Characterization of clinical outcomes after shorter course hypofractionated and standard-course radiotherapy for stage I-III curatively-treated Merkel cell carcinoma

May 27, 2022


Radiotherapy and Oncology

Publication Date

May 27, 2022


Kevin X Liu, Michael G Milligan, Jonathan D Schoenfeld, Roy B Tishler, Andrea K Ng, Phillip M Devlin, Elliott Fite, Guilherme Rabinowits, Glenn J Hanna, Ann W Silk, Charles H Yoon, Manisha Thakuria, Danielle N Margalit Summary

The standard (“conventional”) way to give radiation for Merkel cell carcinoma (MCC) involves about 25 treatments given over a 5-week period. Because MCC patients are often older and may live quite far from a radiation therapy (RT) facility, a conventional course can be difficult to accomplish. For this reason, there has been increasing interest in providing “hypo-fractionated” RT: fewer treatments of a higher dose. This Boston-based team looked at hypo-fractionated RT and compared outcomes to those who received conventional RT. Importantly, they found that the ability of RT to control MCC was essentially the same for both approaches. Our Seattle-based team has also been offering and studying such shorter treatment courses for over a decade. It is reassuring that multiple groups are seeing good results from shorter treatment courses that are more convenient for patients.


Background: Limited data exists regarding the efficacy of curative hypofractionated radiotherapy (hypo-RT) regimens compared to conventionally-fractionated radiotherapy (conv-RT) for Merkel cell carcinoma (MCC).

Methods: A retrospective analysis of 241 patients diagnosed with non-metastatic MCC from 2005-2021 and who received RT at Dana-Farber/Brigham & Women’s Cancer Center. The primary outcome was cumulative incidence of in-field locoregional relapse using Gray’s test with competing risks of death and isolated out-of-field recurrence. Secondary outcomes included overall survival (OS) and MCC-specific survival using log-rank tests, and risk factors of recurrence using Cox-proportional hazards regression.

Results: There were 50 (20.6%) and 193 (79.4%) courses of hypo-RT and conv-RT, respectively. The hypo-RT cohort was older (≥73 years at diagnosis: 78.0% vs. 41.5%, p<0.01), and received a lower equivalent total RT dose in 2 Gy per fraction (<50 Gy: 58.0% vs. 5.2%, p<0.01). Median follow-up was 65.1 months (range: 1.2-194.5) for conv-RT and 25.0 months (range: 1.6-131.3) for hypo-RT cohorts. Two-year cumulative incidence of in-field locoregional relapse was low in both groups (1.1% conv-RT vs. 4.1% hypo-RT, p=0.114). While two-year OS was lower for the hypo-RT group (62.6% vs. 84.4%, p=0.0008), two-year MCC-specific survival was similar (84.7 vs. 86.6%, p=0.743). On multivariable analysis, immunosuppression, clinical stage III disease, and lymphovascular invasion were associated with any-recurrence when controlling for sex, age, and hypo-RT.

Conclusions and relevance: There was no difference in cumulative incidence of in-field locoregional relapse or MCC-specific survival between hypo-RT and conv-RT. Prospective studies are needed to confirm hypo-RT as an efficacious treatment option for MCC.

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