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Blitzblau, Rachel Catherine

Positions:

Butler Harris Assistant Professor in Radiation Oncology

Radiation Oncology
School of Medicine

Associate Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

MD./PhD. 2005

MD./PhD. — Tufts University

News:

Publications:

The Effect of Hospital Volume on Breast Cancer Mortality.

The aim of this study was to determine whether hospital volume was associated with mortality in breast cancer, and what thresholds of case volume impacted survival.Prior literature has demonstrated improved survival with treatment at high volume centers among less common cancers requiring technically complex surgery.All adults (18 to 90 years) with stages 0-III unilateral breast cancer diagnosed from 2004 to 2012 were identified from the American College of Surgeons National Cancer Data Base (NCDB). A multivariable Cox proportional hazards model with restricted cubic splines was used to examine the association of annual hospital volume and overall survival, after adjusting for measured covariates. Intergroup comparisons of patient and treatment characteristics were conducted with X and analysis of variance (ANOVA). The log-rank test was used to test survival differences between groups. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HRs) associated with each volume group.One million sixty-four thousand two hundred and fifty-one patients met inclusion criteria. The median age of the sample was 60 (interquartile range 50 to 70). Hospitals were categorized into 3 groups using restricted cubic spline analysis: low-volume (<148 cases/year), moderate-volume (148 to 298 cases/year), and high-volume (>298 cases/year). Treatment at high volume centers was associated with an 11% reduction in overall mortality for all patients (HR 0.89); those with stage 0-I, ER+/PR+ or ER+/PR- breast cancers derived the greatest benefit.Treatment at high volume centers is associated with improved survival for breast cancer patients regardless of stage. High case volume could serve as a proxy for the institutional infrastructure required to deliver complex multidisciplinary breast cancer treatment.

Authors
Greenup, RA; Obeng-Gyasi, S; Thomas, S; Houck, K; Lane, WO; Blitzblau, RC; Hyslop, T; Hwang, ES
MLA Citation
Greenup, RA, Obeng-Gyasi, S, Thomas, S, Houck, K, Lane, WO, Blitzblau, RC, Hyslop, T, and Hwang, ES. "The Effect of Hospital Volume on Breast Cancer Mortality." Annals of surgery (November 23, 2016).
PMID
27893532
Source
epmc
Published In
Annals of Surgery
Publish Date
2016

Development of an Ultra-Fast, High-Quality Whole-Breast Radiation Therapy Treatment Planning System

Authors
Sheng, Y; Li, T; Yoo, S; Yin, FF; Blitzblau, RC; Sr, HJK; Palta, M; Hahn, CA; Ge, Y; Wu, QRJ
MLA Citation
Sheng, Y, Li, T, Yoo, S, Yin, FF, Blitzblau, RC, Sr, HJK, Palta, M, Hahn, CA, Ge, Y, and Wu, QRJ. "Development of an Ultra-Fast, High-Quality Whole-Breast Radiation Therapy Treatment Planning System." October 1, 2016.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
S228
End Page
S228

Acute Toxicity in Patients With HER2-Positive Breast Cancer Treated With Adjuvant Radiation Therapy and Concurrent Trastuzumab and Pertuzumab

Authors
Spiegel, D; Marcom, K; Peterson, B; Force, J; Howie, L; Palta, M; Blitzblau, RC; Sr, HJK
MLA Citation
Spiegel, D, Marcom, K, Peterson, B, Force, J, Howie, L, Palta, M, Blitzblau, RC, and Sr, HJK. "Acute Toxicity in Patients With HER2-Positive Breast Cancer Treated With Adjuvant Radiation Therapy and Concurrent Trastuzumab and Pertuzumab." October 1, 2016.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
E9
End Page
E10

Dosimetric Effect of the Breast Board and Couch Top for Whole-Breast Radiation Therapy in the Prone Position

Authors
Yoo, S; Sr, HJK; Yin, FF; Blitzblau, RC
MLA Citation
Yoo, S, Sr, HJK, Yin, FF, and Blitzblau, RC. "Dosimetric Effect of the Breast Board and Couch Top for Whole-Breast Radiation Therapy in the Prone Position." October 1, 2016.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
E46
End Page
E47

Development of an Ultra-Fast, High-Quality Whole-Breast Radiation Therapy Treatment Planning System.

Authors
Sheng, Y; Li, T; Yoo, S; Yin, FF; Blitzblau, RC; Horton, JK; Palta, M; Hahn, CA; Ge, Y; Wu, QR
MLA Citation
Sheng, Y, Li, T, Yoo, S, Yin, FF, Blitzblau, RC, Horton, JK, Palta, M, Hahn, CA, Ge, Y, and Wu, QR. "Development of an Ultra-Fast, High-Quality Whole-Breast Radiation Therapy Treatment Planning System." International journal of radiation oncology, biology, physics 96.2S (October 2016): S228-.
PMID
27675847
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
S228
DOI
10.1016/j.ijrobp.2016.06.566

Acute Toxicity in Patients With HER2-Positive Breast Cancer Treated With Adjuvant Radiation Therapy and Concurrent Trastuzumab and Pertuzumab.

Authors
Spiegel, D; Marcom, PK; Peterson, B; Force, J; Howie, L; Palta, M; Blitzblau, RC; Horton, JK
MLA Citation
Spiegel, D, Marcom, PK, Peterson, B, Force, J, Howie, L, Palta, M, Blitzblau, RC, and Horton, JK. "Acute Toxicity in Patients With HER2-Positive Breast Cancer Treated With Adjuvant Radiation Therapy and Concurrent Trastuzumab and Pertuzumab." International journal of radiation oncology, biology, physics 96.2S (October 2016): E9-E10.
PMID
27675495
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
E9
End Page
E10
DOI
10.1016/j.ijrobp.2016.06.619

Dosimetric Effect of the Breast Board and Couch Top for Whole-Breast Radiation Therapy in the Prone Position.

Authors
Yoo, S; Horton, JK; Yin, FF; Blitzblau, RC
MLA Citation
Yoo, S, Horton, JK, Yin, FF, and Blitzblau, RC. "Dosimetric Effect of the Breast Board and Couch Top for Whole-Breast Radiation Therapy in the Prone Position." International journal of radiation oncology, biology, physics 96.2S (October 2016): E46-E47.
PMID
27674749
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
E46
End Page
E47
DOI
10.1016/j.ijrobp.2016.06.710

Metastatic Tumor Volume and Extranodal Tumor Extension: Clinical Significance in Patients with Stage II Breast Cancer Drinka E, Allen P, McBride A, et al (Univ of Texas MD Anderson Cancer Ctr, Houston; Univ of Arizona School of Medicine, Phoenix) Arch Pathol Lab Med 139:1288-1294, 2015

Authors
Chino, F; Blitzblau, RC
MLA Citation
Chino, F, and Blitzblau, RC. "Metastatic Tumor Volume and Extranodal Tumor Extension: Clinical Significance in Patients with Stage II Breast Cancer Drinka E, Allen P, McBride A, et al (Univ of Texas MD Anderson Cancer Ctr, Houston; Univ of Arizona School of Medicine, Phoenix) Arch Pathol Lab Med 139:1288-1294, 2015." Breast Diseases 27.2 (January 1, 2016): 154-155.
Source
scopus
Published In
Breast Diseases: A Year Book Quarterly
Volume
27
Issue
2
Publish Date
2016
Start Page
154
End Page
155
DOI
10.1016/j.breastdis.2016.04.020

Whose Disease Will Recur After Mastectomy for Early Stage, Node-Negative Breast Cancer? A Systematic Review.

Effective local control is associated with improved overall survival, particularly for women with early-stage cancers. No other local therapy is typically offered to women with T1-2 N0 breast cancer after mastectomy, although in select women the 5-year local recurrence rate can be as high as 20%. Therefore, accurately predicting the women who are at highest risk for recurrence after mastectomy will identify those who might benefit from more aggressive adjuvant treatment. A systematic search was conducted identifying risk factors associated with locoregional recurrence, including age, menopausal status, receptor status, lymphovascular invasion (LVI), margin status, use of systemic therapy, size, grade, and genomic classifer score. Although associations varied among studies, the risk factors most consistently identified were age ≤ 40 years, LVI, positive/close margin, and larger tumor size. In women with multiple high risk factors, risk of local recurrence was as high as 20% at 10 years. Additional multicenter studies are needed to investigate risk factors for locoregional recurrence after mastectomy without radiotherapy in T1-2N0 breast cancer. Consideration of additional adjuvant local therapy might be warranted in a subset of women at high risk of local recurrence.

Authors
Kent, C; Horton, J; Blitzblau, R; Koontz, BF
MLA Citation
Kent, C, Horton, J, Blitzblau, R, and Koontz, BF. "Whose Disease Will Recur After Mastectomy for Early Stage, Node-Negative Breast Cancer? A Systematic Review." Clinical breast cancer 15.6 (December 2015): 403-412.
PMID
26198331
Source
epmc
Published In
Clinical Breast Cancer
Volume
15
Issue
6
Publish Date
2015
Start Page
403
End Page
412
DOI
10.1016/j.clbc.2015.06.008

Biological Subtype Predicts Risk of Locoregional Recurrence After Mastectomy and Impact of Postmastectomy Radiation in a Large National Database.

To evaluate locoregional recurrence (LRR) after mastectomy and impact of postmastectomy radiation (PMRT) by breast cancer subtype.Between 2000 and 2009, 5673 patients with stage I to III breast carcinoma underwent mastectomy and nodal evaluation; 30% received PMRT. Isolated LRR (iLRR) and LRR were compared across groups defined by biological subtype and receipt of trastuzumab: luminal A (estrogen [ER]/progesterone [PR]+, HER2-, low/intermediate grade), luminal B (ER/PR+, HER2-, high grade), HER2 with trastuzumab, HER2 without trastuzumab, and triple negative (TN; ER-, PR-, HER2-). LRR hazard ratios (HR) were estimated with multivariable Fine and Gray models. The effect of PMRT on LRR was evaluated with Fine and Gray models stratified by propensity for PMRT.With a median follow-up time of 50.1 months, there were 19 iLRR and 109 LRR events. HER2 patients with trastuzumab had no iLRR and only a single LRR. Compared with luminal A patients, TN patients had significantly greater adjusted risk of iLRR (HR 14.10; 95% CI 2.97%-66.90%), with a similar trend among luminal B (HR 4.94; 95% CI 0.94%-25.82%) and HER2 patients without trastuzumab (HR 4.41; 95% CI 0.61%-32.11%). Although PMRT reduced LRR, the effect of PMRT varied by subgroup, with the greatest and smallest effects seen among luminal A (HR 0.17; 95% CI 0.05%-0.62%) and TN patients (HR 0.59; 95% CI 0.25%-1.35%), respectively.TN patients had the highest risk of LRR and the least benefit from PMRT; these patients may benefit from alternative treatment strategies. In contrast, in the era of HER2-directed therapy, the role of local therapy may need to be reassessed among HER2 patients.

Authors
Tseng, YD; Uno, H; Hughes, ME; Niland, JC; Wong, Y-N; Theriault, R; Blitzblau, RC; Moy, B; Breslin, T; Edge, SB; Hassett, MJ; Punglia, RS
MLA Citation
Tseng, YD, Uno, H, Hughes, ME, Niland, JC, Wong, Y-N, Theriault, R, Blitzblau, RC, Moy, B, Breslin, T, Edge, SB, Hassett, MJ, and Punglia, RS. "Biological Subtype Predicts Risk of Locoregional Recurrence After Mastectomy and Impact of Postmastectomy Radiation in a Large National Database." International journal of radiation oncology, biology, physics 93.3 (November 2015): 622-630.
PMID
26461004
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
622
End Page
630
DOI
10.1016/j.ijrobp.2015.07.006

A phase 1 trial of preoperative partial breast radiation therapy: Patient selection, target delineation, and dose delivery.

Diffusion of accelerated partial breast irradiation into clinical practice is limited by the need for specialized equipment and training. The accessible external beam technique yields unacceptable complication rates, likely from large postoperative target volumes. We designed a phase 1 trial evaluating preoperative radiation therapy to the intact tumor using widely available technology.Patients received 15, 18, or 21 Gy in a single fraction to the breast tumor plus margin. Magnetic resonance imaging (MRI) was used in conjunction with standard computed tomography (CT)-based planning to identify contrast enhancing tumor. Skin markers and an intratumor biopsy marker were used for verification during treatment.MRI imaging was critical for target delineation because not all breast tumors were reliably identified on CT scan. Breast shape differences were consistently seen between CT and MRI but did not impede image registration or tumor identification. Target volumes were markedly smaller than historical postoperative volumes, and normal tissue constraints were easily met. A biopsy marker within the breast proved sufficient for setup localization.This single fraction linear accelerator-based partial breast irradiation approach can be easily incorporated at most treatment centers. In vivo targeting may improve accuracy and can reduce the dose to normal tissues.

Authors
Blitzblau, RC; Arya, R; Yoo, S; Baker, JA; Chang, Z; Palta, M; Duffy, E; Horton, JK
MLA Citation
Blitzblau, RC, Arya, R, Yoo, S, Baker, JA, Chang, Z, Palta, M, Duffy, E, and Horton, JK. "A phase 1 trial of preoperative partial breast radiation therapy: Patient selection, target delineation, and dose delivery." Practical radiation oncology 5.5 (September 2015): e513-e520.
PMID
25834942
Source
epmc
Published In
Practical Radiation Oncology
Volume
5
Issue
5
Publish Date
2015
Start Page
e513
End Page
e520
DOI
10.1016/j.prro.2015.02.002

Exercise behavior and patient-reported outcomes in women with early breast cancer receiving locoregional radiation therapy.

Radiation therapy is associated with acute treatment-related complications that can lead to decreased quality of life (QOL). Exercise has been shown in other cancer treatment settings to improve negative outcomes. We conducted a prospective pilot study to explore the association between exercise, patient-reported outcomes, and acute radiation therapy toxicities.Women receiving curative breast radiation therapy were enrolled. Each patient completed an exercise behavior/QOL survey before or during the first week of treatment and again during the last week of treatment. Exercise behavior was quantified with the Godin Leisure Time Exercise Questionnaire (metabolic equivalent [MET] hours per week). Measurements to evaluate upper extremity lymphedema and shoulder range of motion were completed. Skin toxicity was assessed weekly. Patient-reported outcomes were measured using standardized questionnaires.Forty-five patients were enrolled. Mean patient age was 54 (range, 28-73) years. Mean METs in the exercise cohort (≥9 METs/wk) was 21 per week (range, 11-38, n = 14); 3 per week (range, 0-8, n = 25) in the nonexercise cohort (<9 METs/wk). Women in the exercise cohort showed improvements in treatment-induced quality of life and fatigue (not significant) despite more extensive surgical, medical, and radiation treatment. No differences in treatment-related toxicities, pain, or sleep scores were noted. Lymphedema was mild (<3 cm) in the entire patient cohort.The vast majority of current exercise oncology literature implicates physical activity as an independent predictor of QOL in cancer patients. Our study noted similar trends, but they were not statistically significant. This may be due to our finding that patient-reported outcomes with radiation therapy are relatively high compared with other treatment modalities and remain stable throughout treatment. Thus, it may be that radiation therapy has a limited impact on QOL in breast cancer patients. Exercise may be best used as a targeted therapy in patients at high risk for poor QOL or radiation-related toxicities at baseline.

Authors
Arya, R; Siamakpour-Reihani, S; Palta, M; Massa, L; Broadwater, G; Blitzblau, RC; Horton, JK
MLA Citation
Arya, R, Siamakpour-Reihani, S, Palta, M, Massa, L, Broadwater, G, Blitzblau, RC, and Horton, JK. "Exercise behavior and patient-reported outcomes in women with early breast cancer receiving locoregional radiation therapy." Practical radiation oncology 5.4 (July 2015): e275-e281.
PMID
25731964
Source
epmc
Published In
Practical Radiation Oncology
Volume
5
Issue
4
Publish Date
2015
Start Page
e275
End Page
e281
DOI
10.1016/j.prro.2015.01.003

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers.

Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response.Women aged ≥55 years with clinically node-negative, estrogen receptor-positive, and/or progesterone receptor-positive HER2-, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed.No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation.Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should be tested in future clinical trials because it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.

Authors
Horton, JK; Blitzblau, RC; Yoo, S; Geradts, J; Chang, Z; Baker, JA; Georgiade, GS; Chen, W; Siamakpour-Reihani, S; Wang, C; Broadwater, G; Groth, J; Palta, M; Dewhirst, M; Barry, WT; Duffy, EA; Chi, J-TA; Hwang, ES
MLA Citation
Horton, JK, Blitzblau, RC, Yoo, S, Geradts, J, Chang, Z, Baker, JA, Georgiade, GS, Chen, W, Siamakpour-Reihani, S, Wang, C, Broadwater, G, Groth, J, Palta, M, Dewhirst, M, Barry, WT, Duffy, EA, Chi, J-TA, and Hwang, ES. "Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers." International journal of radiation oncology, biology, physics 92.4 (July 2015): 846-855.
PMID
26104938
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
92
Issue
4
Publish Date
2015
Start Page
846
End Page
855
DOI
10.1016/j.ijrobp.2015.03.007

Abstract P2-12-07: The association between exercise behavior and patient-reported outcomes in women with early breast cancer receiving locoregional radiation therapy

Authors
Arya, R; Jones, LW; Blitzblau, RC; Palta, M; Massa, L; Broadwater, G; Horton, JK
MLA Citation
Arya, R, Jones, LW, Blitzblau, RC, Palta, M, Massa, L, Broadwater, G, and Horton, JK. "Abstract P2-12-07: The association between exercise behavior and patient-reported outcomes in women with early breast cancer receiving locoregional radiation therapy." May 1, 2015.
Source
crossref
Published In
Cancer Research
Volume
75
Issue
9 Supplement
Publish Date
2015
Start Page
P2-12-07
End Page
P2-12-07
DOI
10.1158/1538-7445.SABCS14-P2-12-07

Abstract P1-15-10: Low utilization of hypofractionated radiotherapy for the treatment of early-stage breast cancer in the US

Authors
Mowery, YM; Greenup, RA; Houck, K; Palta, M; Horton, JK; Hwang, E-SS; Sosa, JA; Blitzblau, RC
MLA Citation
Mowery, YM, Greenup, RA, Houck, K, Palta, M, Horton, JK, Hwang, E-SS, Sosa, JA, and Blitzblau, RC. "Abstract P1-15-10: Low utilization of hypofractionated radiotherapy for the treatment of early-stage breast cancer in the US." May 1, 2015.
Source
crossref
Published In
Cancer Research
Volume
75
Issue
9 Supplement
Publish Date
2015
Start Page
P1-15-10
End Page
P1-15-10
DOI
10.1158/1538-7445.SABCS14-P1-15-10

Dosimetric comparison of preoperative single-fraction partial breast radiotherapy techniques: 3D CRT, noncoplanar IMRT, coplanar IMRT, and VMAT.

The purpose of this study was to compare dosimetric parameters of treatment plans among four techniques for preoperative single-fraction partial breast radiotherapy in order to select an optimal treatment technique. The techniques evaluated were noncoplanar 3D conformal radiation therapy (3D CRT), noncoplanar intensity-modulated radiation therapy (IMRTNC), coplanar IMRT (IMRTCO), and volumetric-modulated arc therapy (VMAT). The planning CT scans of 16 patients in the prone position were used in this study, with the single-fraction prescription doses of 15 Gy for the first eight patients and 18 Gy for the remaining eight patients. Six (6) MV photon beams were designed to avoid the heart and contralateral breast. Optimization for IMRT and VMAT was performed to reduce the dose to the skin and normal breast. All plans were normalized such that 100% of the prescribed dose covered greater than 95% of the clinical target volume (CTV) consisting of gross tumor volume (GTV) plus 1.5 cm margin. Mean homogeneity index (HI) was the lowest (1.05 ± 0.02) for 3D CRT and the highest (1.11 ± 0.04) for VMAT. Mean conformity index (CI) was the lowest (1.42 ± 0.32) for IMRTNC and the highest (1.60 ± 0.32) for VMAT. Mean of the maximum point dose to skin was the lowest (73.7 ± 11.5%) for IMRTNC and the highest (86.5 ± 6.68%) for 3D CRT. IMRTCO showed very similar HI, CI, and maximum skin dose to IMRTNC (differences <1%). The estimated mean treatment delivery time, excluding the time spent for patient positioning and imaging, was 7.0 ± 1.0, 8.3 ± 1.1, 9.7 ± 1.0, and 11.0 ± 1.5min for VMAT, IMRTCO, IMRTNC and 3D CRT, respectively. In comparison of all four techniques for preoperative single-fraction partial breast radiotherapy, we can conclude that noncoplanar or coplanar IMRT were optimal in this study as IMRT plans provided homogeneous and conformal target coverage, skin sparing, and relatively short treatment delivery time.

Authors
Yoo, S; Blitzblau, R; Yin, F-F; Horton, JK
MLA Citation
Yoo, S, Blitzblau, R, Yin, F-F, and Horton, JK. "Dosimetric comparison of preoperative single-fraction partial breast radiotherapy techniques: 3D CRT, noncoplanar IMRT, coplanar IMRT, and VMAT." Journal of applied clinical medical physics 16.1 (January 8, 2015): 5126-.
PMID
25679170
Source
epmc
Published In
Journal of applied clinical medical physics / American College of Medical Physics
Volume
16
Issue
1
Publish Date
2015
Start Page
5126
DOI
10.1120/jacmp.v16i1.5126

The use of adjuvant radiotherapy in elderly patients with early-stage breast cancer: Changes in practice patterns after publication of Cancer and Leukemia Group B 9343

© 2014 American Cancer Society.BACKGROUND: The Cancer and Leukemia Group B (CALGB) 9343 randomized phase 3 trial established lumpectomy and adjuvant therapy with tamoxifen alone, rather than both radiotherapy and tamoxifen, as a reasonable treatment course for women aged >70 years with clinical stage I (AJCC 7th edition), estrogen receptor-positive breast cancer. An analysis of the Surveillance, Epidemiology, and End Results (SEER) registry was undertaken to assess practice patterns before and after the publication of this landmark study. METHODS: The SEER database from 2000 to 2009 was used to identify 40,583 women aged ≥70 years who were treated with breast-conserving surgery for clinical stage I, estrogen receptor-positive and/or progesterone receptor-positive breast cancer. The percentage of patients receiving radiotherapy and the type of radiotherapy delivered was assessed over time. Administration of radiotherapy was further assessed across age groups; SEER cohort; and tumor size, grade, and laterality. RESULTS: Approximately 68.6% of patients treated between 2000 and 2004 compared with 61.7% of patients who were treated between 2005 and 2009 received some form of adjuvant radiotherapy (P < .001). Coinciding with a decline in the use of external beam radiotherapy, there was an increase in the use of implant radiotherapy from 1.4% between 2000 and 2004 to 6.2% between 2005 to 2009 (P < .001). There were significant reductions in the frequency of radiotherapy delivery over time across age groups, tumor size, and tumor grade and regardless of laterality (P < .001 for all). CONCLUSIONS: Randomized phase 3 data support the omission of adjuvant radiotherapy in elderly women with early-stage breast cancer. Analysis of practice patterns before and after the publication of these data indicates a significant decline in radiotherapy use; however, nearly two-thirds of women continue to receive adjuvant radiotherapy.

Authors
Palta, M; Palta, P; Bhavsar, NA; Horton, JK; Blitzblau, RC
MLA Citation
Palta, M, Palta, P, Bhavsar, NA, Horton, JK, and Blitzblau, RC. "The use of adjuvant radiotherapy in elderly patients with early-stage breast cancer: Changes in practice patterns after publication of Cancer and Leukemia Group B 9343." Cancer 121.2 (January 1, 2015): 188-193.
Source
scopus
Published In
Cancer
Volume
121
Issue
2
Publish Date
2015
Start Page
188
End Page
193
DOI
10.1002/cncr.28937

Dosimetric comparison of preoperative single-fraction partial breast radiotherapy techniques: 3D CRT, noncoplanar IMRT, coplanar IMRT, and VMAT

The purpose of this study was to compare dosimetric parameters of treatment plans among four techniques for preoperative single-fraction partial breast radiotherapy in order to select an optimal treatment technique. The techniques evaluated were noncoplanar 3D conformal radiation therapy (3D CRT), noncoplanar intensity-modulated radiation therapy (IMRTNC), coplanar IMRT (IMRTCO), and volumetric-modulated arc therapy (VMAT). The planning CT scans of 16 patients in the prone position were used in this study, with the single-fraction prescription doses of 15 Gy for the first eight patients and 18 Gy for the remaining eight patients. Six (6) MV photon beams were designed to avoid the heart and contralateral breast. Optimization for IMRT and VMAT was performed to reduce the dose to the skin and normal breast. All plans were normalized such that 100% of the prescribed dose covered greater than 95% of the clinical target volume (CTV) consisting of gross tumor volume (GTV) plus 1.5 cm margin. Mean homogeneity index (HI) was the lowest (1.05 ± 0.02) for 3D CRT and the highest (1.11 ± 0.04) for VMAT. Mean conformity index (CI) was the lowest (1.42 ± 0.32) for IMRTNC and the highest (1.60 ± 0.32) for VMAT. Mean of the maximum point dose to skin was the lowest (73.7 ± 11.5%) for IMRTNC and the highest (86.5 ± 6.68%) for 3D CRT. IMRTCO showed very similar HI, CI, and maximum skin dose to IMRTNC (differences <1%). The estimated mean treatment delivery time, excluding the time spent for patient positioning and imaging, was 7.0 ± 1.0, 8.3 ± 1.1, 9.7 ± 1.0, and 11.0 ± 1.5min for VMAT, IMRTCO, IMRTNC and 3D CRT, respectively. In comparison of all four techniques for preoperative single-fraction partial breast radiotherapy, we can conclude that noncoplanar or coplanar IMRT were optimal in this study as IMRT plans provided homogeneous and conformal target coverage, skin sparing, and relatively short treatment delivery time.

Authors
Yoo, S; Blitzblau, R; Yin, FF; Horton, JK
MLA Citation
Yoo, S, Blitzblau, R, Yin, FF, and Horton, JK. "Dosimetric comparison of preoperative single-fraction partial breast radiotherapy techniques: 3D CRT, noncoplanar IMRT, coplanar IMRT, and VMAT." Journal of Applied Clinical Medical Physics 16.1 (January 1, 2015): 183-191.
Source
scopus
Published In
Journal of applied clinical medical physics / American College of Medical Physics
Volume
16
Issue
1
Publish Date
2015
Start Page
183
End Page
191

The UK HeartSpare Study (Stage IB): Randomised comparison of a voluntary breath-hold technique and prone radiotherapy after breast conserving surgery

Authors
Mowery, YM; Blitzblau, RC
MLA Citation
Mowery, YM, and Blitzblau, RC. "The UK HeartSpare Study (Stage IB): Randomised comparison of a voluntary breath-hold technique and prone radiotherapy after breast conserving surgery." Breast Diseases: A Year Book Quarterly 26.3 (2015): 237-239.
Source
crossref
Published In
Breast Diseases: A Year Book Quarterly
Volume
26
Issue
3
Publish Date
2015
Start Page
237
End Page
239
DOI
10.1016/j.breastdis.2015.07.001

A PHASE II TRIAL OF BALLOON-CATHETER PARTIAL BREAST BRACHYTHERAPY OPTIMIZATION IN THE TREATMENT OF STAGE 0, I AND IIA BREAST CARCINOMA.

(a) To prospectively determine if multidwell position dose delivery can decrease skin dose and resultant toxicity over single dwell balloon-catheter partial breast irradiation, and (b) to evaluate whether specific skin parameters could be safely used instead of skin-balloon distance alone for predicting toxicity and treatment eligibility.A single-arm phase II study using a Simon two-stage design was performed on 28 women with stage 0-II breast cancer. All patients were treated with multiple dwell position balloon-catheter brachytherapy. The primary endpoint was ≥ grade 2 skin toxicity. Initial entry required a balloon-skin distance ≥ 7 mm. Based on the toxicity in the first 16 patients, additional patients were treated irrespective of skin-balloon distance as long as the Dmax to 1 mm skin thickness was < 130%.Compared to the phantom single dwell plans, multidwell planning yielded superior PTV coverage as per median V90, V95 and V100, but had slightly worse V150, V200 and DHI. Dmax to skin was decreased by multidwell planning at multiple skin thicknesses. The most common acute toxicity was grade 1 erythema (57%), and only two patients (7%) developed acute grade 2 toxicity (erythema). Late grade 1 fibrosis was seen in 32%. No patients experienced grade 3, 4, or 5 toxicity.Multidwell position planning for balloon-catheter brachytherapy results in lower skin doses with equal to superior PTV coverage and an overall low rate of initial skin toxicity. Our data suggest that limiting the Dmax to < 130% to 1 mm thick skin is achievable and results in minimal toxicity.

Authors
Nath, SK; Chen, ZJ; Rowe, BP; Blitzblau, RC; Aneja, S; Grube, BJ; Horowitz, NR; Weidhaas, JB
MLA Citation
Nath, SK, Chen, ZJ, Rowe, BP, Blitzblau, RC, Aneja, S, Grube, BJ, Horowitz, NR, and Weidhaas, JB. "A PHASE II TRIAL OF BALLOON-CATHETER PARTIAL BREAST BRACHYTHERAPY OPTIMIZATION IN THE TREATMENT OF STAGE 0, I AND IIA BREAST CARCINOMA." Journal of radiation oncology 3.4 (December 2014): 371-378.
PMID
25485042
Source
epmc
Published In
Journal of Radiation Oncology
Volume
3
Issue
4
Publish Date
2014
Start Page
371
End Page
378
DOI
10.1007/s13566-014-0153-8

Whole-breast radiation therapy: the long and short of it.

Authors
Mowery, YM; Blitzblau, RC
MLA Citation
Mowery, YM, and Blitzblau, RC. "Whole-breast radiation therapy: the long and short of it." International journal of radiation oncology, biology, physics 90.5 (December 2014): 990-992.
PMID
25539364
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
90
Issue
5
Publish Date
2014
Start Page
990
End Page
992
DOI
10.1016/j.ijrobp.2014.10.028

Local Recurrence Patterns in Breast Cancer Patients Treated with Oncoplastic Reduction Mammaplasty and Radiotherapy

Authors
Blitzblau, RC
MLA Citation
Blitzblau, RC. "Local Recurrence Patterns in Breast Cancer Patients Treated with Oncoplastic Reduction Mammaplasty and Radiotherapy." Breast Diseases: A Year Book Quarterly 25.3 (2014): 257-258.
Source
crossref
Published In
Breast Diseases: A Year Book Quarterly
Volume
25
Issue
3
Publish Date
2014
Start Page
257
End Page
258
DOI
10.1016/j.breastdis.2014.07.025

Abstract P5-14-04: Preoperative single-fraction partial breast radiotherapy – Initial results from a novel phase I dose-escalation protocol with exploration of radiation response biomarkers

Authors
Horton, JK; Blitzblau, RC; Yoo, S; Georgiade, GS; Geradts, J; Baker, JA; Chang, Z; Broadwater, G; Barry, W; Duffy, EA; Hwang, ES
MLA Citation
Horton, JK, Blitzblau, RC, Yoo, S, Georgiade, GS, Geradts, J, Baker, JA, Chang, Z, Broadwater, G, Barry, W, Duffy, EA, and Hwang, ES. "Abstract P5-14-04: Preoperative single-fraction partial breast radiotherapy – Initial results from a novel phase I dose-escalation protocol with exploration of radiation response biomarkers." December 15, 2013.
Source
crossref
Published In
Cancer Research
Volume
73
Issue
24 Supplement
Publish Date
2013
Start Page
P5-14-04
End Page
P5-14-04
DOI
10.1158/0008-5472.SABCS13-P5-14-04

Preoperative Single:Fraction Partial Breast Radiation Therapy: A Novel Phase 1 Dose-Escalation Protocol and Exploration of Breast Cancer Radiation Response

Authors
Horton, JK; Blitzblau, RC; Yoo, S; Georgiade, GS; Geradts, J; Baker, JA; Chang, Z; Duffy, E; Hwang, ES
MLA Citation
Horton, JK, Blitzblau, RC, Yoo, S, Georgiade, GS, Geradts, J, Baker, JA, Chang, Z, Duffy, E, and Hwang, ES. "Preoperative Single:Fraction Partial Breast Radiation Therapy: A Novel Phase 1 Dose-Escalation Protocol and Exploration of Breast Cancer Radiation Response." October 1, 2013.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
2
Publish Date
2013
Start Page
S229
End Page
S229

Evaluating Radiation Dose to the Heart With Left Whole Breast Radiation Therapy in Prone, Supine Breath-Hold, and Supine Free-Breathing Positions

Authors
Perez, BA; Patel, PR; Yoo, S; O'Neill, L; Livengood, KP; Catalano, S; Chollet, CT; Blitzblau, RC
MLA Citation
Perez, BA, Patel, PR, Yoo, S, O'Neill, L, Livengood, KP, Catalano, S, Chollet, CT, and Blitzblau, RC. "Evaluating Radiation Dose to the Heart With Left Whole Breast Radiation Therapy in Prone, Supine Breath-Hold, and Supine Free-Breathing Positions." October 1, 2013.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
2
Publish Date
2013
Start Page
S229
End Page
S229

Radiotherapy After Mastectomy

Classic randomized trials documented the benefit of postmastectomy radiotherapy in women with node-positive or locally advanced breast cancer. Modern advances in surgical therapy, systemic therapy, and radiotherapy, however, along with an improved understanding of cancer biology, have called into question previously assumed recurrence risks and treatment benefits. This article explores the impact of tumor biology and genomic medicine on utilization of postmastectomy radiotherapy and how treatment decision making is moving beyond TNM-based predictors. © 2013 Elsevier Inc. All rights reserved.

Authors
Blitzblau, RC; Horton, JK
MLA Citation
Blitzblau, RC, and Horton, JK. "Radiotherapy After Mastectomy." Surgical Oncology Clinics of North America (2013).
PMID
23622080
Source
scival
Published In
Surgical Oncology Clinics of North America
Publish Date
2013
DOI
10.1016/j.soc.2013.02.012

Radiotherapy After Mastectomy

Classic randomized trials documented the benefit of postmastectomy radiotherapy in women with node-positive or locally advanced breast cancer. Modern advances in surgical therapy, systemic therapy, and radiotherapy, however, along with an improved understanding of cancer biology, have called into question previously assumed recurrence risks and treatment benefits. This article explores the impact of tumor biology and genomic medicine on utilization of postmastectomy radiotherapy and how treatment decision making is moving beyond TNM-based predictors. © 2013 Elsevier Inc.

Authors
Blitzblau, RC; Horton, JK
MLA Citation
Blitzblau, RC, and Horton, JK. "Radiotherapy After Mastectomy." Surgical Oncology Clinics of North America 22.3 (2013): 563-577.
Source
scival
Published In
Surgical Oncology Clinics of North America
Volume
22
Issue
3
Publish Date
2013
Start Page
563
End Page
577
DOI
10.1016/j.soc.2013.02.012

Treatment planning technique in patients receiving postmastectomy radiation therapy

Many of the technical subtleties involved in postmastectomy radiation treatment planning will never be addressed in a robust clinical trial setting. However, these issues are faced daily by practicing radiation oncologists with little to guide them in the published literature. The purpose of this study was to survey a small number of breast care providers in both academic and private practice settings on practical aspects of postmastectomy radiation treatment planning. Topics addressed included the use of sophisticated dose-modulation algorithms, hypofractionation, bolus material, and dose-volume histogram (DVH) constraints. Fifty-two people responded to the survey, 50% in academics and 50% in private practice. As expected, wide variation in clinical practice was seen although a few general trends emerged. We include here, with the survey results, a review of the relevant literature for a number of different treatment-related issues. Although the use of postmastectomy radiation therapy is common, literature guiding the reader on technical aspects of delivery is sparse. The data presented here provide a general framework of what is considered acceptable by currently practicing radiation oncologists in many different practice settings. © 2013 American Society for Radiation Oncology.

Authors
Blitzblau, RC; Horton, JK
MLA Citation
Blitzblau, RC, and Horton, JK. "Treatment planning technique in patients receiving postmastectomy radiation therapy." Practical Radiation Oncology 3.4 (2013): 241-248.
Source
scival
Published In
Practical Radiation Oncology
Volume
3
Issue
4
Publish Date
2013
Start Page
241
End Page
248
DOI
10.1016/j.prro.2012.09.004

Use of Adjuvant Radiation Therapy in Elderly Patients With Early Stage Breast Cancer: Changes in Practice Patterns After Publication of Cancer and Leukemia Group B (CALGB) 9343

Authors
Palta, M; Palta, P; Horton, J; Blitzblau, R
MLA Citation
Palta, M, Palta, P, Horton, J, and Blitzblau, R. "Use of Adjuvant Radiation Therapy in Elderly Patients With Early Stage Breast Cancer: Changes in Practice Patterns After Publication of Cancer and Leukemia Group B (CALGB) 9343." November 1, 2012.
PMID
25488523
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
84
Issue
3
Publish Date
2012
Start Page
S256
End Page
S256

Treatment planning technique in patients receiving postmastectomy radiation therapy

Many of the technical subtleties involved in postmastectomy radiation treatment planning will never be addressed in a robust clinical trial setting. However, these issues are faced daily by practicing radiation oncologists with little to guide them in the published literature. The purpose of this study was to survey a small number of breast care providers in both academic and private practice settings on practical aspects of postmastectomy radiation treatment planning. Topics addressed included the use of sophisticated dose-modulation algorithms, hypofractionation, bolus material, and dose-volume histogram (DVH) constraints. Fifty-two people responded to the survey, 50% in academics and 50% in private practice. As expected, wide variation in clinical practice was seen although a few general trends emerged. We include here, with the survey results, a review of the relevant literature for a number of different treatment-related issues. Although the use of postmastectomy radiation therapy is common, literature guiding the reader on technical aspects of delivery is sparse. The data presented here provide a general framework of what is considered acceptable by currently practicing radiation oncologists in many different practice settings. © 2012 American Society for Radiation Oncology.

Authors
Blitzblau, RC; Horton, JK
MLA Citation
Blitzblau, RC, and Horton, JK. "Treatment planning technique in patients receiving postmastectomy radiation therapy." Practical Radiation Oncology (2012).
PMID
24674393
Source
scival
Published In
Practical Radiation Oncology
Publish Date
2012
DOI
10.1016/j.prro.2012.09.004

Evaluation of single nucleotide polymorphisms (SNPs) in the p53 binding protein 1 (TP53BP1) gene in breast cancer patients treated with breast-conserving surgery and whole-breast irradiation (BCS + RT)

Authors
Blitzblau, RC; Horton, JK
MLA Citation
Blitzblau, RC, and Horton, JK. "Evaluation of single nucleotide polymorphisms (SNPs) in the p53 binding protein 1 (TP53BP1) gene in breast cancer patients treated with breast-conserving surgery and whole-breast irradiation (BCS + RT)." Breast Diseases 23.1 (2012): 44-45.
Source
scival
Published In
Breast Diseases: A Year Book Quarterly
Volume
23
Issue
1
Publish Date
2012
Start Page
44
End Page
45
DOI
10.1016/j.breastdis.2012.01.001

Rare BRCA1 haplotypes including 3′UTR SNPs associated with breast cancer risk

Genetic markers identifying women at an increased risk of developing breast cancer exist, yet the majority of inherited risk remains elusive. While numerous BRCA1 coding sequence mutations are associated with breast cancer risk, BRCA1 mutations account for less then 5% of breast cancer risk. Since 3′ untranslated region (3′UtR) polymorphisms disrupting microRNA (miRNA) binding can be functional and can act as genetic markers of cancer risk, we tested the hypothesis that such polymorphisms in the 3′UtR of BRCA1 and haplotypes containing these functional polymorphisms may be associated with breast cancer risk. We sequenced the BRCA1 3′UtR from breast cancer patients to identify miRNA disrupting polymorphisms. We further evaluated haplotypes of this region including the identified 3′UtR variants in a large population of controls and breast cancer patients (n = 221) with known breast cancer subtypes and ethnicities. We identified three 3′UtR variants in BRCA1 that are polymorphic in breast cancer populations, and haplotype analysis including these variants revealed that breast cancer patients harbor five rare haplotypes not generally found among controls (9.50% for breast cancer chromosomes, 0.11% for control chromosomes, p = 0.0001). three of these rare haplotypes contain the rs8176318 BRCA1 3′UtR functional variant. these haplotypes are not biomarkers for BRCA1 coding mutations, as they are found rarely in BRCA1 mutant breast cancer patients (1/129 patients = 0.78%). these rare BRCA1 haplotypes and 3′UtR SNps may represent new genetic markers of breast cancer risk. © 2011 Landes Bioscience.

Authors
Pelletier, C; Speed, WC; Paranjape, T; Keane, K; Blitzblau, R; Hollestelle, A; Safavi, K; Ouweland, AVD; Zelterman, D; Slack, FJ; Kidd, KK; Weidhaas, JB
MLA Citation
Pelletier, C, Speed, WC, Paranjape, T, Keane, K, Blitzblau, R, Hollestelle, A, Safavi, K, Ouweland, AVD, Zelterman, D, Slack, FJ, Kidd, KK, and Weidhaas, JB. "Rare BRCA1 haplotypes including 3′UTR SNPs associated with breast cancer risk." Cell Cycle 10.1 (2011): 90-99.
PMID
21191178
Source
scival
Published In
Cell Cycle
Volume
10
Issue
1
Publish Date
2011
Start Page
90
End Page
99
DOI
10.4161/cc.10.1.14359

MicroRNA binding-site polymorphisms as potential biomarkers of cancer risk.

Identification of people or populations at risk for developing cancer is a key to improved screening programs and earlier detection, with the hope of a commensurate reduction in cancer mortalities. Genetic alterations that change gene expression levels have long been investigated for association with development of cancer. Misregulation of genes through altered interactions is another potential mechanism of oncogenesis. Gene regulation by microRNAs (miRNAs) is a relatively new area of study, and a growing body of evidence suggests that alterations in this process may be associated with increased cancer risk. This can occur through alterations in miRNA levels, interactions with targets, or perhaps more complicated combinations of the two. Here we review the current data for association between single nucleotide polymorphisms (SNPs) in miRNA binding sites and specific cancers. This growing body of literature suggests that these SNPs have a potential role as biomarkers for cancer risk.

Authors
Blitzblau, RC; Weidhaas, JB
MLA Citation
Blitzblau, RC, and Weidhaas, JB. "MicroRNA binding-site polymorphisms as potential biomarkers of cancer risk." Mol Diagn Ther 14.6 (December 1, 2010): 335-342. (Review)
PMID
21275451
Source
pubmed
Published In
Molecular Diagnosis and Therapy
Volume
14
Issue
6
Publish Date
2010
Start Page
335
End Page
342
DOI
10.2165/11587600-000000000-00000

A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk.

Ovarian cancer (OC) is the single most deadly form of women's cancer, typically presenting as an advanced disease at diagnosis in part due to a lack of known risk factors or genetic markers of risk. The KRAS oncogene and altered levels of the microRNA (miRNA) let-7 are associated with an increased risk of developing solid tumors. In this study, we investigated a hypothesized association between an increased risk of OC and a variant allele of KRAS at rs61764370, referred to as the KRAS-variant, which disrupts a let-7 miRNA binding site in this oncogene. Specimens obtained were tested for the presence of the KRAS-variant from nonselected OC patients in three independent cohorts, two independent ovarian case-control studies, and OC patients with hereditary breast and ovarian cancer syndrome (HBOC) as well as their family members. Our results indicate that the KRAS-variant is associated with more than 25% of nonselected OC cases. Further, we found that it is a marker for a significant increased risk of developing OC, as confirmed by two independent case-control analyses. Lastly, we determined that the KRAS-variant was present in 61% of HBOC patients without BRCA1 or BRCA2 mutations, previously considered uninformative, as well as in their family members with cancer. Our findings strongly support the hypothesis that the KRAS-variant is a genetic marker for increased risk of developing OC, and they suggest that the KRAS-variant may be a new genetic marker of cancer risk for HBOC families without other known genetic abnormalities.

Authors
Ratner, E; Lu, L; Boeke, M; Barnett, R; Nallur, S; Chin, LJ; Pelletier, C; Blitzblau, R; Tassi, R; Paranjape, T; Hui, P; Godwin, AK; Yu, H; Risch, H; Rutherford, T; Schwartz, P; Santin, A; Matloff, E; Zelterman, D; Slack, FJ; Weidhaas, JB
MLA Citation
Ratner, E, Lu, L, Boeke, M, Barnett, R, Nallur, S, Chin, LJ, Pelletier, C, Blitzblau, R, Tassi, R, Paranjape, T, Hui, P, Godwin, AK, Yu, H, Risch, H, Rutherford, T, Schwartz, P, Santin, A, Matloff, E, Zelterman, D, Slack, FJ, and Weidhaas, JB. "A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk." Cancer Res 70.16 (August 15, 2010): 6509-6515.
PMID
20647319
Source
pubmed
Published In
Cancer Research
Volume
70
Issue
16
Publish Date
2010
Start Page
6509
End Page
6515
DOI
10.1158/0008-5472.CAN-10-0689

Surveillance, Epidemiology, and End Results (SEER) database analysis of microcystic adnexal carcinoma (sclerosing sweat duct carcinoma) of the skin.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a very rare cancer of the skin. It has only been described previously in case reports and small retrospective series. OBJECTIVE: To analyze and summarize data from the National Cancer Institute, Surveillance, Epidemiology, and End Results (SEER) database regarding MAC. METHODS: The SEER 1973 to 2004 database was investigated, and patients with MAC were identified. A statistical analysis was performed. RESULTS: Two hundred twenty-three patients were identified. Predominant site of disease was the head and neck skin (74%). There was only 1 case of recorded metastatic disease. Lymph nodes were pathologically involved in 1%. The 10-year overall survival was 86.4% (Standard Error [SE]: 3.3%). US census population-matched relative survival was 97.7% at 10 years (SE: 5.2%). LIMITATIONS: This study is limited by the retrospective nature of the SEER database. CONCLUSIONS: MAC is locally invasive, and rarely metastasizes to lymph nodes. Overall and population-matched relative survival is excellent.

Authors
Yu, JB; Blitzblau, RC; Patel, SC; Decker, RH; Wilson, LD
MLA Citation
Yu, JB, Blitzblau, RC, Patel, SC, Decker, RH, and Wilson, LD. "Surveillance, Epidemiology, and End Results (SEER) database analysis of microcystic adnexal carcinoma (sclerosing sweat duct carcinoma) of the skin." Am J Clin Oncol 33.2 (April 2010): 125-127.
PMID
19675445
Source
pubmed
Published In
American Journal of Clinical Oncology: Cancer Clinical Trials
Volume
33
Issue
2
Publish Date
2010
Start Page
125
End Page
127
DOI
10.1097/COC.0b013e31819791eb

Dystrophin and utrophin isoforms are expressed in glia, but not neurons, of the avian parasympathetic ciliary ganglion.

Muscular dystrophy patients often show cognitive impairment, in addition to muscle degeneration caused by dystrophin gene defects. The cognitive impairments lead to speculation that the dystrophin protein family may play a key role at neuronal synapses. Dystrophin regulates the stability of selected GABA(A) receptor subtypes and alpha3-containing nicotinic acetylcholine receptors (nAChRs) at a subset of central GABAergic and peripheral sympathetic nicotinic neuron synapses. Similarly, utrophin, the autosomal homologue of dystrophin, is not required for clustering but indirectly stabilizes muscle-type nAChRs at the neuromuscular junction. We examined dystrophin and utrophin expression and localization in the avian parasympathetic ciliary ganglion (CG) to determine whether these proteins play a general role at neuronal nicotinic synapses. We have determined that full-length utrophin and dystrophin and the short dystrophin isoform Dp116 are the major isoforms expressed in the CG based on immunoblotting and immunolabeling. Unexpectedly, the cytoskeletal proteins were not detected at nicotinic synapses or in CG neurons. They are expressed in myelinating and non-myelinating Schwann cells. Further, utrophin expression developmentally precedes that of dystrophin. The proteins show partially overlapping distributions, but also differential accumulation along the surface membrane of Schwann cells adjacent to neuronal somata versus axonal processes. Our findings are consistent with reports that dystrophin protein family members function in the maintenance of cell-cell interactions and myelination by anchoring the Schwann cell surface membrane to the basal lamina. In contrast, our results differ from those in skeletal muscle and a subset of sympathetic neurons where utrophin and dystrophin localize at nicotinic synapses.

Authors
Blitzblau, R; Storer, EK; Jacob, MH
MLA Citation
Blitzblau, R, Storer, EK, and Jacob, MH. "Dystrophin and utrophin isoforms are expressed in glia, but not neurons, of the avian parasympathetic ciliary ganglion." Brain Res 1218 (July 7, 2008): 21-34.
PMID
18533135
Source
pubmed
Published In
Brain Research
Volume
1218
Publish Date
2008
Start Page
21
End Page
34
DOI
10.1016/j.brainres.2008.04.071

Analysis of primary CD30+ cutaneous lymphoproliferative disease and survival from the Surveillance, Epidemiology, and End Results database.

PURPOSE: Primary CD30+ cutaneous lymphoproliferative disease (PCLPD) is a spectrum of indolent cutaneous T-cell lymphomas. The primary intention of the analysis of the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database was to report epidemiologic information and overall survival of patients with PCLPD. METHODS: We investigated the SEER database from 1973 to 2004 and performed univariable and multivariable survival analysis. RESULTS: A total of 268 cases of PCLPD were recorded from 1973 to 2004. Median age at diagnosis was 61 years (range, 5 to 98 years). Among cases, 58% were male, and 42% female. Race distribution was 87% white, 7% black, and 4% Asian/Pacific Islander. A total of 157 patients had primary, localized PCLPD. For the total population (N = 268), overall survival at 3 years was 81% (95% CI, 74% to 87%). Population-matched relative survival at 3 years was 87% (SE, 3.6%). Disease-specific survival at 5 years was 92% (95% CI, 86% to 95%). Head and neck skin site predicted for inferior overall survival in patients with primary, localized PCLPD on univariable analysis (hazard ratio [HR] = 4.4; P = .008; 95% CI, 1.5 to 13.2), and was suggestive of decreased overall survival on multivariate analysis (HR = 3.0; P = .06; 95% CI, 0.95 to 9.7). CONCLUSION: Localized PCLPDs are rare diseases with an excellent overall survival and occur more frequently in whites and in men. Head and neck skin primary site may be associated with poorer survival. CONCLUSIONS regarding subsets demonstrating association with survival should be taken with caution, given the small number of deaths analyzed.

Authors
Yu, JB; Blitzblau, RC; Decker, RH; Housman, DM; Wilson, LD
MLA Citation
Yu, JB, Blitzblau, RC, Decker, RH, Housman, DM, and Wilson, LD. "Analysis of primary CD30+ cutaneous lymphoproliferative disease and survival from the Surveillance, Epidemiology, and End Results database." J Clin Oncol 26.9 (March 20, 2008): 1483-1488.
PMID
18349400
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
9
Publish Date
2008
Start Page
1483
End Page
1488
DOI
10.1200/JCO.2007.14.1374

Analysis of gastric MALT lymphomas identified in the SEER database

Authors
Blitzblau, RC; Yu, JB; Wilson, LD; Roberts, KB
MLA Citation
Blitzblau, RC, Yu, JB, Wilson, LD, and Roberts, KB. "Analysis of gastric MALT lymphomas identified in the SEER database." 2007.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
69
Issue
3
Publish Date
2007
Start Page
S537
End Page
S538
DOI
10.1016/j.ijrobp.2007.07.1779

Surveillance, Epidemiology, and End Results (SEER) database analysis of Microcystic Adnexal Carcinoma (sclerosing sweat duct carcinoma) of the skin

Authors
Patel, SC; Yu, JB; Decker, RH; Blitzblau, RC; Housman, DM; Wilson, LD
MLA Citation
Patel, SC, Yu, JB, Decker, RH, Blitzblau, RC, Housman, DM, and Wilson, LD. "Surveillance, Epidemiology, and End Results (SEER) database analysis of Microcystic Adnexal Carcinoma (sclerosing sweat duct carcinoma) of the skin." 2007.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
69
Issue
3
Publish Date
2007
Start Page
S755
End Page
S756
DOI
10.1016/j.ijrobp.2007.07.2319

Characterization of non-gastric MALT lymphomas identified in the SEER database

Authors
Roberts, KB; Blitzblau, RC; Wilson, LD
MLA Citation
Roberts, KB, Blitzblau, RC, and Wilson, LD. "Characterization of non-gastric MALT lymphomas identified in the SEER database." 2007.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
69
Issue
3
Publish Date
2007
Start Page
S532
End Page
S533
DOI
10.1016/j.ijrobp.2007.07.1771

Surveillance, Epidemiology, and End Results (SEER) database analysis of stage IE Primary CD30+ Cutaneous T-Cell Lymphoma (PCCTCL)

Authors
Yu, JB; Blitzblau, RC; Decker, RH; Housman, DM; Wilson, LD
MLA Citation
Yu, JB, Blitzblau, RC, Decker, RH, Housman, DM, and Wilson, LD. "Surveillance, Epidemiology, and End Results (SEER) database analysis of stage IE Primary CD30+ Cutaneous T-Cell Lymphoma (PCCTCL)." 2007.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
69
Issue
3
Publish Date
2007
Start Page
S536
End Page
S537
DOI
10.1016/j.ijrobp.2007.07.1777

Regulatory mechanisms that govern nicotinic synapse formation in neurons.

Individual cholinoceptive neurons express high levels of different neuronal nicotinic acetylcholine receptor (nAChR) subtypes, and target them to the appropriate synaptic regions for proper function. This review focuses on the intercellular and intracellular processes that regulate nAChR expression in vertebrate peripheral nervous system (PNS) and central nervous system (CNS) neurons. Specifically, we discuss the cellular and molecular mechanisms that govern the induction and maintenance of nAChR expression-innervation, target tissue interactions, soluble factors, and activity. We define the regulatory principles of interneuronal nicotinic synapse differentiation that have emerged from these studies. We also discuss the molecular players that target nAChRs to the surface membrane and the interneuronal synapse.

Authors
Rosenberg, MM; Blitzblau, RC; Olsen, DP; Jacob, MH
MLA Citation
Rosenberg, MM, Blitzblau, RC, Olsen, DP, and Jacob, MH. "Regulatory mechanisms that govern nicotinic synapse formation in neurons." J Neurobiol 53.4 (December 2002): 542-555. (Review)
PMID
12436419
Source
pubmed
Published In
Journal of Neurobiology
Volume
53
Issue
4
Publish Date
2002
Start Page
542
End Page
555
DOI
10.1002/neu.10112

Expression of a variant form of the glutamate transporter GLT1 in neuronal cultures and in neurons and astrocytes in the rat brain.

To identify glutamate transporters expressed in forebrain neurons, we prepared a cDNA library from rat forebrain neuronal cultures, previously shown to transport glutamate with high affinity and capacity. Using this library, we cloned two forms, varying in the C terminus, of the glutamate transporter GLT1. This transporter was previously found to be localized exclusively in astrocytes in the normal mature brain. Specific antibodies against the C-terminal peptides were used to show that forebrain neurons in culture express both GLT1a and GLT1b proteins. The pharmacological properties of glutamate transport mediated by GLT1a and GLT1b expressed in COS-7 cells and in neuronal cultures were indistinguishable. Both GLT1a and GLT1b were upregulated in astrocyte cultures by exposure to dibutyryl cAMP. We next investigated the expression of GLT1b in vivo. Northern blot analysis of forebrain RNA revealed two transcripts of approximately 3 and 11 kb that became more plentiful with developmental age. Immunoblot analysis showed high levels of expression in the cortex, hippocampus, striatum, thalamus, and midbrain. Pre-embedding electron microscopic immunocytochemistry with silver-enhanced immunogold detection was used to localize GLT1b in vivo. In the rat somatosensory cortex, GLT1b was clearly expressed in neurons in presynaptic terminals and dendritic shafts, as well as in astrocytes. The presence of GLT1b in neurons may offer a partial explanation for the observed uptake of glutamate by presynaptic terminals, for the preservation of input specificity at excitatory synapses, and may play a role in the pathophysiology of excitotoxicity.

Authors
Chen, W; Aoki, C; Mahadomrongkul, V; Gruber, CE; Wang, GJ; Blitzblau, R; Irwin, N; Rosenberg, PA
MLA Citation
Chen, W, Aoki, C, Mahadomrongkul, V, Gruber, CE, Wang, GJ, Blitzblau, R, Irwin, N, and Rosenberg, PA. "Expression of a variant form of the glutamate transporter GLT1 in neuronal cultures and in neurons and astrocytes in the rat brain." J Neurosci 22.6 (March 15, 2002): 2142-2152.
PMID
11896154
Source
pubmed
Published In
The Journal of neuroscience : the official journal of the Society for Neuroscience
Volume
22
Issue
6
Publish Date
2002
Start Page
2142
End Page
2152

NMDA and glutamate evoke excitotoxicity at distinct cellular locations in rat cortical neurons in vitro.

The development of cortical neurons in vivo and in vitro is accompanied by alterations in NMDA receptor subunit expression and concomitant modifications in the pharmacological profile of NMDA-activated ionic currents. For example, we observed that with decreasing NR2B/NR2A subunit expression ratio, the block of NMDA receptor-mediated whole-cell responses by the NR2B-selective antagonist haloperidol was also decreased. In mature cultures (>22 d in vitro), however, NMDA responses obtained from excised nucleated macropatches, which comprised a large portion of the soma, remained strongly antagonized by haloperidol. These results suggest that in more mature neurons NR1/NR2B receptors appear to be preferentially expressed in the cell body. As predicted from the whole-cell recording pharmacological profile, NMDA-induced toxicity was largely unaffected by haloperidol in mature cultures. However, haloperidol effectively blocked glutamate toxicity in the same cultures, suggesting that the neurotoxic actions of this amino acid were mostly due to the activation of somatic NMDA receptors. In experiments in which the potency of glutamate toxicity was increased by the transport inhibitor l-trans-pyrrolidine-2,4-dicarboxylic acid, the neuroprotective effects of haloperidol were significantly diminished. This was likely because of the fact that glutamate, now toxic at much lower concentrations, was able to reach and activate dendritic receptors under these conditions. These results strongly argue that exogenous glutamate and NMDA normally induce excitotoxicity at distinct cellular locations in mature mixed neuronal cultures and that NR1/NR2B receptors remain an important component in the expression of glutamate, but not NMDA-induced excitotoxicity.

Authors
Sinor, JD; Du, S; Venneti, S; Blitzblau, RC; Leszkiewicz, DN; Rosenberg, PA; Aizenman, E
MLA Citation
Sinor, JD, Du, S, Venneti, S, Blitzblau, RC, Leszkiewicz, DN, Rosenberg, PA, and Aizenman, E. "NMDA and glutamate evoke excitotoxicity at distinct cellular locations in rat cortical neurons in vitro." J Neurosci 20.23 (December 1, 2000): 8831-8837.
PMID
11102491
Source
pubmed
Published In
The Journal of neuroscience : the official journal of the Society for Neuroscience
Volume
20
Issue
23
Publish Date
2000
Start Page
8831
End Page
8837

Receptor targeting and heterogeneity at interneuronal nicotinic cholinergic synapses in vivo.

Within a single neuron the correct targeting of the diverse neurotransmitter receptor types to discrete synaptic regions is crucial for proper function. However, the molecular mechanisms that underlie neuronal receptor clustering and targeting are still largely undefined. Here we report advances in defining the mechanisms that mediate nicotinic acetylcholine receptor (nAChR) targeting to interneuronal synapses. Recent in vivo studies have demonstrated that one subunit plays a critical role in the differentiation of nicotinic cholinergic synapses on vertebrate autonomic neurons. The major cytoplasmic loop of the alpha3 subunit targets specific nAChR subtypes to the synapse. In contrast, nAChR complexes that lack the alpha3 targeting domain are excluded and are perisynaptic. Additional studies have demonstrated a greater complexity to alpha3-nAChR targeting due to a unique postsynaptic receptor microheterogeneity - under one presynaptic terminal, alpha3-nAChR clusters are separate, but proximal to, glycine receptor (GlyR) clusters in discrete postsynaptic membrane microregions. The surprising coexistence under one nerve ending of separate clusters of receptors that respond to different fast-acting transmitters with opposing functions may represent a novel mechanism for modulating synaptic activity. Overall, the receptor targeting and clustering studies reviewed in this issue suggest that a common mechanism underlies the formation of the diverse types of interneuronal synapses but differs from that responsible for neuromuscular junction assembly in vertebrates.

Authors
Temburni, MK; Blitzblau, RC; Jacob, MH
MLA Citation
Temburni, MK, Blitzblau, RC, and Jacob, MH. "Receptor targeting and heterogeneity at interneuronal nicotinic cholinergic synapses in vivo." J Physiol 525 Pt 1 (May 15, 2000): 21-29. (Review)
PMID
10811721
Source
pubmed
Published In
The Journal of Physiology
Volume
525 Pt 1
Publish Date
2000
Start Page
21
End Page
29

The glutamate transport inhibitor L-trans-pyrrolidine-2,4-dicarboxylate indirectly evokes NMDA receptor mediated neurotoxicity in rat cortical cultures.

Because of the well-documented importance of glutamate uptake in protecting neurons against glutamate toxicity, we were interested in testing the effects of L-trans-pyrrolidine-2,4-dicarboxylate (PDC) on rat cortical cultures. This compound is a substrate for glutamate transporters and is a potent glutamate transport inhibitor that does not interact significantly with glutamate receptors. Using a 30 min exposure, and assessing neuronal survival after 20-24 h, PDC was neurotoxic in conventional astrocyte-rich cortical cultures, with an EC50 in these cultures of 320 +/- 157 microM. In astrocyte-poor cultures, an EC50 for PDC of 50 +/- 5 microM was determined. The neurotoxicity of PDC in both astrocyte-rich and astrocyte-poor cultures was blocked by the NMDA antagonist MK-801, but not by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). We tested the possibility that the neurotoxicity of PDC might be due to release of excitatory amino acids using several approaches. After pre-loading cells with the non-metabolizable analogue of glutamate, [3H]-D-aspartate, first we demonstrated that PDC caused significant efflux of [3H]-D-aspartate. This effect of PDC was dependent upon extracellular sodium. In contrast with glutamate neurotoxicity, PDC neurotoxicity was inhibited by removal of extracellular sodium. In the presence of 1 mM PDC, sodium caused neurotoxicity with an EC50 of 18 +/- 7.6 mM. Tetrodotoxin had no effect on either PDC neurotoxicity or on PDC-evoked [3H]-D-aspartate release. PDC-evoked release of [3H]-D-aspartate was demonstrable in astrocyte cultures with no neurons present. PDC also evoked release of endogenous glutamate. Finally, the neurotoxicity of PDC was blocked by coincubation with glutamate-pyruvate transaminase plus pyruvate to degrade extracellular glutamate. These results demonstrate the neurotoxicity of PDC, and suggest that the mechanism of this toxicity is the glutamate transporter-dependent accumulation of glutamate in the extracellular space.

Authors
Blitzblau, R; Gupta, S; Djali, S; Robinson, MB; Rosenberg, PA
MLA Citation
Blitzblau, R, Gupta, S, Djali, S, Robinson, MB, and Rosenberg, PA. "The glutamate transport inhibitor L-trans-pyrrolidine-2,4-dicarboxylate indirectly evokes NMDA receptor mediated neurotoxicity in rat cortical cultures." Eur J Neurosci 8.9 (September 1996): 1840-1852.
PMID
8921275
Source
pubmed
Published In
European Journal of Neuroscience
Volume
8
Issue
9
Publish Date
1996
Start Page
1840
End Page
1852

Comparison of the potency of competitive NMDA antagonists against the neurotoxicity of glutamate and NMDA.

The object of this investigation was to determine whether glutamate uptake affects the apparent potency of the competitive antagonists DL-2-amino-5-phosphonovalerate and CGS-19755 in blocking NMDA receptor-mediated neurotoxicity. In astrocyte-rich rat cortical cultures we observed that DL-2-amino-5-phosphonovalerate and CGS-19755 were 24 and 16 times more potent against NMDA than against glutamate-induced toxicity. In contrast, DL-2-amino-5-phosphonovalerate was equipotent against the two agonists in astrocyte-poor cultures, in which dendrites are directly exposed to the extracellular medium. With the noncompetitive NMDA antagonist MK-801, similar potencies were observed against glutamate (212 +/- 16 nM) and against NMDA (155 +/- 9 nM) neurotoxicity. These results may be explained if we assume that the neuronal cell body is less susceptible than the dendrites to NMDA receptor-mediated toxicity, and that the action of glutamate in astrocyte-rich cultures is confined to the cell body. In this case, one would expect that higher concentrations of glutamate would be needed to produce toxicity in astrocyte-rich cultures, and that higher concentrations of competitive antagonists would be needed to overcome this toxicity. Our observations help explain the pharmacology of the competitive NMDA antagonists against NMDA receptor-mediated neurotoxicity but also suggest the possibility that, because the cell body and dendrites may be distinct sites for neurotoxicity, they might also involve different mechanisms of toxicity.

Authors
Speliotes, EK; Hartnett, KA; Blitzblau, RC; Aizenman, E; Rosenberg, PA
MLA Citation
Speliotes, EK, Hartnett, KA, Blitzblau, RC, Aizenman, E, and Rosenberg, PA. "Comparison of the potency of competitive NMDA antagonists against the neurotoxicity of glutamate and NMDA." J Neurochem 63.3 (September 1994): 879-885.
PMID
7914224
Source
pubmed
Published In
Journal of Neurochemistry
Volume
63
Issue
3
Publish Date
1994
Start Page
879
End Page
885
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