S. Keatts, D. Swanson, A. Farooqi, A. J. Bishop, R. Amaria, J. McQuade, I. Glitza, A. Diab, R. Weiser, S. Fisher, M. I. Ross, B. A. Guadagnolo, and D. Mitra; The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s):As patients with advanced melanoma live longer in the context of systemic therapy improvements, better strategies for durable control of bulky tumors are needed. In this study we evaluated if dose-escalated hypofractionated radiation therapy (HFRT) can provide durable local control and improve tumor-associated symptoms in patients with unresectable or bulky metastatic melanoma for whom stereotactic ablative RT approaches are not feasible due to tumor size or location. Materials/
Methods: We retrospectively reviewed 49 patients with unresectable or bulky metastatic melanoma who were treated to 53 tumor targets with 12-17 fractions HFRT at our institution between 2015-2022. Clinical scenarios included: unresectable, locoregional only disease (26%); oligometastatic disease (1-2 sites total, 17%); oligoprogressive disease ( <5 sites progressing, 17%); and palliation in the context of >4 slowly progressing sites with 1-2 rapidly growing tumor(s) (40%). Results: The median age was 62 (IQR 48-73) with 55% female patients. The most common HFRT target site was the trunk (57%, n=30) followed by mucosal sites (19%, n=10). The target was a metastasis (40%, n=21), nodal disease (34%, n=18), or primary site (26%, n=14). The median HFRT target size was 6 cm (IQR 3.8-10). At the time of HFRT, 94% of patients received prior systemic therapy (median 2, range 0-9 lines); the most common was immune checkpoint inhibition (84%, n=32). Most patients (81%, n=39) had symptoms related to the HFRT target, with the most common being pain with or without neurologic deficits (60%, n=32). The median dose administered was 45 Gy in 15 fractions. Of the 53 HFRT targets, 91% (n=48) had radiographic evidence of response as defined by either stabilization or decreased size (74%, n=39) or decreased FDG avidity (11%, n=6). Of the 43 symptomatic patients, 98% (n=42) had symptomatic improvement. Twenty-six patients died during follow-up (53%) at a median time from HFRT of 8 months. Median follow-up of those alive at last follow-up was 26 months (IQR 12.5-46). Two-year local control was 79%, with 2-year progression free and overall survival of 33% and 39% respectively. There were no grade 3 or 4 acute toxicities. 47% (n=25) had a grade 1-2 acute toxicity with a pain flare being most common (21%, n=11). Seven patients had a late toxicity, all were grade 1 except one patient with pneumonitis requiring steroids and one patient who received skull base RT and synchronous initiation of Ipilimumab/Nivolumab with subsequent chiasm myelitis and vision loss, despite maximum chiasm RT doses well below conventional constraints. Conclusion: HFRT provides favorable local control and symptomatic relief with limited toxicity. For patients with unresectable or bulky metastatic melanoma and limited overall disease progression that is not amenable to stereotactic ablative RT, HFRT can be considered as an effective local therapy approach.
