Presenter(s)
S. Fattahi1, K. Y. Shin2, A. W. Silk3, J. D. Schoenfeld4,5, R. B. Tishler4,5, C. Yoon6, K. X. Liu4,5, K. Melvin4,5, K. Khaddour3, J. V. Cohen3, M. Thakuria7, and D. N. Margalit4,5; 1Harvard Radiation Oncology Program, Boston, MA, 2Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, 3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 4Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA, 5Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, 6Department of Surgical Oncology, Brigham and Women's Hospital, Boston, MA, 7Department of Dermatology, Brigham and Women's Hospital, Boston, MA
Purpose/Objective(s): Merkel cell carcinoma (MCC) is a rare cutaneous tumor with high rates of local-regional and distant recurrence. Optimal treatment of local-regional, non-disseminated M-0 disease is based on retrospective and large-database studies with limited prospective trials. Despite being highly radiosensitive, current NCCN guidelines recommend initial treatment with surgical wide local excision (WLE) or Mohs. At our institution, definitive radiation therapy (RT) is given when surgery may result in poor cosmesis, functional impairment, or delayed wound healing, or for inoperable patients (pts). We hypothesized that definitive RT is associated with high rates of local-regional and in-field control.
Materials/Methods: This IRB-approved retrospective review identified pts with stage I-III MCC treated with definitive RT without a WLE/surgical clearance at a single institution between 2005 and 2025. Pts with unknown primary and node-only disease were also eligible if they received RT rather than an oncologic nodal dissection. All RT plans were reviewed for detailed patterns of failure analysis. Cumulative incidence of recurrence-type and MCC-specific death were calculated using Fine and Gray methods with competing risks of other recurrence type or death. Overall survival (OS) was calculated using the Kaplan-Meier method.
Results: We identified 139 pts who received definitive RT without a WLE/surgical clearance, with a median dose of 60 Gy EQD2 to GTV and 46-50 Gy EQD2 to subclinical at-risk regions. Pt characteristics included median age of 75.0 years (yrs) (range, 45.3-94.9 yrs), 12.2% immunosuppressed, and 46.0% stage III disease (36.7% stage I, 17.3% stage II). At median follow-up of 3.2 yrs (range, 0.3-16.3 yrs), 2-yr cumulative incidence of local-regional recurrence was 5.8% (95% confidence interval (CI): 2.7, 10.6) and 2-yr cumulative incidence of in-field recurrence was 3.8% (95% CI: 1.4, 8.1). The most common sites of isolated recurrence were distant and in-transit (44.2% and 19.2% of recurrences, respectively). The entire cohort had a 2-yr cumulative incidence of MCC-specific death of 15.6% (95% CI: 9.9, 22.5) and 2-yr OS of 78.8% (95% CI: 70.6, 85.0), with poorer 2-yr cumulative incidence of MCC-specific death in pts with stage III disease of 21.7% (95% CI: 12.2, 33.0), driven by distant recurrence as primary failure site (2-yr cumulative incidence of 21.9%).
Conclusion: Definitive RT results in high rates of local-regional control with rare in-field failures, supporting its role as an alternative approach to surgery. Distant and in-transit recurrences are the dominant sites of failure, providing rationale for prospective studies that combine systemic immunotherapy and RT.