Konradsson Elise, Liljedahl Emma, Gustafsson Emma, Adrian Gabriel, Beyer Sarah, Ilaahi Suhayb Ehsaan, Petersson Kristoffer, Ceberg Crister, Nittby Redebrandt Henrietta
Medical Radiation Physics, Department of Clinical Sciences, Lund University, Lund, Sweden.
Rausing Laboratory, Division of Neurosurgery, Department of Clinical Sciences, Lund University, Lund, Sweden.
Adv Radiat Oncol. 2022 Jul 2;7(6):101011. doi: 10.1016/j.adro.2022.101011. eCollection 2022 Nov-Dec.
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 ( < .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.
为确保针对特定肿瘤类型的FLASH放射治疗（FLASH-RT）能够实现临床转化，需要在同一生物系统内开展关于肿瘤控制和毒性的研究。在本研究中，我们的目的是评估在具有免疫活性的大鼠胶质瘤模型中，大分割FLASH-RT和传统放射治疗（CONV-RT）的肿瘤控制情况和毒性。
将NS1胶质瘤细胞皮下接种于68只Fisher 344大鼠，并随机分组（每组9 - 10只）。使用10 MeV电子束，以8 Gy、12.5 Gy或15 Gy的剂量分3次给予CONV-RT（约8 Gy/分钟）或FLASH-RT（70 - 90 Gy/秒）。每周测量最大肿瘤直径，并确定直至第100天的总生存期。长期肿瘤控制定义为在第100天时无明显肿瘤。在放疗完成后2至5周评估动物的急性皮肤副作用，在治疗开始后3个月评估晚期皮肤副作用。
与对照动物相比，所有照射组的生存期均显著延长（P <.001）。一般来说，照射后的肿瘤在放疗完成后1周开始缩小。在40%（58只中的23只）的照射动物中实现了长期肿瘤控制。放射诱导的皮肤毒性作用较轻，包括脱发、红斑和干性脱屑。未观察到严重毒性作用。在任何剂量水平下，FLASH-RT和CONV-RT在总生存期、急性副作用或晚期副作用方面均无显著差异。
本研究表明，对于免疫活性大鼠皮下大的胶质母细胞瘤，大分割FLASH-RT产生的长期肿瘤控制率与CONV-RT相似。两种治疗技术均未引起严重的皮肤毒性作用。因此，无法分辨出毒性方面的显著差异，这表明可能需要更高的剂量才能检测到FLASH对皮肤的保护作用。
