The Abscopal Effect: Optimal Radiation Dose and Fractionation

NCI ’ s Center for Cancer Research (CCR) Grand Rounds Dr. Formenti is the Chair of Radiation Oncology at Weill Cornell Medical College and the Associate Director of the Cancer Center. Trained as a medical and radiation oncologist she devoted her career to translate novel preclinical information to the clinic. Key to her formation was a year spent in Malcolm Mitchell ’ s laboratory at USC, in cancer immunology. Her initial research on how to best combine radiation and systemic therapy, both pre-clinically and clinically evolved on focusing on the systemic effects of radiotherapy, particularly on the immune system. Her lab ’ s original demonstration that the abscopal effect of radiotherapy is immune-mediated has opened a fertile field of research to understand the immune-stimulatory and immune-suppressive effects of ionizing radiation, and to develop strategies directed at harnessing anti-tumor immunity in irradiated subjects. This work has introduced a paradigm shift in radiation and cancer biology. In this novel application, radiotherapy contributes at recovering an immunological equilibrium in the setting of metastatic cancer, by converting an irradiated metastasis into an in situ, individualized vaccine in the presence of immune checkpoint blockade (anti-CTLA ¬ 4, anti-PDL-1). Once successfully immunized against the irradiated site, the host can develop an anti-tumor immune response capable to reject the other metastases. In some patients with metastatic disease the ...
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