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. 2023 Aug 28;9(2):101364.
doi: 10.1016/j.adro.2023.101364. eCollection 2024 Feb.

Postoperative Radiation Therapy Is Indicated for "Low-Risk" Pathologic Stage I Merkel Cell Carcinoma of the Head and Neck Region but Not for Other Locations

Marika M Bierma  1 , Peter H Goff  1   2 , Daniel S Hippe  3 , Kristina Lachance  1 , Stephanie K Schaub  2 , Kent Wallner  2 , Yolanda D Tseng  2 , Jay J Liao  2 , Smith Apisarnthanarax  2 , Paul Nghiem  1 , Upendra Parvathaneni  2
Affiliations

Postoperative Radiation Therapy Is Indicated for "Low-Risk" Pathologic Stage I Merkel Cell Carcinoma of the Head and Neck Region but Not for Other Locations

Marika M Bierma et al. Adv Radiat Oncol. .

Abstract

Purpose: The role of postoperative radiation therapy (PORT) in early stage Merkel cell carcinoma (MCC) is controversial. We analyzed the role of PORT in preventing local recurrences (LR) among patients with low-risk, pathologic stage I MCC based on the location of the primary tumors: head/neck (HN) versus non-HN sites.

Methods and materials: One hundred forty-seven patients with MCC were identified that had "low risk" disease (pathologic T1 primary tumor, negative microscopic margins, negative pathologic node status, no immunosuppression or prior systemic therapy). LR was defined as tumor recurrence within 2 cm of the primary surgical bed, and its frequency was estimated with the cumulative incidence method.

Results: Seventy-nine patients received PORT (30 HN, 49 non-HN) with a median dose of 50 Gy (range, 8-64 Gy) and 68 patients were treated with surgery alone (30 HN, 38 non-HN). Overall, PORT was associated with a decreased risk of LR (5-year rate: 0% vs 9.5%; P = .004) with 6 LRs observed in the surgery alone group. Although the addition of PORT significantly reduced LR rates among patients with HN MCC (0% vs. 21%; P = .034), no LRs were observed in patients with non-HN MCC managed with surgery alone. There was no significant difference in MCC-specific survival comparing HN versus non-HN groups, with or without PORT.

Conclusions: For low-risk, pathologic stage I MCC of the extremities and trunk, excellent local control rates were achieved with surgery, and PORT is not indicated. However, PORT was associated with a significant reduction in LRs among low-risk MCC of the HN.

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Conflict of interest statement

Peter H. Goff reports research funding from Gilead Sciences, Inc, the Conquer Cancer Foundation of the American Society of Clinical Oncology, and the RSNA R&E Foundation not directly related to this work. Daniel S. Hippe reports research grants from GE Health care, Philips Health care, Canon Medical Systems USA, and Siemens Healthineers. Paul Nghiem reports research funding and personal fees from EMD-Serono and Merck & Co. All research funding and personal fees are unrelated to the submitted work.

Figures

Figure 1
Figure 1
Study cohort. Identification of 147 patients with resected, pathologic stage I, Merkel cell carcinoma included in this cohort. *All patients met the following criteria: primary tumor ≤2 cm, no profound immunosuppression, microscopically clear surgical margins, negative sentinel lymph node biopsy, no chemotherapy, and enrollment within 180 days from surgical excision of primary tumor. Abbreviations: HN = primary tumor of the head and neck; non-HN = primary tumor of the trunk, extremities, or buttocks; PORT = postoperative radiation therapy following primary surgical excision.
Figure 2
Figure 2
Local recurrence rate by primary tumor site and treatment modality. Cumulative incidence curves depicting probability of local recurrence is illustrated for 147 patients with resected, pathologic stage I, low-risk MCC stratified by (A) treatment type (surgery vs surgery + PORT), (B) MCC of the head and neck (HN), and (C) MCC of the trunk, extremities, or buttocks (non-HN). Across all disease sites, estimated local recurrence rates were significantly higher in patients treated with surgery alone than surgery + PORT (panel A, 5-year local recurrence rate: 9.5% vs 0.0%; P = .004). There was a significant difference in local recurrence rates among patients with HN treated with surgery alone versus surgery + PORT (panel B, 5-year rate: 21% vs 0%; P = .034), but not for patients with non-HN (panel C; 5-year rate: 0% vs 0%; P > .99). Nonlocalized MCC recurrences and death were treated as competing risks when estimating the cumulative incidence functions. Abbreviations: HN = primary tumor of the head and neck; non-HN = primary tumor of the trunk, extremities, or buttocks; MCC = Merkel cell carcinoma; PORT = postoperative radiation therapy following primary surgical excision.
Figure 3
Figure 3
MCC-specific survival based on primary tumor site and treatment type. Cumulative incidence curves illustrating MCC-specific survival for 147 patients with pathologically stage I low-risk disease stratified by (A) treatment type (surgery vs surgery + PORT), (B) disease of the head and neck (HN), and (C) MCC of the trunk, extremities, or buttocks (non-HN). There were no significant differences in disease-specific mortality between patients who received PORT and those with did not for the entire cohort (panel A, 5-year rate: 3.2% vs 3.9%; P = .94), nor for patients with HN (panel B, 5-year rate: 0% vs 7.9%; P = .48) and non-HN (panel C, 5-year rate: 4.9% vs 0%; P = .24) individually. Non-MCC-related death was treated as a competing risk when estimating the cumulative incidence functions. Abbreviations: HN = primary tumor of the head and neck; non-HN = primary tumor of the trunk, extremities, or buttocks; MCC = Merkel cell carcinoma; PORT = postoperative radiation therapy following primary surgical excision.
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