Abscopal Regressions of Lymphoma After Involved-Site Radiation Therapy Confirmed by Positron Emission Tomography

Abstract

Patients with abscopal regressions of lymphoma after palliative involved-site radiation therapy (ISRT), detected on sequential 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), were identified by audit. A retrospective analysis was subsequently conducted to estimate the frequency of abscopal regression in follicular lymphoma (FL). Potential cases were identified at multidisciplinary lymphoma meetings and fulfilled these criteria: (1) palliative ISRT given for histologically confirmed lymphoma, (2) >2 lesions visualized on FDG-PET, (3) >1 unirradiated lesion(s) outside ISRT volume, (4) no systemic therapy delivered <2 months before radiation therapy or between radiation therapy and response assessment, (5) complete metabolic response (CMR) in ≥1 unirradiated lesions detected on serial FDG-PET/CT. All ISRT patients with FL treated in 2016 to 2018 were systematically reviewed. Seven cases of abscopal regression were identified, including 4 patients with FL. In all cases, a CMR was apparent both within the ISRT volume and in ≥1 unirradiated lesions. One patient each was identified with mantle cell lymphoma (4 Gy in 2 fractions), Hodgkin lymphoma (20 Gy in 3 fractions, then 30 Gy in 15 fractions to the same volume), and Richter transformation of chronic lymphatic leukemia (30 Gy in 10 fractions). The 4 patients with FL received either 4 Gy in 2 fractions (n = 3) or 4 Gy followed 8 months later by 30 Gy in 15 fractions (n = 1). From 2016 to 2018, 29 courses of ISRT were prescribed for multifocal FL, after which 4 of 29 (13.8%) abscopal responses were detected, including in 4 of 9 (44.4%) patients with serial PET scans. Two patients, with relapsed disease after initial abscopal responses, experienced durable CMRs with immunotherapies. In 4 of 7 cases, PET-detected abscopal regression of lymphoma occurred after 4 Gy, in 2 of 7 cases after repeated ISRT to the same volume, and in 2 of 7 was associated with subsequent complete response to immunotherapy, consistent with an immune basis for the abscopal effect. Abscopal regressions in FL appear to be more common than previously suspected.