TO PUT THAT INTO CONTEXT
Roy H. Decker, MD, PhD
Yale University School of Medicine, New Haven, ConnecticutI’ve always hated the term “radioresistant”; it implies a duality of response, when the reality is always more complex. In this review, Dr. Mahadevan and colleagues take us on a 40-year tour of the clinical use of radiation therapy (RT) in patients with melanoma, and paint a thorough and accurate picture of a disease that is both heterogeneously responding and consistently frustrating.What Do We Already Know About RT in Melanoma?We’ve known that melanoma responds atypically to radiation since the 1970s, when it was observed that certain cell lines had a wide “shoulder” on the cell survival curve, implying that they would respond better to larger radiation fractions. This is consistent with the more recent observation that stereotactic body RT and stereotactic radiosurgery (the ultimate examples of hypofractionation) offer better results than more “standard” schedules. But it’s equally clear that despite the use of higher doses, many patients will still experience local recurrences.What Holds Promise for the Future-and WhyWhen interpreting these data, it is important to keep in mind that melanoma is a disease in which the transition from a localized to a metastatic state seems to occur particularly abruptly-the same risk factors that predict local recurrence also predict distant metastasis. Taken together, these two biological characteristics-imperfect local control and a propensity for distant metastasis-suggest where radiation should be applied in patients with melanoma. For definitive treatment of localized disease, the use of radiation should be limited to those who cannot undergo wide excision. The use of adjuvant radiation will improve local or regional control without affecting overall survival, and is, for all intents and purposes, palliative. In my opinion, the most promising role for radiation is in patients with metastases: as simple palliation, to prolong disease-free survival in oligometastatic patients, or potentially to enhance the effects of the targeted biologics and immune checkpoint inhibitors that are currently revolutionizing the treatment of this disease.Financial Disclosure:Dr. Decker receives research support from Merck & Co.