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 to prioritize opportunities and challenges for clinical translation of radiotherapy and immunotherapy combinations.
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. 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.
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. The panels recommended:
- Implementing patient selection and biomarker-guided approaches to clarify potential benefits of RT in the context of immunotherapies
- Applying mechanistic understanding to optimize delivery of RT and selection of and sequence of immunotherapies to maximize treatment effect
- Using rigorous preclinical models including companion canines to refine approaches
- Interrogating clinical data including negative trials, embrace data sharing and standardization, advanced modeling, and multidisciplinary cross-institution collaboration
- Incorporating appropriate clinical endpoints and trial designs in appropriate clinical circumstances
Breakout sessions divided attendees into seven teams to:
- Identify challenges and opportunities for clinical translation of RT and immunotherapy combinations
- Design a study to overcome such challenges and advance the field in pursuit of identified opportunities
Publication
Agenda Table and Recordings
DAY 1 - Sessions 1-5 Recordings
| Speakers | Presentation Title |
|---|---|
| Introduction | |
| Sandra Demaria, Weill Cornell Medicine | History of the study of radiation and immune interactions Zachary Morris, University of Wisconsin-Madison State of the field/identifying needs |
| Zachary Morris, University of Wisconsin-Madison | State of the field/identifying needs |
| 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 |
| Michele Mondini, Gustave Roussy | Radiotherapy quality: Particles and spatial fractionation |
| Michael Kent, UC Davis | Effects of patient heterogeneity and how to best model this |
| Panel Discussion | |
| 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 |
| Lorenzo Galluzzi, Weill Cornell Medicine | Immunosuppressive mechanisms elicited by radiation therapy |
| Sana Karam, University of Colorado | Nodes for immune response... and metastasis |
| Panel Discussion | |
| 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 |
| Joe Chang, MD Anderson Cancer Center | Clinical trials adding immunotherapy to local-regional radiotherapy: Lessons learned from definitive therapy in NSCLC |
| Mai Anh Huynh, Dana Farber Cancer Institute | Radiation therapy to all sites: Oligometastatic settings |
| Panel Discussion | |
| 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 |
| Lawrence Fong, UCSF | Radiopharmaceuticals |
| James Welch, MD Anderson Cancer Center | Next generation radiotherapy and immunotherapy combinations: New approaches and novel agents |
| 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 |
| Heiko Enderling, MD Anderson Cancer Center | Mechanistic mathematical modeling to optimize radiation-immune synergy |
| 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 |
| Panel Discussion | |
| Day 1 Conclusions: Andrew Sikora, MD Anderson Cancer Center | |
Day 2 - Sessions 6-7 and Breakouts Recording
| Speakers | Presentation Title |
|---|---|
| Session 6: Training, funding and clinical research opportunities for investigators with a focus on the interface of radiation and immunotherapies Moderator: Connie Sommers, NCI | |
| 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 |
| Kiran Devisetty, Interventional Oncology at Johnson & Johnson | Perspectives from the pharmaceutical industry on radiation therapy & Immuno/Oncology |
| Kwame Twumasi-Boateng, Telix Pharmaceuticals | Perspectives from radiopharmaceutical industry on combined modality approaches |
| Panel Discussion | |
| 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 | 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? |
| Jon Schoenfeld, Dana Farber Cancer Institute | Team Reports |
Breakout Session 2: Study/Project Design Team Competition | |
Alan Hutson, Roswell Park Comprehensive Cancer Center | Describe a study that you would design to address the most important opportunity or challenge in the clinical translation of radiation-immunotherapy combinations |
| Joshua Brody, Tisch Cancer Institute at Mount Sinai | Team Reports |
| Day 2 and Overall Conclusions: Lawrence Fong, UCSF | |
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