Effect of Immune Status on Outcomes and Response to Radiation Among Merkel Cell Carcinoma Patients

Abstract

Merkel cell carcinoma (MCC) is a rare, radiosensitive neuroendocrine skin cancer seen in elderly and immunosuppressed (IS) patients. Conventionally fractionated radiation (RT) is frequently incorporated as treatment. We hypothesized that as RT efficacy is promoted by an intact immune system, RT in IS MCC patients is less effective (increased local/regional recurrence [LRR]), which translates to inferior relapse-free survival (RFS) compared with immune-competent (IC) patients. We retrospectively reviewed a registry that enrolled MCC patients diagnosed between 1980 and 2016, which yielded 827 stage I-III MCC patients treated with curative intent therapy. Clinical and treatment characteristics were compared among IC and IS MCC patients. Endpoints included MCC-specific RFS, overall survival (OS), and patterns of recurrence. OS and RFS were estimated by the Kaplan-Meier method and cumulative incidence function, respectively. Eleven percent (n=89) of the cohort were IS, which comprised HIV/AIDS (8%), CLL (32%), solid organ transplant (22%), autoimmune disease (20%), and other hematologic malignancies (18%). While age (median 68 yrs for both) and stage were similar between IS and IC groups, more IS patients were male and received chemotherapy (CT) and/or RT (Table). RT dose was similar between IS and IC groups (median, 50.4 vs 50.3 Gy), although more IS patients received RT to the primary site (97% vs 81%) and/or regional nodes (70% vs 66%). With a median follow-up of 56.3 months among living patients, RFS and OS were inferior among IS patients (median RFS 10.2 vs 39.8 mo; median OS 25.1 vs 107.1 mo; p<.0001 for both). Based on analysis of patterns of first recurrence, IS patients experienced increased LRR compared to IC patients (1-yr: 37% vs 20%; p=.001) with a trend for distant disease (1-yr: 18% vs 10%; p=.28). The association between RT and RFS differed between IC and IS patients (interaction p-value =.02). While RT was associated with significantly improved RFS among IC patients (HR 0.68; 95% CI 0.53-0.86), RT either had no effect or decreased RFS compared to IS patients that did not receive RT (HR 1.70; 95% CI 0.81-3.58).Abstract 2857; TableIC (n=738)IS (n=89)Male sex457 (62%)64 (72%)Pathologic stage IA/IIA237 (32%)29 (33%) IB/IIB/IIC170 (23%)23 (26%) IIIA129 (17%)19 (21%) IIIB202 (27%)18 (20%)CT: Yes82 (12%)16 (18%)RT: Yes546 (78%)76 (86%) Open table in a new tab Despite more aggressive treatment of IS MCC patients, outcomes were inferior to IC patients. Notably, IS patients experienced increased LRR suggesting the importance of immune mechanisms in RT tumor control. While these findings require confirmation in other cohorts, they suggest that MCC in IS patients may be more radioresistant to conventional RT. Alternate strategies should be explored, including RT intensification (RBE, dose, acceleration) and/or early integration of systemic/targeted therapy.