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.
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