Objective: There is a growing body of evidence that combining ipilimumab with higher
doses of radiotherapy may improve the response rates and survival in patients with metastatic melanoma
compared to lower doses of radiotherapy. However, the dose cutoff at which improved outcomes
are more likely to occur has not been properly identified.
Methods: We conducted a retrospective analysis of 100 patients treated with ipilimumab and radiotherapy
for metastatic melanoma at a single institution from May 2011 to January 2017. Demographic,
clinical, and treatment factors, including the biological equivalent dose (BED) with an α/β
of 7, were recorded. Endpoints of interest included infield and global complete response (CR) after
the completion of radiation and ipilimumab based on the RECIST criteria (v1.1) and 12-month
overall survival (OS).
Results: The BED cutoffs at which improved outcomes are more likely to occur are 46.5 Gy for infield
CR, 50.9 Gy for global CR, and 46.5 Gy for 12 month OS. The least aggressive fractionation
schedules used in this patient population that have a BED above the threshold for all 3 outcomes include
40 Gy in 20 fractions, 30 Gy in 6 fractions, and 24 Gy in 3 fractions.
Conclusion: This hypothesis-generating study suggests that patients who cannot receive ablative intent
radiotherapy may be more likely to benefit from concurrent radiotherapy with ipilimumab if
their fractionation schedule has a BED above 46.5 - 50.9 Gy. Prospective trials evaluating this question
should be considered.