Comparable Long-Term Tumor Control for Hypofractionated FLASH Versus Conventional Radiation Therapy in an Immunocompetent Rat Glioma Model.
Comparable Long-Term Tumor Control for Hypofractionated FLASH Versus Conventional Radiation Therapy in an Immunocompetent Rat Glioma Model.
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DOI：
10.1016/j.adro.2022.101011
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发表时间：
2022-11
影响因子：
2.3
通讯作者：
Nittby Redebrandt, Henrietta
中科院分区：
文献类型：
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作者：
Konradsson, Elise;Liljedahl, Emma;Gustafsson, Emma;Adrian, Gabriel;Beyer, Sarah;Ilaahi, Suhayb Ehsaan;Petersson, Kristoffer;Ceberg, Crister;Nittby Redebrandt, Henrietta
为了确保FLASH放射治疗（FLASH-RT）对特定肿瘤类型的临床转化，需要在同一生物系统内进行肿瘤控制和毒性研究。在这项研究中，我们的目的是评估肿瘤控制和毒性的大分割FLASH-RT和常规放射治疗（CONV-RT）在免疫活性大鼠胶质瘤模型。将Fisher 344大鼠（N = 68）皮下接种NS 1神经胶质瘤细胞并随机分组（每组n = 9-10）。使用10-MeV电子束，以8戈伊、12.5戈伊或15戈伊的3个部分给予CONV-RT（≥ 8戈伊/min）或FLASH-RT（70-90戈伊/s）。每周测量最大肿瘤直径，并确定总生存期直至第100天。长期肿瘤控制定义为在第100天没有明显的肿瘤。在完成RT后2至5周评价动物的急性皮肤副作用，并在开始治疗后3个月评价晚期皮肤副作用。与对照组相比，所有照射组的存活率均显著增加（P < .001）。在一般情况下，照射肿瘤开始缩小1周后完成RT。在40%（23 58）的照射动物，实现了长期的肿瘤控制。辐射引起的皮肤毒性效应轻微，包括脱发、红斑和干燥脱皮。未观察到严重毒性作用。对于任何剂量水平，FLASH-RT和CONV-RT在总生存率、急性副作用或晚期副作用方面均无显著差异。这项研究表明，大分割FLASH-RT的长期肿瘤控制率与CONV-RT相似，用于治疗免疫功能正常大鼠的大型皮下胶质母细胞瘤。两种处理技术均未引起严重的皮肤毒性作用。因此，无法解决毒性的显著差异，表明可能需要更高的剂量来检测皮肤的FLASH保留。
To ensure a clinical translation of FLASH radiation therapy (FLASH-RT) for a specific tumor type, studies on tumor control and toxicity within the same biological system are needed. In this study, our objective was to evaluate tumor control and toxicity for hypofractionated FLASH-RT and conventional radiation therapy (CONV-RT) in an immunocompetent rat glioma model. Fisher 344 rats (N = 68) were inoculated subcutaneously with NS1 glioma cells and randomized into groups (n = 9-10 per group). CONV-RT (∼8 Gy/min) or FLASH-RT (70-90 Gy/s) was administered in 3 fractions of either 8 Gy, 12.5 Gy, or 15 Gy using a 10-MeV electron beam. The maximum tumor diameter was measured weekly, and overall survival was determined until day 100. Long-term tumor control was defined as no evident tumor on day 100. Animals were evaluated for acute dermal side effects at 2 to 5 weeks after completed RT and for late dermal side effects at 3 months after initiation of treatment. Survival was significantly increased in all irradiated groups compared with control animals (P < .001). In general, irradiated tumors started to shrink at 1 week post–completed RT. In 40% (23 of 58) of the irradiated animals, long-term tumor control was achieved. Radiation-induced skin toxic effects were mild and consisted of hair loss, erythema, and dry desquamation. No severe toxic effect was observed. There was no significant difference between FLASH-RT and CONV-RT in overall survival, acute side effects, or late side effects for any of the dose levels. This study shows that hypofractionated FLASH-RT results in long-term tumor control rates similar to those of CONV-RT for the treatment of large subcutaneous glioblastomas in immunocompetent rats. Neither treatment technique induced severe skin toxic effects. Consequently, no significant difference in toxicity could be resolved, suggesting that higher doses may be required to detect a FLASH sparing of skin.