Radiation therapy, along with surgery and chemotherapy, is one of the main treatments for cancer. While radiotherapy is highly effective in the treatment of localized tumors, its main limitation is its toxicity to normal tissue. Previous preclinical studies have reported that ultra-high dose-rate (FLASH) irradiation results in reduced toxicity to normal tissues while controlling tumor growth to a similar extent relative to conventional-dose-rate (CONV) irradiation. To our knowledge this is the first report of a dose-response study in mice comparing the effect of FLASH irradiation vs. CONV irradiation on skin toxicity. We found that FLASH irradiation results in both a lower incidence and lower severity of skin ulceration than CONV irradiation 8 weeks after single-fraction hemithoracic irradiation at high doses (30 and 40 Gy). Survival was also higher after FLASH hemithoracic irradiation (median survival >180 days at doses of 30 and 40 Gy) compared to CONV irradiation (median survival 100 and 52 days at 30 and 40 Gy, respectively). No ulceration was observed at doses 20 Gy or below in either FLASH or CONV. These results suggest a shifting of the dose-response curve for radiation-induced skin ulceration to the right for FLASH, compared to CONV irradiation, suggesting the potential for an enhanced therapeutic index for radiation therapy of cancer.

放射疗法与手术和化学疗法一起是癌症的主要治疗方法之一。虽然放射疗法在治疗局部肿瘤方面非常有效，但其主要局限性在于其对正常组织的毒性。先前的临床前研究报告称，超高剂量率 (FLASH) 照射可降低对正常组织的毒性，同时将肿瘤生长控制到与常规剂量率 (CONV) 照射相似的程度。据我们所知，这是在小鼠中比较 FLASH 照射与 CONV 照射对皮肤毒性影响的剂量反应研究的第一份报告。我们发现，在高剂量（30 和 40 Gy）单次半胸照射后 8 周，与 CONV 照射相比，FLASH 照射的皮肤溃疡发生率和严重程度均较低。与 CONV 照射（30 和 40 Gy 的中位生存时间分别为 100 和 52 天）相比，FLASH 半胸照射后的存活率（30 和 40 Gy 剂量下的中位存活时间>180 天）也更高。在 FLASH 或 CONV 中，20 Gy 或以下剂量均未观察到溃疡。这些结果表明，与 CONV 照射相比，FLASH 辐射诱发的皮肤溃疡的剂量反应曲线向右移动，表明癌症放射治疗的治疗指数可能会提高。