Melemenidis Stavros, Viswanathan Vignesh, Dutt Suparna, Kapadia Naviya, Lau Brianna, Soto Luis A, Ashraf M Ramish, Thakur Banita, Mutahar Adel Z I, Skinner Lawrie B, Yu Amy S, Surucu Murat, Casey Kerriann M, Rankin Erinn B, Horst Kathleen C, Graves Edward E, Loo Billy W, Dirbas Frederick M
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Surgery, Stanford University School of Medicine, Stanford Cancer Institute, Stanford, CA 94305, USA.
Cancers (Basel). 2025 Mar 25;17(7):1095. doi: 10.3390/cancers17071095.
: 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. : 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). : 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. : 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.
放射疗法对乳腺癌治疗有效，但常常会引起不良副作用，影响生活质量。与传统剂量率放疗（CONV）相比，超高剂量率放疗（FLASH）已显示出正常组织毒性降低，同时实现了相当的肿瘤生长延迟。本研究在原位乳腺癌模型中，以肿瘤根除作为主要终点，评估了FLASH是否能与CONV实现相似的肿瘤控制效果。：使用同基因C57BL/6J小鼠的Py117乳腺肿瘤细胞系，在左第四乳腺脂肪垫中生成非转移性原位肿瘤。使用FLASH（93 - 200 Gy/s）和CONV（0.08 Gy/s）电子束进行了两项连续的照射研究。将20、25或30 Gy的单次剂量应用于具有不同腹壁治疗野（距肿瘤约3.75或2.5 mm治疗边缘）的肿瘤。：FLASH和CONV均显示出相当的疗效。用30 Gy和较大腹壁治疗野治疗的小肿瘤在30天时似乎已完全根除，但也表现出最高的皮肤毒性，限制了随访并妨碍了根除的确认。较小的腹壁治疗野降低了皮肤毒性并允许延长随访时间，这导致在48天时75%的无瘤生存率。较大的肿瘤显示出生长延迟但未根除。：在这个临床前的非转移性原位乳腺癌模型中，FLASH和CONV在20、25或30 Gy的单次剂量下显示出等效的肿瘤控制效果。总体而言，30 Gy实现了最高的根除率，但也导致了最明显的皮肤毒性。
