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Salama, April Kelly Scott

Positions:

Assistant Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2004

M.D. — University of North Carolina at Chapel Hill

Grants:

DV3-MEL-01

Administered By
Duke Cancer Institute
AwardedBy
Dynavax Technologies Corporation
Role
Principal Investigator
Start Date
March 14, 2017
End Date
March 12, 2022

Optimize BMS CA209-357

Administered By
Duke Cancer Institute
AwardedBy
Bristol-Myers Squibb Company
Role
Principal Investigator
Start Date
March 01, 2016
End Date
February 28, 2021

IMCgp100-201

Administered By
Duke Cancer Institute
AwardedBy
Immunocore Limited
Role
Principal Investigator
Start Date
March 01, 2016
End Date
February 28, 2021

Celldex CDX011-05

Administered By
Duke Cancer Institute
AwardedBy
Celldex Therapeutics, Inc.
Role
Principal Investigator
Start Date
October 01, 2015
End Date
September 30, 2020

BMS CA209-238-0025

Administered By
Duke Cancer Institute
AwardedBy
The Bristol-Myers/Sanofi Pharmaceuticals, Inc. Partnership
Role
Principal Investigator
Start Date
April 01, 2015
End Date
March 31, 2020

CA209204 A Multi-Center Phase 2 Open-Label Study to Evaluate Safety and Efficacy in Subjects with Melanoma Metastatic to the Brain treated with Nivolumab in Combination with Ipilimumab followed by

Administered By
Duke Cancer Institute
AwardedBy
Bristol-Myers Squibb Company
Role
Principal Investigator
Start Date
March 18, 2015
End Date
March 17, 2020

An open label, multicenter, dose-escalation, phase 1B/2 study of the safety, efficacy, pharmacodynamics, and pharmacokin

Administered By
Duke Cancer Institute
AwardedBy
Reata Pharmaceuticals, Inc.
Role
Principal Investigator
Start Date
October 01, 2014
End Date
September 30, 2019

A phase Ii trial of Neoadjuvant Ipilimumab follwed by Melphalan (L-PAM) via isolated Limb infusion (ILI) for patients wi

Administered By
Medicine, Medical Oncology
AwardedBy
Bristol-Myers Squibb Company
Role
Principal Investigator
Start Date
February 01, 2014
End Date
June 30, 2017

Expanded access of MK-3475 in metastatic melanoma patients with limited to no treatment options

Administered By
Duke Cancer Institute
AwardedBy
Merck Sharp & Dohme
Role
Principal Investigator
Start Date
June 01, 2014
End Date
October 08, 2015
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Publications:

The efficacy of anti-PD-1 agents in acral and mucosal melanoma.

Therapeutic antibodies against programmed cell death receptor 1 (PD-1) are considered front-line therapy in metastatic melanoma. The efficacy of PD-1 blockade for patients with biologically distinct melanomas arising from acral and mucosal surfaces has not been well described.A multi-institutional, retrospective cohort analysis identified adults with advanced acral and mucosal melanoma who received treatment with nivolumab or pembrolizumab as standard clinical practice through expanded access programs or published prospective trials. Objective responses were determined using investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival and overall survival were assessed using the Kaplan-Meier method.Sixty individuals were identified, including 25 (42%) with acral melanoma and 35 (58%) with mucosal melanoma. Fifty-one patients (85%) had received previous therapy, including 77% who had previously received ipilimumab. Forty patients (67%) received pembrolizumab at a dose of 2 mg/kg or 10 mg/kg, and 20 (33%) received nivolumab at a doses ranging from 0.3 to 10 mg/kg every 2 to 3 weeks. The objective response rate was 32% (95% confidence interval, 15%-54%) in patients with acral melanoma and 23% (95% confidence interval, 10%-40%) in those with mucosal melanoma. After a median follow-up of 20 months in the acral melanoma group and 10.6 months in the mucosal melanoma group, the median progression-free survival was 4.1 months and 3.9 months, respectively. Only 2 patients (3%) discontinued treatment because of toxicity.Response rates to PD-1 blockade in patients with acral and mucosal melanomas were comparable to the published rates in patients with cutaneous melanoma and support the routine use of PD-1 blockade in clinical practice. Further investigation is needed to identify the mechanisms of response and resistance to therapy in these subtypes. Cancer 2016;122:3354-3362. © 2016 American Cancer Society.

Authors
Shoushtari, AN; Munhoz, RR; Kuk, D; Ott, PA; Johnson, DB; Tsai, KK; Rapisuwon, S; Eroglu, Z; Sullivan, RJ; Luke, JJ; Gangadhar, TC; Salama, AKS; Clark, V; Burias, C; Puzanov, I; Atkins, MB; Algazi, AP; Ribas, A; Wolchok, JD; Postow, MA
MLA Citation
Shoushtari, AN, Munhoz, RR, Kuk, D, Ott, PA, Johnson, DB, Tsai, KK, Rapisuwon, S, Eroglu, Z, Sullivan, RJ, Luke, JJ, Gangadhar, TC, Salama, AKS, Clark, V, Burias, C, Puzanov, I, Atkins, MB, Algazi, AP, Ribas, A, Wolchok, JD, and Postow, MA. "The efficacy of anti-PD-1 agents in acral and mucosal melanoma." Cancer 122.21 (November 2016): 3354-3362.
PMID
27533633
Source
epmc
Published In
Cancer
Volume
122
Issue
21
Publish Date
2016
Start Page
3354
End Page
3362
DOI
10.1002/cncr.30259

Health-related quality of life in the randomised KEYNOTE-002 study of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory melanoma

Authors
Schadendorf, D; Dummer, R; Hauschild, A; Robert, C; Hamid, O; Daud, A; van den Eertwegh, A; Cranmer, L; O'Day, S; Puzanov, I; Schachter, J; Blank, C; Salama, A; Loquai, C; Mehnert, JM; Hille, D; Ebbinghaus, S; Kang, SP; Zhou, W; Ribas, A
MLA Citation
Schadendorf, D, Dummer, R, Hauschild, A, Robert, C, Hamid, O, Daud, A, van den Eertwegh, A, Cranmer, L, O'Day, S, Puzanov, I, Schachter, J, Blank, C, Salama, A, Loquai, C, Mehnert, JM, Hille, D, Ebbinghaus, S, Kang, SP, Zhou, W, and Ribas, A. "Health-related quality of life in the randomised KEYNOTE-002 study of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory melanoma." European Journal of Cancer 67 (November 2016): 46-54.
Source
crossref
Published In
European Journal of Cancer
Volume
67
Publish Date
2016
Start Page
46
End Page
54
DOI
10.1016/j.ejca.2016.07.018

Next Steps in Immuno-Oncology: Enhancing Antitumor Effects Through Appropriate Patient Selection and Rationally Designed Combination Strategies.

Cancers escape immune surveillance via distinct mechanisms that involve central (negative selection within the thymus) or peripheral (lack of costimulation, receipt of death/anergic signals by tumor, immunoregulatory cell populations) immune tolerance. During the 1990s, moderate clinical benefit was seen using several cytokine therapies for a limited number of cancers. Over the past 20 years, extensive research has been performed to understand the role of various components of peripheral immune tolerance, with the co-inhibitory immune checkpoint molecules cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand (PD-L1) being the most well characterized at preclinical and clinical levels.We used PubMed and Google Scholar searches to identify key articles published reporting preclinical and clinical studies investigating CTLA-4 and PD-1/PD-L1, frequently cited review articles, and clinical studies of CTLA-4 and PD-1/PD-L1 pathway inhibitors, including combination therapy strategies. We also searched recent oncology congress presentations and clinicaltrials.gov to cover the most up-to-date clinical trial data and ongoing clinical trials of immune checkpoint inhibitor (ICI) combinations.Inhibiting CTLA-4 and PD-1 using monoclonal antibody therapies administered as single agents has been associated with clinical benefit in distinct patient subgroups across several malignancies. Concurrent blockade of CTLA-4 and components of the PD-1/PD-L1 system using various schedules has shown synergy and even higher incidence of durable antitumor responses at the expense of increased rates of immune-mediated adverse events, which can be life-threatening, but are rarely fatal and are reversible in most cases using established treatment guidelines.Dual immune checkpoint blockade has demonstrated promising clinical benefit in numerous solid tumor types. This example of concurrent modulation of multiple components of the immune system is currently being investigated in other cancers using various immunomodulatory strategies.

Authors
Salama, AKS; Moschos, SJ
MLA Citation
Salama, AKS, and Moschos, SJ. "Next Steps in Immuno-Oncology: Enhancing Antitumor Effects Through Appropriate Patient Selection and Rationally Designed Combination Strategies." Annals of oncology : official journal of the European Society for Medical Oncology (October 13, 2016).
PMID
27742649
Source
epmc
Published In
Annals of Oncology
Publish Date
2016

Autoimmune meningoencephalitis in a melanoma patient treated with ipilimumab.

Authors
Choe, JH; Andonian, BJ; Kim, GJ; Salama, AK
MLA Citation
Choe, JH, Andonian, BJ, Kim, GJ, and Salama, AK. "Autoimmune meningoencephalitis in a melanoma patient treated with ipilimumab." Immunotherapy 8.10 (October 2016): 1163-1167.
PMID
27605066
Source
epmc
Published In
Immunotherapy
Volume
8
Issue
10
Publish Date
2016
Start Page
1163
End Page
1167
DOI
10.2217/imt-2016-0058

Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab.

Ipilimumab and radiation therapy (RT) are standard treatments for advanced melanoma; preclinical models suggest the potential for synergy. However, limited clinical information exists regarding safety and optimal timing of the combination.We reviewed the records of consecutive patients with unresectable stage 3 or 4 melanoma treated with ipilimumab. Patients were categorized as having received RT or not. Differences were estimated between these 2 cohorts.We identified 88 patients treated with ipilimumab. At baseline, the ipilimumab-plus-RT group (n=44) had more unfavorable characteristics. Despite this, overall survival, progression-free survival, and both immune-related and non-immune-related toxicity were not statistically different (P=.67). Patients who received ipilimumab before RT had an increased duration of irradiated tumor response compared with patients receiving ipilimumab after RT (74.7% vs 44.8% at 12 months; P=.01, log-rank test). In addition, patients receiving ablative RT had non-statistically significantly improved median overall survival (19.6 vs 10.2 months), as well as 6-month (95.1% vs 72.7%) and 12-month (79.7% vs 48.5%) survival rates, compared with those treated with conventionally fractionated RT.We found that both ablative and conventionally fractionated RT can be safely administered with ipilimumab without a clinically apparent increase in toxicity. Patients who received ipilimumab before RT had an increased duration of irradiated tumor response.

Authors
Qin, R; Olson, A; Singh, B; Thomas, S; Wolf, S; Bhavsar, NA; Hanks, BA; Salama, JK; Salama, AKS
MLA Citation
Qin, R, Olson, A, Singh, B, Thomas, S, Wolf, S, Bhavsar, NA, Hanks, BA, Salama, JK, and Salama, AKS. "Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab." International journal of radiation oncology, biology, physics 96.1 (September 2016): 72-77.
PMID
27375168
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
1
Publish Date
2016
Start Page
72
End Page
77
DOI
10.1016/j.ijrobp.2016.04.017

NCCN Guidelines Insights: Melanoma, Version 3.2016.

The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.

Authors
Coit, DG; Thompson, JA; Algazi, A; Andtbacka, R; Bichakjian, CK; Carson, WE; Daniels, GA; DiMaio, D; Fields, RC; Fleming, MD; Gastman, B; Gonzalez, R; Guild, V; Johnson, D; Joseph, RW; Lange, JR; Martini, MC; Materin, MA; Olszanski, AJ; Ott, P; Gupta, AP; Ross, MI; Salama, AK; Skitzki, J; Swetter, SM; Tanabe, KK; Torres-Roca, JF; Trisal, V; Urist, MM; McMillian, N; Engh, A
MLA Citation
Coit, DG, Thompson, JA, Algazi, A, Andtbacka, R, Bichakjian, CK, Carson, WE, Daniels, GA, DiMaio, D, Fields, RC, Fleming, MD, Gastman, B, Gonzalez, R, Guild, V, Johnson, D, Joseph, RW, Lange, JR, Martini, MC, Materin, MA, Olszanski, AJ, Ott, P, Gupta, AP, Ross, MI, Salama, AK, Skitzki, J, Swetter, SM, Tanabe, KK, Torres-Roca, JF, Trisal, V, Urist, MM, McMillian, N, and Engh, A. "NCCN Guidelines Insights: Melanoma, Version 3.2016." Journal of the National Comprehensive Cancer Network : JNCCN 14.8 (August 2016): 945-958.
PMID
27496110
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
14
Issue
8
Publish Date
2016
Start Page
945
End Page
958

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-.
PMID
27622023
Source
epmc
Published In
OncoImmunology
Volume
5
Issue
7
Publish Date
2016
Start Page
e1172153
DOI
10.1080/2162402x.2016.1172153

Computed Tomography-Based Limb Volume Measurements for Isolated Limb Infusion in Melanoma.

Despite advances in cross-sectional imaging, chemotherapeutic dosing for isolated limb infusion (ILI) in melanoma is currently calculated through cumbersome and potentially imprecise manual measurements. The primary objective of this study was to examine the feasibility of using computed tomography (CT) to calculate limb volume, its concordance with manual measurement, and its ability to predict clinical response and toxicity in patients undergoing ILI.A retrospective analysis of all patients undergoing lower extremity ILI at Duke University Medical Center between 2003 and 2014 was performed. Data pertaining to manually measured limb volume, chemotherapeutic dosing, and patient outcome was obtained. CT-based measurements of limb volume were performed in all patients for whom imaging was available and subsequently compared with manually measured values.CT data were sufficient for measurement in 73 patients. The mean measurement time was 4.61 ± 2.13 min. Although average CT-based measurements were 1.20 L higher in the case of lower limbs, they correlated well with those obtained manually (r (2) = 0.90). Unlike manual measurement, patients with complete responses to chemotherapy had smaller limb volumes than those with disease progression as measured by CT (9.3 vs. 10.7 L; p = .038). Patients suffering grade 3 and 4 toxicities also had statistically lower limb volumes as measured by CT than those who did not (p < .05).CT-based limb volume measurement is feasible for chemotherapy dosing in patients undergoing ILI for melanoma and has predictive value with respect to clinical response and toxicity.

Authors
Brys, AK; Bhatti, L; Bashir, MR; Jaffe, TA; Beasley, GM; Nath, NS; Salama, AKS; Tyler, DS; Mosca, PJ
MLA Citation
Brys, AK, Bhatti, L, Bashir, MR, Jaffe, TA, Beasley, GM, Nath, NS, Salama, AKS, Tyler, DS, and Mosca, PJ. "Computed Tomography-Based Limb Volume Measurements for Isolated Limb Infusion in Melanoma." Annals of surgical oncology 23.4 (April 2016): 1090-1095.
PMID
26572755
Source
epmc
Published In
Annals of Surgical Oncology
Volume
23
Issue
4
Publish Date
2016
Start Page
1090
End Page
1095
DOI
10.1245/s10434-015-4972-7

Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Melanoma focuses on adjuvant therapy and treatment of in-transit disease, because substantial changes were made to the recommendations for the 2016 update. Depending on the stage of the disease, options for adjuvant therapy now include biochemotherapy and high-dose ipilimumab. Treatment options for in-transit disease now include intralesional injection with talimogene laherparepvec (T-VEC), a new immunotherapy. These additions prompted re-assessment of the data supporting older recommended treatment options for adjuvant therapy and in-transit disease, resulting in extensive revisions to the supporting discussion sections.

Authors
Coit, DG; Thompson, JA; Algazi, A; Andtbacka, R; Bichakjian, CK; Carson, WE; Daniels, GA; DiMaio, D; Ernstoff, M; Fields, RC; Fleming, MD; Gonzalez, R; Guild, V; Halpern, AC; Hodi, FS; Joseph, RW; Lange, JR; Martini, MC; Materin, MA; Olszanski, AJ; Ross, MI; Salama, AK; Skitzki, J; Sosman, J; Swetter, SM; Tanabe, KK; Torres-Roca, JF; Trisal, V; Urist, MM; McMillian, N; Engh, A
MLA Citation
Coit, DG, Thompson, JA, Algazi, A, Andtbacka, R, Bichakjian, CK, Carson, WE, Daniels, GA, DiMaio, D, Ernstoff, M, Fields, RC, Fleming, MD, Gonzalez, R, Guild, V, Halpern, AC, Hodi, FS, Joseph, RW, Lange, JR, Martini, MC, Materin, MA, Olszanski, AJ, Ross, MI, Salama, AK, Skitzki, J, Sosman, J, Swetter, SM, Tanabe, KK, Torres-Roca, JF, Trisal, V, Urist, MM, McMillian, N, and Engh, A. "Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology." Journal of the National Comprehensive Cancer Network : JNCCN 14.4 (April 2016): 450-473.
PMID
27059193
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
14
Issue
4
Publish Date
2016
Start Page
450
End Page
473

Isolated recto-sigmoid colitis: a new imaging pattern of ipilimumab-associated colitis.

The purpose of this study is to describe typical CT findings and distinct imaging patterns of ipilimumab-associated colitis in immunotherapeutic treatment of melanoma.This HIPAA-compliant retrospective study included 86 patients with melanoma imaged with CT or PET/CT of the abdomen and pelvis during or shortly after administration of ipilimumab. Twelve of 86 patients (14%) developed symptoms of colitis and underwent CT imaging of the abdomen and pelvis while symptomatic. Two radiologists reviewed CT images to evaluate for the presence of CT findings of colitis including mesenteric vessel engorgement, pericolonic inflammatory change, hyperenhancement of colonic mucosa, colonic wall thickening, fluid-filled colonic distension, pneumoperitoneum, pneumatosis, and diverticulosis in the inflamed segment of colon. One nuclear medicine radiologist reviewed PET images for abnormally increased FDG uptake in the colon. The diagnosis of ipilimumab-associated colitis was made based on clinical presentation, imaging findings, and laboratory data.Common CT findings of ipilimumab-associated colitis included colonic mucosal hyperenhancement (10/12 [83%]), mesenteric vessel engorgement (9/12 [75.0%]), colonic wall thickening (9/12 [75%]), and pericolonic fat stranding (2/12 [16%]). No patient developed pneumatosis or pneumoperitoneum. Diffuse colitis was present in 4/12 (33%) patients. Segmental colitis with associated diverticulosis (was present in 2/12 (17%) patients). A third pattern, isolated recto-sigmoid colitis without diverticulosis, was observed in 6/12 (50%) patients. All patients with colitis demonstrated recto-sigmoid involvement.A third radiologic pattern of ipilimumab-associated colitis was observed in this study: isolated recto-sigmoid colitis without diverticulosis. All patterns of ipilimumab-associated colitis include recto-sigmoid involvement.

Authors
Barina, AR; Bashir, MR; Howard, BA; Hanks, BA; Salama, AK; Jaffe, TA
MLA Citation
Barina, AR, Bashir, MR, Howard, BA, Hanks, BA, Salama, AK, and Jaffe, TA. "Isolated recto-sigmoid colitis: a new imaging pattern of ipilimumab-associated colitis." Abdominal radiology (New York) 41.2 (February 2016): 207-214.
PMID
26867901
Source
epmc
Published In
Abdominal radiology (New York)
Volume
41
Issue
2
Publish Date
2016
Start Page
207
End Page
214
DOI
10.1007/s00261-015-0560-3

Updates in Therapy for Advanced Melanoma.

Cutaneous melanoma is one of the most aggressive forms of skin cancer, and is correlated with a large proportion of skin cancer-related deaths. Therapy for cutaneous melanoma has advanced greatly through careful identification of therapeutic targets and the development of novel immunotherapeutic approaches. The identification of BRAF as well as other driver mutations, have allowed for a specialized approach to treatment. In addition, immune checkpoint inhibition has dramatically changed the treatment landscape over the past 5-10 years. The successful targeting of CTLA-4, as well as PD-1/PD-L1, has been translated into meaningful clinical benefit for patients, with multiple other potential agents in development. Systemic therapy for cutaneous melanoma is becoming more nuanced and often takes a multifaceted strategy. This review aims to discuss the benefits and limitations of current therapies in systemic melanoma treatment as well as areas of future development.

Authors
Singh, BP; Salama, AKS
MLA Citation
Singh, BP, and Salama, AKS. "Updates in Therapy for Advanced Melanoma." Cancers 8.1 (January 15, 2016). (Review)
PMID
26784231
Source
epmc
Published In
Cancers
Volume
8
Issue
1
Publish Date
2016
DOI
10.3390/cancers8010017

Ipilimumab-Associated lymphocytic colitis: A case report

Ipilimumab is a cytotoxic T-lymphocyte-Associated antigen-4 (CTLA-4) inhibitor approved for treatment of metastatic melanoma. Gastrointestinal side effects are common and include diarrhea, colitis, and hepatitis. Histopathology typically shows active neutrophilic colitis, and microscopic colitis is rare with only one biopsy-proven case reported in the literature. We now report a second case of microscopic colitis associated with treatment with ipilimumab. While treatment of ipilimumab-Associated colitis is typically discontinuation of the drug and systemic steroids followed by infliximab if no response to steroids, in our case the patient's symptoms responded to oral budesonide alone, and therapy with ipilimumab was successfully resumed. The etiology of ipilimumab-Associated colitis is unknown but may be related to loss of CTLA-4-expressing T-regulatory cells.

Authors
Romain, PES; Salama, AKS; Lynn Ferguson, N; Burbridge, RA
MLA Citation
Romain, PES, Salama, AKS, Lynn Ferguson, N, and Burbridge, RA. "Ipilimumab-Associated lymphocytic colitis: A case report." Translational Gastroenterology and Hepatology 5.1 (January 1, 2016): 44-46.
Source
scopus
Published In
Translational gastrointestinal cancer
Volume
5
Issue
1
Publish Date
2016
Start Page
44
End Page
46
DOI
10.3978/j.issn.2224-4778.2015.10.11

Phase II study of vemurafenib followed by ipilimumab in patients with previously untreated BRAF-mutated metastatic melanoma.

Ipilimumab (IPI), an anti-CTLA-4 antibody, and vemurafenib (VEM), a BRAF inhibitor, have distinct mechanisms of action and shared toxicities (e.g., skin, gastrointestinal [GI] and hepatobiliary disorders) that may preclude concomitant administration. Concurrent administration of IPI and VEM previously showed significant dose-limiting hepatotoxicity in advanced melanoma. This single-arm, open-label, phase II study evaluated a sequencing strategy with these two agents in previously untreated patients with BRAF-mutated advanced melanoma.This study was divided into two parts. During Part 1 (VEM1-IPI), patients received VEM 960 mg twice daily for 6 weeks followed by IPI 10 mg/kg every 3 weeks for 4 doses (induction), then every 12 weeks (maintenance) beginning at week 24 until disease progression or unacceptable toxicity. During Part 2 (VEM2), patients who progressed after IPI received VEM at their previously tolerated dose. The primary objective was to estimate the incidence of grade 3/4 drug-related skin adverse events (AEs) during VEM1-IPI.All patients who were initially treated with VEM (n = 46) received IPI induction therapy; 8 received IPI maintenance and 19 were treated during VEM2. During VEM1-IPI, the incidence of grade 3/4 drug-related AEs associated with the skin, GI tract, and hepatobiliary system was 32.6 %, 21.7 %, and 4.3 %, respectively. There were no drug-related deaths. At a median follow-up of 15.3 months, median overall survival was 18.5 months. Median progression-free survival was 4.5 months.VEM (960 mg twice daily for 6 weeks) followed by IPI 10 mg/kg has a manageable safety profile. The benefits/risks of BRAF inhibitors followed by immunotherapy should be evaluated further in light of continuing developments in treatment options for metastatic melanoma.ClinicalTrials.gov identifier: NCT01673854 (CA184-240) Registered 24 August 2012.

Authors
Amin, A; Lawson, DH; Salama, AKS; Koon, HB; Guthrie, T; Thomas, SS; O'Day, SJ; Shaheen, MF; Zhang, B; Francis, S; Hodi, FS
MLA Citation
Amin, A, Lawson, DH, Salama, AKS, Koon, HB, Guthrie, T, Thomas, SS, O'Day, SJ, Shaheen, MF, Zhang, B, Francis, S, and Hodi, FS. "Phase II study of vemurafenib followed by ipilimumab in patients with previously untreated BRAF-mutated metastatic melanoma." Journal for immunotherapy of cancer 4 (January 2016): 44-.
PMID
27532019
Source
epmc
Published In
Journal for ImmunoTherapy of Cancer
Volume
4
Publish Date
2016
Start Page
44
DOI
10.1186/s40425-016-0148-7

Genetic risk analysis of a patient with fulminant autoimmune type 1 diabetes mellitus secondary to combination ipilimumab and nivolumab immunotherapy.

Checkpoint inhibitor immunotherapy is becoming an effective treatment modality for an increasing number of malignancies. As a result, autoinflammatory side-effects are also being observed more commonly in the clinic. We are currently unable to predict which patients will develop more severe toxicities associated with these treatment regimens.We present a patient with stage IV melanoma that developed rapid onset autoimmune type 1 diabetes (T1D) in response to combination ipilimumab and nivolumab immunotherapy. At the time of the patient's presentation with diabetes ketoacidosis, a confirmed anti-GAD antibody seroconversion was noted. Longer-term follow-up of this patient has demonstrated a durable complete response based on PET CT imaging along with a persistently undetectable C-peptide level. Single nucleotide polymorphism gene sequencing and HLA risk allele analysis has revealed the patient to lack any established genetic predisposition to the development of autoimmune T1D.While larger studies are necessary to better understand the role of genetic risk factors for the development of autoimmune toxicities in those patients undergoing checkpoint inhibitor immunotherapy, these results suggest that pre-screening patients for known T1D risk alleles may not be indicated. Additional investigation is needed to determine whether an approach such as T cell receptor clonotypic analysis to identify the presence of autoreactive T cell clones may be an effective approach for predicting which patients are at risk for the development of autoinflammatory toxicities while undergoing checkpoint inhibitor immunotherapy.

Authors
Lowe, JR; Perry, DJ; Salama, AKS; Mathews, CE; Moss, LG; Hanks, BA
MLA Citation
Lowe, JR, Perry, DJ, Salama, AKS, Mathews, CE, Moss, LG, and Hanks, BA. "Genetic risk analysis of a patient with fulminant autoimmune type 1 diabetes mellitus secondary to combination ipilimumab and nivolumab immunotherapy." Journal for immunotherapy of cancer 4 (January 2016): 89-.
Website
http://hdl.handle.net/10161/13294
PMID
28031819
Source
epmc
Published In
Journal for ImmunoTherapy of Cancer
Volume
4
Publish Date
2016
Start Page
89
DOI
10.1186/s40425-016-0196-z

Neoadjuvant use of ipilimumab in locally advanced melanoma.

Recent advances in immune modulating therapies show great promise for patients with advanced melanoma, however optimal strategies for achieving long-term disease control in locally advanced melanoma are unclear. We present two cases of neoadjuvant ipilimumab, one case in combination with isolated limb infusion (ILI) followed by surgical resection and one followed by surgery alone. Both patients have had durable responses. These cases highlight the ongoing need for prospective trials in the neoadjuvant setting.

Authors
Howie, LJ; Tyler, DS; Salama, AKS
MLA Citation
Howie, LJ, Tyler, DS, and Salama, AKS. "Neoadjuvant use of ipilimumab in locally advanced melanoma." Journal of surgical oncology 112.8 (December 2015): 841-843.
PMID
26768512
Source
epmc
Published In
Journal of Surgical Oncology
Volume
112
Issue
8
Publish Date
2015
Start Page
841
End Page
843
DOI
10.1002/jso.24079

Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial.

Patients with melanoma that progresses on ipilimumab and, if BRAF(V600) mutant-positive, a BRAF or MEK inhibitor or both, have few treatment options. We assessed the efficacy and safety of two pembrolizumab doses versus investigator-choice chemotherapy in patients with ipilimumab-refractory melanoma.We carried out a randomised phase 2 trial of patients aged 18 years or older from 73 hospitals, clinics, and academic medical centres in 12 countries who had confirmed progressive disease within 24 weeks after two or more ipilimumab doses and, if BRAF(V600) mutant-positive, previous treatment with a BRAF or MEK inhibitor or both. Patients had to have resolution of all ipilimumab-related adverse events to grade 0-1 and prednisone 10 mg/day or less for at least 2 weeks, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and at least one measurable lesion to be eligible. Using a centralised interactive voice response system, we randomly assigned (1:1:1) patients in a block size of six to receive intravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide). Randomisation was stratified by ECOG performance status, lactate dehydrogenase concentration, and BRAF(V600) mutation status. Individual treatment assignment between pembrolizumab and chemotherapy was open label, but investigators and patients were masked to assignment of the dose of pembrolizumab. We present the primary endpoint at the prespecified second interim analysis of progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01704287. The study is closed to enrolment but continues to follow up and treat patients.Between Nov 30, 2012, and Nov 13, 2013, we enrolled 540 patients: 180 patients were randomly assigned to receive pembrolizumab 2 mg/kg, 181 to receive pembrolizumab 10 mg/kg, and 179 to receive chemotherapy. Based on 410 progression-free survival events, progression-free survival was improved in patients assigned to pembrolizumab 2 mg/kg (HR 0·57, 95% CI 0·45-0·73; p<0·0001) and those assigned to pembrolizumab 10 mg/kg (0·50, 0·39-0·64; p<0·0001) compared with those assigned to chemotherapy. 6-month progression-free survival was 34% (95% CI 27-41) in the pembrolizumab 2 mg/kg group, 38% (31-45) in the 10 mg/kg group, and 16% (10-22) in the chemotherapy group. Treatment-related grade 3-4 adverse events occurred in 20 (11%) patients in the pembrolizumab 2 mg/kg group, 25 (14%) in the pembrolizumab 10 mg/kg group, and 45 (26%) in the chemotherapy group. The most common treatment-related grade 3-4 adverse event in the pembrolizumab groups was fatigue (two [1%] of 178 patients in the 2 mg/kg group and one [<1%] of 179 patients in the 10 mg/kg group, compared with eight [5%] of 171 in the chemotherapy group). Other treatment-related grade 3-4 adverse events include generalised oedema and myalgia (each in two [1%] patients) in those given pembrolizumab 2 mg/kg; hypopituitarism, colitis, diarrhoea, decreased appetite, hyponatremia, and pneumonitis (each in two [1%]) in those given pembrolizumab 10 mg/kg; and anaemia (nine [5%]), fatigue (eight [5%]), neutropenia (six [4%]), and leucopenia (six [4%]) in those assigned to chemotherapy.These findings establish pembrolizumab as a new standard of care for the treatment of ipilimumab-refractory melanoma.Merck Sharp & Dohme.

Authors
Ribas, A; Puzanov, I; Dummer, R; Schadendorf, D; Hamid, O; Robert, C; Hodi, FS; Schachter, J; Pavlick, AC; Lewis, KD; Cranmer, LD; Blank, CU; O'Day, SJ; Ascierto, PA; Salama, AKS; Margolin, KA; Loquai, C; Eigentler, TK; Gangadhar, TC; Carlino, MS; Agarwala, SS; Moschos, SJ; Sosman, JA; Goldinger, SM; Shapira-Frommer, R; Gonzalez, R; Kirkwood, JM; Wolchok, JD; Eggermont, A; Li, XN; Zhou, W; Zernhelt, AM; Lis, J; Ebbinghaus, S; Kang, SP; Daud, A
MLA Citation
Ribas, A, Puzanov, I, Dummer, R, Schadendorf, D, Hamid, O, Robert, C, Hodi, FS, Schachter, J, Pavlick, AC, Lewis, KD, Cranmer, LD, Blank, CU, O'Day, SJ, Ascierto, PA, Salama, AKS, Margolin, KA, Loquai, C, Eigentler, TK, Gangadhar, TC, Carlino, MS, Agarwala, SS, Moschos, SJ, Sosman, JA, Goldinger, SM, Shapira-Frommer, R, Gonzalez, R, Kirkwood, JM, Wolchok, JD, Eggermont, A, Li, XN, Zhou, W, Zernhelt, AM, Lis, J, Ebbinghaus, S, Kang, SP, and Daud, A. "Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial." The Lancet. Oncology 16.8 (August 2015): 908-918.
PMID
26115796
Source
epmc
Published In
The Lancet Oncology
Volume
16
Issue
8
Publish Date
2015
Start Page
908
End Page
918
DOI
10.1016/s1470-2045(15)00083-2

Nivolumab and ipilimumab versus ipilimumab in untreated melanoma.

In a phase 1 dose-escalation study, combined inhibition of T-cell checkpoint pathways by nivolumab and ipilimumab was associated with a high rate of objective response, including complete responses, among patients with advanced melanoma.In this double-blind study involving 142 patients with metastatic melanoma who had not previously received treatment, we randomly assigned patients in a 2:1 ratio to receive ipilimumab (3 mg per kilogram of body weight) combined with either nivolumab (1 mg per kilogram) or placebo once every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) or placebo every 2 weeks until the occurrence of disease progression or unacceptable toxic effects. The primary end point was the rate of investigator-assessed, confirmed objective response among patients with BRAF V600 wild-type tumors.Among patients with BRAF wild-type tumors, the rate of confirmed objective response was 61% (44 of 72 patients) in the group that received both ipilimumab and nivolumab (combination group) versus 11% (4 of 37 patients) in the group that received ipilimumab and placebo (ipilimumab-monotherapy group) (P<0.001), with complete responses reported in 16 patients (22%) in the combination group and no patients in the ipilimumab-monotherapy group. The median duration of response was not reached in either group. The median progression-free survival was not reached with the combination therapy and was 4.4 months with ipilimumab monotherapy (hazard ratio associated with combination therapy as compared with ipilimumab monotherapy for disease progression or death, 0.40; 95% confidence interval, 0.23 to 0.68; P<0.001). Similar results for response rate and progression-free survival were observed in 33 patients with BRAF mutation-positive tumors. Drug-related adverse events of grade 3 or 4 were reported in 54% of the patients who received the combination therapy as compared with 24% of the patients who received ipilimumab monotherapy. Select adverse events with potential immunologic causes were consistent with those in a phase 1 study, and most of these events resolved with immune-modulating medication.The objective-response rate and the progression-free survival among patients with advanced melanoma who had not previously received treatment were significantly greater with nivolumab combined with ipilimumab than with ipilimumab monotherapy. Combination therapy had an acceptable safety profile. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT01927419.).

Authors
Postow, MA; Chesney, J; Pavlick, AC; Robert, C; Grossmann, K; McDermott, D; Linette, GP; Meyer, N; Giguere, JK; Agarwala, SS; Shaheen, M; Ernstoff, MS; Minor, D; Salama, AK; Taylor, M; Ott, PA; Rollin, LM; Horak, C; Gagnier, P; Wolchok, JD; Hodi, FS
MLA Citation
Postow, MA, Chesney, J, Pavlick, AC, Robert, C, Grossmann, K, McDermott, D, Linette, GP, Meyer, N, Giguere, JK, Agarwala, SS, Shaheen, M, Ernstoff, MS, Minor, D, Salama, AK, Taylor, M, Ott, PA, Rollin, LM, Horak, C, Gagnier, P, Wolchok, JD, and Hodi, FS. "Nivolumab and ipilimumab versus ipilimumab in untreated melanoma." The New England journal of medicine 372.21 (May 2015): 2006-2017.
PMID
25891304
Source
epmc
Published In
The New England journal of medicine
Volume
372
Issue
21
Publish Date
2015
Start Page
2006
End Page
2017
DOI
10.1056/nejmoa1414428

Rapid complete response of metastatic melanoma in a patient undergoing ipilimumab immunotherapy in the setting of active ulcerative colitis.

While blockade of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) T cell regulatory receptor has become a commonly utilized strategy in the management of advanced melanoma, many questions remain regarding the use of this agent in patient populations with autoimmune disease. We present a case involving the treatment of a patient with stage IV melanoma and ulcerative colitis (UC) with anti-CTLA-4 antibody immunotherapy. Upon initial treatment, the patient developed grade III colitis requiring tumor necrosis factor-alpha (TNF-α) blocking antibody therapy, however re-treatment with anti-CTLA-4 antibody following a total colectomy resulted in a rapid complete response accompanied by the development of a tracheobronchitis, a previously described extra-intestinal manifestation of UC. This case contributes to the evolving literature on the use of checkpoint inhibitors in patients also suffering from autoimmune disease, supports future clinical trials investigating the use of these agents in patients with autoimmune diseases, and suggests that an understanding of the specific molecular pathways involved in a patient's autoimmune pathology may provide insight into the development of more effective novel combinatorial immunotherapeutic strategies.

Authors
Bostwick, AD; Salama, AK; Hanks, BA
MLA Citation
Bostwick, AD, Salama, AK, and Hanks, BA. "Rapid complete response of metastatic melanoma in a patient undergoing ipilimumab immunotherapy in the setting of active ulcerative colitis." Journal for immunotherapy of cancer 3 (January 2015): 19-.
Website
http://hdl.handle.net/10161/11661
PMID
25992290
Source
epmc
Published In
Journal for ImmunoTherapy of Cancer
Volume
3
Publish Date
2015
Start Page
19
DOI
10.1186/s40425-015-0064-2

Clinical applications of PD-1-based therapy: a focus on pembrolizumab (MK-3475) in the management of melanoma and other tumor types.

Preclinical work has led to an increased understanding of the immunomodulatory mechanisms involved in the regulation of the antitumor response in a variety of tumor types. PD-1 (programmed death 1) appears to be a key checkpoint involved in immune suppression in the tumor microenvironment, even in diseases not previously thought to be sensitive to immune manipulation. More recently, the subsequent clinical development of PD-1-based therapy has resulted in a major breakthrough in the field of oncology. Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the treatment of advanced melanoma based on promising early-phase clinical data. Encouraging results have also been seen in other malignancies, and PD-1-targeted therapies are likely to markedly change the treatment landscape. Future work will center on rationally designed combination strategies in order to potentiate the antitumor immune response and overcome mechanisms of resistance.

Authors
Gangadhar, TC; Salama, AK
MLA Citation
Gangadhar, TC, and Salama, AK. "Clinical applications of PD-1-based therapy: a focus on pembrolizumab (MK-3475) in the management of melanoma and other tumor types." OncoTargets and therapy 8 (January 2015): 929-937. (Review)
PMID
25960664
Source
epmc
Published In
OncoTargets and Therapy
Volume
8
Publish Date
2015
Start Page
929
End Page
937
DOI
10.2147/ott.s53164

A randomized controlled comparison of pembrolizumab and chemotherapy in patients with ipilimumab-refractory melanoma

Authors
Dummer, R; Daud, A; Puzanov, I; Hamid, O; Schadendorf, D; Robert, C; Schachter, J; Pavlick, A; Gonzalez, R; Hodi, F; Cranmer, LD; Blank, C; O’Day, SJ; Ascierto, PA; Salama, AKS; Li, NX; Zhou, W; Lis, J; Ebbinghaus, S; Kang, PS; Ribas, A
MLA Citation
Dummer, R, Daud, A, Puzanov, I, Hamid, O, Schadendorf, D, Robert, C, Schachter, J, Pavlick, A, Gonzalez, R, Hodi, F, Cranmer, LD, Blank, C, O’Day, SJ, Ascierto, PA, Salama, AKS, Li, NX, Zhou, W, Lis, J, Ebbinghaus, S, Kang, PS, and Ribas, A. "A randomized controlled comparison of pembrolizumab and chemotherapy in patients with ipilimumab-refractory melanoma." Journal of Translational Medicine 13.Suppl 1 (2015): O5-O5.
Source
crossref
Published In
Journal of Translational Medicine
Volume
13
Issue
Suppl 1
Publish Date
2015
Start Page
O5
End Page
O5
DOI
10.1186/1479-5876-13-S1-O5

Immunotherapy following regional chemotherapy treatment of advanced extremity melanoma.

Following regional chemotherapy (RC) for melanoma, approximately 75 % of patients will progress. The role of immunotherapy after RC has not been well established.A prospective, single-institution database of 243 patients with in-transit melanoma (1995-2013) was queried for patients who had progression of disease after RC with melphalan and subsequently received systemic immunotherapy. Fifteen patients received IL-2 only, 12 received ipilimumab only, and 6 received IL-2 followed by ipilimumab. Fisher's exact test was used to determine if there was a difference in number of complete responders after immunotherapy.With IL-2 alone, all patients progressed. After ipilimumab alone, three patients had a complete response and nine had progressive disease. Six additional patients received IL-2 first then ipilimumab. All six progressed on IL-2 but three went on to have a complete response to ipilimumab while three progressed. The use of ipilimumab at any time in patients who progressed after RC was associated with higher rate of complete response compared to use of IL-2 alone (33 vs. 0 %; p = 0.021).Patients with progression after regional therapy for melanoma may benefit from immunologic therapy. In this group of patients, immune checkpoint blockade with ipilimumab has a higher complete response rate than T cell stimulation with IL-2, with no complete responders in the IL-2 only group. Furthermore, the complete response rate for ipilimumab in our cohort is higher than reported response rates in the literature for ipilimumab alone, suggesting that the effects of immunotherapy may be bolstered by previous regional treatment.

Authors
Jiang, BS; Beasley, GM; Speicher, PJ; Mosca, PJ; Morse, MA; Hanks, B; Salama, A; Tyler, DS
MLA Citation
Jiang, BS, Beasley, GM, Speicher, PJ, Mosca, PJ, Morse, MA, Hanks, B, Salama, A, and Tyler, DS. "Immunotherapy following regional chemotherapy treatment of advanced extremity melanoma." Annals of surgical oncology 21.8 (August 2014): 2525-2531.
PMID
24700302
Source
epmc
Published In
Annals of Surgical Oncology
Volume
21
Issue
8
Publish Date
2014
Start Page
2525
End Page
2531
DOI
10.1245/s10434-014-3671-0

Melanoma, version 4.2014.

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. These NCCN Guidelines Insights highlight notable recent updates. Dabrafenib and trametinib, either as monotherapy (category 1) or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. Controversy continues regarding the value of adjuvant radiation for patients at high risk of nodal relapse. This is reflected in the category 2B designation to consider adjuvant radiation following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease.

Authors
Coit, DG; Thompson, JA; Andtbacka, R; Anker, CJ; Bichakjian, CK; Carson, WE; Daniels, GA; Daud, A; Dimaio, D; Fleming, MD; Gonzalez, R; Guild, V; Halpern, AC; Hodi, FS; Kelley, MC; Khushalani, NI; Kudchadkar, RR; Lange, JR; Martini, MC; Olszanski, AJ; Ross, MI; Salama, A; Swetter, SM; Tanabe, KK; Trisal, V; Urist, MM; McMillian, NR; Ho, M
MLA Citation
Coit, DG, Thompson, JA, Andtbacka, R, Anker, CJ, Bichakjian, CK, Carson, WE, Daniels, GA, Daud, A, Dimaio, D, Fleming, MD, Gonzalez, R, Guild, V, Halpern, AC, Hodi, FS, Kelley, MC, Khushalani, NI, Kudchadkar, RR, Lange, JR, Martini, MC, Olszanski, AJ, Ross, MI, Salama, A, Swetter, SM, Tanabe, KK, Trisal, V, Urist, MM, McMillian, NR, and Ho, M. "Melanoma, version 4.2014." Journal of the National Comprehensive Cancer Network : JNCCN 12.5 (May 2014): 621-629.
PMID
24812131
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
12
Issue
5
Publish Date
2014
Start Page
621
End Page
629

Efficacy of repeat sentinel lymph node biopsy in patients who develop recurrent melanoma.

Even after negative sentinel lymph node biopsy (SLNB) for primary melanoma, patients who develop in-transit (IT) melanoma or local recurrences (LR) can have subclinical regional lymph node involvement.A prospective database identified 33 patients with IT melanoma/LR who underwent technetium 99m sulfur colloid lymphoscintigraphy alone (n = 15) or in conjunction with lymphazurin dye (n = 18) administered only if the IT melanoma/LR was concurrently excised.Seventy-nine percent (26 of 33) of patients undergoing SLNB in this study had earlier removal of lymph nodes in the same lymph node basin as the expected drainage of the IT melanoma or LR at the time of diagnosis of their primary melanoma. Lymphoscintography at time of presentation with IT melanoma/LR was successful in 94% (31 of 33) cases, and at least 1 sentinel lymph node was found intraoperatively in 97% (30 of 31) cases. The SLNB was positive in 33% (10 of 30) of these cases. Completion lymph node dissection was performed in 90% (9 of 10) of patients. Nine patients with negative SLNB and IT melanoma underwent regional chemotherapy. Patients in this study with a positive sentinel lymph node at the time the IT/LR was mapped had a considerably shorter time to development of distant metastatic disease compared with those with negative sentinel lymph nodes.In this study, we demonstrate the technical feasibility and clinical use of repeat SLNB for recurrent melanoma. Performing SLNB cannot only optimize local, regional, and systemic treatment strategies for patients with LR or IT melanoma, but also appears to provide important prognostic information.

Authors
Beasley, GM; Speicher, P; Sharma, K; Seigler, H; Salama, A; Mosca, P; Tyler, DS
MLA Citation
Beasley, GM, Speicher, P, Sharma, K, Seigler, H, Salama, A, Mosca, P, and Tyler, DS. "Efficacy of repeat sentinel lymph node biopsy in patients who develop recurrent melanoma." Journal of the American College of Surgeons 218.4 (April 2014): 686-692.
PMID
24529806
Source
epmc
Published In
Journal of The American College of Surgeons
Volume
218
Issue
4
Publish Date
2014
Start Page
686
End Page
692
DOI
10.1016/j.jamcollsurg.2013.12.025

Efficacy of repeat sentinel lymph node biopsy in patients who develop recurrent melanoma

Background Even after negative sentinel lymph node biopsy (SLNB) for primary melanoma, patients who develop in-transit (IT) melanoma or local recurrences (LR) can have subclinical regional lymph node involvement. Study Design A prospective database identified 33 patients with IT melanoma/LR who underwent technetium 99m sulfur colloid lymphoscintigraphy alone (n = 15) or in conjunction with lymphazurin dye (n = 18) administered only if the IT melanoma/LR was concurrently excised. Results Seventy-nine percent (26 of 33) of patients undergoing SLNB in this study had earlier removal of lymph nodes in the same lymph node basin as the expected drainage of the IT melanoma or LR at the time of diagnosis of their primary melanoma. Lymphoscintography at time of presentation with IT melanoma/LR was successful in 94% (31 of 33) cases, and at least 1 sentinel lymph node was found intraoperatively in 97% (30 of 31) cases. The SLNB was positive in 33% (10 of 30) of these cases. Completion lymph node dissection was performed in 90% (9 of 10) of patients. Nine patients with negative SLNB and IT melanoma underwent regional chemotherapy. Patients in this study with a positive sentinel lymph node at the time the IT/LR was mapped had a considerably shorter time to development of distant metastatic disease compared with those with negative sentinel lymph nodes. Conclusions In this study, we demonstrate the technical feasibility and clinical use of repeat SLNB for recurrent melanoma. Performing SLNB cannot only optimize local, regional, and systemic treatment strategies for patients with LR or IT melanoma, but also appears to provide important prognostic information. © 2014 by the American College of Surgeons.

Authors
Beasley, GM; Speicher, P; Sharma, K; Seigler, H; Salama, A; Mosca, P; Tyler, DS
MLA Citation
Beasley, GM, Speicher, P, Sharma, K, Seigler, H, Salama, A, Mosca, P, and Tyler, DS. "Efficacy of repeat sentinel lymph node biopsy in patients who develop recurrent melanoma." Journal of the American College of Surgeons 218.4 (January 1, 2014): 686-692.
Source
scopus
Published In
Journal of The American College of Surgeons
Volume
218
Issue
4
Publish Date
2014
Start Page
686
End Page
692
DOI
10.1016/j.jamcollsurg.2013.12.025

Immunotherapy following regional chemotherapy treatment of advanced extremity melanoma

Purpose. Following regional chemotherapy (RC) for melanoma, approximately 75 % of patients will progress. The role of immunotherapy after RC has not been well established. Methods. A prospective, single-institution database of 243 patients with in-transit melanoma (1995-2013) was queried for patients who had progression of disease after RC with melphalan and subsequently received systemic immunotherapy. Fifteen patients received IL-2 only, 12 received ipilimumab only, and 6 received IL-2 followed by ipilimumab. Fisher's exact test was used to determine if there was a difference in number of complete responders after immunotherapy. Results. With IL-2 alone, all patients progressed. After ipilimumab alone, three patients had a complete response and nine had progressive disease. Six additional patients received IL-2 first then ipilimumab. All six progressed on IL-2 but three went on to have a complete response to ipilimumab while three progressed. The use of ipilimumab at any time in patients who progressed after RC was associated with higher rate of complete response compared to use of IL-2 alone (33 vs. 0 %; p = 0.021). Conclusions. Patients with progression after regional therapy for melanoma may benefit from immunologic therapy. In this group of patients, immune checkpoint blockade with ipilimumab has a higher complete response rate than T cell stimulation with IL-2, with no complete responders in the IL-2 only group. Furthermore, the complete response rate for ipilimumab in our cohort is higher than reported response rates in the literature for ipilimumab alone, suggesting that the effects of immunotherapy may be bolstered by previous regional treatment. © 2014 Society of Surgical Oncology.

Authors
Jiang, BS; Beasley, GM; Speicher, PJ; Mosca, PJ; Morse, MA; Hanks, B; Salama, A; Tyler, DS
MLA Citation
Jiang, BS, Beasley, GM, Speicher, PJ, Mosca, PJ, Morse, MA, Hanks, B, Salama, A, and Tyler, DS. "Immunotherapy following regional chemotherapy treatment of advanced extremity melanoma." Annals of Surgical Oncology 21.8 (January 1, 2014): 2525-2531.
Source
scopus
Published In
Annals of Surgical Oncology
Volume
21
Issue
8
Publish Date
2014
Start Page
2525
End Page
2531
DOI
10.1245/s10434-014-3671-0

BRAF in Melanoma: Current Strategies and Future Directions

Authors
Salama, AKS; Flaherty, KT
MLA Citation
Salama, AKS, and Flaherty, KT. "BRAF in Melanoma: Current Strategies and Future Directions." CLINICAL CANCER RESEARCH 19.16 (August 15, 2013): 4326-4334.
PMID
23770823
Source
wos-lite
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
19
Issue
16
Publish Date
2013
Start Page
4326
End Page
4334
DOI
10.1158/1078-0432.CCR-13-0779

Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion.

BACKGROUND: Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity melanoma. METHODS: Multiplex immunobead assay technology (Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel, Millipore Corp., Billerica, MA; and Magpix analytical test instrument, Luminex Corp., Austin, TX) was performed on pre-ILI plasma to determine concentrations of selected cytokines (MIP-1α, IL-1Rα, IP-10, IL-1β, IL-1α, MCP-1, IL-6, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β) on a subset of patients (n = 180) who experienced CR (n = 23) or PD (n = 24) after ILI. Plasma from normal donors (n = 12) was also evaluated. RESULTS: Of 180 ILIs performed, 28 % (95 % confidence interval 22-35, n = 50) experienced a CR, 14 % (n = 25) experienced a partial response, 11 % (n = 21) had stable disease, 34 % (n = 61) had PD, and 13 % (n = 23) were not evaluable for response. Tumor characteristics and pharmacokinetics appeared similar between CR (n = 23) and PD (n = 24) patients who underwent cytokine analysis. Although there were no differences in cytokine levels between CR and PD patients, there were differences between the melanoma patients and controls. MIP-1α, IL-1Rα, IL-1β, IL-1α, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β were significantly higher in normal controls compared to melanoma patients, while IP-10 was lower (p < 0.001) in controls compared to melanoma patients. CONCLUSIONS: Patients with unresectable in-transit melanoma appear to have markedly decreased levels of immune activating cytokines compared to normal healthy controls. This further supports a potential role for immune-targeted therapies and immune monitoring in patients with regionally advanced melanoma.

Authors
Shetty, G; Beasley, GM; Sparks, S; Barfield, M; Masoud, M; Mosca, PJ; Pruitt, SK; Salama, AKS; Chan, C; Tyler, DS; Weinhold, KJ
MLA Citation
Shetty, G, Beasley, GM, Sparks, S, Barfield, M, Masoud, M, Mosca, PJ, Pruitt, SK, Salama, AKS, Chan, C, Tyler, DS, and Weinhold, KJ. "Plasma cytokine analysis in patients with advanced extremity melanoma undergoing isolated limb infusion." Ann Surg Oncol 20.4 (April 2013): 1128-1135.
PMID
23456379
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
20
Issue
4
Publish Date
2013
Start Page
1128
End Page
1135
DOI
10.1245/s10434-012-2785-5

Trametinib (GSK1120212) in the treatment of melanoma

Authors
Salama, AKS; Kim, KB
MLA Citation
Salama, AKS, and Kim, KB. "Trametinib (GSK1120212) in the treatment of melanoma." EXPERT OPINION ON PHARMACOTHERAPY 14.5 (April 2013): 619-627.
PMID
23432625
Source
wos-lite
Published In
Expert Opinion on Pharmacotherapy
Volume
14
Issue
5
Publish Date
2013
Start Page
619
End Page
627
DOI
10.1517/14656566.2013.770475

Hazard-rate analysis and patterns of recurrence in early stage melanoma: moving towards a rationally designed surveillance strategy.

BACKGROUND: While curable at early stages, few treatment options exist for advanced melanoma. Currently, no consensus exists regarding the optimal surveillance strategy for patients after resection. The objectives of this study were to identify patterns of metastatic recurrence, to determine the influence of metastatic site on survival, and to identify high-risk periods for recurrence. METHODS: A retrospective review of the Duke Melanoma Database from 1970 to 2004 was conducted that focused on patients who were initially diagnosed without metastatic disease. The time to first recurrence was computed from the date of diagnosis, and the associated hazard function was examined to determine the peak risk period of recurrence. Metastatic sites were coded by the American Joint Committee on Cancer (AJCC) system including local skin, distant skin and nodes (M1a), lung (M1b), and other distant (M1c). RESULTS: Of 11,615 patients initially diagnosed without metastatic disease, 4616 (40%) had at least one recurrence. Overall the risk of initial recurrence peaked at 12 months. The risk of initial recurrence at the local skin, distant skin, and nodes peaked at 8 months, and the risk at lung and other distant sites peaked at 24 months. Patients with a cutaneous or nodal recurrence had improved survival compared to other recurrence types. CONCLUSIONS: The risk of developing recurrent melanoma peaked at one year, and the site of first recurrence had a significant impact on survival. Defining the timing and expected patterns of recurrence will be important in creating an optimized surveillance strategy for this patient population.

Authors
Salama, AKS; de Rosa, N; Scheri, RP; Pruitt, SK; Herndon, JE; Marcello, J; Tyler, DS; Abernethy, AP
MLA Citation
Salama, AKS, de Rosa, N, Scheri, RP, Pruitt, SK, Herndon, JE, Marcello, J, Tyler, DS, and Abernethy, AP. "Hazard-rate analysis and patterns of recurrence in early stage melanoma: moving towards a rationally designed surveillance strategy." PLoS One 8.3 (2013): e57665-.
PMID
23516415
Source
pubmed
Published In
PloS one
Volume
8
Issue
3
Publish Date
2013
Start Page
e57665
DOI
10.1371/journal.pone.0057665

Evolving pharmacotherapies for the treatment of metastatic melanoma

Metastatic melanoma remains a difficult disease to treat, and long term survivors are rare. Over the past few years, however, breakthroughs in both immunotherapy as well as targeted agents have had a tremendous impact on patients diagnosed with this disease. This review summarizes recent advances in systemic therapies for melanoma, including immune modulators directed against cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1), as well as a number of targeted agents. These approaches hold great promise as the landscape of therapeutic options for advanced melanoma continues to evolve. © the author(s), publisher and licensee Libertas Academica Ltd.

Authors
Salama, AKS
MLA Citation
Salama, AKS. "Evolving pharmacotherapies for the treatment of metastatic melanoma." Clinical Medicine Insights: Oncology 7 (2013): 137-149.
PMID
23843723
Source
scival
Published In
Clinical Medicine Insights: Oncology
Volume
7
Publish Date
2013
Start Page
137
End Page
149
DOI
10.4137/CMO.S9565

MEK Inhibition in the Treatment of Advanced Melanoma

The RAS-RAF-MEK-ERK pathway is considered to be the most important signal transduction pathway in melanoma, and alterations in this pathway via various genetic mutations, such as BRAF and NRAS mutations, are known to be important drivers of melanomagenesis. As MEK is an essential intermediary kinase protein within this pathway, inhibition of MEK has been of a great interest as a molecular target therapy in melanoma. In fact, trametinib, a selective MEK inhibitor, has been shown to have a survival benefit over cytotoxic chemotherapy in patients with V600 BRAF-mutant metastatic melanoma, leading to the FDA approval for this patient population. MEK inhibitors may also be useful in treatment of advanced melanoma harboring other genetic mutations, such as NRAS and GNAQ/GNA11 mutations. Here, we review and discuss the preclinical and clinical data regarding MEK inhibitors and their role in the treatment of advanced melanoma. © 2013 Springer Science+Business Media New York.

Authors
Salama, AKS; Kim, KB
MLA Citation
Salama, AKS, and Kim, KB. "MEK Inhibition in the Treatment of Advanced Melanoma." Current Oncology Reports (2013): 1-10.
PMID
23975010
Source
scival
Published In
Current Oncology Reports
Publish Date
2013
Start Page
1
End Page
10
DOI
10.1007/s11912-013-0336-2

MEK inhibition in the treatment of advanced melanoma

The RAS-RAF-MEK-ERK pathway is considered to be the most important signal transduction pathway in melanoma, and alterations in this pathway via various genetic mutations, such as BRAF and NRAS mutations, are known to be important drivers of melanomagenesis. As MEK is an essential intermediary kinase protein within this pathway, inhibition of MEK has been of a great interest as a molecular target therapy in melanoma. In fact, trametinib, a selective MEK inhibitor, has been shown to have a survival benefit over cytotoxic chemotherapy in patients with V600 BRAF-mutant metastatic melanoma, leading to the FDA approval for this patient population. MEK inhibitors may also be useful in treatment of advanced melanoma harboring other genetic mutations, such as NRAS and GNAQ/GNA11 mutations. Here, we review and discuss the preclinical and clinical data regarding MEK inhibitors and their role in the treatment of advanced melanoma. © 2013 Springer Science+Business Media New York.

Authors
Salama, AKS; Kim, KB
MLA Citation
Salama, AKS, and Kim, KB. "MEK inhibition in the treatment of advanced melanoma." Current Oncology Reports 15.5 (2013): 473-482.
Source
scival
Published In
Current Oncology Reports
Volume
15
Issue
5
Publish Date
2013
Start Page
473
End Page
482
DOI
10.1007/s11912-013-0336-2

Phase II study of the farnesyltransferase inhibitor R115777 in advanced melanoma (CALGB 500104)

Authors
Gajewski, TF; Salama, AKS; Niedzwiecki, D; Johnson, J; Linette, G; Bucher, C; Blaskovich, MA; Sebti, SM; Haluska, F; Canc, LGB
MLA Citation
Gajewski, TF, Salama, AKS, Niedzwiecki, D, Johnson, J, Linette, G, Bucher, C, Blaskovich, MA, Sebti, SM, Haluska, F, and Canc, LGB. "Phase II study of the farnesyltransferase inhibitor R115777 in advanced melanoma (CALGB 500104)." JOURNAL OF TRANSLATIONAL MEDICINE 10 (December 10, 2012).
PMID
23228035
Source
wos-lite
Published In
Journal of Translational Medicine
Volume
10
Publish Date
2012
DOI
10.1186/1479-5876-10-246

The effect of metastatic site and decade of diagnosis on the individual burden of metastatic melanoma: contemporary estimates of average years of life lost.

OBJECTIVES: Metastatic melanoma (MM) is a leading cause of years of life lost due to malignancy. This study aimed to identify the average years of life lost (AYLL) in MM patients. METHODS: MM patients were identified from a prospectively maintained database, and a linear model predicting AYLL was developed. RESULTS: Between 1970 and 1999, 4,774 patients diagnosed with MM died. The AYLL was 23.2 years. AYLL remained stable across three decades. CONCLUSIONS: AYLL for MM is greater than 20 years, and has not improved. This burden underscores the need for continued research and access to funding for this disease.

Authors
Salama, AKS; Rosa, ND; Scheri, RP; Herndon, JE; Tyler, DS; Marcello, J; Pruitt, SK; Abernethy, AP
MLA Citation
Salama, AKS, Rosa, ND, Scheri, RP, Herndon, JE, Tyler, DS, Marcello, J, Pruitt, SK, and Abernethy, AP. "The effect of metastatic site and decade of diagnosis on the individual burden of metastatic melanoma: contemporary estimates of average years of life lost." Cancer Invest 30.9 (November 2012): 637-641.
PMID
23020583
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
30
Issue
9
Publish Date
2012
Start Page
637
End Page
641
DOI
10.3109/07357907.2012.726387

A multicenter prospective evaluation of the clinical utility of F-18 FDG-PET/CT in patients with AJCC stage IIIB or IIIC extremity melanoma.

OBJECTIVE/BACKGROUND: There is a high risk of relapse in stage IIIB/IIIC melanoma. The utility of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography integrated with computed tomography (FDG-PET/CT) in these patients to evaluate response to treatment or for surveillance after treatment is currently not well defined. METHODS: Prospective data from 2 centers identified 97 patients with stage IIIB/IIIC extremity melanoma undergoing isolated limb infusion (ILI) who had whole body FDG-PET/CT scans before and every 3 months after treatment. Clinical response was determined at 3 months by Response Evaluation Criteria In Solid Tumors. RESULTS: Complete response (CR) after ILI occurred in 33% (32/97) of patients. FDG-PET/CT accurately identified 59% of patients who were CRs (19/32), whereas 41% (13/32) had residual metabolic activity in the extremity that was histologically negative for melanoma. The 3-year disease-free rate was 62.2% (95% CI: 40.1%-96.4%) for those patients who were CRs by both clinical/pathologic examination and FDG-PET/CT (n = 19) compared to only 29.4% (95% CI: 9.9%-87.2%) of those CRs who still had residual FDG-PET/CT activity (n = 13). FDG-PET/CT was utilized for surveillance of disease recurrence outside the regional field of treatment. Fifty-two percent (51/97) of patients developed disease outside the extremity at a median time of 212 days from pre-ILI FDG-PET/CT. In 47% (29/62) of these cases, the recurrence was resected. CONCLUSIONS: Although FDG-PET/CT does not appear to accurately identify patients who appear to be CRs to ILI, it does appear to identify a subgroup of patients whose regional progression-free survival is markedly worse. However, FDG-PET/CT appears to be an excellent method for surveillance in stage IIIB/IIIC patients after ILI with ability to identify surgically resectable recurrent disease in these high-risk patients.

Authors
Beasley, GM; Parsons, C; Broadwater, G; Selim, MA; Marzban, S; Abernethy, AP; Salama, AKS; Eikman, EA; Wong, T; Zager, JS; Tyler, DS
MLA Citation
Beasley, GM, Parsons, C, Broadwater, G, Selim, MA, Marzban, S, Abernethy, AP, Salama, AKS, Eikman, EA, Wong, T, Zager, JS, and Tyler, DS. "A multicenter prospective evaluation of the clinical utility of F-18 FDG-PET/CT in patients with AJCC stage IIIB or IIIC extremity melanoma." Ann Surg 256.2 (August 2012): 350-356.
PMID
22691370
Source
pubmed
Published In
Annals of Surgery
Volume
256
Issue
2
Publish Date
2012
Start Page
350
End Page
356
DOI
10.1097/SLA.0b013e318256d1f5

Proteomic characterization of non-small cell lung cancer in a comprehensive translational thoracic oncology database.

In recent years, there has been tremendous growth and interest in translational research, particularly in cancer biology. This area of study clearly establishes the connection between laboratory experimentation and practical human application. Though it is common for laboratory and clinical data regarding patient specimens to be maintained separately, the storage of such heterogeneous data in one database offers many benefits as it may facilitate more rapid accession of data and provide researchers access to greater numbers of tissue samples.The Thoracic Oncology Program Database Project was developed to serve as a repository for well-annotated cancer specimen, clinical, genomic, and proteomic data obtained from tumor tissue studies. The TOPDP is not merely a library-it is a dynamic tool that may be used for data mining and exploratory analysis. Using the example of non-small cell lung cancer cases within the database, this study will demonstrate how clinical data may be combined with proteomic analyses of patient tissue samples in determining the functional relevance of protein over and under expression in this disease. Clinical data for 1323 patients with non-small cell lung cancer has been captured to date. Proteomic studies have been performed on tissue samples from 105 of these patients. These tissues have been analyzed for the expression of 33 different protein biomarkers using tissue microarrays. The expression of 15 potential biomarkers was found to be significantly higher in tumor versus matched normal tissue. Proteins belonging to the receptor tyrosine kinase family were particularly likely to be over expressed in tumor tissues. There was no difference in protein expression across various histologies or stages of non-small cell lung cancer. Though not differentially expressed between tumor and non-tumor tissues, the over expression of the glucocorticoid receptor (GR) was associated improved overall survival. However, this finding is preliminary and warrants further investigation.Though the database project is still under development, the application of such a database has the potential to enhance our understanding of cancer biology and will help researchers to identify targets to modify the course of thoracic malignancies.

Authors
Surati, M; Robinson, M; Nandi, S; Faoro, L; Demchuk, C; Rolle, CE; Kanteti, R; Ferguson, BD; Hasina, R; Gangadhar, TC; Salama, AK; Arif, Q; Kirchner, C; Mendonca, E; Campbell, N; Limvorasak, S; Villaflor, V; Hensing, TA; Krausz, T; Vokes, EE; Husain, AN; Ferguson, MK; Karrison, TG; Salgia, R
MLA Citation
Surati, M, Robinson, M, Nandi, S, Faoro, L, Demchuk, C, Rolle, CE, Kanteti, R, Ferguson, BD, Hasina, R, Gangadhar, TC, Salama, AK, Arif, Q, Kirchner, C, Mendonca, E, Campbell, N, Limvorasak, S, Villaflor, V, Hensing, TA, Krausz, T, Vokes, EE, Husain, AN, Ferguson, MK, Karrison, TG, and Salgia, R. "Proteomic characterization of non-small cell lung cancer in a comprehensive translational thoracic oncology database." Journal of clinical bioinformatics 1.8 (February 2011): 1-11.
PMID
21603121
Source
epmc
Published In
Journal of Clinical Bioinformatics
Volume
1
Issue
8
Publish Date
2011
Start Page
1
End Page
11
DOI
10.1186/2043-9113-1-8

Cytotoxic T-lymphocyte-associated antigen-4

Cancer immunotherapy relies on the ability of the immune system to target tumor-specific antigens to generate an immune response. This initial response requires both binding of the MHC/antigen peptide to T-cell receptor complex, along with a second costimulatory signal created by the binding of CD28 on the T cell, with B7 located on the antigen-presenting cell. Regulatory checkpoints, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), serve to attenuate this signal, thereby preventing autoimmunity. Its key role in regulating the immune system has made CTLA-4 an attractive therapeutic target for cancer, with the development of fully human monoclonal antibodies that have successfully targeted CTLA-4 in clinical trials. Augmentation of the immune response via blockade of CTLA-4 represents a significant advance in the field of oncology and has shown an improvement in survival for patients with metastatic melanoma. An increased understanding of the components of this pathway and the identification of other methods to modulate the immune system hold great promise for future therapy. ©2011 AACR.

Authors
Salama, AKS; Hodi, FS
MLA Citation
Salama, AKS, and Hodi, FS. "Cytotoxic T-lymphocyte-associated antigen-4." Clinical Cancer Research 17.14 (2011): 4622-4628.
PMID
21467163
Source
scival
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
17
Issue
14
Publish Date
2011
Start Page
4622
End Page
4628
DOI
10.1158/1078-0432.CCR-10-2232

Personalized treatment of lung cancer

Lung cancer is a heterogenous group of disorders, and a difficult disease to treat. The traditional approach of surgical resection for early-stage disease, potentially followed by chemotherapy, as well chemotherapy (with or without radiation) in later stages of disease is being supplemented with a personalized approach. The personalized approach has classically been used by the oncologist based on clinical/pathological parameters such as the performance status of the patient and histology of lung cancer. As molecular mechanisms have been explored in lung cancer more recently, the personalized approach also has incorporated molecular abnormalities. In particular, EGFR, K-ras, ALK, MET, CBL, and COX2, have come to the forefront as potential biomarkers and therapeutic targets. Thus, we review the various molecular mechanisms in lung cancer and the role of novel therapeutics. © 2011 Elsevier Inc.

Authors
Salgia, R; Hensing, T; Campbell, N; Salama, AK; Maitland, M; Hoffman, P; Villaflor, V; Vokes, EE
MLA Citation
Salgia, R, Hensing, T, Campbell, N, Salama, AK, Maitland, M, Hoffman, P, Villaflor, V, and Vokes, EE. "Personalized treatment of lung cancer." Seminars in Oncology 38.2 (2011): 274-283.
PMID
21421117
Source
scival
Published In
Seminars in Oncology
Volume
38
Issue
2
Publish Date
2011
Start Page
274
End Page
283
DOI
10.1053/j.seminoncol.2011.01.012

MET and phosphorylated MET as potential biomarkers in lung cancer

This study aimed to investigate the expression and prognostic role of the receptor tyrosine kinase MET, phosphorylated MET, and the ligand hepatocyte growth factor (HGF) in patients with lung cancer. This retrospective study included 129 patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with available tumor tissue and survival data. MET, pMET, and HGF expression were assessed using immunohistochemistry. MET, pMET, and HGF were more highly expressed in tumor tissue when compared to the adjacent lung parenchyma. A specific localization pattern was also evident: membranous, cytoplasmic, and nuclear patterns of expression were seen for MET, pMET, and HGF. In addition, high expression of two specific forms of phosphorylated MET-cytoplasmic expression of Y1003 and nuclear expression of Y1365-appeared to correlate with a worse overall survival (P=.016; hazard ratio [HR], 1.86; 95% confidence interval [95% CI], 1.12- 3.07; and P=.034; HR, 1.70; 95% CI, 1.04-2.78, respectively). In summary, MET, pMET, and HGF are highly expressed in both NSCLC and SCLC. Specific forms of pMET may serve as potential biomarkers in lung cancer. © 2011 Begell House, Inc.

Authors
Tretiakova, M; Salama, AKS; Karrison, T; Ferguson, MK; Husain, AN; Vokes, EE; Salgia, R
MLA Citation
Tretiakova, M, Salama, AKS, Karrison, T, Ferguson, MK, Husain, AN, Vokes, EE, and Salgia, R. "MET and phosphorylated MET as potential biomarkers in lung cancer." Journal of Environmental Pathology, Toxicology and Oncology 30.4 (2011): 341-354.
PMID
22181983
Source
scival
Published In
Journal of Environmental Pathology, Toxicology and Oncology
Volume
30
Issue
4
Publish Date
2011
Start Page
341
End Page
354

Mind-mapping for lung cancer: Towards a personalized therapeutics approach

There were over 220,000 people diagnosed with lung cancer and over 160,000 people dying of lung cancer during 2010 alone in the United States. In order to arrive at better control, prevention, diagnosis, and therapeutics for lung cancer, we must be able to personalize the approach towards the disease. Mind-mapping has existed for centuries for physicians to properly think about various "flows" of personalized medicine. We include here the epidemiology, diagnosis, histology, and treatment of lung cancer - in particular, non-small cell lung cancer. As we have new molecular signatures for lung cancer, this is further detailed. This review is not meant to be a comprehensive review, but rather its purpose is to highlight important aspects of lung cancer diagnosis, management, and personalized treatment options. © Springer Healthcare 2011.

Authors
Mollberg, N; Surati, M; Demchuk, C; Fathi, R; Salama, AK; Husain, AN; Hensing, T; Salgia, R
MLA Citation
Mollberg, N, Surati, M, Demchuk, C, Fathi, R, Salama, AK, Husain, AN, Hensing, T, and Salgia, R. "Mind-mapping for lung cancer: Towards a personalized therapeutics approach." Advances in Therapy 28.3 (2011): 173-194.
PMID
21337123
Source
scival
Published In
Advances in Therapy
Volume
28
Issue
3
Publish Date
2011
Start Page
173
End Page
194
DOI
10.1007/s12325-010-0103-9
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