Abscopal Response Rates After Salvage Radiation In Patients With Progressive Disease On Immunotherapy

To report abscopal lesion response rates from an ongoing prospective phase II trial of salvage radiation with concurrent immunotherapy for patients with disease progression on immunotherapy alone (NCT02710253). Eligible patients had metastatic disease that progressed during treatment with an immunotherapy agent. Patients received conventionally fractionated or stereotactic radiotherapy (SBRT) to one or more metastatic lesions. Abscopal tumors (that is, unirradiated lesions) were included if they were not exposed to scatter radiation and were considered “measurable”; measurability and response were assessed by RECIST 1.1 criteria. Complete blood counts, including absolute lymphocyte counts (ALC), were measured at a median 10 days before and after completing radiation. Linear regression analysis was used to identify factors associated with response. At the time of analysis, 22 patients treated with high dose irradiation had 36 total evaluable unirradiated lesions. Tumor histology was non-small cell lung cancer (NSCLC) in 17 and melanoma in 5. Although most patients received radiation to only 1 lesion, five patients received irradiation to 2 or 3 sites. Irradiated tumors were most often in the lung (55%) or liver (19%); 55% of patients received SBRT. Unirradiated tumors were most often in the lung (16), lymph nodes (8), adrenals (4), and liver (3). At a median follow-up time of 3 months, the abscopal response rate was 11% (complete response 5.5%, partial response 5.5%, stable disease 67%). Lesions from melanoma seemed to show greater shrinkage than lesions from NSCLC (15% decrease vs. 10% increase), but this apparent difference was not significant (p = 0.10). Moreover, 13% of unirradiated melanoma showed a complete or partial response vs. 11% of unirradiated NSCLC lesions. Three of the four unirradiated adrenal lesions progressed, but none of the lymph node or liver lesions progressed. Size of abscopal lesion prior to radiation treatment was not associated with response (p = 0.73). ALC before or after radiotherapy did not predict response (p>0.05), but decreases in ALC by >500/μL after radiotherapy predicted worse response (p = 0.04). Use of SBRT was associated with improved abscopal responses (p = 0.03) and smaller decreases in ALC after radiotherapy (p<0.001). Irradiation of multiple lesions did not affect ALC (p = 0.70) and was not associated with abscopal lesion response (p = 0.92). In patients with disease progression on immunotherapy, radiation may induce systemic benefits in unirradiated tumors. SBRT minimizes lymphopenia after treatment, and thus may be associated with better response.