Identifying an Optimal Adjuvant Radiotherapy Dose for Extremity and Trunk Merkel Cell Carcinoma Following Resection: An Analysis of the National Cancer Database

JAMA Dermatol. 2017 Oct 1;153(10):1007-1014. doi: 10.1001/jamadermatol.2017.2176.

Abstract

Importance: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine neoplasm with a high risk of recurrence following resection. Despite a rising incidence over the past 3 decades, there is a paucity of prospective data owing to the rarity of this disease.

Objective: To determine the optimal adjuvant radiation therapy (RT) dose following resection of localized MCC of the extremities or trunk.

Design, setting, and participants: Using the National Cancer Database, a large national database consisting of a heterogeneous population and treatment settings, we retrospectively analyzed a cohort of 2093 patients 18 years or older with stage I to III MCC of the extremities and/or trunk treated with definitive surgery and adjuvant RT between 1998 and 2011. Exclusion criteria included receiving treatment with palliative intent, preoperative RT, non-external-beam RT, and radiation dose of 30 Gy or lower or 70 Gy or higher. Cox proportional hazards regression model was used to compare overall survival (OS) between RT dose groups, accounting for age, sex, race, stage, surgery type, margin status, comorbidities, and use of chemotherapy.

Exposures: Radiation therapy dose was categorized into 4 groups: group 1 received the lowest dose (>30 to <40 Gy); group 2, the next lowest (40 to <50 Gy); group 3, the second highest dose (50 to 55 Gy); and group 4, the highest dose (>55 to 70 Gy).

Main outcome and measure: Overall survival.

Results: Data from 2093 patients were analyzed; there were 1293 men (61.8%) and 800 women (38.2%) (median age, 73 years). After a median follow-up of 37 months for the entire cohort, 904 deaths were reported. The 3-year OS rates for groups 1, 2, 3, and 4 were 41.8%, 69%, 69.2%, and 66%, respectively (omnibus P < .001). Compared with group 3 (50 to 55 Gy), equivalent OS was seen in group 2 (40 to <50 Gy; adjusted hazard ratio [AHR], 0.89; 95% CI, 0.63-1.27; P = .52) and group 4 (>55 to 70 Gy; AHR, 1.18; 95% CI, 0.93-1.48; P = .17), but worse OS was found in group 1 (>30 to <40 Gy; AHR, 2.63; 95% CI, 1.44-4.80; P < .001).

Conclusions and relevance: Adjuvant RT dose from 40 to lower than 50 Gy appears adequate for extremities and/or trunk stage I to III MCC, with OS equivalent to that found at higher-dose regimens (>50 to 70 Gy).

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Merkel Cell / pathology
  • Carcinoma, Merkel Cell / radiotherapy*
  • Carcinoma, Merkel Cell / surgery
  • Databases, Factual
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant
  • Retrospective Studies
  • Skin Neoplasms / pathology
  • Skin Neoplasms / radiotherapy*
  • Skin Neoplasms / surgery
  • Survival Rate