High Rate of Abscopal Regression of Follicular Lymphoma after Low Dose Involved-Site Radiation Therapy Detected by FDG-PET Scans

Abstract

We conducted a retrospective analysis to estimate the frequency of abscopal regression of follicular lymphoma (FL), detected by FDG-PET/CT scanning. Potential cases were identified from an institutional radiation therapy database. All FL patients treated with palliative involved site radiation therapy (ISRT) in a 3-year period were systematically reviewed. The cases of abscopal regression reported here met the following criteria. a) Palliative ISRT given for histologically confirmed FL b) >2 lesions visualized on FDG-PET c) >1 un-irradiated lesion(s) outside ISRT volume d) no systemic therapy <2 months before RT or between RT and response assessment, e) complete metabolic response (CMR) in >1 unirradiated lesions detected on serial FDG-PET/CT. Four cases of abscopal regression of FL were identified between January 2016 to December 2018. In all cases a CMR was apparent both within the ISRT volume and in >1 unirradiated lesions. During the study period, 29 ISRT courses were prescribed for multifocal FL, following which 4/29 (13.8%) abscopal responses were observed. Treatment received was either 4Gy in 2 fractions, (n = 3) or 4Gy followed 8 months later by 30Gy in 15 fractions (n = 1). Sites irradiated were abdominal lymph nodes (n = 1) neck node (n = 1), lower leg soft tissue (n = 1) and epitrochlear node (n = 1). In 3 cases a CMR was observed at all disease sites. In one case a CMR was observed only at some disease sites. If all 29 ISRT courses, where some disease sites were not irradiated are considered to be the denominator, the rate of abscopal response in FL was 4/29 (13.8%). If only the 14 courses where no systemic therapy was given and wide-field of view imaging was performed that could potentially have detected abscopal regression are considered, the abscopal response rate was 4/14 (28.6%). If only the cases with serial FDG-PET imaging are considered, the abscopal response rate was 4/9 (44.4%). The lower limit of the estimated abscopal rate was thus 13.8% (95% confidence interval (CI) 6-34%)) and the upper limit was 44.4% (95% CI 21-92%). One patient who had an allogeneic bone marrow transplantation after a complete abscopal regression of FL later relapsed and had a subsequent complete response to immunotherapy (donor lymphocyte infusion). Abscopal regression of FL may be more common than previously-suspected and can be induced by very low dose ISRT. In 3/4 cases, PET-detected abscopal regression of FL occurred after only 4Gy ISRT, and in 1/4 cases, only after a second ISRT course to the same volume. In one case, abscopal regression was associated with a subsequent complete response to immunotherapy.