A. J. Arifin, O. Jerez, S. Keatts, A. F. M. Salem Jr, A. Farooqi, A. J. Bishop, A. K. Yoder, R. P. Goepfert, R. Weiser, R. Amaria, J. McQuade, M. I. Ross, B. A. Guadagnolo, and D. Mitra; The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): The management of high-risk primary and locoregionally metastatic melanoma has changed in recent years with improvements in systemic therapy and evolving surgical recommendations. Data regarding the use of adjuvant radiotherapy (RT) in the contemporary era for patients at high risk of local recurrence is sparse. Herein we present a cohort of patients with cutaneous melanoma who received adjuvant primary site RT at a high-volume center in the immunotherapy era. Materials/
Methods: 123 patients with melanoma who received adjuvant primary site RT between 12/1/2017 (FDA approval of adjuvant anti-PD–1 for Stage III melanoma) and 12/31/2021 were identified. All patients received 30 Gy in 5 fractions over 2–2.5 weeks. For electrons, the plan was normalized to a Dmax of 30 Gy. Correspondingly, photon plans were normalized such that the PTV V95% > 27 Gy and D30 Gy < 1 cc. Results: The median age at diagnosis was 67 (interquartile range [IQR]: 59–76). 46 patients (37%) had nodal disease (41 with sentinel lymph node biopsy positive [SLNB+] disease and 5 with clinically involved nodes [cN+]). 55 patients (45%) received adjuvant systemic therapy: 29 with SLNB+ (71%), 5 with cN+ (100%) and 21 with stage II disease (27%). Of these, most (93%) received single-agent anti-PD–1 therapy and the median duration of systemic therapy was 7.5 months (IQR: 3–11 months). At our institution, indications for adjuvant primary site RT included microsatellitosis (n=46, 37%), prior local recurrence (n=23, 19%), pure desmoplasia (n=5, 4%), and positive margins (n=5, 4%). Additional risk factors for local recurrence whose cumulative effect we used to gauge the appropriateness of adjuvant primary site RT included a primary site in the head and neck (n=72, 59%), perineural invasion (n=60, 49%) and Breslow thickness = 4 mm (n=70, 57%). Radiotherapy techniques included electron RT (n=84, 68%), 3D photons (n=16, 13%) and IMRT/VMAT (n=23, 19%). With a median follow-up of 25 months, 2-year local recurrence-free survival was 92%. The crude in-field local recurrence rate was 8%. For lymph node negative patients, the 2-year progression-free survival and overall survival were 61% and 88%. Most RT-associated acute toxicities were grade 1–2; however, 14 patients (11%) had grade 3 radiation dermatitis. Late toxicities occurred in 7 patients (6%), of which a majority were grade 1 (n=2 fibrosis; n=1 lymphedema; n=1 dry eye). 3 patients had late surgical site complications (2 scalp graft failures of 31 total grafts radiated [6%] and 1 pretibial nonhealing wound). Conclusion: Five-fraction adjuvant primary site RT for melanoma is well tolerated with low rates of toxicity. Local control rates are favorable at > 90%, which is similar to historical rates with this regimen. Given the low risks and track-record of efficacy, our data suggests adjuvant primary site radiotherapy should continue to be considered for high-risk melanoma patients in the modern era.
