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Comparison of Tumor Control between FLASH and CONV in an Orthotopic Breast Cancer Model. International journal of radiation oncology, biology, physics Melemenidis, S., Viswanathan, V., Dutt, S., Manjappa, R., Ashraf, M. R., Soto, L. A., Skinner, L., Yu, S. J., Surucu, M., Graves, E. E., Loo, B., Dirbas, F. M. 2023; 117 (2S): e251-e252

Abstract

PURPOSE/OBJECTIVE(S): Post-lumpectomy radiotherapy (RT) reduces in-breast tumor recurrence by eradicating residual, occult breast cancer (BC) that may be in the mm size scale. The ability of FLASH-RT to eradicate BC relative to conventional dose rate (CONV) RT is unknown. 20Gy RT is currently used clinically for single-fraction breast IORT. Determine the effectiveness of FLASH compared to CONV in eradicating small tumors in an orthotopic, syngeneic model of BC using single-fraction 20 or 30Gy RT.MATERIALS/METHODS: Radiation sensitive, mammary tumor cell line Py117 from the transgenic model of the mouse mammary tumor virus promoter driving the polyoma middle T antigen (MMTV- PyMT) efficiently forms non-metastatic, orthotopic tumors in C57BL/6 mice. 106 Py117 cells were injected orthotopically into the left 4th mammary fat pad of C57Bl/6J mice. Radiotherapy was performed with a custom jig that allows for fixed positioning of the target volume (2x2cm radiation field) with 5mm of margin into surrounding tissue. Tumors were irradiated at 30mm3 volume or, for comparison, at a range of greater volumes (200-800mm3) with 20 or 30Gy FLASH or CONV with 16-17 MeV electrons.RESULTS: Small 30mm3 tumors regressed until day 15 after 20Gy single fraction RT then regrew for both FLASH and CONV. 30mm3 tumors were eradicated with both FLASH and CONV at 30Gy with no regrowth up to day 35 post-RT. Larger tumors irradiated with 30Gy regressed until day 12 post-RT then regrew for both FLASH and CONV. There was no significant difference in growth delay or tumor eradication between FLASH and CONV in any cohort.CONCLUSION: FLASH was as effective as CONV in controlling growth and eradicating murine BC. Based on other preclinical studies, single-fraction doses between 20 and 30Gy, as well as hypofractioned RT schedules, may identify FLASH doses that achieve comparable tumor control with less toxicity than CONV. Such findings would encourage clinical trials of FLASH in human BC.

View details for DOI 10.1016/j.ijrobp.2023.06.1194

View details for PubMedID 37784977