Thomas L. Andresen (Denmark)
Technical University of Denmark Department of Health Technology, Biotherapeutic Engineering and Drug TargetingAuthor Of 1 Presentation
FLASH SPARING OF MELANOMA CELLS IN VITRO AND IN VIVO
Abstract
Background and Aims
We have previously found that FLASH-irradiation with a pulsed electron beam (average doserate ≥600Gy/s) was less efficient to sterilize cancer cells in-vitro compared with conventional doserate irradiation (CONV, 0.2Gy/s). In the current work we aimed at investigating the effect for a malignant cell line both in vitro and in vivo.
Methods
Radiation response of melanoma cell line B16_F10 was determined in-vitro by clonogenic assays for an absorbed dose in the range 0-9 Gy comparing FLASH to CONV. In-vivo-response was studied in a syngeneic mice model (C57BL/6J) with subcutaneously injected B16_F10-tumors, irradiated to an absorbed dose of 15, 20 or 25Gy (FLASH and CONV). The tumor growth was quantified by using the relative tumor volume, normalized to unity at the time of irradiation, TVrel.
Results
The in-vitro results showed a significantly increased survival after FLASH compared with CONV (F-test: p=0.02). Tumor growth curves in-vivo were similar for CONV and FLASH at 15 and 20Gy, but FLASH was relatively less efficient at 25Gy. Four weeks after irradiation with 25Gy, a relative tumor volume of TVrel<1 was seen in 2/9 mice in the CONV group but in 0/8 mice in the FLASH group. A relative tumor volume of TVrel<4 was seen in 5/9 mice in the CONV group but 0/8 mice in the FLASH group. Severe skin toxicity was observed in 5/9 vs 0/8.
Conclusions
FLASH may be less efficient than CONV to sterilize malignant cells in-vitro as well as in-vivo. Future work will address the differential response between normal tissue and tumors at higher doses.