To the Editor:
I read the report by Cook and colleagues1 describing the outcome of adjuvant single-fraction radiation therapy (RT) for Merkel cell carcinoma (MCC) of the head and neck with interest. As the authors point out, patients with MCC are often elderly and frail, which makes “conventional” RT a challenging proposition. More convenient, safe, and effective strategies are desirable for this reason. However, I am concerned about the data that were selected for presentation in the current manuscript, and the validity of this “unconventional” approach.
The authors previously presented results of a similar study at the 2019 Society of Investigative Dermatology and the 2020 American Radium Society meetings.2,3 Table 1 compares the findings of the prior abstract and the present manuscript. In the published abstract, 3 of 23 irradiated volumes (13%) subsequently developed “in-field” recurrences.
Table 1.
Comparison of previously published abstract and current manuscript
| Characteristics | 2019 Abstract | 2020 Manuscript |
|---|---|---|
| Patients (n =) | 17 | 12 |
| Disease sites | (not given) | Head and neck |
| Radiation therapy doses | 8-24 Gy in 1-3 fractions of 8 Gy | 8 Gy in 1 fraction |
| Primary tumor sites irradiated (n =) | 17 | 12 |
| Regional lymph node beds irradiated (n =) | 6 | 1 |
| Follow up (median [range]) | 483 days (range not given) | 19 months (8-34 months) |
| Median age (years [range]) | 75 (range not given) | 81 (58-96) |
| In-field recurrences | 3/23 irradiated sites (calculated 95% CI of 2.7-33.6%) | 0/13 irradiated sites (calculated 95% CI of 0-24.7%) |
Abbreviation: CI = confidence interval.
One of the patients not described in the present manuscript was a 46-year-old man with pT2N1bM0R0 MCC of upper extremity who underwent wide excision of the primary tumor and lymphadenectomy at my center. He subsequently received a single fraction of 8 Gy at the author’s institution to his primary tumor site and 2 regional lymph node basins. Two months later he developed an unresectable recurrence in 1 of the treated lymph node basins, which was initially treated with an ineffective course of immunotherapy and subsequent reirradiation, complicated by autoimmune complications and lymphedema, respectively. This narrative provides additional context to the possible sequelae of a treatment regimen that causes “minimal toxicity.”
Finally, it should be noted that the estimated risk of in-field recurrence in this study is 0%, but given the small sample size, the 95% confidence interval of this event is estimated to be 0% to 25% using binomial “exact” methods. Given the short follow-up of the current series, this is unlikely to be statistically different than the cited 26.3% to 31.9% rates of local recurrence noted 3 to 5 years after surgery alone. Moreover, several centers have reported low rates of excised primary tumor recurrence after wide excision alone (without adjuvant RT).4,5 Prospective randomized clinical trials have yet to identify which patients benefit from adjuvant RT to the site of the primary tumor after resection of MCC, thereby making this topic controversial.
The authors are congratulated on studying a novel strategy for a rare malignancy, but the current report does not provide substantive evidence that the approach of surgical excision followed by adjuvant single-fraction RT is superior to either “conventional” surgery or RT.6
Footnotes
Sources of support: This study was funded in part by a grant from the National Cancer Institute/National Institutes of Health (P30-CA008748) made to the Memorial Sloan Kettering Cancer Center.
Disclosures: none.
References
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