Int J Radiat Oncol Biol Phys. 2023 Jun 3:S0360-3016(23)00535-7. doi: 10.1016/j.ijrobp.2023.05.045. Online ahead of print.
ABSTRACT
PURPOSE: When compared to conventional dose rate irradiation (CONV), ultra-high dose rate irradiation (UHDR) has shown superior normal tissue sparing. However, a clinically relevant widening of the therapeutic window by UHDR, termed “FLASH effect”, also depends on the tumour toxicity obtained by UHDR. Based on a combined analysis of published literature, the current study re-examines the hypothesis of tumour isoefficacy for UHDR versus CONV and aims to identify potential knowledge gaps to inspire future in vivo studies.
METHODS: A systematic literature search identified publications assessing in vivo tumour responses comparing UHDR and CONV. Qualitative and quantitative analyses were performed, including combined analyses of tumour growth and survival data.
RESULTS: We identified 66 data sets from 15 publications that compared UHDR and CONV for tumour efficacy. The median number of animals per group was 9 (range: 3-15) and the median follow-up period was 30.5 (range: 11-230) days after the first irradiation. Tumour growth assays were the predominant model used. Combined statistical analyses of tumour growth and survival data are consistent with UHDR isoefficacy compared to CONV. Only one study determined tumour-controlling dose (TCD50) and reported statistically non-significant differences.
CONCLUSION: The combined quantitative analyses of tumour responses support the assumption of UHDR isoefficacy compared to CONV. However, the comparisons are primarily based on heterogeneous tumour growth assays with limited numbers of animals and short follow-up, and most studies do not assess long-term tumour control probability. Therefore, the assays may be insensitive in resolving smaller response differences, such as responses of radio-resistant tumour sub-clones. Hence, tumour cure experiments, including additional TCD50 experiments, are needed to confirm the assumption of isoeffectiveness in curative settings.
PMID:37276928 | DOI:10.1016/j.ijrobp.2023.05.045
