Immunotherapy and Radiation : Charting a Path Forward Together - 24/10/19

Doi : 10.1016/j.hoc.2019.08.001

Vishwajith Sridharan, MD, MBA ^a, Jonathan D. Schoenfeld, MD, MPhil, MPH ^b,^⁎
^a Department of Medicine, Massachusetts General Hospital, 75 Fruit Street, Boston, MA 02114, USA
^b Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, 75 Francis Street, L2, Boston, MA 02115, USA

^∗Corresponding author. Department of Radiation Oncology, Dana-Farber/Brigham and Women’s Cancer Center, 450 Brookline Avenue, DA L2-57, Boston, MA 02114.Department of Radiation OncologyDana-Farber/Brigham and Women’s Cancer Center450 Brookline AvenueDA L2-57BostonMA02114

Résumé

Preclinical studies combining immunotherapy and radiation therapy have suggested promising synergy, prompting translation into clinical trials. Radiation has been shown to significantly alter the tumor microenvironment, cause immunogenic cell death, and potentiate anti–tumor immune responses. Several radiation parameters may modulate these effects. Clinical data to date have suggested that combination therapy is largely well tolerated, but additional study is warranted to better estimate both short-term and long-term risks of combination treatment and extend these data to new immunotherapy agents. Ensuring proper radiation access and quality is critical to the success of future trials.

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Keywords : Radiation therapy, Immunotherapy, Clinical trials, Abscopal, Immune checkpoint, PD-1

Plan

Key points

Introduction

Translating preclinical data

Critical radiation therapy parameters

Sequencing radiation therapy with immune checkpoint inhibitors

Dose and Fractionation Schedule

Selecting Appropriate Disease Types and Disease Burden

Monitoring Patterns of Response and Toxicity

Barriers to further development of radiation therapy and immunotherapy combinations

Summary

Conflict of Interest: Dr J.D. Schoenfeld reports grants, personal fees, and nonfinancial support from Bristol-Myers Squibb; grants from Merck; personal fees and nonfinancial support from AstraZeneca; personal fees and nonfinancial support from Debiopharm; personal fees from Nanobiotix; personal fees from Tilos Therapeutics; and grants from Regeneron. Mr V. Sridharan reports consulting fees from Takeda Pharmaceuticals and Volcano Capital Management.