NCI-IOTN-SITC-AAI Workshop on Combining Immunotherapy with Radiotherapy: Opportunities and Challenges for Clinical Translation

The NCI, in collaboration with the Immuno-Oncology Translational Network (IOTN), the Society for Immunotherapy of Cancer (SITC), and the American Association of Immunologists (AAI), convened a two-day workshop January 16-17, 2024.

On this page:

• Full PDF Agenda
• Workshop Recordings: Day 1 – January 16;     Day 2 – January 17
• Background
• Workshop Summary
• Agenda Table – Day 1; Day 2 (speakers, presentation titles, and recording time stamps)
• Contact

Background

Radiation therapy (RT) modifies the immunogenicity of tumor cells, modifies the tumor microenvironment (TME), and can promote or antagonize immune anti-tumor responses. Some clinical studies demonstrate improved patient outcomes via integration of immunotherapies with RT. While cytotoxic or ablative RT has been safely paired with immunotherapies, greater than additive clinical response to the combination has been limited to a subset of patients, and it remains unclear how RT alters response to immunotherapies to achieve a clinical benefit.

Workshop Summary

This workshop gathered more than 400 senior leaders, junior investigators, and trainees to identify and prioritize opportunities and challenges for clinical translation of RT and immunotherapy combinations.

Expert panel sessions examined immune effects of radiation, barriers to anti-tumor immune response, prior clinical trial data, immunologic and computational methods of response assessments, and next-generation combinations. Panel recommendations included:

• Implement patient selection and biomarker-guided approaches to clarify potential benefits of RT in the context of immunotherapies.
• Apply mechanistic understanding to optimize delivery of RT and selection of and sequence of immunotherapies to maximize treatment effect.
• Use rigorous preclinical models including companion canines to refine approaches.
• Interrogate clinical data including negative trials, embrace data sharing and standardization, advanced modeling, and multidisciplinary cross-institution collaboration.
• Incorporate appropriate clinical endpoints and trial designs in appropriate clinical circumstances.

Breakout sessions divided attendees into seven teams to:

1. Identify challenges and opportunities for clinical translation of RT and immunotherapy combinations
2. Design a study to overcome such challenges and advance the field in pursuit of identified opportunities.

Agenda Table

DAY 1 (Sessions 1-5) Link to Recording
Speaker(s)	Presentation Title	Recording Time Stamp
Introduction
Sandra Demaria, Weill Cornell Medicine	History of the study of radiation and immune interactions	7:37
Zachary Morris, University of Wisconsin-Madison	State of the field/identifying needs	24:06
Session 1: The radiated TME: challenges, opportunities and appropriate models Moderator: Arta Monjazeb, UC Davis Comprehensive Cancer Center
Heather McGee, City of Hope	Radiotherapy quality: Effects of time, dose, fractionation and irradiated site on the immune response	46:35
Michele Mondini, Gustave Roussy	Radiotherapy quality: Particles and spatial fractionation	1:04:30
Michael Kent, UC Davis	Effects of patient heterogeneity and how to best model this	1:24:25
Panel Discussion		1:45:10
Session 2: Barriers that hinder immune response in the irradiated tumor: an insurmountable challenge or opportunity for innovation? Moderator: Ralph Weichselbaum, University of Chicago
Kristina Young, Providence Cancer Institute	Radiation Therapy Effects on the TME	2:08:13
Lorenzo Galluzzi, Weill Cornell Medicine	Immunosuppressive mechanisms elicited by radiation therapy	2:20:37
Sana Karam, University of Colorado	Nodes for immune response... and metastasis	2:31:29
Panel Discussion		2:46:27
Session 3: Appraisal of clinical trials combining radiation and immunotherapy: Post-mortems and next generation approaches to study design and patient selection Moderator: Silvia Formenti, Weill Cornell Medicine
Willemijn Theelen, Netherlands Cancer Institute	Clinical trials evaluating abscopal effects	3:18:51
Joe Chang, MD Anderson Cancer Center	Clinical trials adding immunotherapy to local-regional radiotherapy: Lessons learned from definitive therapy in NSCLC	3:39:04
Mai Anh Huynh, Dana Farber Cancer Institute	Radiation therapy to all sites: Oligometastatic settings	3:55:56
Panel Discussion		4:12:40
Session 4: Next generation radiotherapy and immunotherapy combinations: New approaches and novel agents Moderator: James Welch, MD Anderson Cancer Center
Sean Pitroda, University of Chicago	Tumor aneuploidy as a predictor of response to radiation therapy in combination with immunotherapy	4:40:12
Lawrence Fong, UCSF	Radiopharmaceuticals	5:02:38
James Welch, MD Anderson Cancer Center	Next generation radiotherapy and immunotherapy combinations: New approaches and novel agents	5:27:52
Session 5: Immunologic and computational assessment of radiotherapy and immunotherapy interactions: State of the art in treatment effect assessment in digital twins Moderator: Heiko Enderling, MD Anderson Cancer Center
Caroline Chung, MD Anderson Cancer Center	Leveraging data in context to improve clinical outcomes	5:51:09
Heiko Enderling, MD Anderson Cancer Center	Mechanistic mathematical modeling to optimize radiation-immune synergy	6:23:19
Clemens Grassburger, UW Medicine, Fred Hutch	Using clinical and experimental data to build mathematical and computational models that help decipher the biological consequences of radiation and immunotherapy	6:34:22
Panel Discussion		6:48:32
Day 1 Conclusions Andrew Sikora, MD Anderson Cancer Center		7:09:09

DAY 2 (Sessions 6 and 7; Breakouts 1 and 2) Link to Recording
Speaker(s)	Title	Time Stamp
Session 6: Training, funding and clinical research opportunities for investigators with a focus on the interface of radiation and immunotherapies Moderator: Connie Sommers, NCI		0:00
Session 7: Fostering academic-corporate partnerships at the interface of radiation and immunotherapies Moderator: Charles Drake, Johnson & Johnson Innovative Medicine
Charles Drake, Johnson & Johnson Innovative Medicine	Perspectives from IO pharmaceutical industry	13:50
Kiran Devisetty, Interventional Oncology at Johnson & Johnson	Perspectives from the pharmaceutical industry on radiation therapy & Immuno/Oncology	16:07
Kwame Twumasi-Boateng, Telix Pharmaceuticals	Perspectives from radiopharmaceutical industry on combined modality approaches	35:09
Panel Discussion		53:41
Breakout Session 1: Opportunities and challenges for clinical translation of radiation-immunotherapy combinations Moderator: Jon Schoenfeld, Dana Farber Cancer Institute
Alan Hutson, Roswell Park Comprehensive Cancer Center Dee Dee Smart, NCI	What is the most important question(s) that need to be addressed in the field? What are the challenges and opportunities that you see in addressing this question? What is your vision for how we can answer this critical question?	1:10:13
Jon Schoenfeld, Dana Farber Cancer Institute	Team Reports	1:31:36
Breakout Session 2: Study/Project Design Team Competition Moderator: Joshua Brody, Tisch Cancer Institute at Mount Sinai
Alan Hutson, Roswell Park Comprehensive Cancer Center Dee Dee Smart, NCI	Describe a study that you would design to address the most important opportunity or challenge in the clinical translation of radiation-immunotherapy combinations	2:02:44
Joshua Brody, Tisch Cancer Institute at Mount Sinai	Team Reports	2:25:25
Day 2 and Overall Conclusions Lawrence Fong, UCSF		3:19:28

Contact

For more information on the workshop, please contact: Julie Hong, Radiation Research Program (hongj@mail.nih.gov).