FLASH Irradiation Results in Reduced Severe Skin Toxicity Compared to Conventional-Dose-Rate Irradiation.
FLASH Irradiation Results in Reduced Severe Skin Toxicity Compared to Conventional-Dose-Rate Irradiation.
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与传统剂量辐射相比，闪光照射会导致严重的皮肤毒性降低。
DOI：
10.1667/rade-20-00090
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发表时间：
2020-12-01
影响因子：
3.4
通讯作者：
Loo BW
中科院分区：
文献类型：
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作者：
Soto LA;Casey KM;Wang J;Blaney A;Manjappa R;Breitkreutz D;Skinner L;Dutt S;Ko RB;Bush K;Yu AS;Melemenidis S;Strober S;Englemann E;Maxim PG;Graves EE;Loo BW
放射治疗与手术和化疗一样，是癌症的主要治疗方法之一。虽然放射治疗在治疗局部肿瘤方面非常有效，但其主要局限性是对正常组织的毒性。以往的临床前研究已报道，超高剂量率(Flash)照射可降低对正常组织的毒性，同时控制肿瘤生长的程度与常规剂量率(CONV)照射相似。据我们所知，这是在小鼠身上进行的第一次剂量反应研究，比较了闪光照射和普通照射对皮肤毒性的影响。我们发现闪光照射的皮肤溃疡发生率和严重程度都低于普通照射，在高剂量(30和40Gy)的单次半开胸照射后8周。与常规照射(30和40Gy时的中位生存期分别为100天和52天)相比，闪光半胸部照射(30和40Gy时的中位生存期为180天)的存活率也更高。闪光照射或照射剂量低于20Gy时，均未见溃疡形成。这些结果表明，与常规照射相比，辐射引起的皮肤溃疡的剂量-反应曲线右移，这表明癌症放射治疗的治疗指数有可能提高。
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.