Combined Immunotherapy and Hypofractionated Radiotherapy for Metastatic Cancers

Abstract

The effects of treatment with immunotherapy (IO) and hypofractionated radiotherapy (HFRT) are poorly understood. HFRT could enhance the efficacy of IO; however randomized data regarding clinical significance and safety are lacking. Here we reviewed a series of patients who underwent both IO and HFRT in the setting of metastatic disease to assess for characteristics of treatments and outcomes. After obtaining institutional review board approval, records from a single institution were reviewed to identify patients who received immunotherapy and HFRT. Patient information including demographics, tumor characteristics, treatment types, and outcomes were retrospectively extracted. Local failure was assessed as progression on post-treatment imaging or recurrence of symptomatic disease. Abscopal effect was defined as radiographic or clinical response of non-radiated lesions following HFRT. Concurrent treatment was defined as any overlap in dates of immunotherapy and HFRT. A total 36 patients treated for 91 metastatic lesions with HFRT over a median 2 courses per patient (course number ranged 1-12) from 07/2014 – 12/2019 were reviewed with 9.6 months of median follow up. The most common primary tumor site was liver/gallbladder (50%) followed by colorectal/small bowel (19%) and the most common radiation targets were bone (51%) and liver (22%). Radiation was given as 8-60 Gy in 1-5 fractions. HFRT treatment rationale was for oligometastatic disease (7%), oligoprogression (46%), palliative intent (41%), or IO enhancement (7%). Patients received a median 2 (range 0-5) lines of systemic therapy prior to HFRT. Sequencing of therapies was variable with 45% receiving IO before HFRT, 28% concurrent, and 27% HFRT before IO. Overall, local failure occurred in 9 (10%) irradiated lesions among 6 (17%) patients, distant control was achieved in 14% of patients, and abscopal effects were observed in 2 patients (6%). Most local failure occurred in irradiated bone (8 of 9 cases) and received 8 Gy in 1 fraction (4 of 9 cases). Both patients with observed abscopal effect were treated with IO preceding HFRT, with single agent IO, and with RT to one site. This single institution experience reviews a modern cohort of patients in the immunotherapy era. The combination of IO and HFRT was most commonly used in patients previously failing several prior lines of systemic therapy and often with oligoprogressive disease or palliative intent. Further study may identify predictors for improved response such as treatment timing, the role of dose and fractionation, and tumor characteristic which will inform design of prospective trials.