. In the mammary window chamber, vascular length density (VLD) measurements in serial images of both placebo-treated and Epo-treated rats revealed no difference in angiogenesis between the Epo-treated tumours and placebo-treated tumours at any time point. These experiments are important because they suggest that the recent clinical detriment seen with the use of Epo is not due to its tumour growth effects or angiogenesis. These studies also suggest that further preclinical studies need to examine rEpo's direct tumour effects in efforts to improve the therapeutic benefits of Epo in solid tumour patients.

Authors
Hardee, ME; Kirkpatrick, JP; Shan, S; Snyder, SA; Vujaskovic, Z; Rabbani, ZN; Dewhirst, MW; Blackwell, KL
MLA Citation
Hardee, ME, Kirkpatrick, JP, Shan, S, Snyder, SA, Vujaskovic, Z, Rabbani, ZN, Dewhirst, MW, and Blackwell, KL. "Human recombinant erythropoietin (rEpo) has no effect on tumour growth or angiogenesis." Br J Cancer 93.12 (December 12, 2005): 1350-1355.
PMID
16288305
Source
pubmed
Published In
British Journal of Cancer
Volume
93
Issue
12
Publish Date
2005
Start Page
1350
End Page
1355
DOI
10.1038/sj.bjc.6602846

Radiotherapy for locally recurrent prostate cancer.

The optimal treatment of the patient at high risk for local recurrence of prostate cancer after radical prostatectomy is controversial. Similarly, there is much controversy over how to treat patients with a rising prostate-specific antigen (PSA), but without overt metastases, after radical prostatectomy. A recent randomized controlled trial of adjuvant radiotherapy versus observation following radical prostatectomy shows a significantly higher freedom from recurrence for patients receiving adjuvant radiotherapy, which may help to resolve the question of whether or not to wait for a rise in the PSA before offering treatment. For patients with biochemical recurrence after prostatectomy, part of the problem lies in the difficulty in determining whether a rise in the PSA is a sign of local recurrence or a harbinger of distant metastases. Making this distinction is critical, since patients with local disease may be cured with radiation therapy to the prostate bed, whereas those with metastatic disease will require a different treatment approach. In this article, we discuss the factors that must be taken into consideration when making treatment recommendations for these patients. In addition, approaches to the evaluation and management of patients with this difficult clinical problem are presented.

Authors
Kirkpatrick, JP; Anscher, MS
MLA Citation
Kirkpatrick, JP, and Anscher, MS. "Radiotherapy for locally recurrent prostate cancer." Clin Adv Hematol Oncol 3.12 (December 2005): 933-942. (Review)
PMID
16555435
Source
pubmed
Published In
Clinical advances in hematology & oncology : H&O
Volume
3
Issue
12
Publish Date
2005
Start Page
933
End Page
942

Enhancement of cancer radiation therapy by use of adenovirus-mediated secretable glucose-regulated protein 94/gp96 expression.

Tumor-derived glucose-regulated protein 94 (GRP94/gp96) has shown great promise as a tumor vaccine. However, current protein-based approaches require the availability of large quantities of tumor tissue, which are often not possible. In addition, the efficacy of immunotherapy is often not ideal when used alone. In this study, we explored the therapeutic efficacy of a combined GRP94/gp96-based genetic immunotherapy and radiation therapy strategy in the weakly immunogenic and highly metastatic 4T1 murine mammary cancer model. An adenovirus encoding a modified, secretable form of GRP94 gene (AdsGRP94) was constructed and evaluated in various antitumor experiments. Lethally irradiated, virus-infected cells were used as vaccines. Adenoviral vectors were also injected directly into tumors in conjunction with tumor irradiation. Vaccination with lethally irradiated, AdsGRP94-infected 4T1 cells completely prevented subsequent tumor growth from challenge inoculations of as many as 10(7) cells per mouse. In established tumor models, vaccinations alone had minimal effect on local and metastatic tumor growth. However, when vaccination was combined with radiation therapy and i.t. AdsGRP94 injections, local tumor growth and pulmonary metastasis were markedly inhibited. In some cases, complete tumor regression was observed. In these cases, the mice were resistant to subsequent tumor challenge and remain tumor free up to 10 months after initial therapy. Our results indicate that combined AdsGRP94-based immunotherapy and radiation therapy may be a potentially effective strategy for cancer treatment.

Authors
Liu, S; Wang, H; Yang, Z; Kon, T; Zhu, J; Cao, Y; Li, F; Kirkpatrick, J; Nicchitta, CV; Li, C-Y
MLA Citation
Liu, S, Wang, H, Yang, Z, Kon, T, Zhu, J, Cao, Y, Li, F, Kirkpatrick, J, Nicchitta, CV, and Li, C-Y. "Enhancement of cancer radiation therapy by use of adenovirus-mediated secretable glucose-regulated protein 94/gp96 expression." Cancer Res 65.20 (October 15, 2005): 9126-9131.
PMID
16230366
Source
pubmed
Published In
Cancer Research
Volume
65
Issue
20
Publish Date
2005
Start Page
9126
End Page
9131
DOI
10.1158/0008-5472.CAN-05-0945

SU-FF-T-366: Radiation Dose Response Curve of Human Cerebral Cortex Measured with [F-18]-FDG and [O-15]-H2O PET Imaging

Authors
Zhou, S; Hahn, C; Shafman, T; Kirkpatrick, J; Tisch, A; Marks, L; Hawk, T; Turkington, T; Wong, T; Coleman, R
MLA Citation
Zhou, S, Hahn, C, Shafman, T, Kirkpatrick, J, Tisch, A, Marks, L, Hawk, T, Turkington, T, Wong, T, and Coleman, R. "SU-FF-T-366: Radiation Dose Response Curve of Human Cerebral Cortex Measured with [F-18]-FDG and [O-15]-H2O PET Imaging." June 2005.
Source
crossref
Published In
Medical physics
Volume
32
Issue
6Part12
Publish Date
2005
Start Page
2035
End Page
2035
DOI
10.1118/1.1998095

Elevated CAIX expression is associated with an increased risk of distant failure in early-stage cervical cancer

Authors
Kirkpatrick, JP; Rabbani, Z; Bentley, R; Hardee, M; Karol, S; Meyer, J; Oosterwijk, E; Havrilesky, L; Secord, A; Vujaskovic, Z; Dewhirst, M; Jones, E
MLA Citation
Kirkpatrick, JP, Rabbani, Z, Bentley, R, Hardee, M, Karol, S, Meyer, J, Oosterwijk, E, Havrilesky, L, Secord, A, Vujaskovic, Z, Dewhirst, M, and Jones, E. "Elevated CAIX expression is associated with an increased risk of distant failure in early-stage cervical cancer." 2005.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
63
Issue
2
Publish Date
2005
Start Page
S211
End Page
S212
DOI
10.1016/j.ijrobp.2005.07.364

Enhancement of hypoxia-induced tumor cell death in vitro and radiation therapy in vivo by use of small interfering RNA targeted to hypoxia-inducible factor-1alpha.

Hypoxia-inducible factor-1alpha (HIF-1alpha) is an important transcriptional factor that is activated when mammalian cells experience hypoxia, a tumor microenvironmental condition that plays pivotal roles in tumor progression and treatment. In this study, we examined the idea of down-regulating HIF-1alpha in tumor cells for therapeutic gain. We show that the expression levels of HIF-1alpha can be significantly attenuated by use of the recently established small interfering RNA technology in combination with adenovirus-mediated gene transfer. Down-regulation of the HIF-1alpha protein enhanced hypoxia-mediated tumor cell apoptosis in vitro. Subcutaneous tumor growth was also prevented from cells with attenuated HIF-1alpha expression. In addition, intratumoral injection of adenovirus encoding the HIF-1alpha-targeted small interfering RNA had a small but significant effect on tumor growth when combined with ionizing radiation. Therefore, our results provide proof of HIF-1alpha as an effective target for anticancer therapy. They also suggest that an adenovirus-based small interfering RNA gene transfer approach may be a potentially effective adjuvant strategy for cancer treatment.

Authors
Zhang, X; Kon, T; Wang, H; Li, F; Huang, Q; Rabbani, ZN; Kirkpatrick, JP; Vujaskovic, Z; Dewhirst, MW; Li, C-Y
MLA Citation
Zhang, X, Kon, T, Wang, H, Li, F, Huang, Q, Rabbani, ZN, Kirkpatrick, JP, Vujaskovic, Z, Dewhirst, MW, and Li, C-Y. "Enhancement of hypoxia-induced tumor cell death in vitro and radiation therapy in vivo by use of small interfering RNA targeted to hypoxia-inducible factor-1alpha." Cancer Res 64.22 (November 15, 2004): 8139-8142.
PMID
15548675
Source
pubmed
Published In
Cancer Research
Volume
64
Issue
22
Publish Date
2004
Start Page
8139
End Page
8142
DOI
10.1158/0008-5472.CAN-03-2301

Erythropoietin (EPO) has no direct effect on tumor growth or angiogenesis in animal models.

Authors
Hardee, ME; Kirkpatrick, JP; Snyder, S; Shan, S; Vujaskovic, Z; Rabbani, ZN; Dewhirst, MW; Blackwell, KL
MLA Citation
Hardee, ME, Kirkpatrick, JP, Snyder, S, Shan, S, Vujaskovic, Z, Rabbani, ZN, Dewhirst, MW, and Blackwell, KL. "Erythropoietin (EPO) has no direct effect on tumor growth or angiogenesis in animal models." July 15, 2004.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
22
Issue
14
Publish Date
2004
Start Page
842S
End Page
842S

Predicting the effect of temporal variations in PO2 on tumor radiosensitivity.

PURPOSE: Tumor hypoxia is associated with less effective radiation-mediated cell killing, increased metastatic potential, and poorer prognosis. Transient variations in hypoxia, with characteristic periodicity on the order of 1 to 10 min, have been observed in animal models. This article explores the effect of these temporal variations in PO(2) on the oxygen enhancement ratio, effective radiation dose to the tumor, and tumor control probability. METHODS AND MATERIALS: PO(2) over a 50-60 min period was determined at multiple sites in rat fibrosarcomas, 9L gliomas, and R3230Ac mammary adenocarcinomas. Using a correlation derived from the data of Elkind et al. (1965), PO(2) data are converted into oxygen enhancement ratios (OERs.) A tumor is assumed to consist of 10(3)-10(4) independent oxygenation subvolumes, each with a randomly chosen starting point on the OER-time curve. The effect of temporal variations in OER is examined for three cases: conventionally fractionated external beam radiotherapy (EBRT), stereotactic radiosurgery (SRS) and intraoperative radiotherapy (IORT). The oxygen effective dose (OED) for a subvolume is calculated from the dose to that subvolume modified by the OER. In turn, the distribution of OED for a tumor is analyzed for each treatment case and representative tumor control probabilities (TCPs) calculated. RESULTS: Oxygen enhancement ratio varied from 1 to 3 over the range of PO(2) measured in this study. Mean OER ranged from 1.6 to 2.6, and the variation in OER vs. time was greater with decreasing PO(2). In EBRT, the standard deviation in OED was small, <2%. In contrast, the standard deviation in OED was much higher for both SRS and IORT, typically ranging from 3 to 6%, with the greatest variation at the lowest PO(2)s. Compared with a tumor with equal mean OED and uniform PO(2), TCP was minimally poorer for either EBRT or well-oxygenated tumors. However, for both SRS and IORT, temporal variations in more hypoxic tumors can produce a significant decrease in TCP. CONCLUSION: Temporal variations in tumor PO(2) can produce significant variations OER, particularly at low PO(2), resulting in decreased TCP for hypofractionated treatment regimens.

Authors
Kirkpatrick, JP; Cárdenas-Navia, LI; Dewhirst, MW
MLA Citation
Kirkpatrick, JP, Cárdenas-Navia, LI, and Dewhirst, MW. "Predicting the effect of temporal variations in PO2 on tumor radiosensitivity." Int J Radiat Oncol Biol Phys 59.3 (July 1, 2004): 822-833.
PMID
15183486
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
59
Issue
3
Publish Date
2004
Start Page
822
End Page
833
DOI
10.1016/j.ijrobp.2004.02.015

Erythropoietin (EPO) has no direct effect on tumor growth or angiogenesis in animal models.

9530 Background: Erythropoietin (EPO) increases tumor oxygenation in several pre-clinical models. This improvement in oxygenation should lead to enhanced treatment responses. However, EPO has failed to show improved treatment outcomes in 2 recent, randomized clinical trials involving non-anemic patients with head and neck and metastatic breast cancer. In this study we characterize the direct effects of EPO on tumor growth and angiogenesis in both breast and colorectal carcinoma.Effects of EPO (Ortho Biotech, Raritan, NJ) on murine tumor growth (CT-26 and R3230) in over 200 non-anemic rodents randomized to either EPO or control was measured. EPO receptor expression was determined using standard IHC in both tumor types before and after treatment. Tumor proliferation, assessed by Ki-67 IHC staining, was also determined. In vivo angiogenesis was measured by vascular length density (VLD) and was calculated from intravital microscopy images of R3230 tumors grown in mammary window chambers.EPO increased the hematocrit significantly in all treated animals. Measured bidimensionally over the entire growth period, EPO had no effect on CT-26 or R3230 tumor growth at any time point. Both tumors expressed the EPO receptor. Ki-67 staining revealed no differences in proliferation between EPO-treated and control animals. In addition, angiogenesis was unaffected by systemic treatment with EPO.This study suggests that although EPO improves tumor oxygenation, this physiologic change is not attributable to either direct effects on tumor growth or angiogenesis. The cause for improvement in oxygenation remains under investigation. It is likely due to subtle changes in perfusion or tumor consumption that are not detected by simple vascular length density measurements. Besides its known effects on tumor oxygenation, other direct effects of EPO on tumor biology need to be examined. No significant financial relationships to disclose.

Authors
Hardee, ME; Kirkpatrick, JP; Snyder, S; Shan, S; Vujaskovic, Z; Rabbani, ZN; Dewhirst, MW; Blackwell, KL
MLA Citation
Hardee, ME, Kirkpatrick, JP, Snyder, S, Shan, S, Vujaskovic, Z, Rabbani, ZN, Dewhirst, MW, and Blackwell, KL. "Erythropoietin (EPO) has no direct effect on tumor growth or angiogenesis in animal models." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 22.14_suppl (July 2004): 9530-.
PMID
28016827
Source
epmc
Published In
Journal of Clinical Oncology
Volume
22
Issue
14_suppl
Publish Date
2004
Start Page
9530

A novel conditionally replicative adenovirus vector targeting telomerase-positive tumor cells.

PURPOSE: To develop a novel conditionally replicative adenovirus vector that targets telomerase-positive cancer cells. EXPERIMENTAL DESIGN: A telomerase gene-derived promoter was used to control the expression of the E1a gene so that the E1a gene is only expressed in telomerase-positive tumor cells. In addition, a reporter gene was also engineered into the vector so that its infection and replication can be monitored easily. RESULTS: A novel recombinant adenovirus vector that could selectively replicate in telomerase-positive cancer cells was made successfully. This vector showed active replication in a panel of cancer cells and minimal replication in normal human fibroblast or epithelial cells. The recombinant vector could effectively lyse various cultured tumor cells even at very low multiplicity of infection. The replication efficiency in tumor cells is over 10(3)-fold more than normal fibroblast and epithelial cells. In s.c. tumor models, the newly developed telomerase-selective adenovirus vectors exhibited significantly more virus replication and reporter gene expression. CONCLUSIONS: The telomerase-targeted adenovirus vector has significant potential as an oncolytic virus as well as a tumor-specific therapeutic gene delivery vehicle.

Authors
Huang, Q; Zhang, X; Wang, H; Yan, B; Kirkpatrick, J; Dewhrist, MW; Li, C-Y
MLA Citation
Huang, Q, Zhang, X, Wang, H, Yan, B, Kirkpatrick, J, Dewhrist, MW, and Li, C-Y. "A novel conditionally replicative adenovirus vector targeting telomerase-positive tumor cells." Clin Cancer Res 10.4 (February 15, 2004): 1439-1445.
PMID
14977847
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
10
Issue
4
Publish Date
2004
Start Page
1439
End Page
1445

Modeling killing and repopulation kinetics of subclinical cancer: direct calculations from clinical data.

PURPOSE: Models for cell killing and repopulation can provide insight into the efficacy of therapies. Using clinical data on breast cancer recurrence after lumpectomy with or without radiotherapy (L+/-RT) and brain metastases after chemotherapy with or without prophylactic cranial irradiation (C+/-PCI) for small-cell lung cancer, estimates of cell killing and subclinical repopulation were tested against the results from simple radiobiologic models. METHODS AND MATERIALS: The rates of local breast cancer recurrence after L+/-RT and of brain metastases after C+/-PCI were extracted from published randomized trials. In Method 1, assuming simple exponential growth, the cell number distributions after L+/-RT and C+/-PCI were calculated from the clinical data, and the impact of RT on these distributions was determined. In Method 2, "classic" radiobiology dictates that a typical course of breast RT and PCI results in approximately =7 and approximately =4.5 log of cell kill, respectively. Using an assumption of uniform log-kill, the clinical doubling times (CDTs) can be calculated directly from the clinical data. RESULTS: Using Method 1, for breast cancer and assuming a CDT of 110 days and a clinically detectable cell number of 10(9), the calculated cell number distribution would be approximately uniformly distributed from 1 to 10(8) cells, with RT reducing the frequency at all points by approximately =75%. From the brain metastasis data, assuming a CDT of 55 days, a cell number distribution of 10(3) to 10(8) cells would be calculated. PCI reduces the frequency of metastases by roughly 40%. For both the breast and the brain data, the effects of RT on the cell number distribution are not consistent with uniform radiosensitivity. Using Method 2, assuming a cell number of 10 after L+/-RT, the calculated CDTs range from 14 to 124 days. For the brain metastasis case, assuming a starting cell number of 3.16 x 10(3), the CDTs would primarily be in the 10-30-day range. CONCLUSION: The distribution of clinical responses to adjuvant RT suggests a broad range of radiosensitivity, rather than uniform log cell kill. The subpopulation of tumors with minimal cell kill appears to be significant. This heterogeneity may be due to radioresistant subpopulations, failure to irradiate tumor cells, and/or new tumor formation. Similarly, the computed CDTs consistent with the clinical data are shorter than those reported in the literature. Simple radiobiologic models that fail to incorporate heterogeneity of radiosensitivity and/or tumor cell repopulation do not adequately describe clinical outcomes.

Authors
Kirkpatrick, JP; Marks, LB
MLA Citation
Kirkpatrick, JP, and Marks, LB. "Modeling killing and repopulation kinetics of subclinical cancer: direct calculations from clinical data." Int J Radiat Oncol Biol Phys 58.2 (February 1, 2004): 641-654.
PMID
14751538
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
58
Issue
2
Publish Date
2004
Start Page
641
End Page
654

Adjuvant and salvage radiotherapy following radical prostatectomy

Authors
Kirkpatrick, JP; Calingaert, B; Clough, RW; Oleson, JR; Quaranta, BP; Hahn, CA; Montana, GS; Ingram, SS; Anscher, MS
MLA Citation
Kirkpatrick, JP, Calingaert, B, Clough, RW, Oleson, JR, Quaranta, BP, Hahn, CA, Montana, GS, Ingram, SS, and Anscher, MS. "Adjuvant and salvage radiotherapy following radical prostatectomy." 2004.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
60
Issue
1
Publish Date
2004
Start Page
S450
End Page
S451

Human recombinant erythropoietin significantly improves tumor oxygenation independent of its effects on hemoglobin.

Tumor oxygenation is known to be an important predictive/prognostic marker in a variety of tumors, including cervix, head/neck, sarcoma, non-small cell of the lung, and breast. Tumor oxygenation is influenced by many interactions, including oxygen delivery (angiogenesis, permeability, and HgB) and consumption (metabolic and growth rates). This study randomized 30 nonanemic, female Fischer 344 rats into three treatment arms to examine the effects of recombinant human erythropoietin (EPO) on R3230 rodent mammary carcinoma oxygenation. The three treatment arms were: (a) placebo; (b) EPO after tumor implantation (2000 units/kg/SQdose, M/W/F for six doses); and (c) EPO before tumor implantation (2000 units/kg/SQdose, M/W/F for six doses). Tumors were implanted in the hindflank, and in vivo oxygenation was measured at day 22 after implantation using the Oxylite system (Oxford Optronix, Oxford, England). An average of 180 measurements/animal were performed. On day 22, median tumor volume was 399 mm(3) (range: 65-950 mm(3)), and no differences in tumor volume were seen between treatment arms. Mean hematocrit was equal between arms at therapy initiation but were significantly higher for both arms receiving EPO at day 22 (placebo versus Arm B versus Arm C; Wilcoxon P = 0.052). EPO-treated tumors had significantly less hypoxic measurements when compared with either the placebo or those receiving EPO before implantation. These data confirm that tumor oxygenation in nonanemic individuals may be improved through the administration of EPO, and this improvement appears to be independent of HgB effects.

Authors
Blackwell, KL; Kirkpatrick, JP; Snyder, SA; Broadwater, G; Farrell, F; Jolliffe, L; Brizel, DM; Dewhirst, MW
MLA Citation
Blackwell, KL, Kirkpatrick, JP, Snyder, SA, Broadwater, G, Farrell, F, Jolliffe, L, Brizel, DM, and Dewhirst, MW. "Human recombinant erythropoietin significantly improves tumor oxygenation independent of its effects on hemoglobin." Cancer Res 63.19 (October 1, 2003): 6162-6165.
PMID
14559797
Source
pubmed
Published In
Cancer Research
Volume
63
Issue
19
Publish Date
2003
Start Page
6162
End Page
6165

Low-dose radiation for posttransplant lymphoproliferative disorder.

Initial treatment for posttransplant lymphoproliferative disorder (PTLD) usually involves discontinuation of immunosuppressants. Anti-CD20 monoclonal antibody and/or antivirals are typically employed for persistent disease. Chemotherapy is generally reserved as a final option. The role of radiation therapy, and doses required, have not been well established. Low-dose involved field radiation therapy was used in three pediatric bone marrow transplant (BMT) patients with biopsy-proven PTLD. One patient received a matched T-cell-depleted BMT for dyskeratosis congenita. Two patients with acute myelogenous leukemia received an unrelated umbilical cord blood transplant, and a matched-related allogeneic BMT. All patients required intubation for respiratory distress due to PTLD. Initial treatment was discontinuation or decrease in FK-506. Anti-CD20 antibody was started in all patients, and foscarnet in one patient. All patients were treated with three 150-cGy fractions, for a total dose of 450 cGy. Time from BMT to development of PTLD was 4, 2, and 32 months, respectively. Duration of observation on initial medical therapy prior to irradiation was 11 days, 12 days, and 1 day, respectively. The radiation was well tolerated with no acute complications. Two patients were extubated at 8 and 4 days postradiation, respectively. The first patient had complete radiographic resolution of the mass and adenopathy at 4 months after radiation. The second died of pulmonary hemorrhage and disseminated aspergillosis infection, but had significant regression of disease in the irradiated area 15 days after radiation. The third had pronounced shrinkage of his mediastinal mass. A biopsy was taken of a persistent mass 4 months after radiation, with no evidence of lymphoproliferative disease. These cases demonstrate that low-dose radiation for PTLD is effective for palliation and produces a durable response with no acute toxicity.

Authors
Kang, SK; Kirkpatrick, JP; Halperin, EC
MLA Citation
Kang, SK, Kirkpatrick, JP, and Halperin, EC. "Low-dose radiation for posttransplant lymphoproliferative disorder." Am J Clin Oncol 26.2 (April 2003): 210-214.
PMID
12714899
Source
pubmed
Published In
American Journal of Clinical Oncology: Cancer Clinical Trials
Volume
26
Issue
2
Publish Date
2003
Start Page
210
End Page
214
DOI
10.1097/01.COC.0000020580.59825.75

A mathematical model of tumor oxygen and glucose mass transport and metabolism with complex reaction kinetics.

Hypoxia imparts radioresistance to tumors, and various approaches have been developed to enhance oxygenation, thereby improving radiosensitivity. This study explores the influence of kinetic and physical factors on substrate metabolism in a tumor model, based on a Krogh cylinder. In tissue, aerobic metabolism is assumed to depend on glucose and oxygen, represented by the product of Michaelis-Menten expressions. For the base case, an inlet pO(2) of 40 mmHg, a hypoxic limit of 5 mmHg, and a tissue/capillary radius ratio of 10 are used. For purely aerobic metabolism, a hypoxic fraction of 0.16 and volume-average pO(2) of 8 mmHg are calculated. Reducing the maximum oxygen rate constant by 9%, decreasing the tissue cylinder radius by 5%, or increasing the capillary radius by 8% abolishes the hypoxic fraction. When a glycolytic term is added, concentration profiles are similar to the base case. Using a distribution of tissue/capillary radius ratios increases the hypoxic fraction and reduces sensitivity to the oxygen consumption rate, compared to the case with a single tissue/capillary radius ratio. This model demonstrates that hypoxia is quite sensitive to metabolic rate and geometric factors. It also predicts quantitatively the effects of inhibited oxygen metabolism and enhanced mass transfer on tumor oxygenation.

Authors
Kirkpatrick, JP; Brizel, DM; Dewhirst, MW
MLA Citation
Kirkpatrick, JP, Brizel, DM, and Dewhirst, MW. "A mathematical model of tumor oxygen and glucose mass transport and metabolism with complex reaction kinetics." Radiat Res 159.3 (March 2003): 336-344.
PMID
12600236
Source
pubmed
Published In
Radiation Research
Volume
159
Issue
3
Publish Date
2003
Start Page
336
End Page
344

Patterns of failure in prostate cancer after primary or post-prostatectomy salvage radiotherapy in the PSA era

Authors
Kirkpatrick, JP; Clough, R; Anscher, MS; Montana, GS
MLA Citation
Kirkpatrick, JP, Clough, R, Anscher, MS, and Montana, GS. "Patterns of failure in prostate cancer after primary or post-prostatectomy salvage radiotherapy in the PSA era." November 2002.
Source
wos-lite
Published In
Radiology
Volume
225
Publish Date
2002
Start Page
166
End Page
166

Regulation of fibrinolysis by platelet-released plasminogen activator inhibitor 1: Light scattering and ultrastructural examination of lysis of a model platelet-fibrin thrombus

We have investigated the role of plasminogen activator inhibitor 1 (PAI-1) in the regulation of fibrinolysis using a model thrombus composed of thrombin-stimulated platelets, fibrin(ogen), plasminogen, and recombinant tissue-type plasminogen activator. Laser light scattering kinetic measurements showed that clot lysis was significantly delayed both by thrombin-stimulated platelets and their cell-free releasate. This delay in lysis was almost fully reversed by the addition of a PAI-1-specific monoclonal antibody that blocks the ability of PAI-1 to inhibit plasminogen activators. Lysis half-times exhibited a linear dependence on the concentration of PAI-1 antigen present, as determined by enzyme-linked immunosorbent assay (ELISA). Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting confirmed the presence of PAI-1 antigen in the platelet releasates. Scanning electron micrographs of the model thrombus components sampled late in lysis showed considerable unproteolyzed fibrin still attached to platelets, Immunogold cytochemistry detected large amounts of PAI-1 antigen in the partially lysed platelet-fibrin thrombi. This PAI-1 appeared to be bound to the fibrin network rather than to the platelet surface itself. We conclude that the residual clots observed late in lysis represent platelet-associated fibrin to which platelet-released PAI-1 has bound, rendering it less susceptible to degradation. © 1993 by The American Society of Hematology.

Authors
Braaten, JV; Handt, S; Jerome, WG; Kirkpatrick, J; Lewis, JC; Hantgan, RR
MLA Citation
Braaten, JV, Handt, S, Jerome, WG, Kirkpatrick, J, Lewis, JC, and Hantgan, RR. "Regulation of fibrinolysis by platelet-released plasminogen activator inhibitor 1: Light scattering and ultrastructural examination of lysis of a model platelet-fibrin thrombus." Blood 81.5 (1993): 1290-1299.
PMID
8443390
Source
scival
Published In
Blood
Volume
81
Issue
5
Publish Date
1993
Start Page
1290
End Page
1299

Differential effects of cytochalasin B on platelet release, aggregation and contractility: evidence against a contractile mechanism for the release of platelet granular contents.

Cytochalasin B alters the structure and functional properties of filamentous actin. Platelet-mediated clot retraction in dilute platelet-rich plasma (PRP) is inhibited progressively at cytochalasin B concentrations of 0.01 mg/ml, 0.05 mg/ml and 0.1 mg/ml. Dynamic rheological measurements of recalcified PRP in a Weissenberg Rheogoniometer indicate that platelet contractility (as reflected in measurements of elastic moduli) is reduced by 33%, 57% and 63% at cytochalasin B concentrations of 0.01, 0.05 and 0.1 mg/ml, respectively. In contrast, pre-incubation of human platelet-rich plasma (PRP) with 0.01 mg/ml or 0.05 mg/ml cytochalasin B does not inhibit collagen-induced [14C]serotonin release on collagen-induced-platelet aggregation, which is dependent on the release of ADP from platelet dense granules. Even at a cytochalasin B concentration of 0.1 mg/ml, collagen-induced [14C-]serotonin release and aggregation are impaired only moderately. Cytochalasin B does not interfere with the uptake by platelets of [14C-]-serotonin, or with the kinetics and extent of clot formation in platelet-free plasma. Thus, concentrations of cytochalasin B which impair platelet contractility do not inhibit the release of platelet dense granule contents. It is concluded that neither the platelet release reaction nor platelet aggregation is dependent on platelet contractile mechanisms.

Authors
Kirkpatrick, JP; McIntire, LV; Moake, JL; Cimo, PL
MLA Citation
Kirkpatrick, JP, McIntire, LV, Moake, JL, and Cimo, PL. "Differential effects of cytochalasin B on platelet release, aggregation and contractility: evidence against a contractile mechanism for the release of platelet granular contents." Thromb Haemost 42.5 (February 29, 1980): 1483-1489.
PMID
6892735
Source
pubmed
Published In
Thrombosis and haemostasis
Volume
42
Issue
5
Publish Date
1980
Start Page
1483
End Page
1489

Metabolic requirements of contractile force generation in platelet rich plasma - a rheological study.

Authors
Kirkpatrick, JP; McIntire, LV; Moake, JL; Peterson, DM
MLA Citation
Kirkpatrick, JP, McIntire, LV, Moake, JL, and Peterson, DM. "Metabolic requirements of contractile force generation in platelet rich plasma - a rheological study." Biorheology 17.5-6 (1980): 411-418.
PMID
7306692
Source
pubmed
Published In
Biorheology
Volume
17
Issue
5-6
Publish Date
1980
Start Page
411
End Page
418

Mass and heat transfer in a circular tube with biofouling

A mathematical model of heat and mass transfer for a fluid flowing in a hollow cylinder with a tubular biofilm is developed. Results in dimensionless form are presented for mass transfer in isothermal laminar and turbulent flow and for heat transfer and combined heat-mass transfer in turbulent flow. For each system, the dominant resistance to the transport of heat and mass is determined. In a typical heat exchanger, the presence of a biofilm is found to decrease heat transfer significantly. For systems of interest, the biofilm thickness is nearly constant over the length of the tube in isothermal turbulent flow. In tubes with combined heat and mass transfer the thickness varies appreciably with the temperature of the fluid.

Authors
Kirkpatrick, JP; McIntire, LV; Characklis, WG
MLA Citation
Kirkpatrick, JP, McIntire, LV, and Characklis, WG. "Mass and heat transfer in a circular tube with biofouling." Water Research 14.2 (1980): 117-127.
Source
scival
Published In
Water Research
Volume
14
Issue
2
Publish Date
1980
Start Page
117
End Page
127
DOI
10.1016/0043-1354(80)90227-4

DYNAMIC RHEOLOGICAL STUDIES OF COAGULATION AND FIBRINOLYSIS.

In the reported experiments, a Weissenberg rheogoniometer in the oscillatory mode was employed to determine the effect of fibrinolysis and fibrinogen degradation products (FDP) on the development of the dynamic shear moduli in coagulating platelet-free plasma (PFP) and platelet-rich plasma (PRP). While the FDP produced by incubation of PFP for 3 min with streptokinase (SK) increased the maximum shear storage modulus (G prime (max) of PFP, these early FDP decreased the G prime (max) of PRP clots also. The decreased G prime (max) in PRP containing FDP appears due to FDP inhibiting the binding of polymerizing fibrin to the platelet membrane. While 10 mu /ml of SK did not produce FDP or induce significant fibrinolysis, clot lysis was complete and rapid in the presence of 20 mu /ml SK. Experiments with crosslinking inhibitors indicate that poorly crosslinked clots are more susceptible to fibrinolysis. In addition, a model for coagulation is presented which accurately fits the entire storage modulus-versus-time curve for PFP.

Authors
Kirkpatrick, JP; McIntire, LV; Moake, JL; Peterson, DL
MLA Citation
Kirkpatrick, JP, McIntire, LV, Moake, JL, and Peterson, DL. "DYNAMIC RHEOLOGICAL STUDIES OF COAGULATION AND FIBRINOLYSIS." Journal of Rheology 23.6 (1979): 769-787.
Source
scival
Published In
Journal of Rheology
Volume
23
Issue
6
Publish Date
1979
Start Page
769
End Page
787
DOI
10.1122/1.549546

Streptokinase-induced degradation of crosslinked and uncrosslinked clots.

Authors
Kirkpatrick, JP; McIntire, LV; Moake, JL
MLA Citation
Kirkpatrick, JP, McIntire, LV, and Moake, JL. "Streptokinase-induced degradation of crosslinked and uncrosslinked clots." Thromb Res 13.3 (September 1978): 569-575.
PMID
741446
Source
pubmed
Published In
Thrombosis Research
Volume
13
Issue
3
Publish Date
1978
Start Page
569
End Page
575
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