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Melanoma: HELP
Articles by Charlotte E. Ariyan
Based on 43 articles published since 2010
(Why 43 articles?)
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Between 2010 and 2020, Charlotte Ariyan wrote the following 43 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update. 2018

Wong, Sandra L / Faries, Mark B / Kennedy, Erin B / Agarwala, Sanjiv S / Akhurst, Timothy J / Ariyan, Charlotte / Balch, Charles M / Berman, Barry S / Cochran, Alistair / Delman, Keith A / Gorman, Mark / Kirkwood, John M / Moncrieff, Marc D / Zager, Jonathan S / Lyman, Gary H. ·Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. · The Angeles Clinic and Research Institute, Santa Monica, CA, USA. · American Society of Clinical Oncology, Alexandria, VA, USA. guidelines@asco.org. · St Luke's Cancer Center, Easton, PA, USA. · Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. · Memorial Sloan Kettering Cancer Center, New York, NY, USA. · MD Anderson Cancer Center, Houston, TX, USA. · Broward Health, Fort Lauderdale, FL, USA. · Los Angeles Center for Health Services, University of California, Los Angeles, CA, USA. · Emory University, Atlanta, GA, USA. · , Silver Spring, MD, USA. · University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. · Norfolk and Norwich University Hospital, Norwich, UK. · H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ·Ann Surg Oncol · Pubmed #29236202.

ABSTRACT: PURPOSE: To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma. METHODS: An ASCO-SSO panel was formed, and a systematic review of the literature was conducted regarding SLN biopsy and completion lymph node dissection (CLND) after a positive sentinel node in patients with melanoma. RESULTS: Nine new observational studies, two systematic reviews and an updated randomized controlled trial (RCT) of SLN biopsy, as well as two randomized controlled trials of CLND after positive SLN biopsy, were included. RECOMMENDATIONS: Routine SLN biopsy is not recommended for patients with thin melanomas that are T1a (non-ulcerated lesions < 0.8 mm in Breslow thickness). SLN biopsy may be considered for thin melanomas that are T1b (0.8 to 1.0 mm Breslow thickness or <0.8 mm Breslow thickness with ulceration) after a thorough discussion with the patient of the potential benefits and risk of harms associated with the procedure. SLN biopsy is recommended for patients with intermediate-thickness melanomas (T2 or T3; Breslow thickness of >1.0 to 4.0 mm). SLN biopsy may be recommended for patients with thick melanomas (T4; > 4.0 mm in Breslow thickness), after a discussion of the potential benefits and risks of harm. In the case of a positive SLN biopsy, CLND or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathological factors. For higher risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND. Important qualifying statements outlining relevant clinicopathological factors, and details of the reference patient populations are included within the guideline.

2 Guideline Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update. 2018

Wong, Sandra L / Faries, Mark B / Kennedy, Erin B / Agarwala, Sanjiv S / Akhurst, Timothy J / Ariyan, Charlotte / Balch, Charles M / Berman, Barry S / Cochran, Alistair / Delman, Keith A / Gorman, Mark / Kirkwood, John M / Moncrieff, Marc D / Zager, Jonathan S / Lyman, Gary H. ·Sandra L. Wong, Dartmouth-Hitchcock Medical Center, Lebanon, NH · Mark B. Faries, The Angeles Clinic and Research Institute, Santa Monica · Alistair Cochran, University of California, Los Angeles Center for Health Services, Los Angeles, CA · Erin B. Kennedy, American Society of Clinical Oncology, Alexandria, VA · Sanjiv S. Agarwala, St Luke's Cancer Center, Easton · John M. Kirkwood, University of Pittsburgh Cancer Institute, Pittsburgh, PA · Timothy J. Akhurst, Peter MacCallum Cancer Centre, Victoria, Australia · Charlotte Ariyan, Memorial Sloan Kettering Cancer Center, New York, NY · Charles M. Balch, MD Anderson Cancer Center, Houston, TX · Barry S. Berman, Broward Health, Fort Lauderdale · Jonathan S. Zager, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL · Keith A. Delman, Emory University, Atlanta, GA · Mark Gorman, Silver Spring, MD · Marc D. Moncrieff, Norfolk and Norwich University Hospital, Norwich, United Kingdom · and Gary H. Lyman, Fred Hutchinson Cancer Research Center, Seattle, WA. ·J Clin Oncol · Pubmed #29232171.

ABSTRACT: Purpose To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma. Methods An ASCO-SSO panel was formed, and a systematic review of the literature was conducted regarding SLN biopsy and completion lymph node dissection (CLND) after a positive sentinel node in patients with melanoma. Results Nine new observational studies, two systematic reviews, and an updated randomized controlled trial of SLN biopsy, as well as two randomized controlled trials of CLND after positive SLN biopsy, were included. Recommendations Routine SLN biopsy is not recommended for patients with thin melanomas that are T1a (nonulcerated lesions < 0.8 mm in Breslow thickness). SLN biopsy may be considered for thin melanomas that are T1b (0.8 to 1.0 mm Breslow thickness or < 0.8 mm Breslow thickness with ulceration) after a thorough discussion with the patient of the potential benefits and risk of harms associated with the procedure. SLN biopsy is recommended for patients with intermediate-thickness melanomas (T2 or T3; Breslow thickness of > 1.0 to 4.0 mm). SLN biopsy may be recommended for patients with thick melanomas (T4; > 4.0 mm in Breslow thickness), after a discussion of the potential benefits and risks of harm. In the case of a positive SLN biopsy, CLND or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathological factors. For higher-risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND. Important qualifying statements outlining relevant clinicopathological factors and details of the reference patient populations are included within the guideline. Additional information is available at www.asco.org/melanoma-guidelines and www.asco.org/guidelineswiki .

3 Editorial MelMART Trial: It's Now or Never. 2018

Coit, Daniel / Ariyan, Charlotte. ·Memorial Sloan Kettering Cancer Center, New York, USA. · Memorial Sloan Kettering Cancer Center, New York, USA. ariyanc@mskcc.org. ·Ann Surg Oncol · Pubmed #29946999.

ABSTRACT: -- No abstract --

4 Review An Update on Randomized Clinical Trials in Melanoma. 2017

Karakousis, Giorgos / Ariyan, Charlotte. ·Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce St # 4, Philadelphia, PA 19104, USA. · Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: ariyanc@mskcc.org. ·Surg Oncol Clin N Am · Pubmed #28923220.

ABSTRACT: Despite many advances in the treatment of melanoma, it still continues to be a disease that affects many people. Fortunately, there have been a multitude of randomized trials that have refined the treatment of this prevalent disease. From 1975 to 2000, there were 154 prospective randomized trials on the treatment of local, regional, and metastatic melanoma. From 2001 to now, additional randomized trials have focused on the role of surgery, adjuvants to surgery, and treatment of metastatic disease. The results of the practice-changing trials are summarized in this review.

5 Review Update on immunotherapy in melanoma. 2015

Green, Jamie / Ariyan, Charlotte. ·Memorial Sloan Kettering Cancer Center, Department of Surgery, 1275 York Avenue, New York, NY 10065, USA. · Memorial Sloan Kettering Cancer Center, Department of Surgery, 1275 York Avenue, New York, NY 10065, USA. Electronic address: ariyanc@mskcc.org. ·Surg Oncol Clin N Am · Pubmed #25769716.

ABSTRACT: Immunotherapy is now recognized as a viable option for patients with metastatic melanoma. The field of immunotherapy now offers treatments with the potential for a long-term cure. As the field moves forward, studies will focus on improving the response rates with new immunotherapy agents or novel treatment combinations.

6 Review The GIST of targeted therapy for malignant melanoma. 2014

Bello, Danielle M / Dematteo, Ronald P / Ariyan, Charlotte E. ·Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. ·Ann Surg Oncol · Pubmed #24531699.

ABSTRACT: The high response rates to the tyrosine kinase inhibitor imatinib in KIT-mutated gastrointestinal stromal tumors (GIST) has led to a paradigm shift in cancer treatment. In a parallel fashion, the field of melanoma is shifting with the utilization of targeted therapy to treat BRAF-mutated melanoma. We reviewed published literature in PubMed on GIST and melanoma, with a focus on both past and current clinical trials. The data presented centers on imatinib, vemurafenib, and most recently dabrafenib, targeting KIT and BRAF mutations and their outcomes in GIST and melanoma. The BRAF(V600E) melanoma mutation, like the KIT exon 11 mutation in GIST, has the highest response to therapy. High response rates with inhibition of KIT in GIST have not been recapitulated in KIT-mutated melanoma. Median time to resistance to targeted agents occurs in ~7 months with BRAF inhibitors and 2 years for imatinib in GIST. In GIST, the development of secondary mutations leads to resistance; however, there have been no similar gatekeeper mutations found in melanoma. Although surgery remains an important component of the treatment of early GIST and melanoma, surgeons will need to continue to define the thresholds and timing for operation in the setting of metastatic disease with improved targeted therapies. Combination treatment strategies may result in more successful clinical outcomes in the management of melanoma in the future.

7 Review The delicate balance of melanoma immunotherapy. 2013

Gyorki, David E / Callahan, Margaret / Wolchok, Jedd D / Ariyan, Charlotte E. ·Memorial Sloan-Kettering Cancer Center , New York, NY, USA. · Memorial Sloan-Kettering Cancer Center , New York, NY, USA ; Ludwig Center, Memorial Sloan-Kettering Cancer Center , New York, NY, USA. · Memorial Sloan-Kettering Cancer Center , New York, NY, USA ; Ludwig Center, Memorial Sloan-Kettering Cancer Center , New York, NY, USA ; Weill Cornell Medical College , New York, NY, USA. · Memorial Sloan-Kettering Cancer Center , New York, NY, USA ; Weill Cornell Medical College , New York, NY, USA. ·Clin Transl Immunology · Pubmed #25505953.

ABSTRACT: The strategy of immune modulation for the treatment of cancer is being refined with the introduction of multiple new therapeutic agents into the clinic. Melanoma is a disease where many of these agents have demonstrated efficacy. The mechanisms of action of these agents exploit the counter-regulatory mechanisms of the immune response. However, these agents are also associated with immune-related adverse events (IRAEs), which represent tissue-specific inflammatory responses. These IRAEs highlight the delicate balance of immunologic homeostasis and, with some interventions, may occur more frequently in patients who sustain a therapeutic response. This review will discuss melanoma immunogenicity and immunotherapy. Furthermore, the spectrum and distinction between a reversible immune adverse event and autoimmunity will be highlighted.

8 Review Melanoma mutagenesis and aberrant cell signaling. 2013

Bello, Danielle M / Ariyan, Charlotte E / Carvajal, Richard D. ·Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. carvajar@mskcc.org. ·Cancer Control · Pubmed #24077403.

ABSTRACT: BACKGROUND: Malignant melanoma is the most fatal type of skin cancer. Traditional melanoma classification has been based on histological subtype or anatomical location. However, recent evidence suggests that melanoma comprises a group of diseases characterized by distinct molecular mutations. These mutations affect disease behavior but provide unique opportunities for targeted therapy. METHODS: In this review, several signaling pathways in melanoma are described as well as how mutations of BRAF, NRAS, KIT, GNAQ, and GNA11 genes cause aberrant signaling and malignant transformation. RESULTS: Multiple genes affecting both the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathway are mutated in melanoma. Melanomas harboring the BRAF V600E mutation have demonstrated sensitivity to both RAF and MAPK/extracellular signal regulated kinase (ERK) inhibitors in vitro and in vivo. In addition, KIT-mutant melanomas, often arising from mucosal, acral, and chronically sun-damaged skin surfaces, have shown clinical response to several inhibitors of the type III transmembrane receptor tyrosine kinase KIT. Uveal melanoma, which often harbors GNAQ or GNA11 mutations, may also be sensitive to MAPK/ERK or protein kinase C/PI3K pathway inhibition. CONCLUSIONS: Emerging knowledge of these molecular alterations has led to clinical advances in patients with melanoma. The study of known mutations and identification of new potential targets must continue in an effort to develop more effective therapies for this disease.

9 Review Controversies in the management of regional nodes in melanoma. 2012

Plitas, George / Ariyan, Charlotte E. ·Memorial Sloan-Kettering Cancer Center, Gastric and Mixed Tumor Service, New York, New York 10021, USA. ·J Natl Compr Canc Netw · Pubmed #22393199.

ABSTRACT: The surgical management of the regional lymph node basin of melanoma has undergone significant changes in the past 2 decades, most of which have been guided by prospective randomized trials. Historically, routine elective lymph node dissection was recommended for the management of melanoma regardless of clinical nodal involvement. Subsequent randomized trials failed to show a clear benefit for all patients, and sentinel lymph node (SLN) biopsy emerged as an alternative. Although the prognostic value of SLN biopsy in intermediate-thickness melanoma is well accepted, its value for patients with thin and thick lesions is debated. The therapeutic advantage of removing an involved SLN, and the need for a completion lymph node dissection after the identification of a positive SLN, are areas of continued controversy. This article discusses these issues in the management of the regional lymph node basin in patients with melanoma.

10 Clinical Trial Robust Antitumor Responses Result from Local Chemotherapy and CTLA-4 Blockade. 2018

Ariyan, Charlotte E / Brady, Mary Sue / Siegelbaum, Robert H / Hu, Jian / Bello, Danielle M / Rand, Jamie / Fisher, Charles / Lefkowitz, Robert A / Panageas, Kathleen S / Pulitzer, Melissa / Vignali, Marissa / Emerson, Ryan / Tipton, Christopher / Robins, Harlan / Merghoub, Taha / Yuan, Jianda / Jungbluth, Achim / Blando, Jorge / Sharma, Padmanee / Rudensky, Alexander Y / Wolchok, Jedd D / Allison, James P. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. ariyanc@mskcc.org. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Anesthesia, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Statistics, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. · Adaptive Biotechnology, Seattle, Washington. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Immunology, MD Anderson Cancer Center, Houston, Texas. · Department of Immunology, Memorial Sloan Kettering Cancer Center, New York, New York. ·Cancer Immunol Res · Pubmed #29339377.

ABSTRACT: Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a noninflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8

11 Clinical Trial Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. 2017

Faries, Mark B / Thompson, John F / Cochran, Alistair J / Andtbacka, Robert H / Mozzillo, Nicola / Zager, Jonathan S / Jahkola, Tiina / Bowles, Tawnya L / Testori, Alessandro / Beitsch, Peter D / Hoekstra, Harald J / Moncrieff, Marc / Ingvar, Christian / Wouters, Michel W J M / Sabel, Michael S / Levine, Edward A / Agnese, Doreen / Henderson, Michael / Dummer, Reinhard / Rossi, Carlo R / Neves, Rogerio I / Trocha, Steven D / Wright, Frances / Byrd, David R / Matter, Maurice / Hsueh, Eddy / MacKenzie-Ross, Alastair / Johnson, Douglas B / Terheyden, Patrick / Berger, Adam C / Huston, Tara L / Wayne, Jeffrey D / Smithers, B Mark / Neuman, Heather B / Schneebaum, Schlomo / Gershenwald, Jeffrey E / Ariyan, Charlotte E / Desai, Darius C / Jacobs, Lisa / McMasters, Kelly M / Gesierich, Anja / Hersey, Peter / Bines, Steven D / Kane, John M / Barth, Richard J / McKinnon, Gregory / Farma, Jeffrey M / Schultz, Erwin / Vidal-Sicart, Sergi / Hoefer, Richard A / Lewis, James M / Scheri, Randall / Kelley, Mark C / Nieweg, Omgo E / Noyes, R Dirk / Hoon, Dave S B / Wang, He-Jing / Elashoff, David A / Elashoff, Robert M. ·From the John Wayne Cancer Institute at Saint John's Health Center, Santa Monica (M.B.F., D.S.B.H.), and the Departments of Pathology (A.J.C.), Biomathematics (H.-J.W., D.A.E., R.M.E.), and Medicine (D.A.E.), University of California, Los Angeles - both in California · Melanoma Institute Australia and the University of Sydney, Sydney (J.F.T., O.E.N.), Peter MacCallum Cancer Centre, Melbourne, VIC (M.H.), Princess Alexandra Hospital, Brisbane, QLD (B.M.S.), and Newcastle Melanoma Unit, Waratah, NSW (P.H.) - all in Australia · Huntsman Cancer Institute, Salt Lake City (R.H.A., R.D.N.), and Intermountain Healthcare Cancer Services-Intermountain Medical Center, Murray (T.L.B.) - both in Utah · Istituto Nazionale dei Tumori Napoli, Naples (N.M.), Istituto Europeo di Oncologia, Milan (A.T.), and Istituto Oncologico Veneto-University of Padua, Padua (C.R.R.) - all in Italy · H. Lee Moffitt Cancer Center, Tampa, FL (J.S.Z.) · Helsinki University Hospital, Helsinki (T.J.) · Dallas Surgical Group, Dallas (P.D.B.) · Universitair Medisch Centrum Groningen, Groningen (H.J.H.), and Netherlands Cancer Institute, Amsterdam (M.W.J.M.W.) - both in the Netherlands · Norfolk and Norwich University Hospital, Norwich (M. Moncrieff), and Guy's and St. Thomas' NHS Foundation Trust, London (A.M.-R.) - both in the United Kingdom · Swedish Melanoma Study Group-University Hospital Lund, Lund, Sweden (C.I.) · University of Michigan, Ann Arbor (M.S.S.) · Wake Forest University, Winston-Salem (E.A.L.), and Duke University, Durham (R.S.) - both in North Carolina · Ohio State University, Columbus (D.A.) · University of Zurich, Zurich (R.D.), and Centre Hospitalier Universitaire Vaudois, Lausanne (M. Matter) - both in Switzerland · Penn State Hershey Cancer Institute, Hershey (R.I.N.), Thomas Jefferson University (A.C.B.) and Fox Chase Cancer Center (J.M.F.), Philadelphia, and St. Luke's University Health Network, Bethlehem (D.C.D.) - all in Pennsylvania · Greenville Health System Cancer Center, Greenville, SC (S.D.T.) · Sunnybrook Research Institute, Toronto (F.W.), and Tom Baker Cancer Centre, Calgary, AB (G.M.) - both in Canada · University of Washington, Seattle (D.R.B.) · Saint Louis University, St. Louis (E.H.) · Vanderbilt University (D.B.J., M.C.K.), Nashville, and University of Tennessee, Knoxville (J.M.L.) - both in Tennessee · University Hospital Schleswig-Holstein-Campus Lübeck, Lübeck (P.T.), University Hospital of Würzburg, Würzburg (A.G.), and City Hospital of Nürnberg, Nuremberg (E.S.) - all in Germany · SUNY at Stony Brook Hospital Medical Center, Stony Brook (T.L.H.), Memorial Sloan Kettering Cancer Center, New York (C.E.A.), and Roswell Park Cancer Institute, Buffalo (J.M.K.) - all in New York · Northwestern University Feinberg School of Medicine (J.D.W.) and Rush University Medical Center (S.D.B.), Chicago · University of Wisconsin, Madison (H.B.N.) · Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (S.S.) · M.D. Anderson Medical Center, Houston (J.E.G.) · Johns Hopkins University School of Medicine, Baltimore (L.J.) · University of Louisville, Louisville, KY (K.M.M.) · Dartmouth-Hitchcock Medical Center, Lebanon, NH (R.J.B.) · Hospital Clinic Barcelona, Barcelona (S.V.-S.) · and Sentara CarePlex Hospital, Hampton, VA (R.A.H.). ·N Engl J Med · Pubmed #28591523.

ABSTRACT: BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS: Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS: Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .).

12 Clinical Trial Safety and Feasibility of Minimally Invasive Inguinal Lymph Node Dissection in Patients With Melanoma (SAFE-MILND): Report of a Prospective Multi-institutional Trial. 2017

Jakub, James W / Terando, Alicia M / Sarnaik, Amod / Ariyan, Charlotte E / Faries, Mark B / Zani, Sabino / Neuman, Heather B / Wasif, Nabil / Farma, Jeffrey M / Averbook, Bruce J / Bilimoria, Karl Y / Grotz, Travis E / Allred, Jacob B Jake / Suman, Vera J / Brady, Mary Sue / Tyler, Douglas / Wayne, Jeffrey D / Nelson, Heidi. ·*Department of Surgery, Mayo Clinic, Rochester, MN †Department of Surgery, Ohio State University Medical Center, Columbus, OH ‡Department of Surgery, H. Lee Moffitt Cancer Center, Tampa, FL §Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY ¶Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, CA ||Department of Surgery, Duke University School of Medicine, Durham, NC **Division of General Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI ††Department of Surgery, Mayo Clinic, Phoenix, AZ ‡‡Department of Surgery, Fox Chase Cancer Center, Philadelphia, PA §§Department of Surgery, MetroHealth Medical Center, Cleveland, OH ¶¶Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL ||||Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN ***Department of Surgery, University of Texas Medical Branch, Galveston, TX. ·Ann Surg · Pubmed #28009745.

ABSTRACT: BACKGROUND: Minimally invasive inguinal lymph node dissection (MILND) is a novel approach to inguinal lymphadenectomy. SAFE-MILND (NCT01500304) is a multicenter, phase I/II clinical trial evaluating the safety and feasibility of MILND for patients with melanoma in a group of surgeons newly adopting the procedure. METHODS: Twelve melanoma surgeons from 10 institutions without any previous MILND experience, enrolled patients into a prospective study after completing specialized training including didactic lectures, participating in a hands-on cadaveric laboratory, and being provided an instructional DVD of the procedure. Complications and adverse postoperative events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.0. RESULTS: Eighty-seven patients underwent a MILND. Seventy-seven cases (88.5%) were completed via a minimally invasive approach. The median total inguinal lymph nodes pathologically examined (SLN + MILND) was 12.0 (interquartile range 8.0, 14.0). Overall, 71% of patients suffered an adverse event (AE); the majority of these were grades 1 and 2, with 26% of patients experiencing a grade 3 AE. No grade 4 or 5 AEs were observed. CONCLUSIONS: After a structured training program, high-volume melanoma surgeons adopted a novel surgical technique with a lymph node retrieval rate that met or exceeded current oncologic guidelines and published benchmarks, and a favorable morbidity profile.

13 Clinical Trial Training High-Volume Melanoma Surgeons to Perform a Novel Minimally Invasive Inguinal Lymphadenectomy: Report of a Prospective Multi-Institutional Trial. 2016

Jakub, James W / Terando, Alicia M / Sarnaik, Amod / Ariyan, Charlotte E / Faries, Mark B / Zani, Sabino / Neuman, Heather B / Wasif, Nabil / Farma, Jeffrey M / Averbook, Bruce J / Bilimoria, Karl Y / Allred, Jacob B Jake / Suman, Vera J / Grotz, Travis E / Zendejas, Benjamin / Wayne, Jeffrey D / Tyler, Douglas S. ·Department of Surgery, Mayo Clinic, Rochester, MN. Electronic address: jakub.james@mayo.edu. · Department of Surgery, Ohio State University Medical Center, Columbus, OH. · Department of Surgery, H Lee Moffitt Cancer Center, Tampa, FL. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, CA. · Department of Surgery, Duke University School of Medicine, Durham, NC. · Division of General Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI. · Department of Surgery, Mayo Clinic, Phoenix, AZ. · Department of Surgery, Fox Chase Cancer Center, Philadelphia, PA. · Department of Surgery, MetroHealth Medical Center, Cleveland, OH. · Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL. · Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN. · Department of Surgery, Mayo Clinic, Rochester, MN. · Department of Surgery, University of Texas Medical Branch, Galveston, TX. ·J Am Coll Surg · Pubmed #26711792.

ABSTRACT: BACKGROUND: Minimally invasive inguinal lymphadenectomy (MILND) is a novel procedure with the potential to decrease surgical morbidity compared with the traditional open approach. The current study examined the feasibility of a combined didactic and hands-on training program to prepare high-volume melanoma surgeons to perform this procedure safely and proficiently. STUDY DESIGN: A select group of melanoma surgeons with no MILND experience were recruited. After completing a structured training program, surgeons enrolled patients with melanoma who required inguinal lymphadenectomy and performed the procedure in the minimally invasive fashion. A proficiency score composed of lymph node yield, operative time, and blood loss (or adverse events) was assigned for each case. After performing six cases, surgeons meeting a threshold score were considered proficient in the procedure. RESULTS: Twelve surgeons from 10 institutions enrolled 88 patients. The majority of surgeons were deemed proficient within 6 cases (83%). No differences in operative time or lymph node yield were noted during the course of the study. The rate of conversion was higher during an individual surgeon's early experience (9 of 49 [18%]), and only 1 procedure was converted in the 39 cases performed after a surgeon had performed 5 cases (late conversion rate, 3%; p = 0.038); however, this did not remain significant after controlling for surgeon. CONCLUSIONS: After a structured training program, experienced melanoma surgeons adopted a novel surgical technique with acceptable operative times, conversions, and lymph node yield. Eighty-four percent of the surgeons who completed at least 6 MILND procedures were considered proficient based on our predetermined definition.

14 Clinical Trial Factors associated with response, survival, and limb salvage in patients undergoing isolated limb infusion. 2014

Steinman, Jonathan / Ariyan, Charlotte / Rafferty, Brian / Brady, Mary S. ·Department of Surgery, Gastric, Mixed Tumor Service, Memorial Sloan-Kettering Cancer Center, New York, New York. ·J Surg Oncol · Pubmed #24318953.

ABSTRACT: BACKGROUND: Isolated limb infusion (ILI) is a percutaneous method of delivering regional chemotherapy to patients with recurrent tumors of the extremity. This study determines predictors of response, survival, and limb salvage. METHODS: Single institution data from a prospective clinical trial and subsequent ILI experience were reviewed. Limb tumor burden was assessed in melanoma patients with "high" (≥10 lesions or one lesion >3 cm) or "low" burden (<10 lesions and no lesion >3 cm). Response was assessed at 3 months from ILI. RESULTS: Between 1999 and 2011, 62 patients underwent ILI (58 melanoma, 2 Merkel cell carcinoma (MCC), 2 soft tissue sarcoma (STS)). Low tumor burden patients had more complete responses (CR) (11/23, 48%) than high tumor burden (3/32, 9%, P < 0.001); they had higher 5-year survival (69% vs. 29%, P = .007). Five-year survival rates based on response: 91% CR, 53% partial response (PR), 25% less than PR (P = 0.042, CR vs. PR). 7 patients (11%) underwent amputation due to disease progression; 3 had prior CR or PR. CONCLUSIONS: Low tumor burden is a significant predictor of response in melanoma patients. Response to ILI is a significant predictor of survival. Progression of limb disease requiring amputation is not associated with any factors.

15 Clinical Trial Prognosis of acral melanoma: a series of 281 patients. 2013

Bello, Danielle M / Chou, Joanne F / Panageas, Katherine S / Brady, Mary S / Coit, Daniel G / Carvajal, Richard D / Ariyan, Charlotte E. ·Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. ·Ann Surg Oncol · Pubmed #23838913.

ABSTRACT: BACKGROUND: Acral melanoma (AM) is an unusual malignancy with poor survival. This study defines a cohort of patients, treated at a single institution, and the factors associated with survival and comparison with nonacral cutaneous melanoma (NACM). METHODS: All patients with AM presenting from 1995 to 2010 were identified from a prospectively maintained database. Analysis of clinicopathologic features of AM associated with disease-specific survival (DSS) was performed. A stratified, stage-matched survival analysis compared the outcome of 281 acral to 843 extremity NACM patients. RESULTS: A total of 281 AM patients (170 volar, 111 subungual) were identified. Pathologic stage (p < 0.001), ulceration (p < 0.001), Breslow thickness (p < 0.001), and a positive sentinel lymph node (p < 0.001) were found to be poor prognostic indicators associated with DSS. In stage-matched analysis, AM had a worse DSS compared with NACM (hazard ratio 1.8; 95 % CI 1.2-2.7; p < 0.01). CONCLUSIONS: This study represents the largest, single-institution series describing the characteristics and outcomes of AM. AM tumors exhibit aggressive histopathologic features associated with a poorer survival outcome. AM patients have an inferior survival than extremity NACM when matched for stage, perhaps reflecting inherent alterations in tumor biology. This warrants further investigation into the differences between acral and cutaneous melanoma.

16 Clinical Trial Nivolumab plus ipilimumab in advanced melanoma. 2013

Wolchok, Jedd D / Kluger, Harriet / Callahan, Margaret K / Postow, Michael A / Rizvi, Naiyer A / Lesokhin, Alexander M / Segal, Neil H / Ariyan, Charlotte E / Gordon, Ruth-Ann / Reed, Kathleen / Burke, Matthew M / Caldwell, Anne / Kronenberg, Stephanie A / Agunwamba, Blessing U / Zhang, Xiaoling / Lowy, Israel / Inzunza, Hector David / Feely, William / Horak, Christine E / Hong, Quan / Korman, Alan J / Wigginton, Jon M / Gupta, Ashok / Sznol, Mario. ·Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. wolchokj@mskcc.org ·N Engl J Med · Pubmed #23724867.

ABSTRACT: BACKGROUND: In patients with melanoma, ipilimumab (an antibody against cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4]) prolongs overall survival, and nivolumab (an antibody against the programmed death 1 [PD-1] receptor) produced durable tumor regression in a phase 1 trial. On the basis of their distinct immunologic mechanisms of action and supportive preclinical data, we conducted a phase 1 trial of nivolumab combined with ipilimumab in patients with advanced melanoma. METHODS: We administered intravenous doses of nivolumab and ipilimumab in patients every 3 weeks for 4 doses, followed by nivolumab alone every 3 weeks for 4 doses (concurrent regimen). The combined treatment was subsequently administered every 12 weeks for up to 8 doses. In a sequenced regimen, patients previously treated with ipilimumab received nivolumab every 2 weeks for up to 48 doses. RESULTS: A total of 53 patients received concurrent therapy with nivolumab and ipilimumab, and 33 received sequenced treatment. The objective-response rate (according to modified World Health Organization criteria) for all patients in the concurrent-regimen group was 40%. Evidence of clinical activity (conventional, unconfirmed, or immune-related response or stable disease for ≥24 weeks) was observed in 65% of patients. At the maximum doses that were associated with an acceptable level of adverse events (nivolumab at a dose of 1 mg per kilogram of body weight and ipilimumab at a dose of 3 mg per kilogram), 53% of patients had an objective response, all with tumor reduction of 80% or more. Grade 3 or 4 adverse events related to therapy occurred in 53% of patients in the concurrent-regimen group but were qualitatively similar to previous experience with monotherapy and were generally reversible. Among patients in the sequenced-regimen group, 18% had grade 3 or 4 adverse events related to therapy and the objective-response rate was 20%. CONCLUSIONS: Concurrent therapy with nivolumab and ipilimumab had a manageable safety profile and provided clinical activity that appears to be distinct from that in published data on monotherapy, with rapid and deep tumor regression in a substantial proportion of patients. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; ClinicalTrials.gov number, NCT01024231.).

17 Article High neutrophil-to-lymphocyte ratio (NLR) is associated with treatment failure and death in patients who have melanoma treated with PD-1 inhibitor monotherapy. 2020

Bartlett, Edmund K / Flynn, Jessica R / Panageas, Katherine S / Ferraro, Richard A / Sta Cruz, Jessica M / Postow, Michael A / Coit, Daniel G / Ariyan, Charlotte E. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. ·Cancer · Pubmed #31584709.

ABSTRACT: BACKGROUND: An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor survival in patients with cancer, including those who receive immunotherapies. The authors sought to investigate NLR as a biomarker of treatment outcomes in patients with melanoma who were treated with PD-1 inhibition. METHODS: Patients undergoing initial treatment with PD-1 inhibitor monotherapy for stage IV melanoma at a single center from 2012 to 2015 were included. Clinical characteristics and the NLR at baseline and before subsequent treatment cycles were collected. The time to treatment failure (TTF) and overall survival (OS) were evaluated using Kaplan-Meier and landmark analyses. RESULTS: Among 224 study patients, 63 (28%) had a baseline NLR ≥5. The baseline NLR was significantly associated with Eastern Cooperative Oncology Group performance status and the number of involved metastatic sites. With a median follow-up of 39 months in survivors, a baseline NLR ≥5 was independently associated with shorter OS (hazard ratio, 2.0; 95% CI, 1.3-2.9) and TTF (hazard ratio, 1.7; 95% CI, 1.2-2.4). An NLR increase ≥30% during the first 2 cycles of treatment was associated with worse OS (median, 47 vs 13.5 months; P < .001) and a trend toward shorter TTF (12.8 vs 5.9 months; P = .05). A combined baseline NLR ≥5 and an NLR increase ≥30% identified a small cohort with markedly shortened OS (median, 5.8 months) and TTF (median, 1.8 months). CONCLUSIONS: Elevated baseline NLR and an increased NLR early during treatment are prognostic for TTF and OS in patients who have melanoma treated with PD-1 inhibitor monotherapy. Combined, these biomarkers can widely risk-stratify patients for treatment failure and survival.

18 Article Observational study of talimogene laherparepvec use for melanoma in clinical practice in the United States (COSMUS-1). 2019

Perez, Matthew C / Zager, Jonathan S / Amatruda, Thomas / Conry, Robert / Ariyan, Charlotte / Desai, Anupam / Kirkwood, John M / Treichel, Sheryl / Cohan, David / Raskin, Leon. ·Moffitt Cancer Center, Tampa, FL 33612, USA. · Minnesota Oncology, Fridley, MN 55432, USA. · The University of Alabama at Birmingham, Birmingham, AL 35294, USA. · Memorial Sloan Kettering Cancer Center, NY 10065, USA. · Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. · UPMC Hillman Center, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15232, USA. · Amgen Inc., Thousand Oaks, CA 91320, USA. ·Melanoma Manag · Pubmed #31406563.

ABSTRACT: Aim: Talimogene laherparepvec (T-VEC) is an intralesional treatment for unresectable cutaneous, subcutaneous and nodal melanoma. COSMUS-1 was conducted to examine how T-VEC is used in US clinical practice. Materials & methods: A chart review was conducted at seven centers, with 78 patients screened and 76 eligible. Results: Patients began treatment with T-VEC between October 2015 and December 2016. Median follow-up was 9.4 months. Twenty percent of patients (n = 15) completed T-VEC treatment with no remaining injectable lesions or pathologic complete response. Flu-like symptoms were the most commonly reported adverse events (n = 8; 10.5%), followed by lesion ulceration (n = 4; 5.3%). No herpetic lesions or infections were reported. Conclusion: T-VEC was well tolerated and showed clinical utility.

19 Article Adipocyte-Derived Lipids Mediate Melanoma Progression via FATP Proteins. 2018

Zhang, Maomao / Di Martino, Julie S / Bowman, Robert L / Campbell, Nathaniel R / Baksh, Sanjeethan C / Simon-Vermot, Theresa / Kim, Isabella S / Haldeman, Pearce / Mondal, Chandrani / Yong-Gonzales, Vladimir / Abu-Akeel, Mohsen / Merghoub, Taha / Jones, Drew R / Zhu, Xiphias Ge / Arora, Arshi / Ariyan, Charlotte E / Birsoy, Kivanç / Wolchok, Jedd D / Panageas, Katherine S / Hollmann, Travis / Bravo-Cordero, Jose Javier / White, Richard M. ·Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Medicine, Division of Hematology and Medical Oncology, Icahn School of Medicine, Tisch Cancer Institute at Mount Sinai, New York, New York. · Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York. · Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, New York. · Department of Computational and Systems Biology, Memorial Sloan Kettering Cancer Center, New York, New York. · Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, New York. · Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York. · Metabolomics Core Resource Library, New York University Langone Health, New York, New York. · Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, New York. · Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York. whiter@mskcc.org. ·Cancer Discov · Pubmed #29903879.

ABSTRACT: Advanced, metastatic melanomas frequently grow in subcutaneous tissues and portend a poor prognosis. Though subcutaneous tissues are largely composed of adipocytes, the mechanisms by which adipocytes influence melanoma are poorly understood. Using

20 Article Primary and Metastatic Melanoma With NTRK Fusions. 2018

Lezcano, Cecilia / Shoushtari, Alexander N / Ariyan, Charlotte / Hollmann, Travis J / Busam, Klaus J. ·Departments of Pathology. · Medicine. · Surgery, Memorial Sloan Kettering Cancer, New York, NY. ·Am J Surg Pathol · Pubmed #29683819.

ABSTRACT: A number of oncogenic driver mutations have been identified in melanocytic nevi and melanoma, but translocations also play a role in tumorigenesis and provide potential therapeutic targets for malignant lesions. Various translocations, such as those involving the anaplastic lymphoma kinase (ALK), neurotrophic tropomyosin receptor kinase 1 (NTRK1), and NTRK3 have been reported in spitzoid melanocytic neoplasms leading to kinase-fusion proteins that result in immunohistochemically detectable ALK or NTRK expression. We have previously reported that ALK expression can be found in nonspitzoid primary and metastatic cutaneous melanomas. In this study we report that nonspitzoid metastasizing melanomas of adults may also harbor NTRK fusions and that NTRK expression can be immunohistochemically detected in these tumors. Of 751 melanomas analyzed by next-generation sequencing, 4 metastatic melanomas were identified with NTRK fusions, 3 involving NTRK1, 1 involving NTRK2. They occurred in 3 women and 1 man. Two of the corresponding primary tumors were from the trunk, 1 from an extremity and 1 tumor arose in anal skin. One primary tumor displayed features of superficial spreading melanoma and 3 were nodular melanomas. All tumors were cytologically characterized by the presence of large epithelioid melanocytes. All tumors were immunoreactive with anti-Trk antibody. Next-generation sequencing documented that the NTRK1 fusion partners included TRIM63, DDR2, and GON4L. One tumor harbored an NTRK2-TRAF2 fusion. Thus, our findings document that NTRK kinase fusions can occur in nonspitzoid metastasizing melanomas of adults. The presence of an NTRK family fusion in these tumors may provide a therapeutic opportunity in a small subset of patients with metastatic melanoma.

21 Article Adjuvant Therapy in the Treatment of Melanoma. 2018

Bello, Danielle M / Ariyan, Charlotte E. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. ariyanc@mskcc.org. ·Ann Surg Oncol · Pubmed #29468608.

ABSTRACT: -- No abstract --

22 Article Transected thin melanoma: Implications for sentinel lymph node staging. 2018

Herbert, Garth / Karakousis, Giorgos C / Bartlett, Edmund K / Zaheer, Salman / Graham, Danielle / Czerniecki, Brian J / Fraker, Douglas L / Ariyan, Charlotte / Coit, Daniel G / Brady, Mary S. ·Department of Surgery, San Antonio Military Medical Center, San Antonio, Texas. · Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. ·J Surg Oncol · Pubmed #29194673.

ABSTRACT: BACKGROUND AND OBJECTIVES: Indications for sentinel lymph node (SLN) biopsy in patients with thin melanoma (≤1 mm thick) are controversial. We asked whether deep margin (DM) positivity at initial biopsy of thin melanoma is associated with SLN positivity. METHODS: Cases were identified using prospectively maintained databases at two melanoma centers. Patients who had undergone SLN biopsy for melanoma ≤1 mm were included. DM status was assessed for association with SLN metastasis in univariate and multivariate analyses. RESULTS: 1413 cases were identified, but only 1129 with known DM status were included. 39% of patients had a positive DM on original biopsy. DM-positive and DM-negative patients did not differ significantly in primary thickness, ulceration, or mitotic activity. DM-positive and DM-negative patients had similar incidence of SLN metastasis (5.7% vs 3.5%; P = 0.07). Positive DM was not associated with SLN metastasis on univariate analysis (OR 1.69, 95% CI: 0.95-3.00, P = 0.07) or on multivariate analysis adjusted for Breslow depth, Clark level, mitotic rate, and ulceration (OR = 1.59, 95% CI: 0.89-2.85; P = 0.12). CONCLUSIONS: For patients with thin melanoma, a positive DM on initial biopsy is not associated with risk of SLN metastasis, so DM positivity should not be considered an indication for SLN staging in an otherwise low-risk patient.

23 Article Integrated genomic analyses reveal frequent 2017

Liang, Winnie S / Hendricks, William / Kiefer, Jeffrey / Schmidt, Jessica / Sekar, Shobana / Carpten, John / Craig, David W / Adkins, Jonathan / Cuyugan, Lori / Manojlovic, Zarko / Halperin, Rebecca F / Helland, Adrienne / Nasser, Sara / Legendre, Christophe / Hurley, Laurence H / Sivaprakasam, Karthigayini / Johnson, Douglas B / Crandall, Holly / Busam, Klaus J / Zismann, Victoria / Deluca, Valerie / Lee, Jeeyun / Sekulic, Aleksandar / Ariyan, Charlotte E / Sosman, Jeffrey / Trent, Jeffrey. ·Translational Genomics Research Institute, Phoenix, Arizona 85004, USA. · Mayo Clinic, Scottsdale, Arizona 85259, USA. · University of Arizona, College of Pharmacy, Tucson, Arizona 85721, USA. · Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. · Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. · Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea. · Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, USA. ·Genome Res · Pubmed #28373299.

ABSTRACT: Genomic analyses of cutaneous melanoma (CM) have yielded biological and therapeutic insights, but understanding of non-ultraviolet (UV)-derived CMs remains limited. Deeper analysis of acral lentiginous melanoma (ALM), a rare sun-shielded melanoma subtype associated with worse survival than CM, is needed to delineate non-UV oncogenic mechanisms. We thus performed comprehensive genomic and transcriptomic analysis of 34 ALM patients. Unlike CM, somatic alterations were dominated by structural variation and absence of UV-derived mutation signatures. Only 38% of patients demonstrated driver

24 Article Neutrophil to Lymphocyte Ratio is Associated With Outcome During Ipilimumab Treatment. 2017

Cassidy, Michael R / Wolchok, Rachel E / Zheng, Junting / Panageas, Katherine S / Wolchok, Jedd D / Coit, Daniel / Postow, Michael A / Ariyan, Charlotte. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States. Electronic address: cassidym@mskcc.org. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Weill Cornell Medical College, New York, NY, United States. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Weill Cornell Medical College, New York, NY, United States. ·EBioMedicine · Pubmed #28356222.

ABSTRACT: BACKGROUND: Ipilimumab (IPI) and BRAF inhibitors (BRAFi) improve survival in melanoma, but not all patients will benefit and toxicity can be significant. Pretreatment neutrophil to lymphocyte ratio (NLR) has been associated with outcome in IPI-treated patients, but has not been studied during treatment or in BRAFi-treated patients. METHODS: Using a prospectively maintained database, patients with unresectable stage III or IV melanoma treated with IPI or a BRAFi (vemurafenib or dabrafenib as monotherapy) from 2006 to 2011 were identified. NLR was calculated before treatment and at 3-week intervals after treatment initiation until 9weeks. Baseline NLR was tested for association with overall survival (OS), progression free survival (PFS), and clinical response to treatment. On-treatment NLRs were tested for association with the same outcomes using landmark survival analyses and time-dependent Cox regression models. The association of relative change of NLR from baseline with outcomes was also examined. A multivariate model tested the association of NLR and OS/PFS with additional clinical factors. RESULTS: There were 197 IPI patients and 65 BRAFi patients. In multivariable analysis adjusting for M stage, and disease type (in OS)/gender (in PFS), an NLR value of 5 or above at every timepoint was associated with worse OS (HR 2.03-3.37, p<0.001), PFS (HR 1.81-2.51, p<0.001), and response to therapy (OR 3.92-9.18, p<0.007), in the IPI cohort. In addition, a >30% increase in NLR above baseline at any timepoint was associated with a worse OS and PFS (HR 1.81 and 1.66, p<0.004). In BRAFi patients, NLR was not consistently associated with outcomes. CONCLUSIONS: A high NLR, whether measured prior to or during treatment with IPI, is associated with worse OS, PFS, and clinical response in patients with advanced melanoma. An increasing NLR from baseline during treatment was correlated with worse OS and PFS in IPI-treated patients. In comparison, as NLR was not associated with outcomes in BRAFi patients, NLR may have a uniquely predictive value in patients treated with immunotherapy.

25 Article Elevated Blood Neutrophil-to-Lymphocyte Ratio: A Readily Available Biomarker Associated with Death due to Disease in High Risk Nonmetastatic Melanoma. 2017

Davis, Jeremy L / Langan, Russell C / Panageas, Katherine S / Zheng, Junting / Postow, Michael A / Brady, Mary S / Ariyan, Charlotte / Coit, Daniel G. ·Department of Surgery; Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Melanoma and Immunotherapeutics Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Weill Cornell Medical College, New York, NY, USA. · Department of Surgery; Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. coitd@mskcc.org. ·Ann Surg Oncol · Pubmed #28303429.

ABSTRACT: BACKGROUND: Elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) is associated with poor oncologic outcomes in patients with stage IV melanoma and other solid tumors, but its impact has not been characterized for patients with high-risk, nonmetastatic melanoma. METHODS: Retrospective review of a melanoma database identified patients with high-risk melanoma who underwent operation with curative intent at a single institution. NLR was calculated from blood samples obtained within 2 weeks before operation. Multiple primary melanomas and concurrent hematologic or other metastatic malignancies were excluded. Cumulative incidence of death due to disease was estimated, and Gray's test was used to examine the effect of NLR on melanoma disease-specific death (DOD). Multivariable competing risks regression models assessed associated factors. RESULTS: Data on 1431 patients with high-risk, nonmetastatic melanoma were analyzed. Median follow-up for survivors was 4 years. High NLR (≥3 or as continuous variable) was associated with older age, male sex, thicker primaries, higher mitotic index, and more advanced nodal status. On multivariate analysis, high NLR (≥3 or as a continuous variable), older age, male sex, ulcerated primary, lymphovascular invasion, and positive nodal status were all independently associated with worse DOD. CONCLUSIONS: NLR is a readily available blood test that was independently associated with DOD in patients with high-risk, nonmetastatic melanoma. It is unclear whether high NLR is a passive indicator of poor prognosis or a potential therapeutic target. Further studies to evaluate the prognostic role of NLR to potentially identify those more likely to benefit from adjuvant immunotherapy may prove informative.

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