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1. Adjuvant Pembrolizumab in Stage II Melanoma: Outcomes by Primary Tumor Location in the Randomized, Double-Blind, Phase III KEYNOTE-716 Trial: KEYNOTE-716 Outcomes by Tumor Location

Author

Yoon, Charles H., Ross, Merrick I., Gastman, Brian R., Luke, Jason J., Ascierto, Paolo A., Long, Georgina V., Rutkowski, Piotr, Khattak, Muhammad, Del Vecchio, Michele, de la Cruz Merino, Luis, Mackiewicz, Jacek, Chiarion-Sileni, Vanna, Schadendorf, Dirk, Carlino, Matteo S., Zhao, Yujie, Fukunaga-Kalabis, Mizuho, Krepler, Clemens, Eggermont, Alexander M. M., Gershenwald, Jeffrey E., and Sondak, Vernon K.

Published
2025
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3. Durable local control with hypofractionated radiation therapy for unresectable or metastatic melanoma

Author

Sydney A. Keatts, Aya F. Salem, David M. Swanson, Ahsan S. Farooqi, Andrew J. Bishop, Rodabe N. Amaria, Jennifer L. McQuade, Isabella C. Glitza Oliva, Adi Diab, Roi Weiser, Sarah B. Fisher, Ryan P. Goepfert, Merrick I. Ross, B. Ashleigh Guadagnolo, and Devarati Mitra

Subjects
Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background and purpose: As patients with advanced melanoma live longer in the context of systemic therapy advancements, better strategies for durable control of bulky tumors are needed. In this study, we evaluated if dose-escalated hypofractionated radiation therapy (HFRT) can provide durable local control and improve tumor-associated symptoms in patients with unresectable or bulky metastatic melanoma for whom stereotactic ablative radiotherapy (RT) approaches are not feasible due to tumor size or location. Materials and methods: We retrospectively reviewed 49 patients with unresectable or bulky metastatic melanoma who were treated to a total of 53 tumor targets with 12–17 fractions HFRT at our institution between 2015–2022. Clinical scenarios included: unresectable, locoregional only disease (26 %); oligometastatic disease (5 known sites of disease or with at least 3 sites progressing, 40 %). Results: Of the 53 HFRT targets, 91 % (n = 48) had radiographic evidence of response as defined by either stabilization (6 %, n = 3), decreased size (74 %, n = 39), or decreased FDG avidity (11 %, n = 6). Of the 43 symptomatic patients, 98 % (n = 42) had symptomatic improvement. One −year local control was 79 %, with 2-year progression-free and overall survival of 33 % and 39 % respectively. The most common acute toxicities were radiation dermatitis (16 %, n = 8) or a pain flare (14 %, n = 7). Late toxicities were uncommon and typically grade 1. Conclusion: HFRT provides favorable local control and symptomatic relief with limited toxicity in tumors not amenable to surgical resection or stereotactic ablative RT.

Published
2024
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4. Neoadjuvant relatlimab and nivolumab in resectable melanoma

Author

Amaria, Rodabe N., Postow, Michael, Burton, Elizabeth M., Tezlaff, Michael T., Ross, Merrick I., Torres-Cabala, Carlos, Glitza, Isabella C., Duan, Fei, Milton, Denái R., Busam, Klaus, Simpson, Lauren, McQuade, Jennifer L., Wong, Michael K., Gershenwald, Jeffrey E., Lee, Jeffrey E., Goepfert, Ryan P., Keung, Emily Z., Fisher, Sarah B., Betof-Warner, Allison, Shoushtari, Alexander N., Callahan, Margaret, Coit, Daniel, Bartlett, Edmund K., Bello, Danielle, Momtaz, Parisa, Nicholas, Courtney, Gu, Aidi, Zhang, Xuejun, Korivi, Brinda Rao, Patnana, Madhavi, Patel, Sapna P., Diab, Adi, Lucci, Anthony, Prieto, Victor G., Davies, Michael A., Allison, James P., Sharma, Padmanee, Wargo, Jennifer A., Ariyan, Charlotte, and Tawbi, Hussein A.

Published
2022
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5. Adjuvant pembrolizumab versus placebo in resected high-risk stage II melanoma: Health-related quality of life from the randomized phase 3 KEYNOTE-716 study

Author

Khattak, Muhammad A., Luke, Jason J., Long, Georgina V., Ascierto, Paolo A., Rutkowski, Piotr, Schadendorf, Dirk, Robert, Caroline, Grob, Jean-Jacques, de la Cruz Merino, Luis, Del Vecchio, Michele, Spagnolo, Francesco, Mackiewicz, Jacek, Chiarion-Sileni, Vanna, Carlino, Matteo S., Mohr, Peter, De Galitiis, Federica, Ross, Merrick I., Eroglu, Zeynep, Chen, Ke, Jiang, Ruixuan, Fukunaga-Kalabis, Mizuho, Krepler, Clemens, Eggermont, Alexander M.M., and Kirkwood, John M.

Published
2022
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7. Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy

Author

Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., and Wargo, Jennifer A.

Published
2022
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8. A phase II study of talimogene laherparepvec for patients with inoperable locoregional recurrence of breast cancer

Author

Megumi Kai, Angela N. Marx, Diane D. Liu, Yu Shen, Hui Gao, James M. Reuben, Gary Whitman, Savitri Krishnamurthy, Merrick I. Ross, Jennifer K. Litton, Bora Lim, Nuhad Ibrahim, Takahiro Kogawa, and Naoto T. Ueno

Subjects
Medicine, Science
Abstract

Abstract Talimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as monotherapy for inoperable locoregional recurrence of breast cancer. T-VEC was injected intratumorally at 106 PFU/mL on day 1 (cycle 1), 108 PFU/mL on day 22 (cycle 2), and 108 PFU/mL every 2 weeks thereafter (cycles ≥ 3). Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3–8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63–NA) and 361 days (95% CI, 240–NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n = 7, 78%). Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.

Published
2021
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11. Prognostic model for patient survival in primary anorectal mucosal melanoma: stage at presentation determines relevance of histopathologic features

Author

Nagarajan, Priyadharsini, Piao, Jin, Ning, Jing, Noordenbos, Laura E., Curry, Jonathan L., Torres-Cabala, Carlos A., Diwan, A.Hafeez, Ivan, Doina, Aung, Phyu P., Ross, Merrick I., Royal, Richard E., Wargo, Jennifer A., Wang, Wei-Lien, Samdani, Rashmi, Lazar, Alexander J., Rashid, Asif, Davies, Michael A., Prieto, Victor G., Gershenwald, Jeffrey E., and Tetzlaff, Michael T.

Published
2020
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13. Neoadjuvant systemic therapy in melanoma: recommendations of the International Neoadjuvant Melanoma Consortium

Author

Andrews, Miles C, Berry, Donald A, Block, Matthew S, Boland, Genevieve M, Bollin, Kathryn B, Carlino, Matteo S, Carvajal, Richard D, Cohen, Jonathan, Davar, Diwakar, Delman, Keith A, Dummer, Reinhard, Farwell, Michael D, Fisher, David E, Fusi, Alberto, Glitza, Isabella C, de Gruijl, Tanja D, Gyorki, David E, Hauschild, Axel, Hieken, Tina J, Larkin, James, Lawson, David H, Lebbe, Celeste, Lee, Jeffrey E, Lowe, Michael C, Luke, Jason J, McArthur, Grant A, McDermott, David F, McQuade, Jennifer L, Mitchell, Tara C, Petrella, Teresa M, Prieto, Peter A, Puzanov, Igor, Robert, Caroline, Salama, April K, Sandhu, Shaneen, Schadendorf, Dirk, Shoushtari, Alexander N, Sosman, Jeffrey A, Swetter, Susan M, Tanabe, Ken K, Turajlic, Samra, Tyler, Douglas S, Woodman, Scott E, Wright, Frances C, Zager, Jonathan S, Amaria, Rodabe N, Menzies, Alexander M, Burton, Elizabeth M, Scolyer, Richard A, Tetzlaff, Michael T, Antdbacka, Robert, Ariyan, Charlotte, Bassett, Roland, Carter, Brett, Daud, Adil, Faries, Mark, Fecher, Leslie A, Flaherty, Keith T, Gershenwald, Jeffrey E, Hamid, Omid, Hong, Angela, Kirkwood, John M, Lo, Serigne, Margolin, Kim, Messina, Jane, Postow, Michael A, Rizos, Helen, Ross, Merrick I, Rozeman, Elisa A, Saw, Robyn P M, Sondak, Vernon, Sullivan, Ryan J, Taube, Janis M, Thompson, John F, van de Wiel, Bart A, Eggermont, Alexander M, Davies, Michael A, Ascierto, Paolo A, Spillane, Andrew J, van Akkooi, Alexander C J, Wargo, Jennifer A, Blank, Christian U, Tawbi, Hussein A, and Long, Georgina V

Published
2019
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14. Spitz melanocytic neoplasms with MLPH::ALK fusions: Report of two cases with previously unreported features and literature review.

Author

Salah, Haneen T., Yang, Richard K., Roy‐Chowdhuri, Sinchita, Ross, Merrick I., Aung, Phyu P., Rothrock, Aimi T., Torres‐Cabala, Carlos A., Curry, Jonathan L., Prieto, Victor G., Nagarajan, Priyadharsini, and Cho, Woo Cheal

Subjects
LITERATURE reviews, TUMORS, NEVUS, ENGLISH literature, GENE fusion, MELANOCYTES
Abstract

ALK‐fused Spitz melanocytic neoplasms are a distinct subgroup of melanocytic lesions exhibiting unique histopathologic characteristics. These lesions often manifest as exophytic or polypoid tumors, characterized by fusiform‐to‐epithelioid melanocytes arranged in a nested, fascicular, or plexiform growth pattern. Several fusion partners of the ALK gene have been identified in spitzoid melanocytic neoplasms, with TPM3 and DCTN1 being the most prevalent. Less common fusion partners include NPM1, TPR, CLIP1, GTF3C2, EEF2, MYO5A, KANK1, and EHBP1. The MLPH gene, which encodes melanophilin (MLPH), playing a crucial role in regulating skin pigmentation by acting as a linker between RAB27A and myosin Va during melanosome transport, has also recently been recognized as a rare fusion partner of ALK in Spitz melanocytic neoplasms. Currently, there exists a sparse documentation within English literature, illustrating a limited number of cases featuring MLPH::ALK fusion in Spitz melanocytic neoplasms. In this report, we present two additional cases, including a previously unreported instance of Spitz melanoma, contributing to the expanding knowledge on ALK‐fused Spitz melanocytic neoplasms. In addition, we provide a comprehensive review of the clinical, histopathologic, and molecular features observed in documented cases with this novel fusion. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Neoadjuvant–Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma

Author

Sapna P. Patel, Megan Othus, Yuanbin Chen, G. Paul Wright, Kathleen J. Yost, John R. Hyngstrom, Siwen Hu-Lieskovan, Christopher D. Lao, Leslie A. Fecher, Thach-Giao Truong, Jennifer L. Eisenstein, Sunandana Chandra, Jeffrey A. Sosman, Kari L. Kendra, Richard C. Wu, Craig E. Devoe, Gary B. Deutsch, Aparna Hegde, Maya Khalil, Ankit Mangla, Amy M. Reese, Merrick I. Ross, Andrew S. Poklepovic, Giao Q. Phan, Adedayo A. Onitilo, Demet G. Yasar, Benjamin C. Powers, Gary C. Doolittle, Gino K. In, Niels Kokot, Geoffrey T. Gibney, Michael B. Atkins, Montaser Shaheen, James A. Warneke, Alexandra Ikeguchi, Jose E. Najera, Bartosz Chmielowski, Joseph G. Crompton, Justin D. Floyd, Eddy Hsueh, Kim A. Margolin, Warren A. Chow, Kenneth F. Grossmann, Eliana Dietrich, Victor G. Prieto, Michael C. Lowe, Elizabeth I. Buchbinder, John M. Kirkwood, Larissa Korde, James Moon, Elad Sharon, Vernon K. Sondak, and Antoni Ribas

Subjects
General Medicine
Published
2023
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17. 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

Author

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, and Wargo, Jennifer A

Published
2018
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18. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

Author

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., and Wargo, Jennifer A.

Published
2018
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19. Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma

Author

Alexander C J, van Akkooi, Tina J, Hieken, Elizabeth M, Burton, Charlotte, Ariyan, Paolo A, Ascierto, Salvatore V M A, Asero, Christian U, Blank, Matthew S, Block, Genevieve M, Boland, Corrado, Caraco, Sydney, Chng, B Scott, Davidson, Joao Pedreira, Duprat Neto, Mark B, Faries, Jeffrey E, Gershenwald, Dirk J, Grunhagen, David E, Gyorki, Dale, Han, Andrew J, Hayes, Winan J, van Houdt, Giorgos C, Karakousis, Willem M C, Klop, Georgina V, Long, Michael C, Lowe, Alexander M, Menzies, Roger, Olofsson Bagge, Thomas E, Pennington, Piotr, Rutkowski, Robyn P M, Saw, Richard A, Scolyer, Kerwin F, Shannon, Vernon K, Sondak, Hussein, Tawbi, Alessandro A E, Testori, Mike T, Tetzlaff, John F, Thompson, Jonathan S, Zager, Charlotte L, Zuur, Jennifer A, Wargo, Andrew J, Spillane, Merrick I, Ross, and Surgery

Subjects
Skin Neoplasms, Oncology, Humans, Surgery, Melanoma, Neoadjuvant Therapy
Abstract

Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.

Published
2022
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21. Genomic Classification of Cutaneous Melanoma

Author

Akbani, Rehan, Akdemir, Kadir C., Aksoy, B. Arman, Albert, Monique, Ally, Adrian, Amin, Samirkumar B., Arachchi, Harindra, Arora, Arshi, Auman, J. Todd, Ayala, Brenda, Baboud, Julien, Balasundaram, Miruna, Balu, Saianand, Barnabas, Nandita, Bartlett, John, Bartlett, Pam, Bastian, Boris C., Baylin, Stephen B., Behera, Madhusmita, Belyaev, Dmitry, Benz, Christopher, Bernard, Brady, Beroukhim, Rameen, Bir, Natalie, Black, Aaron D., Bodenheimer, Tom, Boice, Lori, Boland, Genevieve M., Bono, Riccardo, Bootwalla, Moiz S., Bosenberg, Marcus, Bowen, Jay, Bowlby, Reanne, Bristow, Christopher A., Brockway-Lunardi, Laura, Brooks, Denise, Brzezinski, Jakub, Bshara, Wiam, Buda, Elizabeth, Burns, William R., Butterfield, Yaron S.N., Button, Michael, Calderone, Tiffany, Cappellini, Giancarlo Antonini, Carter, Candace, Carter, Scott L., Cherney, Lynn, Cherniack, Andrew D., Chevalier, Aaron, Chin, Lynda, Cho, Juok, Cho, Raymond J., Choi, Yoon-La, Chu, Andy, Chudamani, Sudha, Cibulskis, Kristian, Ciriello, Giovanni, Clarke, Amanda, Coons, Stephen, Cope, Leslie, Crain, Daniel, Curley, Erin, Danilova, Ludmila, D’Atri, Stefania, Davidsen, Tanja, Davies, Michael A., Delman, Keith A., Demchok, John A., Deng, Qixia A., Deribe, Yonathan Lissanu, Dhalla, Noreen, Dhir, Rajiv, DiCara, Daniel, Dinikin, Michael, Dubina, Michael, Ebrom, J. Stephen, Egea, Sophie, Eley, Greg, Engel, Jay, Eschbacher, Jennifer M., Fedosenko, Konstantin V., Felau, Ina, Fennell, Timothy, Ferguson, Martin L., Fisher, Sheila, Flaherty, Keith T., Frazer, Scott, Frick, Jessica, Fulidou, Victoria, Gabriel, Stacey B., Gao, Jianjiong, Gardner, Johanna, Garraway, Levi A., Gastier-Foster, Julie M., Gaudioso, Carmelo, Gehlenborg, Nils, Genovese, Giannicola, Gerken, Mark, Gershenwald, Jeffrey E., Getz, Gad, Gomez-Fernandez, Carmen, Gribbin, Thomas, Grimsby, Jonna, Gross, Benjamin, Guin, Ranabir, Gutschner, Tony, Hadjipanayis, Angela, Halaban, Ruth, Hanf, Benjamin, Haussler, David, Haydu, Lauren E., Hayes, D. Neil, Hayward, Nicholas K., Heiman, David I., Herbert, Lynn, Herman, James G., Hersey, Peter, Hoadley, Katherine A., Hodis, Eran, Holt, Robert A., Hoon, Dave SB., Hoppough, Susan, Hoyle, Alan P., Huang, Franklin W., Huang, Mei, Huang, Sharon, Hutter, Carolyn M., Ibbs, Matthew, Iype, Lisa, Jacobsen, Anders, Jakrot, Valerie, Janning, Alyssa, Jeck, William R., Jefferys, Stuart R., Jensen, Mark A., Jones, Corbin D., Jones, Steven J.M., Ju, Zhenlin, Kakavand, Hojabr, Kang, Hyojin, Kefford, Richard F., Khuri, Fadlo R., Kim, Jaegil, Kirkwood, John M., Klode, Joachim, Korkut, Anil, Korski, Konstanty, Krauthammer, Michael, Kucherlapati, Raju, Kwong, Lawrence N., Kycler, Witold, Ladanyi, Marc, Lai, Phillip H., Laird, Peter W., Lander, Eric, Lawrence, Michael S., Lazar, Alexander J., Łaźniak, Radoslaw, Lee, Darlene, Lee, Jeffrey E., Lee, Junehawk, Lee, Kenneth, Lee, Semin, Lee, William, Leporowska, Ewa, Leraas, Kristen M., Li, Haiyan I., Lichtenberg, Tara M., Lichtenstein, Lee, Lin, Pei, Ling, Shiyun, Liu, Jia, Liu, Ouida, Liu, Wenbin, Long, Georgina V., Lu, Yiling, Ma, Singer, Ma, Yussanne, Mackiewicz, Andrzej, Mahadeshwar, Harshad S., Malke, Jared, Mallery, David, Manikhas, Georgy M., Mann, Graham J., Marra, Marco A., Matejka, Brenna, Mayo, Michael, Mehrabi, Sousan, Meng, Shaowu, Meyerson, Matthew, Mieczkowski, Piotr A., Miller, John P., Miller, Martin L., Mills, Gordon B., Moiseenko, Fedor, Moore, Richard A., Morris, Scott, Morrison, Carl, Morton, Donald, Moschos, Stergios, Mose, Lisle E., Muller, Florian L., Mungall, Andrew J., Murawa, Dawid, Murawa, Pawel, Murray, Bradley A., Nezi, Luigi, Ng, Sam, Nicholson, Dana, Noble, Michael S., Osunkoya, Adeboye, Owonikoko, Taofeek K., Ozenberger, Bradley A., Pagani, Elena, Paklina, Oxana V., Pantazi, Angeliki, Parfenov, Michael, Parfitt, Jeremy, Park, Peter J., Park, Woong-Yang, Parker, Joel S., Passarelli, Francesca, Penny, Robert, Perou, Charles M., Pihl, Todd D., Potapova, Olga, Prieto, Victor G., Protopopov, Alexei, Quinn, Michael J., Radenbaugh, Amie, Rai, Kunal, Ramalingam, Suresh S., Raman, Ayush T., Ramirez, Nilsa C., Ramirez, Ricardo, Rao, Uma, Rathmell, W. Kimryn, Ren, Xiaojia, Reynolds, Sheila M., Roach, Jeffrey, Robertson, A. Gordon, Ross, Merrick I., Roszik, Jason, Russo, Giandomenico, Saksena, Gordon, Saller, Charles, Samuels, Yardena, Sander, Chris, Sander, Cindy, Sandusky, George, Santoso, Netty, Saul, Melissa, Saw, Robyn PM., Schadendorf, Dirk, Schein, Jacqueline E., Schultz, Nikolaus, Schumacher, Steven E., Schwallier, Charles, Scolyer, Richard A., Seidman, Jonathan, Sekhar, Pedamallu Chandra, Sekhon, Harmanjatinder S., Senbabaoglu, Yasin, Seth, Sahil, Shannon, Kerwin F., Sharpe, Samantha, Sharpless, Norman E., Shaw, Kenna R. Mills, Shelton, Candace, Shelton, Troy, Shen, Ronglai, Sheth, Margi, Shi, Yan, Shiau, Carolyn J., Shmulevich, Ilya, Sica, Gabriel L., Simons, Janae V., Sinha, Rileen, Sipahimalani, Payal, Sofia, Heidi J., Soloway, Matthew G., Song, Xingzhi, Sougnez, Carrie, Spillane, Andrew J., Spychała, Arkadiusz, Stretch, Jonathan R., Stuart, Joshua, Suchorska, Wiktoria M., Sucker, Antje, Sumer, S. Onur, Sun, Yichao, Synott, Maria, Tabak, Barbara, Tabler, Teresa R., Tam, Angela, Tan, Donghui, Tang, Jiabin, Tarnuzzer, Roy, Tarvin, Katherine, Tatka, Honorata, Taylor, Barry S., Teresiak, Marek, Thiessen, Nina, Thompson, John F., Thorne, Leigh, Thorsson, Vesteinn, Trent, Jeffrey M., Triche, Timothy J., Jr., Tsai, Kenneth Y., Tsou, Peiling, Van Den Berg, David J., Van Allen, Eliezer M., Veluvolu, Umadevi, Verhaak, Roeland G., Voet, Douglas, Voronina, Olga, Walter, Vonn, Walton, Jessica S., Wan, Yunhu, Wang, Yuling, Wang, Zhining, Waring, Scot, Watson, Ian R., Weinhold, Nils, Weinstein, John N., Weisenberger, Daniel J., White, Peter, Wilkerson, Matthew D., Wilmott, James S., Wise, Lisa, Wiznerowicz, Maciej, Woodman, Scott E., Wu, Chang-Jiun, Wu, Chia-Chin, Wu, Junyuan, Wu, Ye, Xi, Ruibin, Xu, Andrew Wei, Yang, Da, Yang, Liming, Yang, Lixing, Zack, Travis I., Zenklusen, Jean C., Zhang, Hailei, Zhang, Jianhua, Zhang, Wei, Zhao, Xiaobei, Zhu, Jingchun, Zhu, Kelsey, Zimmer, Lisa, Zmuda, Erik, and Zou, Lihua

Published
2015
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26. Presence of Circulating Tumor Cells Predates Imaging Detection of Relapse in Patients with Stage III Melanoma.

Author

Lucci, Anthony, Addanki, Sridevi, Chiang, Yi-Ju, Meas, Salyna, Sarli, Vanessa N., Upshaw, Joshua R., Manchem, Mayank, Patel, Sapna P., Wargo, Jennifer A., Gershenwald, Jeffrey E., and Ross, Merrick I.

Subjects
MELANOMA prognosis, PUBLIC health surveillance, MELANOMA, CANCER relapse, METASTASIS, DESCRIPTIVE statistics, RESEARCH funding, DECISION making in clinical medicine, PROGRESSION-free survival, BODY fluid examination, TUMOR markers, LONGITUDINAL method
Abstract

Simple Summary: In this study, we investigated how frequently and how early circulating tumor cells (CTCs) were identified prior to the surveillance imaging detection of melanoma progression. This paper reports the results from 325 stage III melanoma patients from a prospective, IRB-approved study at our institution. These patients had blood drawn at baseline and then every 6–12 months to identify CTCs up to 3.5 years from diagnosis. Imaging (CT, PET/CT, MRI, and/or ultrasound) was conducted at baseline and then every 3 months as standard follow-up. We found that CTCs were detected in 76% of stage III melanoma patients who eventually had radiologically detected disease recurrence/metastasis and were identified at a median time of 9 months before imaging confirmation of disease progression. We believe that this finding is important as it provides the basis for future studies using CTCs to risk stratifying melanoma patients. Stage III melanoma includes nodal metastasis or in-transit disease. Five-year survival rates vary between 32% and 93%. The identification of high-risk patients is important for clinical decision making. We demonstrated previously that ≥1 circulating tumor cells (CTCs) at baseline was associated with recurrence. In this study, we investigated how frequently CTCs were identified prior to radiologically detected recurrence. Stage III patients (n = 325) had imaging at baseline and q 3 months. Baseline and q 6–12 months blood draws (7.5 mL) were performed to identify CTCs up to 3.5 years from diagnosis. CTC assessment was performed using the immunomagnetic capture of CD146-positive cells and anti-MEL-PE. The presence of one or more CTCs was considered positive. We analyzed the cohort of patients with relapse confirmed by radiologic imaging. CTC collection dates were assessed to determine the lead time for CTC detection. CTC-negative patients were significantly less likely to relapse compared to patients positive for CTCs (p-value < 0.001). Within the 325-patient cohort, 143 patients (44%) had recurrence, with a median follow-up of 52 months from diagnosis. The cohort (n = 143) with positive imaging and CTC results revealed 76% of patients (108/143) had CTC+ results before the radiological identification of relapse. The median time between positive CTC and positive imaging was 9 months. CTCs were positive in >75% of patients prior to relapse at a median of 9 months before radiologic detection. [ABSTRACT FROM AUTHOR]

Published
2023
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29. Neoadjuvant relatlimab and nivolumab in resectable melanoma

Author

Rodabe N. Amaria, Michael Postow, Elizabeth M. Burton, Michael T. Tetzlaff, Merrick I. Ross, Carlos Torres-Cabala, Isabella C. Glitza, Fei Duan, Denái R. Milton, Klaus Busam, Lauren Simpson, Jennifer L. McQuade, Michael K. Wong, Jeffrey E. Gershenwald, Jeffrey E. Lee, Ryan P. Goepfert, Emily Z. Keung, Sarah B. Fisher, Allison Betof-Warner, Alexander N. Shoushtari, Margaret Callahan, Daniel Coit, Edmund K. Bartlett, Danielle Bello, Parisa Momtaz, Courtney Nicholas, Aidi Gu, Xuejun Zhang, Brinda Rao Korivi, Madhavi Patnana, Sapna P. Patel, Adi Diab, Anthony Lucci, Victor G. Prieto, Michael A. Davies, James P. Allison, Padmanee Sharma, Jennifer A. Wargo, Charlotte Ariyan, and Hussein A. Tawbi

Subjects
Survival Rate, Multidisciplinary, Nivolumab, Macrophages, Humans, Antibodies, Monoclonal, Drug Therapy, Combination, Immune Checkpoint Inhibitors, Melanoma, Neoadjuvant Therapy, Neoplasm Staging
Abstract

Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma1. We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate2. The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid Tumors 1.1 was 57%. No grade 3–4 immune-related adverse events were observed in the neoadjuvant setting. The 1- and 2-year recurrence-free survival rate was 100% and 92% for patients with any pathologic response, compared to 88% and 55% for patients who did not have a pathologic response (P = 0.005). Increased immune cell infiltration at baseline, and decrease in M2 macrophages during treatment, were associated with pathologic response. Our results indicate that neoadjuvant relatlimab and nivolumab induces a high pCR rate. Safety during neoadjuvant therapy is favourable compared to other combination immunotherapy regimens. These data, in combination with the results of the RELATIVITY-047 trial1, provide further confirmation of the efficacy and safety of this new immunotherapy regimen.

Published
2022

34. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response

Author

Christine N. Spencer, Jennifer L. McQuade, Vancheswaran Gopalakrishnan, John A. McCulloch, Marie Vetizou, Alexandria P. Cogdill, Md A. Wadud Khan, Xiaotao Zhang, Michael G. White, Christine B. Peterson, Matthew C. Wong, Golnaz Morad, Theresa Rodgers, Jonathan H. Badger, Beth A. Helmink, Miles C. Andrews, Richard R. Rodrigues, Andrey Morgun, Young S. Kim, Jason Roszik, Kristi L. Hoffman, Jiali Zheng, Yifan Zhou, Yusra B. Medik, Laura M. Kahn, Sarah Johnson, Courtney W. Hudgens, Khalida Wani, Pierre-Olivier Gaudreau, Angela L. Harris, Mohamed A. Jamal, Erez N. Baruch, Eva Perez-Guijarro, Chi-Ping Day, Glenn Merlino, Barbara Pazdrak, Brooke S. Lochmann, Robert A. Szczepaniak-Sloane, Reetakshi Arora, Jaime Anderson, Chrystia M. Zobniw, Eliza Posada, Elizabeth Sirmans, Julie Simon, Lauren E. Haydu, Elizabeth M. Burton, Linghua Wang, Minghao Dang, Karen Clise-Dwyer, Sarah Schneider, Thomas Chapman, Nana-Ama A. S. Anang, Sheila Duncan, Joseph Toker, Jared C. Malke, Isabella C. Glitza, Rodabe N. Amaria, Hussein A. Tawbi, Adi Diab, Michael K. Wong, Sapna P. Patel, Scott E. Woodman, Michael A. Davies, Merrick I. Ross, Jeffrey E. Gershenwald, Jeffrey E. Lee, Patrick Hwu, Vanessa Jensen, Yardena Samuels, Ravid Straussman, Nadim J. Ajami, Kelly C. Nelson, Luigi Nezi, Joseph F. Petrosino, P. Andrew Futreal, Alexander J. Lazar, Jianhua Hu, Robert R. Jenq, Michael T. Tetzlaff, Yan Yan, Wendy S. Garrett, Curtis Huttenhower, Padmanee Sharma, Stephanie S. Watowich, James P. Allison, Lorenzo Cohen, Giorgio Trinchieri, Carrie R. Daniel, and Jennifer A. Wargo

Subjects
Dietary Fiber, Male, Multidisciplinary, Probiotics, T-Lymphocytes, Melanoma, Experimental, Fecal Microbiota Transplantation, Fatty Acids, Volatile, Progression-Free Survival, Gastrointestinal Microbiome, Cohort Studies, Mice, Inbred C57BL, Feces, Mice, Animals, Humans, Female, Immunotherapy, Immune Checkpoint Inhibitors, Melanoma
Abstract

Another benefit of dietary fiber The gut microbiome can modulate the immune system and influence the therapeutic response of cancer patients, yet the mechanisms underlying the effects of microbiota are presently unclear. Spencer et al . add to our understanding of how dietary habits affect microbiota and clinical outcomes to immunotherapy. In an observational study, the researchers found that melanoma patients reporting high fiber (prebiotic) consumption had a better response to checkpoint inhibitor immunotherapy compared with those patients reporting a low-fiber diet. The most marked benefit was observed for those patients reporting a combination of high fiber consumption and no use of over-the-counter probiotic supplements. These findings provide early insights as to how diet-related factors may influence the immune response. —PNK

Published
2021

35. Age as a Predictor of Sentinel Node Metastasis among Patients with Localized Melanoma: An Inverse Correlation of Melanoma Mortality and Incidence of Sentinel Node Metastasis Among Young and Old Patients

Author

Balch, Charles M., Thompson, John F., Gershenwald, Jeffrey E., Soong, Seng-jaw, Ding, Shouluan, McMasters, Kelly M., Coit, Daniel G., Eggermont, Alexander M. M., Gimotty, Phyllis A., Johnson, Timothy M., Kirkwood, John M., Leong, Stanley P., Ross, Merrick I., Byrd, David R., Cochran, Alistair J., Mihm, Jr, Martin C., Morton, Donald L., Atkins, Michael B., Flaherty, Keith T., and Sondak, Vernon K.

Published
2014
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37. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: Analysis of 5823 cases as the basis of the first consensus staging system

Author

Lemos, Bianca D., Storer, Barry E., Iyer, Jayasri G., Phillips, Jerri Linn, Bichakjian, Christopher K., Fang, L. Christine, Johnson, Timothy M., Liegeois-Kwon, Nanette J., Otley, Clark C., Paulson, Kelly G., Ross, Merrick I., Yu, Siegrid S., Zeitouni, Nathalie C., Byrd, David R., Sondak, Vernon K., Gershenwald, Jeffrey E., Sober, Arthur J., and Nghiem, Paul

Published
2010
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39. Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes

Author

Michael A. Davies, Miles C. Andrews, Russell G. Witt, Scott E. Woodman, Rodabe N. Amaria, Jeffrey E. Gershenwald, Khalida Wani, Lauren E. Haydu, Anik Banerjee, Chantale Bernatchez, Robert Sloane, Elizabeth M. Burton, Jennifer A. Wargo, Nadim J. Ajami, Jennifer L. McQuade, Emily Z. Keung, Julie M. Simon, Merrick I. Ross, Linghua Wang, Hussein Abdul-Hassan Tawbi, Michael G. White, Guangchun Han, and Alexander J. Lazar

Subjects
Cancer Research, microRNA, business.industry, Melanoma, Cell, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, immune checkpoint blockade, Malignancy, medicine.disease, Article, Blockade, Transcriptome, medicine.anatomical_structure, Immune system, Oncology, Gene expression, medicine, Cancer research, melanoma, business, RC254-282
Abstract

Simple Summary We conducted a network analysis of microRNA–mRNA associations in melanoma tissue and cell lines to identify the microRNAs central to melanoma biology and their associated gene expression profiles. Further, we evaluated expression of these microRNAs in melanoma patient biopsies and found that increased expression of miR-100-5p and miR-125b-5p were associated with improved outcomes with anti-PD-1 immunotherapy. Further investigation of these microRNAs as biomarkers and potential targets to improve immunotherapy response in melanoma is warranted. Abstract Metastatic melanoma is a deadly malignancy with poor outcomes historically. Immuno-oncology (IO) agents, targeting immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1), have revolutionized melanoma treatment and outcomes, achieving significant response rates and remarkable long-term survival. Despite these vast improvements, roughly half of melanoma patients do not achieve long-term clinical benefit from IO therapies and there is an urgent need to understand and mitigate mechanisms of resistance. MicroRNAs are key post-transcriptional regulators of gene expression that regulate many aspects of cancer biology, including immune evasion. We used network analysis to define two core microRNA–mRNA networks in melanoma tissues and cell lines corresponding to ‘MITF-low’ and ‘Keratin’ transcriptomic subsets of melanoma. We then evaluated expression of these core microRNAs in pre-PD-1-inhibitor-treated melanoma patients and observed that higher expression of miR-100-5p and miR-125b-5p were associated with significantly improved overall survival. These findings suggest that miR-100-5p and 125b-5p are potential markers of response to PD-1 inhibitors, and further evaluation of these microRNA–mRNA interactions may yield further insight into melanoma resistance to PD-1 inhibitors.

Published
2021
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48. Age as a Prognostic Factor in Patients with Localized Melanoma and Regional Metastases

Author

Balch, Charles M., Soong, Seng-jaw, Gershenwald, Jeffrey E., Thompson, John F., Coit, Daniel G., Atkins, Michael B., Ding, Shouluan, Cochran, Alistair J., Eggermont, Alexander M. M., Flaherty, Keith T., Gimotty, Phyllis A., Johnson, Timothy M., Kirkwood, John M., Leong, Stanley P., McMasters, Kelly M., Mihm, Jr., Martin C., Morton, Donald L., Ross, Merrick I., and Sondak, Vernon K.

Published
2013
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