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Articles by Mithat Gonen
End-to-end multimodal pathology foundation model with clinical dialogue
Abstract Recent rapid progress in the field of computational pathology has been enabled by foundation models. These models are beginning to move beyond encoding image patches toward whole-slide understanding, but their clinical utility remains limited. Here we present PRISM2, a multimodal slide-level foundation model trained on 2.3 million whole-slide images and 14 million question−answer pairs derived from 700,000 pathology reports.
Improving preoperative risk stratification in colorectal liver metastases: a multi-institutional evaluation of multimodal prediction models
Abstract Reliable prognostic models of death or liver recurrence following resection of colorectal liver metastases are critical to stratify patients for treatment. The study aimed to develop models incorporating clinical and imaging data into multimodal preoperative prediction models of hepatic disease-free survival and overall survival.
Quality, Cost, and Timeliness of Cancer Treatment in Medicare Advantage and Traditional Medicare
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Quality, Cost, and Timeliness of Cancer Treatment in Medicare Advantage and Traditional Medicare Key Points Question Are Medicare Advantage (MA) insurance plans associated with use of lower-cost or lower-quality cancer treatments?
By Aaron Mitchell, Stacie B. Dusetzina, Akriti Mishra Meza, Grace Gallagher Verified, Patrick A Augello, Hannah Fuchs, Abdullah I. Abdelaziz, Sara M. Tabatabai, Sonia Persaud, Nirjhar Chakraborty, Victoria Blinder, Andrew Epstein, Bobby Daly, William Wood, Aaron N. Winn, Mithat Gonen, Jeah Jung, Gabrielle Guzman
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JAMA Network
Verified
Tumor-informed circulating tumor DNA stratifies recurrence risk and survival in anal squamous cell carcinoma - Nature Communications
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Abstract Patients with anal squamous cell carcinoma (ASCC) who fail chemoradiation (CRT) have poor outcomes, underscoring the need for biomarkers to guide risk stratification. In a real-world two-center cohort of 84 adults with non-metastatic ASCC treated with curative-intent CRT, we prospectively evaluate a tumor-informed circulating tumor DNA (ctDNA) assay (SignateraTM, Natera).
By Paul B Romesser, Aron Bercz, Janet Alvarez, Caroline Kostrzewa, Elisa Liu, Yu-Jui Ho, Natasha Mohan, Marsha Reyngold, Rona Yaeger, John Cuaron, Jeanine Lisanti, Wini Zambare, Vasily N. Aushev, SHRUTI SHARMA, Meenakshi Malhotra, Samuel Rivero-Hinojosa, Nathan J. Schauer, Adham Jurdi, Minetta C. Liu, Abraham Noah Wu, Vonetta M. Williams, Louise Connell, Emmanouil Pappou, Devika Rao Verified, Neil H. Segal, Philip B. Paty, Martin Weiser, Andrea Cercek, Jorge E. Marcet, Julio Garcia-Aguilar, Chris Crane, Mithat Gonen, J. Joshua Smith, Angela Adames, Diana A. Roth O’Brien, Melissa Zinovoy, Christine Olinger, Revathi Ravella, Richard Tuli
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Nature
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RNA neoantigen vaccines prime long-lived CD8 + T cells in pancreatic cancer
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Abstract A fundamental challenge for cancer vaccines is to generate long-lived functional T cells that are specific for tumour antigens. Here we find that mRNA–lipoplex vaccines against somatic mutation-derived neoantigens may solve this challenge in pancreatic ductal adenocarcinoma (PDAC), a lethal cancer with few mutations.
By Zachary Sethna, Pablo Guasp, Charlotte Reiche, Martina Milighetti, Nicholas Ceglia, Erin Patterson, Jayon Lihm, George Payne, Olga Lyudovyk, Luis Rojas, Nan Pang, Akihiro Ohmoto, Masataka Amisaki, Abderezak Zebboudj, Zagaa Odgerel, Emmanuel Bruno, Siqi Zhang, Charlotte Cheng, Yuval Elhanati, Evelyna Derhovanessian, Luisa Manning, Ina Rhee, Mahesh Yadav, Taha Merghoub, Jedd D. Wolchok, Olca Basturk, Mithat Gonen, Andrew Epstein, Parisa Momtaz, Wungki Park, Ryan Sugarman, Anna Varghese, Avni Desai, Alice C Wei, Michael I. D’Angelica, T. Peter Kingham, Kevin C. Soares, William R. Jarnagin, Jeffrey Drebin, Eileen M. O’Reilly, Ira Mellman, Ugur Sahin, Ozlem Tureci, Benjamin D. Greenbaum, Vinod P. Balachandran, Felicitas Müller, Elizabeth Won
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Nature
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HIV immune evasin Nef enhances allogeneic CAR T cell potency - Nature
Abstract Autologous chimeric antigen receptor (CAR) T cells are a genetically engineered therapy that is highly effective against B cell malignancies and multiple myeloma1. However, the length and cost of personalized manufacturing limits access and leaves patients vulnerable to disease progression. Allogeneic cell therapies have the potential to increase patient access and improve treatment outcomes but are limited by immune rejection2,3.
IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer - Nature
Abstract Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)–LTβ receptor (LTβR) pathway1, the inflammatory signals and cells that induce TLSs remain incompletely identified.
New clinical trial design borrowing information across patient subgroups based on fusion-penalized regression models
Get full access to this article View all access and purchase options for this article. References 1. Hyman DM, Puzanov I, Subbiah V, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. New Engl J Med 2015; 373: 726–736. 2. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion–positive cancers in adults and children. New Engl J Med 2018; 378: 731–739. 3. Hainsworth JD, Meric-Bernstam F, Swanton C, et al.
Use of Response Permutation to Measure an Imaging Dataset’s Susceptibility to Overfitting by Selected Standard Analysis Pipelines
This study demonstrates a method for quantifying the impact of overfitting on the receiving operator characteristic curve (AUC) when using standard analysis pipelines to develop imaging biomarkers. We illustrate the approach using two publicly available repositories of radiology and pathology images for breast cancer diagnosis. For each dataset, we permuted the outcome (cancer diagnosis) values to eliminate any true association between imaging features and outcome.
Oncologic Outcomes of Salvage Abdominoperineal Resection for Anal Squamous Cell Carcinoma Initially Managed with Chemoradiation
All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to https://www.mdpi.com/openaccess.
Tumour deposits are independently associated with recurrence in colon cancer
DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request.
An imaging signature to predict outcome in metastatic colorectal cancer using routine computed tomography scans
Highlights • Response evaluation using RECIST1.1 generalises across tissues and treatments. • Radiomics can better predict survival for metastatic colorectal cancer patients. • Clinical trial data proved generalizability across lesion sites and treatment arms. • This approach can evaluate patients at minimal cost using standard of care CT.
Immuno-Fluorescent Assessment of Ablated Colorectal Liver Metastases: The Frozen Section of Image-Guided Tumor Ablation?
This paper is only available as a PDF. To read, Please Download here. Research Highlights • Intraprocedural tissue immunofluorescent assay (IFA) was investigated in patients undergoing thermal ablation of colorectal liver metastases to detect residual viable tumor cells after ablation. • For 155 ablated tumors in 99 patients, biopsies were performed of the ablation zone and of the margin, and evaluated for cellular morphology and mitochondrial viability.
Induction FOLFIRINOX for patients with locally unresectable pancreatic ductal adenocarcinoma
RESEARCH ARTICLE Caitlin A. McIntyre MD, orcid.org/0000-0002-7206-2433 Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA Search for more papers by this author Noah A. Cohen MD, Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA Search for more papers by this author Debra A.
Treatment patterns and survival in patients with early‐onset pancreatic cancer
Original Article Lily V. Saadat MD, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York Search for more papers by this author Joanne F. Chou MPH, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York Search for more papers by this author Mithat Gonen PhD, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York Search for more papers by this author Kevin C.
The Problem of Heterogeneity Within Stage
By Murray F. Brennan, MD, and Mithat Gönen, PhD December 10, 2020 Advertisement The more senior of this duo grew up with prognostication by disease stage and was taught that all stage IV cancers behaved the same. In the past 3 decades, we have become much more cognizant of the heterogeneity in outcome within stage.
Regional differences in gallbladder cancer pathogenesis: Insights from a multi‐institutional comparison of tumor mutations
Abstract Background Although rare in the United States, gallbladder cancer (GBCA) is a common cause of cancer death in some parts of the world. To investigate regional differences in pathogenesis and outcomes for GBCA, tumor mutations were analyzed from a sampling of specimens. Methods Primary tumors from patients with GBCA who were treated in Chile, Japan, and the United States between 1999 and 2016 underwent targeted sequencing of known cancer‐associated genes.
Editorial: Clinical trial design in the era of COVID-19
The COVID-19 pandemic arrived very suddenly and presented an immediate challenge to the clinical trials community. How should clinical research into treatments and prevention strategies be organized and conducted for a fast-moving, global pandemic?
JCO Clinical Cancer Informatics
PREDICTIVE MODELS RISING No trend is more visible in medicine than integrating machine learning and artificial intelligence (AI) into clinical care. Terms like “random forests” and “convolutional neural networks” that were previously the domain of computer science PhDs are now part of the vocabulary of both C-suite administrators and frontline clinicians.
Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia
From February 2010 through June 2016, we enrolled 83 adult patients with relapsed or refractory B-cell ALL. A total of 53 patients were treated with 19-28z CAR T cells and included in the study analysis, and 30 patients did not receive treatment during the study for the reasons listed in Figure S2 in the Supplementary Appendix.
Basket Trials in Oncology: A Trade-Off Between Complexity and Efficiency
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Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013
Purpose The objective of this study was to determine whether the 21-gene Recurrence Score (RS) provides clinically meaningful information in patients with de novo stage IV breast cancer enrolled in the Translational Breast Cancer Research Consortium (TBCRC) 013. Patients and Methods TBCRC 013 was a multicenter prospective registry that evaluated the role of surgery of the primary tumor in patients with de novo stage IV breast cancer.
Randomized Trial of Hepatic Artery Embolization for Hepatocellular Carcinoma Using Doxorubicin-Eluting Microspheres Compared With Embolization With Microspheres Alone
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Presented in part at the 10th Annual American Society of Clinical Oncology Gastrointestinal Cancers Symposium, San Francisco, CA, January 24-26, 2013, and at the 39th Annual Meeting of the Society of Interventional Radiology, San Diego, CA, March 22-27, 2014. Purpose Transarterial chemoembolization is accepted therapy for hepatocellular carcinoma (HCC). No randomized trial has demonstrated superiority of chemoembolization compared with embolization, and the role of chemotherapy remains unclear.
By Mithat Gonen, Peter Allen, Kristian Johnson Verified, Stephen Solomon, Lawrence H. Schwartz, Richard K. Do, Anne M. Covey, George I. Getrajdman, Constantinos T. Sofocleous, William R. Jarnagin, Michael I. D’Angelica, Joseph P. Erinjeri, Lynn A. Brody, Gerald P. O’Neill, Alessandra R. Garcia, Christopher Beattie, Binsheng Zhao, Ronald DeMatteo
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Journal of Clinical Oncology
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Response Rate as a Regulatory End Point in Single-Arm Studies of Advanced Solid Tumors
Importance Objective response rate (ORR) is an increasingly important end point for accelerated development of highly active anticancer therapies, yet its relationship to regulatory approval is not well characterized. Objective To identify circumstances in which a high ORR is associated with regulatory approval, and therefore might be an appropriate end point for definitive single-arm studies of anticancer therapies.
Interaction of splenectomy and perioperative blood transfusions on prognosis of patients with proximal gastric and gastroesophageal junction cancer
Purpose: To assess the interaction of splenectomy and perioperative allogeneic blood transfusions on the prognosis of patients undergoing a potentially curative resection of proximal gastric and gastroesophageal junction (GEJ) cancer, because reports from the transplantation literature demonstrated that the immunosuppressive effects of transfusions are dependent on the presence of an intact spleen.
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