Women with advanced cervical cancer are often in the quagmire of having a disease that both calls for radiosensitization with platinum chemotherapy while also challenging its safe delivery. An alternative radiosensitizer in the setting of renal compromise used more commonly in other parts of the world is none other than hyperthermia. However, two largely logistical debates persist: timing and sequence. A friendly rad bio reminder on two key theoretical mechanisms of hyperthermic radiosensitization: [1] vasodilation increasing reoxygenation (in which case hyperthermia should come first) and [2] inhibition of DNA damage repair (in which case hyperthermia should come second). This Dutch basic science work developed both in vivo and in vitro mouse models that demonstrated shortening the time interval between RT and hyperthermia resulted in more DNA double-strand breaks, lower cell survival, and delayed tumor growth in mice. On the other hand, sequencing didn’t seem to matter. They then looked back at 58 women treated with thermoradiotherapy at a single center in Amsterdam with a radiotherapy-hyperthermia interval ranging from 34 to 125 minutes. Dichotomizing at the median of 80 minutes, survival at 3 years was 62% after short- versus 37% after long-interval thermoradiotherapy, a clear significant discrepancy that persisted out to 10 and 20 years. | Mei, Int J Radiat Oncol Biol Phys 2023
