Introduction: Radiotherapy is effective for breast cancer treatment but often causes undesirable side effects that impair quality of life. Ultra-high dose rate radiotherapy (FLASH) has shown reduced normal tissue toxicity while achieving comparable tumor growth delay compared to conventional dose rate radiotherapy (CONV). This study evaluated whether FLASH could achieve similar tumor control as CONV with tumor eradication as the primary endpoint, in an orthotopic breast cancer model.Methods: Non-metastatic, orthotopic tumors were generated in the left fourth mammary fat pad using the Py117 mammary tumor cell line in syngeneic C57BL/6J mice. Two sequential irradiation studies were performed using FLASH (93–200 Gy/s) and CONV (0.08 Gy/s) electron beams. Single fractions of 20, 25, or 30 Gy were applied to tumors with varying abdominal wall treatment fields (~3.75 or 2.5 mm treatment margin to tumor).Results: Both FLASH and CONV demonstrated comparable efficacy. Small tumors treated with 30 Gy and larger abdominal wall treatment fields appeared to have complete eradication at 30 days but also exhibited the highest skin toxicity, limiting follow-up and preventing confirmation of eradication. Smaller abdominal wall treatment fields reduced skin toxicity and allowed for extended follow-up, which resulted in 75% tumor-free survival at 48 days. Larger tumors showed growth delay but no eradication.Conclusions: In this preclinical, non-metastatic orthotopic breast cancer model, FLASH and CONV demonstrated equivalent tumor control with single-fraction doses of 20, 25, or 30 Gy. Overall, 30 Gy achieved the highest eradication rate but also resulted in the most pronounced skin toxicity.
引言：放射治疗是乳腺癌的有效治疗手段，但常引起不良副作用，影响患者生活质量。与传统剂量率放疗相比，超高剂量率放疗在实现相当肿瘤生长抑制的同时，已显示出降低正常组织毒性的优势。本研究以原位乳腺癌模型为对象，以肿瘤完全消退为主要终点，评估超高剂量率放疗能否达到与传统放疗相似的肿瘤控制效果。 方法：采用同源C57BL/6J小鼠，通过Py117乳腺肿瘤细胞系在左侧第四乳腺脂肪垫建立非转移性原位肿瘤模型。使用超高剂量率（93-200 Gy/s）和传统剂量率（0.08 Gy/s）电子束进行连续两次照射研究。对肿瘤实施单次20、25或30 Gy照射，并设置不同范围的腹壁照射野（肿瘤外扩约3.75 mm或2.5 mm边界）。 结果：两种放疗方式显示出相当的疗效。接受30 Gy照射且采用较大腹壁照射野的小型肿瘤在30天时呈现完全消退趋势，但同时也表现出最严重的皮肤毒性，限制了随访观察并阻碍了消退确认。较小腹壁照射野可减轻皮肤毒性，延长随访时间，在48天时实现75%的无瘤生存率。较大肿瘤仅显示生长延迟，未见完全消退。 结论：在此临床前非转移性原位乳腺癌模型中，单次20、25或30 Gy剂量的超高剂量率放疗与传统放疗在肿瘤控制方面效果相当。总体而言，30 Gy剂量可获得最高消退率，但同时也导致最显著的皮肤毒性反应。
肿瘤(癌症)患者之家