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JOURNAL ARTICLE
Yee Peng Phoon, Jared E Lopes, Lukas W Pfannenstiel, Claudia Marcela Diaz-Montero, Ye F Tian, Marc S Ernstoff, Pauline Funchain, Jennifer S Ko, Raymond Winquist, Heather C Losey, Jan Joseph Melenhorst, Brian R Gastman
BACKGROUND: Despite recent advances in immunotherapy, a substantial population of late-stage melanoma patients still fail to achieve sustained clinical benefit. Lack of translational preclinical models continues to be a major challenge in the field of immunotherapy; thus, more optimized translational models could strongly influence clinical trial development. To address this unmet need, we designed a preclinical model reflecting the heterogeneity in melanoma patients' clinical responses that can be used to evaluate novel immunotherapies and synergistic combinatorial treatment strategies...
April 11, 2024: Journal for Immunotherapy of Cancer
#2
JOURNAL ARTICLE
Alan Shen, Michelle Arbesman, Roshan Lodha, Patricia Rayman, Brandon Bungo, Ying Ni, Timothy Chan, Brian Gastman, Jennifer Ko, C Marcela Diaz-Montero, Joshua Arbesman, Pauline Funchain
PURPOSE: Malignant melanoma represents the most lethal skin cancer with germline predispositions thought to comprise 10-15% of all melanoma cases. No studies to date examine the immunologic features that may differentiate survival differences between germline pathogenic variant (gPV) positive patients with melanoma from gPV negative patients with melanoma. EXPERIMENTAL DESIGN: Adult patients with melanoma and clinical characteristics suggesting hereditary predisposition to cancer were prospectively recruited to undergo germline testing and flow cytometric analysis of peripheral immune suppressor cells...
November 30, 2023: Clinical Cancer Research
#3
JOURNAL ARTICLE
Vipin Shankar Chelakkot, Kiara Thomas, Todd Romigh, Andrew Fong, Lin Li, Shira Ronen, Shuyang Chen, Pauline Funchain, Ying Ni, Joshua Arbesman
MC1R, a G-protein coupled receptor, triggers ultraviolet light-induced melanin synthesis and DNA repair in melanocytes and is implicated in the pathogenesis of melanoma. Although widely expressed in different tissue types, its function in non-cutaneous tissue is relatively unknown. Herein, we demonstrate that disruptive MC1R variants associated with melanomagenesis are less frequently found in patients with several cancers. Further exploration revealed that breast cancer tissue shows a significantly higher MC1R expression than normal breast tissue, and knocking down MC1R significantly reduced cell proliferation in vitro and in vivo...
September 7, 2023: NPJ Precision Oncology
#4
JOURNAL ARTICLE
Rahul Seth, Sanjiv S Agarwala, Hans Messersmith, Krishna C Alluri, Paolo A Ascierto, Michael B Atkins, Kathryn Bollin, Matias Chacon, Nancy Davis, Mark B Faries, Pauline Funchain, Jason S Gold, Samantha Guild, David E Gyorki, Varinder Kaur, Nikhil I Khushalani, John M Kirkwood, Jennifer Leigh McQuade, Michael O Meyers, Anthony Provenzano, Caroline Robert, Mario Santinami, Amikar Sehdev, Vernon K Sondak, Gilliosa Spurrier, Umang Swami, Thach-Giao Truong, Katy K Tsai, Alexander van Akkooi, Jeffrey Weber
PURPOSE: To provide guidance to clinicians regarding the use of systemic therapy for melanoma. METHODS: American Society of Clinical Oncology convened an Expert Panel and conducted an updated systematic review of the literature. RESULTS: The updated review identified 21 additional randomized trials. UPDATED RECOMMENDATIONS: Neoadjuvant pembrolizumab was newly recommended for patients with resectable stage IIIB to IV cutaneous melanoma...
October 20, 2023: Journal of Clinical Oncology
#5
JOURNAL ARTICLE
Cynthia Liu, Malek Shatila, Antony Mathew, Antonio Pizuorno Machado, Austin Thomas, Hao Chi Zhang, Anusha S Thomas, David Faleck, Pauline Funchain, Jessica Philpott, Petros Grivas, Michel Obeid, Franck Carbonnel, Yinghong Wang
Background: Immune-mediated diarrhea and colitis (IMDC) frequently develop after treatment with immune checkpoint inhibitors. C-reactive protein (CRP) is a serum inflammatory biomarker used to stratify and monitor disease severity in many inflammatory conditions. However, CRP level is not specific and is widely influenced by various factors non-specific to bowel inflammation. We aimed to study the utility of CRP as a predictor of disease severity and therapy response in IMDC. Methods: We performed a retrospective analysis of patients diagnosed with IMDC who had CRP measured at IMDC onset and after treatment with selective immunosuppressive therapy (SIT: infliximab and vedolizumab), between 01/2016 and 02/2022 at MD Anderson Cancer Center...
2023: Journal of Cancer
#6
JOURNAL ARTICLE
Chen Yan, Merry Huang, Carol Swetlik, Karlo Toljan, Ahmad Z Mahadeen, James Bena, Amy Kunchok, Pauline Funchain, Marisa McGinley
BACKGROUND: Little is known about risk factors for developing neurological immunological adverse events (neuro-irAEs) from immune check point inhibitors (ICI). We report the incidence, predictors for development, impact on mortality of neuro-irAEs, and impact of ICI on pre-existing neurological conditions in a large clinical cohort. METHODS: Patients who received ICI between January 2011 and December 2018 were identified from a tertiary cancer center registry. Descriptive statistics were used to summarize patient, cancer, and treatment data...
June 23, 2023: European Journal of Neurology
#7
JOURNAL ARTICLE
Talal El Zarif, Amin H Nassar, Elio Adib, Bailey G Fitzgerald, Jiaming Huang, Tarek H Mouhieddine, Paul G Rubinstein, Taylor Nonato, Rana R McKay, Mingjia Li, Arjun Mittra, Dwight H Owen, Robert A Baiocchi, Michael Lorentsen, Christopher Dittus, Nazli Dizman, Adewunmi Falohun, Noha Abdel-Wahab, Adi Diab, Anand Bankapur, Alexandra Reed, Chul Kim, Aakriti Arora, Neil J Shah, Edward El-Am, Elie Kozaily, Wassim Abdallah, Ahmad Al-Hader, Batool Abu Ghazal, Anwaar Saeed, Claire Drolen, Melissa G Lechner, Alexandra Drakaki, Javier Baena, Caroline A Nebhan, Tarek Haykal, Michael A Morse, Alessio Cortellini, David J Pinato, Alessia Dalla Pria, Evan Hall, Veli Bakalov, Nathan Bahary, Aarthi Rajkumar, Ankit Mangla, Vishal Shah, Parminder Singh, Frank Aboubakar Nana, Nerea Lopetegui-Lia, Danai Dima, Ryan W Dobbs, Pauline Funchain, Rabia Saleem, Rachel Woodford, Georgina V Long, Alexander M Menzies, Carlo Genova, Giulia Barletta, Sonam Puri, Vaia Florou, Dame Idossa, Maristella Saponara, Paola Queirolo, Giuseppe Lamberti, Alfredo Addeo, Melissa Bersanelli, Dory Freeman, Wanling Xie, Erin G Reid, Elizabeth Y Chiao, Elad Sharon, Douglas B Johnson, Ramya Ramaswami, Mark Bower, Brinda Emu, Thomas U Marron, Toni K Choueiri, Lindsey R Baden, Kathryn Lurain, Guru P Sonpavde, Abdul Rafeh Naqash
PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS)...
May 16, 2023: Journal of Clinical Oncology
#8
JOURNAL ARTICLE
Lorvens Decosma, Ying Ni, Pauline Funchain, Joshua Arbesman
No abstract text is available yet for this article.
June 2023: JAAD international
#9
EDITORIAL
Pauline Funchain
No abstract text is available yet for this article.
May 1, 2023: Cleveland Clinic Journal of Medicine
#10
JOURNAL ARTICLE
Irene Orlow, Keimya D Sadeghi, Sharon N Edmiston, Jessica M Kenney, Cecilia Lezcano, James S Wilmott, Anne E Cust, Richard A Scolyer, Graham J Mann, Tim K Lee, Hazel Burke, Valerie Jakrot, Ping Shang, Peter M Ferguson, Tawny W Boyce, Jennifer S Ko, Peter Ngo, Pauline Funchain, Judy R Rees, Kelli O'Connell, Honglin Hao, Eloise Parrish, Kathleen Conway, Paul B Googe, David W Ollila, Stergios J Moschos, Eva Hernando, Douglas Hanniford, Diana Argibay, Christopher I Amos, Jeffrey E Lee, Iman Osman, Li Luo, Pei-Fen Kuan, Arshi Aurora, Bonnie E Gould Rothberg, Marcus W Bosenberg, Meg R Gerstenblith, Cheryl Thompson, Paul N Bogner, Ivan P Gorlov, Sheri L Holmen, Elise K Brunsgaard, Yvonne M Saenger, Ronglai Shen, Venkatraman Seshan, Eduardo Nagore, Marc S Ernstoff, Klaus J Busam, Colin B Begg, Nancy E Thomas, Marianne Berwick
INTRODUCTION: We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing...
2023: PloS One
#11
JOURNAL ARTICLE
Natalie Farha, Muhammad Salman Faisal, Daniela S Allende, Joseph Sleiman, Ravi Shah, Nicole Farha, Pauline Funchain, Jessica R Philpott
BACKGROUND: Immune checkpoint inhibitors (ICIs) have increased our ability to treat an ever-expanding number of cancers. We describe a case series of 25 patients who were diagnosed with gastritis following ICI therapy. MATERIALS AND METHODS: This was a retrospective study involving 1712 patients treated for malignancy with immunotherapy at Cleveland Clinic from January 2011 to June 2019 (IRB 18-1225). We searched electronic medical records using ICD-10 codes for gastritis diagnosis confirmed on endoscopy and histology within 3 months of ICI therapy...
August 3, 2023: Oncologist
#12
RANDOMIZED CONTROLLED TRIAL
Joseph M Unger, Amy Darke, Megan Othus, Thach-Giao Truong, Nikhil Khushalani, Kari Kendra, Karl D Lewis, Bryan Faller, Pauline Funchain, Elizabeth I Buchbinder, Ahmad A Tarhini, John M Kirkwood, Elad Sharon, Vernon Sondak, Samantha R Guild, Kenneth Grossmann, Antoni Ribas, Sapna P Patel
IMPORTANCE: A key issue for the adjuvant treatment of patients with melanoma is the assessment of the effect of treatment on relapse, survival, and quality of life (QOL). OBJECTIVE: To compare QOL in patients with resected melanoma at high risk for relapse who were treated with adjuvant pembrolizumab vs standard of care with either ipilimumab or high-dose interferon α 2b (HDI). DESIGN, SETTING, AND PARTICIPANTS: The S1404 phase 3 randomized clinical trial was conducted by the SWOG Cancer Research Network at 211 community/academic sites in the US, Canada, and Ireland...
February 1, 2023: JAMA Oncology
#13
RANDOMIZED CONTROLLED TRIAL
Michael B Atkins, Sandra J Lee, Bartosz Chmielowski, Ahmad A Tarhini, Gary I Cohen, Thach-Giao Truong, Helen H Moon, Diwakar Davar, Mark O'Rourke, Joseph J Stephenson, Brendan D Curti, Walter J Urba, Joanna M Brell, Pauline Funchain, Kari L Kendra, Alexandra P Ikeguchi, Anthony Jaslowski, Charles L Bane, Mark A Taylor, Madhuri Bajaj, Robert M Conry, Robert J Ellis, Theodore F Logan, Noel Laudi, Jeffrey A Sosman, David G Crockett, Andrew L Pecora, Ian J Okazaki, Sowjanya Reganti, Sunandana Chandra, Samantha Guild, Helen X Chen, Howard Z Streicher, Jedd D Wolchok, Antoni Ribas, John M Kirkwood
PURPOSE: Combination programmed cell death protein 1/cytotoxic T-cell lymphocyte-4-blockade and dual BRAF/MEK inhibition have each shown significant clinical benefit in patients with BRAFV600 -mutant metastatic melanoma, leading to broad regulatory approval. Little prospective data exist to guide the choice of either initial therapy or treatment sequence in this population. This study was conducted to determine which initial treatment or treatment sequence produced the best efficacy. PATIENTS AND METHODS: In a phase III trial, patients with treatment-naive BRAFV600 -mutant metastatic melanoma were randomly assigned to receive either combination nivolumab/ipilimumab (arm A) or dabrafenib/trametinib (arm B) in step 1, and at disease progression were enrolled in step 2 to receive the alternate therapy, dabrafenib/trametinib (arm C) or nivolumab/ipilimumab (arm D)...
January 10, 2023: Journal of Clinical Oncology
#14
JOURNAL ARTICLE
Joshua Longinow, Mohammad Zmaili, Warren Skoza, Nicholas Kondoleon, Robert Marquardt, Cassandra Calabrese, Pauline Funchain, Rohit Moudgil
BACKGROUND: Immune checkpoint inhibitors can result in overlap syndrome comprised of myasthenia gravis, myositis and myocarditis. However, the mortality predictors have not been clearly delineated. METHODS: We examined the characteristics of 11 patients diagnosed with overlap syndrome at Cleveland Clinic. All the available clinical, diagnostic, biochemical and disease specific factors were examined. Clinical predictors of increased mortality were using student t-test for parametric data and Wilcoxon-signed rank testing for nonparametric data...
September 21, 2022: Cancer Medicine
#15
REVIEW
Jordi Rodón, Pauline Funchain, Theodore W Laetsch, Hendrik-Tobias Arkenau, Alice Hervieu, Christian F Singer, Yonina R Murciano-Goroff, Sant P Chawla, Kristin Anthony, Ikuo Yamamiya, Mei Liu, Abdel-Baset Halim, Karim A Benhadji, Osamu Takahashi, Suzette Delaloge
PTEN acts as a potent tumor suppressor within the PI3K/AKT/mTOR pathway. Germline mutations in the PTEN gene are a hallmark of PTEN hamartoma tumor syndrome, which includes Cowden syndrome, where they appear to elevate lifetime risk of cancer. Targeted AKT directed therapy has been proposed as an effective approach in cancer patients having germline PTEN mutations. The mechanism of action, safety and dosing regimen for the novel allosteric AKT inhibitor TAS-117 have been explored in a phase I study in Japan in which activity was observed against certain tumor types...
August 30, 2022: Future Oncology
#16
JOURNAL ARTICLE
Tamara A Sussman, Rebecca Knackstedt, Wei Wei, Pauline Funchain, Brian R Gastman
BACKGROUND: To evaluate factors affecting the utilization of immunotherapy and to stratify results based on the approval of ipilimumab in 2011 and programmed death-1 inhibitors in 2014, an analysis of available data from the National Cancer Database (NCDB) was performed. METHODS: The NCDB was analyzed to identify patients with stage IV melanoma from 2004 to 2016. Patients were categorized during the time periods 2004-2010, 2011-2014, and 2015-2016. Overall survival (OS) was analyzed by Kaplan-Meier, log-rank, and Cox proportional hazard models; IO status was analyzed using logistic regression...
August 2022: Journal for Immunotherapy of Cancer
#17
JOURNAL ARTICLE
Iris Y Sheng, Shilpa Gupta, Chandana A Reddy, Dana Angelini, Pauline Funchain, Tamara A Sussman, Joseph Sleiman, Moshe C Ornstein, Keith McCrae, Alok A Khorana
BACKGROUND: Immunotherapy has become one of the mainstays for metastatic urothelial carcinoma treatment. Whether immune checkpoint inhibitor therapy increases thromboembolism (TE) risk is unknown. OBJECTIVE: We investigated the incidence of arterial thromboembolism (ATE) and venous thromboembolism (VTE) events and its associated outcomes in patients with metastatic urothelial cancer treated with immune checkpoint inhibitors. METHODS: Patients with urothelial cancer treated with immune checkpoint inhibitors at the Cleveland Clinic from 1/1/2015 to 12/31/2019 were identified...
August 20, 2022: Targeted Oncology
#18
JOURNAL ARTICLE
Li Luo, Ronglai Shen, Arshi Arora, Irene Orlow, Klaus J Busam, Cecilia Lezcano, Tim K Lee, Eva Hernando, Ivan Gorlov, Christopher Amos, Marc S Ernstoff, Venkatraman E Seshan, Anne E Cust, James Wilmott, Richard A Scolyer, Graham Mann, Eduardo Nagore, Pauline Funchain, Jennifer Ko, Peter Ngo, Sharon N Edmiston, Kathleen Conway, Paul B Googe, David Ollila, Jeffrey E Lee, Shenying Fang, Judy R Rees, Cheryl L Thompson, Meg Gerstenblith, Marcus Bosenberg, Bonnie Gould Rothberg, Iman Osman, Yvonne Saenger, Adam Z Reynolds, Matthew Schwartz, Tawny Boyce, Sheri Holmen, Elise Brunsgaard, Paul Bogner, Pei Fen Kuan, Charles Wiggins, Nancy E Thomas, Colin B Begg, Marianne Berwick
It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments. Untreated cases with Stage II/III cutaneous melanoma were identified from institutions throughout the United States, Australia and Spain. FFPE tumor sections were profiled for mutation, methylation and microRNAs...
July 25, 2022: Pigment Cell & Melanoma Research
#19
Tapas Ranjan Behera, Jung Min Song, Jennifer Ko, Donald Eicher, Joshua Arbesman, Brian Gastman, Daniel H Farkas, Pauline Funchain
Treatment of metastatic melanoma includes the option of targeted therapy in patients with driver BRAF mutations. BRAF-MEK inhibitor drugs improve survival in the approximately 50% of patients with melanoma that harbor BRAF mutations. As BRAF mutation detection in tissue often takes days to weeks, it is not always possible or timely to obtain BRAF status in tissue using immunohistochemistry or next generation sequencing. Plasma-derived circulating tumor DNA (ctDNA) is a potential alternative analyte in such treatment settings...
2022: Frontiers in Oncology
#20
JOURNAL ARTICLE
Rahul Seth, Hans Messersmith, Pauline Funchain
ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options.
July 20, 2022: Journal of Clinical Oncology
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