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Wide excision of neurotropic melanoma (NM) in the head and neck region is not always achievable and has been previously associated with an elevated risk of local recurrence. We performed a randomised trial to compare the effect on local relapse of adjuvant radiation therapy (RT) to the primary site to that of observation after excision.1 For inclusion, initial surgery required complete macroscopic removal of all visible disease with a ≥1 cm clinical margin (when practical) and ≥5 mm microscopically negative margin unless constrained by an anatomical boundary.
To our knowledge, this is the largest trial ever performed specifically in NM. However, it remained underpowered for the primary endpoint, because participant accrual was slower and the total number of local recurrence events in the control arm was much lower than anticipated. These results do not support routine use of adjuvant RT for NM. However, in cases where adjuvant RT might still be recommended (for example if ≥ 5-mm pathologic margins cannot be achieved or following re-excision of locally recurrent disease), this study provides useful data to show that generally long-term toxicity and quality of life is not negatively impacted.
Distant failure was the most common mode of recurrence, occurring in 18% (9/50) of participants. Adjuvant immunotherapy has now been shown to reduce the risk of recurrence and death following resection of high-risk stage II disease.2,3 The effect appears greater on distant rather than local or locoregional recurrence.2,3 NM with co-existing desmoplasia may also respond more favourably to immunotherapy than other melanoma subtypes and was an effective salvage strategy for localised recurrence in at least one study participant.4 SWOG 1512 reported a 56% pathological complete response rate following neoadjuvant immunotherapy for resectable desmoplastic melanoma.5 Future studies could investigate the benefit of adjuvant RT in patients with residual disease after neoadjuvant immunotherapy and surgery or compared with adjuvant immunotherapy alone in patients with resected disease and narrow or positive margins that cannot be improved.
References
Pinkham MB, Herschtal A, Hong AM, et al. Randomised trial of post-operative radiation therapy following wide excision of neurotropic melanoma of the head and neck (RTN2 trial 01.09). Ann Surg Oncol. 2024. https://doi.org/10.1245/s10434-024-15569-2.
Luke JJ, Rutkowski P, Queirolo P, et al. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial. Lancet. 2022;399(10336):1718–29. https://doi.org/10.1016/S0140-6736(22)00562-1.
Kirkwood JM, Del Vecchio M, Weber J, et al. Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial. Nat Med. 2023;29(11):2835–43. https://doi.org/10.1038/s41591-023-02583-2.
Eroglu Z, Zaretsky JM, Hu-Lieskovan S, et al. High response rate to PD-1 blockade in desmoplastic melanomas. Nature. 2018;553(7688):347–50. https://doi.org/10.1038/nature25187.
Kendra KL, Moon J, Eroglu Z, et al. Neoadjuvant PD-1 blockade in patients with resectable desmoplastic melanoma (SWOG 1512). J Clin Oncol. 2022;40(16_suppl):9502–9502. https://doi.org/10.1200/JCO.2022.40.16_suppl.9502.
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MBP has received fees for professional services from Servier, Roche, Bristol-Myers Squibb, Astra Zenica, Elekta. AMH has received fees for professional service from Telix. RAS has received fees for professional services from SkylineDx BV, IO Biotech ApS, MetaOptima Technology Inc., F. Hoffmann-La Roche Ltd, Evaxion, Provectus Biopharmaceuticals Australia, Qbiotics, Novartis, Merck Sharp & Dohme, NeraCare, AMGEN Inc., Bristol-Myers Squibb, Myriad Genetics, GlaxoSmithKline. CAB leads clinical trials supported by Elekta, Merck, Amgen, EMD Serono, Alpha Tau Medical and Regeneron for which his institution has received funding. He has served as a paid scientific advisor to Regeneron and an unpaid scientific advisor to Castle Biosciences. His institution received funding from the trial sponsor to support conduct of this clinical trial. He acknowledges the United States National Cancer Institute for providing a Cancer Center Support Grant (P30 VA008748) to Memorial Sloan Kettering Cancer Center (PI: Selwyn Vickers, MD). The origin of this funding was from "Cancer Australia." Institution also received support from the United States National Cancer Institute Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center (P30 CA008748). MCF has received fees for professional services from Elekta and Varian. All other authors have no competing interests to declare.
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This article refers to: Pinkham MB, Herschtal A, Hong AM, et al. Randomised trial of post-operative radiation therapy following wide excision of neurotropic melanoma of the head and neck (RTN2 trial 01.09). Annals Surgical Oncology. (2024). https://doi.org/10.1245/s10434-024-15569-2.
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Pinkham, M.B., Herschtal, A., Hong, A.M. et al. ASO Author Reflections: The Role of Postoperative Radiation Therapy Following Wide Excision of Neurotropic Melanoma of the Head and Neck: Now and into the Future. Ann Surg Oncol 31, 6118–6119 (2024). https://doi.org/10.1245/s10434-024-15657-3
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DOI: https://doi.org/10.1245/s10434-024-15657-3