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Melanoma: HELP
Articles by Merrick I. Ross
Based on 105 articles published since 2008
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Between 2008 and 2019, M. I. Ross wrote the following 105 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Guideline NCCN Guidelines Insights: Melanoma, Version 3.2016. 2016

Coit, Daniel G / Thompson, John A / Algazi, Alain / Andtbacka, Robert / Bichakjian, Christopher K / Carson, William E / Daniels, Gregory A / DiMaio, Dominick / Fields, Ryan C / Fleming, Martin D / Gastman, Brian / Gonzalez, Rene / Guild, Valerie / Johnson, Douglas / Joseph, Richard W / Lange, Julie R / Martini, Mary C / Materin, Miguel A / Olszanski, Anthony J / Ott, Patrick / Gupta, Aparna Priyanath / Ross, Merrick I / Salama, April K / Skitzki, Joseph / Swetter, Susan M / Tanabe, Kenneth K / Torres-Roca, Javier F / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole / Engh, Anita. ·From Memorial Sloan Kettering Cancer Center; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; UCSF Helen Diller Family Comprehensive Cancer Center; Huntsman Cancer Institute at the University of Utah; University of Michigan Comprehensive Cancer Center; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; UC San Diego Moores Cancer Center; Fred & Pamela Buffett Cancer Center; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; The University of Tennessee Health Science Center; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute; University of Colorado Cancer Center; Aim at Melanoma; Vanderbilt-Ingram Cancer Center; Mayo Clinic Cancer Center; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Yale Cancer Center/Smilow Cancer Hospital; Fox Chase Cancer Center; Dana-Farber/Brigham and Women's Cancer Center; The University of Texas MD Anderson Cancer Center; Duke Cancer Institute; Roswell Park Cancer Institute; Stanford Cancer Institute; Massachusetts General Hospital Cancer Center; Moffitt Cancer Center; City of Hope Comprehensive Cancer Center; University of Alabama at Birmingham Comprehensive Cancer Center; and National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #27496110.

ABSTRACT: 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.

2 Guideline Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. 2016

Coit, Daniel G / Thompson, John A / Algazi, Alain / Andtbacka, Robert / Bichakjian, Christopher K / Carson, William E / Daniels, Gregory A / DiMaio, Dominick / Ernstoff, Marc / Fields, Ryan C / Fleming, Martin D / Gonzalez, Rene / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Joseph, Richard W / Lange, Julie R / Martini, Mary C / Materin, Miguel A / Olszanski, Anthony J / Ross, Merrick I / Salama, April K / Skitzki, Joseph / Sosman, Jeff / Swetter, Susan M / Tanabe, Kenneth K / Torres-Roca, Javier F / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole / Engh, Anita. · ·J Natl Compr Canc Netw · Pubmed #27059193.

ABSTRACT: 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.

3 Guideline Melanoma, version 4.2014. 2014

Coit, Daniel G / Thompson, John A / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daniels, Gregory A / Daud, Adil / Dimaio, Dominick / Fleming, Martin D / Gonzalez, Rene / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Martini, Mary C / Olszanski, Anthony J / Ross, Merrick I / Salama, April / Swetter, Susan M / Tanabe, Kenneth K / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole R / Ho, Maria / Anonymous5170793. ·From 1Memorial Sloan-Kettering Cancer Center; 2Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; 3Huntsman Cancer Institute at the University of Utah; 4University of Michigan Comprehensive Cancer Center; 5The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; 6UC San Diego Moores Cancer Center; 7UCSF Helen Diller Family Comprehensive Cancer Center; 8Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center; 9St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; 10University of Colorado Cancer Center; 11Aim at Melanoma; 12Dana-Farber/Brigham and Women's Cancer Center; 13Vanderbilt-Ingram Cancer Center; 14Roswell Park Cancer Institute; 15Moffitt Cancer Center; 16The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 17Robert H. Lurie Comprehensive Cancer Center of Northwestern University; 18Fox Chase Cancer Center; 19The University of Texas MD Anderson Cancer Center; 20Duke Cancer Institute; 21Stanford Cancer Institute; 22Massachusetts General Hospital Cancer Center; 23City of Hope Comprehensive Cancer Center; 24University of Alabama at Birmingham Comprehensive Cancer Center; and 25National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #24812131.

ABSTRACT: 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.

4 Guideline Melanoma, version 2.2013: featured updates to the NCCN guidelines. 2013

Coit, Daniel G / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daud, Adil / Dimaio, Dominick / Fleming, Martin D / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Lind, Anne / Martini, Mary C / Olszanski, Anthony J / Pruitt, Scott K / Ross, Merrick I / Swetter, Susan M / Tanabe, Kenneth K / Thompson, John A / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole / Ho, Maria / Anonymous4310755. ·Memorial Sloan-Kettering Cancer Center. ·J Natl Compr Canc Netw · Pubmed #23584343.

ABSTRACT: The NCCN Guidelines for Melanoma provide multidisciplinary recommendations on the clinical management of patients with melanoma. This NCCN Guidelines Insights report highlights notable recent updates. Foremost of these is the exciting addition of the novel agents ipilimumab and vemurafenib for treatment of advanced melanoma. The NCCN panel also included imatinib as a treatment for KIT-mutated tumors and pegylated interferon alfa-2b as an option for adjuvant therapy. Also important are revisions to the initial stratification of early-stage lesions based on the risk of sentinel lymph node metastases, and revised recommendations on the use of sentinel lymph node biopsy for low-risk groups. Finally, the NCCN panel reached clinical consensus on clarifying the role of imaging in the workup of patients with melanoma.

5 Guideline Melanoma. 2012

Coit, Daniel G / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daud, Adil / Dilawari, Raza A / Dimaio, Dominick / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Lind, Anne / Martini, Mary C / Olszanski, Anthony J / Pruitt, Scott K / Ross, Merrick I / Swetter, Susan M / Tanabe, Kenneth K / Thompson, John A / Trisal, Vijay / Urist, Marshall M / Anonymous590720. · ·J Natl Compr Canc Netw · Pubmed #22393197.

ABSTRACT: -- No abstract --

6 Guideline Melanoma. 2009

Coit, Daniel G / Andtbacka, Robert / Bichakjian, Christopher K / Dilawari, Raza A / Dimaio, Dominick / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kashani-Sabet, Mohammed / Lange, Julie R / Lind, Anne / Martin, Lainie / Martini, Mary C / Pruitt, Scott K / Ross, Merrick I / Sener, Stephen F / Swetter, Susan M / Tanabe, Kenneth K / Thompson, John A / Trisal, Vijay / Urist, Marshall M / Weber, Jeffrey / Wong, Michael K / Anonymous5080627. · ·J Natl Compr Canc Netw · Pubmed #19401060.

ABSTRACT: -- No abstract --

7 Editorial Excision Margins of Melanoma Make a Difference: New Data Support an Old Paradigm. 2016

Ross, Merrick I / Balch, Charles M. ·Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA. charles.balch@UTSouthwestern.edu. ·Ann Surg Oncol · Pubmed #26561402.

ABSTRACT: -- No abstract --

8 Review Intralesional therapy with PV-10 (Rose Bengal) for in-transit melanoma. 2014

Ross, Merrick I. ·Department of Surgical Oncology, Melanoma Section, M. D. Anderson Cancer Center, Houston, Texas. ·J Surg Oncol · Pubmed #24510477.

ABSTRACT: Rose Bengal is a novel injectable agent that has been evaluated as a rational treatment strategy for melanoma patients with recurrent unresectable local/regional metastases accessible for intralesional injection. PV-10 (10% Rose Bengal) has completed phase 1 and phase 2 multi-center clinical trials demonstrating significant local/regional disease control and also responses in non-injected regional bystander lesions and distant metastases. The published results of studies that have assessed PV-10 are presented, and the rationale for combining its use with recently approved immunotherapeutic agents is discussed.

9 Review Sentinel lymph node biopsy for melanoma: a critical update for dermatologists after two decades of experience. 2013

Ross, Merrick I / Gershenwald, Jeffrey E. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. mross@mdanderson.org ·Clin Dermatol · Pubmed #23608449.

ABSTRACT: The technique of lymphatic mapping and sentinel node biopsy represents a minimally invasive approach to accurately stage the regional lymph node basin as a component of the initial management of selected patients with stage I and II cutaneous melanomas. In addition to its significant role in accurate regional nodal staging and prognosis, important goals of this procedure include improved regional disease control and possible survival benefit. After 20 years of experience, questions and some controversy persist. This review provides the dermatology community with a critical analysis of major publications that have defined the role of sentinel node biopsy, addresses several contemporary issues, and provides recommendations for appropriate patient referral.

10 Review Variability in melanoma post-treatment surveillance practices by country and physician specialty: a systematic review. 2012

Cromwell, Kate D / Ross, Merrick I / Xing, Yan / Gershenwald, Jeffrey E / Royal, Richard E / Lucci, Anthony / Lee, Jeffrey E / Cormier, Janice N. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA. ·Melanoma Res · Pubmed #22914178.

ABSTRACT: There are no evidence-based guidelines for the surveillance of patients with melanoma following surgical treatment. We carried out a systematic review to identify by country and physician specialty the current stage-specific surveillance practices for patients with melanoma. Three major medical indices, MEDLINE, the Cochrane Library database, and Scopus, were reviewed to identify articles published from January 1970 to October 2011 that included detailed information about the surveillance of patients with melanoma after the initial surgical treatment. Data on surveillance intervals and recommended evaluation were extracted and categorized by country and, when reported, physician specialty. One hundred and four articles from 10 countries and four physician specialties (dermatology, surgical oncology, medical oncology, and general practice) fulfilled the inclusion criteria, including 43 providing specific patient-level data. The articles showed a wide variation with respect to the surveillance intervals and recommended evaluations. The variation was greatest for patients with stage I disease, for whom the follow-up frequency ranged from one to six visits per year during years 1 and 2 after treatment. All four physician specialties agreed that for years 1-3, the follow-up frequency should be four times per year for all patients. For years 4 and 5, surgical oncologists recommended two follow-up visits per year, whereas general practitioners, dermatologists, and medical oncologists recommended four visits per year. Recommended imaging and laboratory evaluations were most intense in the UK and most minimalist in the Netherlands. Although general practitioners did not recommend routine laboratory or imaging tests for surveillance, all other specialties utilized both in their surveillance practice. Self skin-examination was recommended for surveillance in all countries and by all practitioner specialties. There are significant intercountry and interspecialty variations in the surveillance of patients with melanoma. As the number of melanoma survivors increases, it will be critical to examine the benefits and costs of various follow-up strategies to establish consensus guidelines for melanoma post-treatment surveillance.

11 Review Health-related quality of life in patients with melanoma: overview of instruments and outcomes. 2012

Cormier, Janice N / Cromwell, Kate D / Ross, Merrick I. ·Department of Surgical Oncology, Unit 444, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Boulevard, Houston, TX 77030-4009, USA. jcormier@mdanderson.org ·Dermatol Clin · Pubmed #22284139.

ABSTRACT: The increasing public health burden of melanoma warrants evaluation of quality-of-life outcomes and the instruments most commonly used to measure quality of life in patients with melanoma. A review of the published literature focusing on quality-of-life outcomes in melanoma patients was performed to appraise the instruments used for assessment and the significant findings. In general, generic instruments continue to be most commonly used in the evaluation of quality of life despite the lack of responsiveness to changes in quality of life in subsets of patients. Cancer-specific and melanoma-specific instruments may be more suited for longitudinal clinical assessments.

12 Review Evidence-based treatment of early-stage melanoma. 2011

Ross, Merrick I / Gershenwald, Jeffrey E. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. mross@mdanderson.org ·J Surg Oncol · Pubmed #21858828.

ABSTRACT: The vast majority of patients with newly diagnosed melanoma are "early-stage" - ie, clinically localized to the primary cutaneous site. For such patients, surgery represents the mainstay of treatment; current standards of surgical management have evolved based on evidence obtained from randomized trials, large multi-center and single institutional databases, and consensus panels. Treatment strategies include wide excision of the primary site with margins dictated by important biological features such as Breslow tumor thickness, and sentinel node biopsy to surgically evaluate the regional nodal basins at risk. Sentinel node biopsy has become an important component of the initial management of many of these patients for accurate staging of regional lymph nodes, as well as enhanced regional disease control and improved survival in the patients with microscopically involved nodes. Evidence is presented that supports the rational use of these surgical strategies and reconciles some of the controversies that have emerged. The degree to which established national treatment guidelines are followed and the consequences of non-compliance with these guidelines have become the focus of recent clinical investigations; results of these efforts are also discussed.

13 Review Sentinel-lymph-node biopsy for cutaneous melanoma. 2011

Gershenwald, Jeffrey E / Ross, Merrick I. ·Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77230-1402, USA. jgershen@mdanderson.org ·N Engl J Med · Pubmed #21542744.

ABSTRACT: -- No abstract --

14 Review Metastasectomy for stage IV melanoma: for whom and how much? 2011

Caudle, Abigail S / Ross, Merrick I. ·Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 444, Houston, TX 77030, USA. ascaudle@mdanderson.org ·Surg Oncol Clin N Am · Pubmed #21111963.

ABSTRACT: Although the conventional paradigm for treating metastatic melanoma relies on systemic therapies, a surgical approach should be strongly considered in selected patients. A surgical approach may not be appropriate for all patients, but it can offer a rapid clearance of disease without the toxicity of systemic therapy. Patient selection is of paramount importance for surgery to be effective. The rationale for surgical intervention in the management of metastatic melanoma, selection factors to be considered, published results, and future directions are discussed in this article.

15 Review Sentinel lymph node biopsy for melanoma: critical assessment at its twentieth anniversary. 2011

Ross, Merrick I / Thompson, John F / Gershenwald, Jeffrey E. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 444, Houston, TX 77030, USA. ·Surg Oncol Clin N Am · Pubmed #21111959.

ABSTRACT: The technique of lymphatic mapping and sentinel lymph node (SLN) biopsy was introduced 20 years ago as an important advance in the management of patients with stage I and II melanoma. After 2 decades of experience, SLN biopsy and the practice of selective lymphadenectomy represents a minimally invasive standard of care that facilitates the accurate staging of the clinically negative regional lymph node basin, provides durable regional disease control, and improves survival in node-positive patients.

16 Review Sentinel node biopsy for melanoma: an update after two decades of experience. 2010

Ross, Merrick I. ·mross@mdanderson.org ·Semin Cutan Med Surg · Pubmed #21277537.

ABSTRACT: When detected and treated early, melanoma has an excellent prognosis. Unfortunately, as the tumor invades deeper into tissue the risk of metastatic spread to regional lymph nodes and beyond increases and the prognosis worsens significantly. Therefore, accurately detecting any regional lymphatic metastasis would significantly aid in determining a patient's prognosis and help guide his or her treatment plan. In 1991, Don Morton and colleagues presented new paradigm in diagnosing regional lymphatic involvement of tumors termed sentinel lymph node biopsy (SLNB). By mapping the regional lymph system around a tumor and tracing the lymphatic flow, a determination of the most likely lymph node or nodes the cancer will spread to first is made. Then, a limited biopsy of the most likely nodes is performed rather than a more-invasive removal of the entire local lymphatic chain. In 20 years that have followed, a great deal of information has been gained as to its accuracy, prognostic value, appropriate candidates, and its impact on regional disease control and survival. The SLNB has been shown to accurately stage regional lymph node basins in stage I and II melanoma patients with minimal morbidity. More sensitive histologic techniques are now being applied that may allow even greater accuracy in the staging of melanoma patients. Although specific percent risk thresholds are still in question, recommendation for SLNB when melanomas are 1 mm or thicker has gained wide acceptance. SLNB may also be appropriate for patients with melanomas that are between 0.76 and 1 mm thick and have ulceration, high mitotic rates, or reach a Clark level IV. Therefore, melanomas with IB or greater staging should be considered for SLNB.

17 Review Future directions in regional treatment strategies for melanoma and sarcoma. 2008

Beasley, G M / Ross, M I / Tyler, D S. ·Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. ·Int J Hyperthermia · Pubmed #18393007.

ABSTRACT: Hyperthermic isolated limb perfusion (HILP) with melphalan and more recently isolated limb infusion (ILI) with melphalan +/- dactinomycin are common treatment modalities for both in-transit melanoma of the extremity and advanced extremity sarcoma. In order to further optimize treatment, future research should focus on selection of appropriate patients, verification of a technique that produces consistent results while maintaining acceptable toxicity, and development of novel strategies and agents. Development of these novel agents and strategies has potential to not only improve the efficacy of regional chemotherapy but may also help guide future strategies for systemic treatment.

18 Review Current status of hyperthermic limb perfusion for in-transit melanoma. 2008

Ross, Merrick I. ·MD Anderson Cancer Center, Houston, TX 77030, USA. mross@mdanderson.org ·Int J Hyperthermia · Pubmed #18392999.

ABSTRACT: In-transit disease is a unique form of regional lymphatic spread of melanoma that is considered an infrequent event although certain high-risk subgroups have been identified with higher incidence rates. Although this disease entity is associated with a high risk for distant relapse, regionally focused treatment of disease is important due to the high morbidity associated with in-transit disease. Isolated limb perfusion has been a utilized method of regional treatment since the 1950's. The technical aspects, indications, historical results, and toxicity of limb perfusion are reviewed. Finally, perfusion based treatment of in-transit melanoma is an excellent model for studying novel agents and regimens in both the pre-clinical and patient care setting.

19 Clinical Trial Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. 2018

Amaria, Rodabe N / Reddy, Sangeetha M / Tawbi, Hussein A / Davies, Michael A / Ross, Merrick I / Glitza, Isabella C / Cormier, Janice N / Lewis, Carol / Hwu, Wen-Jen / Hanna, Ehab / Diab, Adi / Wong, Michael K / Royal, Richard / Gross, Neil / Weber, Randal / Lai, Stephen Y / Ehlers, Richard / Blando, Jorge / Milton, Denái R / Woodman, Scott / Kageyama, Robin / Wells, Daniel K / Hwu, Patrick / Patel, Sapna P / Lucci, Anthony / Hessel, Amy / Lee, Jeffrey E / Gershenwald, Jeffrey / Simpson, Lauren / Burton, Elizabeth M / Posada, Liberty / Haydu, Lauren / Wang, Linghua / Zhang, Shaojun / Lazar, Alexander J / Hudgens, Courtney W / Gopalakrishnan, Vancheswaran / Reuben, Alexandre / Andrews, Miles C / Spencer, Christine N / Prieto, Victor / Sharma, Padmanee / Allison, James / Tetzlaff, Michael T / Wargo, Jennifer A. ·Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA. · Department of Breast Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA. · Department of Head and Neck Surgery, MD Anderson Cancer Center, Houston, TX, USA. · Department of Immunology, MD Anderson Cancer Center, Houston, TX, USA. · Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA. · Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA. · Department of Genomic Medicine, MD Anderson Cancer Center, Houston, TX, USA. · Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA. · Department of Genitourinary Cancers, MD Anderson Cancer Center, Houston, TX, USA. · Department of Translational and Molecular Pathology, MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA. jwargo@mdanderson.org. · Department of Genomic Medicine, MD Anderson Cancer Center, Houston, TX, USA. jwargo@mdanderson.org. ·Nat Med · Pubmed #30297909.

ABSTRACT: Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses compared with adjuvant treatment

20 Clinical Trial Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial. 2018

Amaria, Rodabe N / Prieto, Peter A / Tetzlaff, Michael T / Reuben, Alexandre / Andrews, Miles C / Ross, Merrick I / Glitza, Isabella C / Cormier, Janice / Hwu, Wen-Jen / Tawbi, Hussein A / Patel, Sapna P / Lee, Jeffrey E / Gershenwald, Jeffrey E / Spencer, Christine N / Gopalakrishnan, Vancheswaran / Bassett, Roland / Simpson, Lauren / Mouton, Rosalind / Hudgens, Courtney W / Zhao, Li / Zhu, Haifeng / Cooper, Zachary A / Wani, Khalida / Lazar, Alexander / Hwu, Patrick / Diab, Adi / Wong, Michael K / McQuade, Jennifer L / Royal, Richard / Lucci, Anthony / Burton, Elizabeth M / Reddy, Sangeetha / Sharma, Padmanee / Allison, James / Futreal, Phillip A / Woodman, Scott E / Davies, Michael A / Wargo, Jennifer A. ·Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jwargo@mdanderson.org. ·Lancet Oncol · Pubmed #29361468.

ABSTRACT: BACKGROUND: Dual BRAF and MEK inhibition produces a response in a large number of patients with stage IV BRAF-mutant melanoma. The existing standard of care for patients with clinical stage III melanoma is upfront surgery and consideration for adjuvant therapy, which is insufficient to cure most patients. Neoadjuvant targeted therapy with BRAF and MEK inhibitors (such as dabrafenib and trametinib) might provide clinical benefit in this high-risk p opulation. METHODS: We undertook this single-centre, open-label, randomised phase 2 trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Eligible participants were adult patients (aged ≥18 years) with histologically or cytologically confirmed surgically resectable clinical stage III or oligometastatic stage IV BRAF FINDINGS: Between Oct 23, 2014, and April 13, 2016, we randomly assigned seven patients to standard of care, and 14 to neoadjuvant plus adjuvant dabrafenib and trametinib. The trial was stopped early after a prespecified interim safety analysis that occurred after a quarter of the participants had been accrued revealed significantly longer event-free survival with neoadjuvant plus adjuvant dabrafenib and trametinib than with standard of care. After a median follow-up of 18·6 months (IQR 14·6-23·1), significantly more patients receiving neoadjuvant plus adjuvant dabrafenib and trametinib were alive without disease progression than those receiving standard of care (ten [71%] of 14 patients vs none of seven in the standard of care group; median event-free survival was 19·7 months [16·2-not estimable] vs 2·9 months [95% CI 1·7-not estimable]; hazard ratio 0·016, 95% CI 0·00012-0·14, p<0·0001). Neoadjuvant plus adjuvant dabrafenib and trametinib were well tolerated with no occurrence of grade 4 adverse events or treatment-related deaths. The most common adverse events in the neoadjuvant plus adjuvant dabrafenib and trametinib group were expected grade 1-2 toxicities including chills (12 patients [92%]), headache (12 [92%]), and pyrexia (ten [77%]). The most common grade 3 adverse event was diarrhoea (two patients [15%]). INTERPRETATION: Neoadjuvant plus adjuvant dabrafenib and trametinib significantly improved event-free survival versus standard of care in patients with high-risk, surgically resectable, clinical stage III-IV melanoma. Although the trial finished early, limiting generalisability of the results, the findings provide proof-of-concept and support the rationale for further investigation of neoadjuvant approaches in this disease. This trial is currently continuing accrual as a single-arm study of neoadjuvant plus adjuvant dabrafenib and trametinib. FUNDING: Novartis Pharmaceuticals Corporation.

21 Clinical Trial Durable response rate as an endpoint in cancer immunotherapy: insights from oncolytic virus clinical trials. 2017

Kaufman, Howard L / Andtbacka, Robert H I / Collichio, Frances A / Wolf, Michael / Zhao, Zhongyun / Shilkrut, Mark / Puzanov, Igor / Ross, Merrick. ·Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08901, USA. howard.kaufman@rutgers.edu. · Huntsman Cancer Institute, University of Utah, 1950 Circle of Hope Drive, Salt Lake City, UT, 84112, USA. · The University of North Carolina Chapel Hill, 170 Manning Drive, Box 7305, Chapel Hill, NC, 27599, USA. · Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA. · Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA. · MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. ·J Immunother Cancer · Pubmed #28923101.

ABSTRACT: BACKGROUND: Traditional response criteria may be insufficient to characterize full clinical benefits of anticancer immunotherapies. Consequently, endpoints such as durable response rate (DRR; a continuous response [complete or partial objective response] beginning within 12 months of treatment and lasting ≥6 months) have been employed. There has not, however, been validation that DRR correlates with other more traditional endpoints of clinical benefit such as overall survival. METHODS: We evaluated whether DRR was associated with clinically meaningful measures of benefit (eg, overall survival [OS], quality of life [QoL], or treatment-free interval [TFI]) in a phase 3 clinical trial of an oncolytic virus for melanoma treatment. To evaluate the association between DRR and OS and to mitigate lead time bias, landmark analyses were used. QoL was evaluated using the FACT-BRM questionnaire (comprising the FACT-BRM Physical, Social/Family, Emotional, and Functional well-being domains, the Additional Concerns, Physical and Mental treatment-specific subscales, and the Trial Outcome Index [TOI]). TFI was defined as time from the last study therapy dose to first subsequent therapy dose (including any systemic anticancer therapy for melanoma after study therapy discontinuation). RESULTS: Four hundred thirty-six patients were included in the intent-to-treat population. Achieving DR was associated with a statistically significant improvement in OS in a landmark analysis at 9 months (HR = 0.07; P = 0.0003), 12 months (HR = 0.05, P < 0.0001), and 18 months (HR = 0.11; P = 0.0002) that persisted after adjusting for disease stage and line of therapy. Achieving a DR was associated with a longer median TFI (HR = 0.33; P = 0.0007) and a higher TOI improvement rate (58.1% versus 30.0%; P = 0.025). CONCLUSIONS: Achieving a DR was associated with clinical benefits such as improved OS and QoL and prolonged TFI, thus supporting the usefulness of DR as a meaningful immunotherapy clinical trial endpoint. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT00769704 ( https://clinicaltrials.gov/ct2/show/NCT00769704 ) October 7, 2008.

22 Clinical Trial Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma. 2016

Andtbacka, Robert H I / Agarwala, Sanjiv S / Ollila, David W / Hallmeyer, Sigrun / Milhem, Mohammed / Amatruda, Thomas / Nemunaitis, John J / Harrington, Kevin J / Chen, Lisa / Shilkrut, Mark / Ross, Merrick / Kaufman, Howard L. ·University of Utah Huntsman Cancer Institute, Salt Lake City, Utah. · St. Luke's University Hospital and Temple University, Philadelphia, Pennsylvania. · University of North Carolina, Chapel Hill, North Carolina. · Advocate Lutheran General Hospital, Park Ridge, Illinois. · University of Iowa Hospitals and Clinics, Iowa City, Iowa. · Minnesota Oncology, Fridley, Minnesota. · Mary Crowley Cancer Research Center, Dallas, Texas. · The Institute of Cancer Research/The Royal Marsden Hospital, London, UK. · Amgen, Inc, Thousand Oaks, California. · The University of Texas MD Anderson Cancer Center, Houston, Texas. · Rutgers Cancer Institute of New Jersey, Rutgers, New Jersey. ·Head Neck · Pubmed #27407058.

ABSTRACT: BACKGROUND: Cutaneous head and neck melanoma has poor outcomes and limited treatment options. In OPTiM, a phase 3 study in patients with unresectable stage IIIB/IIIC/IV melanoma, intralesional administration of the oncolytic virus talimogene laherparepvec improved durable response rate (DRR; continuous response ≥6 months) compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). METHODS: Retrospective review of OPTiM identified patients with cutaneous head and neck melanoma given talimogene laherparepvec (n = 61) or GM-CSF (n = 26). Outcomes were compared between talimogene laherparepvec and GM-CSF treated patients with cutaneous head and neck melanoma. RESULTS: DRR was higher for talimogene laherparepvec-treated patients than for GM-CSF treated patients (36.1% vs 3.8%; p = .001). A total of 29.5% of patients had a complete response with talimogene laherparepvec versus 0% with GM-CSF. Among talimogene laherparepvec-treated patients with a response, the probability of still being in response after 12 months was 73%. Median overall survival (OS) was 25.2 months for GM-CSF and had not been reached with talimogene laherparepvec. CONCLUSION: Treatment with talimogene laherparepvec was associated with improved response and survival compared with GM-CSF in patients with cutaneous head and neck melanoma. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1752-1758, 2016.

23 Clinical Trial Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial. 2016

Andtbacka, Robert H I / Ross, Merrick / Puzanov, Igor / Milhem, Mohammed / Collichio, Frances / Delman, Keith A / Amatruda, Thomas / Zager, Jonathan S / Cranmer, Lee / Hsueh, Eddy / Chen, Lisa / Shilkrut, Mark / Kaufman, Howard L. ·Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. Robert.Andtbacka@hci.utah.edu. · University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Vanderbilt University Medical Center, Nashville, TN, USA. · University of Iowa Hospitals and Clinics, Iowa City, IA, USA. · University of North Carolina, Chapel Hill, NC, USA. · Emory University, Atlanta, GA, USA. · Minnesota Oncology, Fridley, MN, USA. · Moffitt Cancer Center, Tampa, FL, USA. · University of Washington School of Medicine, Seattle, WA, USA. · Saint Louis University Cancer Center, St Louis, MO, USA. · Amgen Inc., Thousand Oaks, CA, USA. · Rutgers Cancer Institute of New Jersey, Rutgers, NJ, USA. ·Ann Surg Oncol · Pubmed #27342831.

ABSTRACT: PURPOSE: Talimogene laherparepvec (T-VEC) is an oncolytic immunotherapy designed to induce tumor regression of injected lesions through direct lytic effects, and of uninjected lesions through induction of systemic antitumor immunity. In this study, we describe the patterns and time course of response to T-VEC from the phase III OPTiM trial of 436 patients with unresected stages IIIB-IV melanoma. METHODS: Lesion-level response analyses were performed based on the type of lesion (injected or uninjected cutaneous, subcutaneous, or nodal lesions; or visceral lesions [uninjected]), and the best percentage change from baseline of the sum of products of the longest diameters was calculated. Patients randomized to T-VEC (n = 295) who experienced a durable response (continuous partial or complete response for ≥6 months) were evaluated for progression prior to response (PPR), defined as the appearance of a new lesion or >25 % increase in total baseline tumor area. RESULTS: T-VEC resulted in a decrease in size by ≥50 % in 64 % of injected lesions (N = 2116), 34 % of uninjected non-visceral lesions (N = 981), and 15 % of visceral lesions (N = 177). Complete resolution of lesions occurred in 47 % of injected lesions, 22 % of uninjected non-visceral lesions, and 9 % of visceral lesions. Of 48 patients with durable responses, 23 (48 %) experienced PPR, including 14 who developed new lesions only. No difference in overall survival was observed, and median duration of response was not reached in patients with PPR versus those without PPR. CONCLUSIONS: Responses in uninjected lesions provide validation of T-VEC-induced systemic immunotherapeutic effects against melanoma. PPR did not negatively impact the clinical effectiveness of T-VEC.

24 Clinical Trial Final Results of the Sunbelt Melanoma Trial: A Multi-Institutional Prospective Randomized Phase III Study Evaluating the Role of Adjuvant High-Dose Interferon Alfa-2b and Completion Lymph Node Dissection for Patients Staged by Sentinel Lymph Node Biopsy. 2016

McMasters, Kelly M / Egger, Michael E / Edwards, Michael J / Ross, Merrick I / Reintgen, Douglas S / Noyes, R Dirk / Martin, Robert C G / Goydos, James S / Beitsch, Peter D / Urist, Marshall M / Ariyan, Stephan / Sussman, Jeffrey J / Davidson, B Scott / Gershenwald, Jeffrey E / Hagendoorn, Lee J / Stromberg, Arnold J / Scoggins, Charles R. ·Kelly M. McMasters, Michael E. Egger, Robert C.G. Martin II, and Charles R. Scoggins, University of Louisville, James Graham Brown Cancer Center · Arnold J. Stromberg, University of Kentucky · and Lee J. Hagendoorn, Advertek Louisville, KY · Michael J. Edwards and Jeffrey J. Sussman, University of Cincinnati, Cincinnati, OH · Merrick I. Ross and Jeffrey E. Gershenwald, University of Texas MD Anderson Cancer Center, Houston · Peter D. Beitsch, Dallas Surgical Group, Dallas, TX · Douglas S. Reintgen, University of South Florida School of Medicine, Tampa, FL · R. Dirk Noyes, LDS Hospital, Salt Lake City, UT · James S. Goydos, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ · Marshall M. Urist, University of Alabama School of Medicine, Birmingham, AL · Stephan Ariyan, Yale University School of Medicine, New Haven, CT · and B. Scott Davidson, Northside Hospital Cancer Institute, Melanoma and Sarcoma Specialists of Georgia, Atlanta, GA. ·J Clin Oncol · Pubmed #26858331.

ABSTRACT: PURPOSE: The Sunbelt Melanoma Trial is a prospective randomized trial evaluating the role of high-dose interferon alfa-2b therapy (HDI) or completion lymph node dissection (CLND) for patients with melanoma staged by sentinel lymph node (SLN) biopsy. PATIENTS AND METHODS: Patients were eligible if they were age 18 to 70 years with primary cutaneous melanoma ≥ 1.0 mm Breslow thickness and underwent SLN biopsy. In Protocol A, patients with a single tumor-positive lymph node after SLN biopsy underwent CLND and were randomly assigned to observation versus HDI. In Protocol B, patients with tumor-negative SLN by standard histopathology and immunohistochemistry underwent molecular staging by reverse transcriptase polymerase chain reaction (RT-PCR). Patients positive by RT-PCR were randomly assigned to observation versus CLND versus CLND+HDI. Primary end points were disease-free survival (DFS) and overall survival (OS). RESULTS: In the Protocol A intention-to-treat analysis, there were no significant differences in DFS (hazard ratio, 0.82; P = .45) or OS (hazard ratio, 1.10; P = .68) for patients randomly assigned to HDI versus observation. In the Protocol B intention-to-treat analysis, there were no significant differences in overall DFS (P = .069) or OS (P = .77) across the three randomized treatment arms. Similarly, efficacy analysis (excluding patients who did not receive the assigned treatment) did not demonstrate significant differences in DFS or OS in Protocol A or Protocol B. Median follow-up time was 71 months. CONCLUSION: No survival benefit for adjuvant HDI in patients with a single positive SLN was found. Among patients with tumor-negative SLN by conventional pathology but with melanoma detected in the SLN by RT-PCR, there was no OS benefit for CLND or CLND+HDI.

25 Clinical Trial Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. 2015

Andtbacka, Robert H I / Kaufman, Howard L / Collichio, Frances / Amatruda, Thomas / Senzer, Neil / Chesney, Jason / Delman, Keith A / Spitler, Lynn E / Puzanov, Igor / Agarwala, Sanjiv S / Milhem, Mohammed / Cranmer, Lee / Curti, Brendan / Lewis, Karl / Ross, Merrick / Guthrie, Troy / Linette, Gerald P / Daniels, Gregory A / Harrington, Kevin / Middleton, Mark R / Miller, Wilson H / Zager, Jonathan S / Ye, Yining / Yao, Bin / Li, Ai / Doleman, Susan / VanderWalde, Ari / Gansert, Jennifer / Coffin, Robert S. ·Robert H.I. Andtbacka, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT · Howard L. Kaufman, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ · Frances Collichio, University of North Carolina Medical Center, Chapel Hill, NC · Thomas Amatruda, Minnesota Oncology, Fridley, MN · Neil Senzer, Mary Crowley Cancer Research Center, Dallas · Merrick Ross, University of Texas MD Anderson Cancer Center, Houston, TX · Jason Chesney, University of Louisville, Louisville, KY · Keith A. Delman, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA · Lynn E. Spitler, Northern California Melanoma Center, San Francisco · Gregory A. Daniels, University of California San Diego Medical Center, Moores Cancer Center, La Jolla · Yining Ye, Bin Yao, Ai Li, Ari Vander Walde, and Jennifer Gansert, Amgen, Thousand Oaks, CA · Igor Puzanov, Vanderbilt University, Nashville, TN · Sanjiv S. Agarwala, St Luke's University Hospital and Health Network, Bethlehem, and Temple University School of Medicine, Philadelphia, PA · Mohammed Milhem, University of Iowa Hospitals and Clinics, Iowa City, IA · Lee Cranmer, University of Arizona, Tucson, AZ · Brendan Curti, Earle A. Chiles Research Institute, Portland, OR · Karl Lewis, University of Colorado Cancer Center, Aurora, CO · Troy Guthrie, Baptist Cancer Institute, Jacksonville · Jonathan S. Zager, Moffitt Cancer Center, Tampa, FL · Gerald P. Linette, Washington University School of Medicine, St Louis, MO · Kevin Harrington, Institute of Cancer Research, Royal Marsden Hospital, London · Mark R. Middleton, National Institute for Health Research Biomedical Research Centre, Oxford, United Kingdom · Wilson H. Miller Jr, McGill University, Montreal, Quebec, Canada · and Susan Doleman and Robert S. Coffin, Amgen, Woburn, MA. ·J Clin Oncol · Pubmed #26014293.

ABSTRACT: PURPOSE: Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial. PATIENTS AND METHODS: Patients with injectable melanoma that was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T-VEC or subcutaneous GM-CSF. The primary end point was durable response rate (DRR; objective response lasting continuously ≥ 6 months) per independent assessment. Key secondary end points included overall survival (OS) and overall response rate. RESULTS: Among 436 patients randomly assigned, DRR was significantly higher with T-VEC (16.3%; 95% CI, 12.1% to 20.5%) than GM-CSF (2.1%; 95% CI, 0% to 4.5%]; odds ratio, 8.9; P < .001). Overall response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4% to 31.5% v 5.7%; 95% CI, 1.9% to 9.5%). Median OS was 23.3 months (95% CI, 19.5 to 29.6 months) with T-VEC and 18.9 months (95% CI, 16.0 to 23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P = .051). T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease. The most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. The only grade 3 or 4 AE occurring in ≥ 2% of T-VEC-treated patients was cellulitis (2.1%). No fatal treatment-related AEs occurred. CONCLUSION: T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P < .001) and longer median OS (P = .051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma.

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