Effect of host immune status on the efficacy of radiotherapy and recurrence-free survival among 805 Merkel cell carcinoma patients

Publication date: Available online 5 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Yolanda D. Tseng, Macklin H. Nguyen, Kelsey Baker, Maclean Cook, Mary Redman, Kristina Lachance, Shailender Bhatia, Jay J. Liao, Smith Apisarnthanarax, Paul T. Nghiem, Upendra Parvathaneni
PurposeMerkel cell carcinoma (MCC) patients with chronic immunosuppression (IS) have worse outcomes, but the mechanisms are not well understood. We hypothesized that these differences may be mediated in part by differential response to treatment and evaluated whether RT efficacy is altered among IS compared with immune competent (IC) MCC patients.MethodsAmong 805 MCC patients, recurrence-free survival (RFS) and patterns of first recurrence were compared between 89 IS and 716 IC patients with stage I-III MCC treated with curative-intent. We used a Fine and Gray's competing risk multivariable analysis to estimate associations with RFS.ResultsIS and IC MCC patients had similar demographic and disease characteristics. Most (77% IC,86% IS) were irradiated (median, 50.4Gy IC, 50.3Gy IS), although more IS patients were irradiated to the primary site (97% vs 81%). With a median follow-up of 54.4 months, IS patients had inferior RFS (2-year 30% vs 57%; p<0.0001) and higher local recurrence as the first site of relapse (25% vs 12%; p=0.0002). The association between RT and RFS differed by immune status (interaction p=0.01). While RT was associated with significantly improved RFS among IC patients (HR 0.56, 95% CI 0.44-0.72), no difference in RFS was observed with RT among IS patients (HR 1.49, 95% CI 0.70-3.17).ConclusionsRadiotherapy efficacy at current, standard RT doses for MCC is impaired among immunosuppressed MCC patients. While a strong link between durability of RT response and immune function does not appear to be evident in most cancers, our results may reflect an especially dynamic interaction between immune status and RT efficacy in MCC.

Teaser

The impact of chronic immunosuppression on RT efficacy was evaluated among non-metastatic Merkel cell carcinoma (MCC) patients treated with curative-intent. Despite higher proportions of immunosuppressed MCC patients receiving RT to the primary site compared with immune-competent MCC patients, immunosuppressed MCC patients experienced increased local failures as first relapse (25% versus 12%; p=0.0002) and lower recurrence-free survival (2-year 30% versus 57%;p<0.0001). The efficacy of conventional radiotherapy on tumor control may be impaired in an immunosuppressed host.


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