Quality of radiation shapes survival, invasiveness, and migration in ovarian cancer cell lines with different molecular profiles and varying alpha/beta ratios: an in vitro study on behalf of the Multicenter Italian Trials in Ovarian Cancer (MITO) group

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Objective The results of radiotherapy (RT) in oligometastatic ovarian cancers (OCs) lead to the query whether it is possible to stratify patients based on tumor hallmarks to ensure the best-personalized RT treatment. To address this question, we designed a preclinical study to evaluate the effects of high and low linear energy transfer (LET) radiation while considering molecular features and alpha/beta ratios of different OC cell lines.Methods Exponentially growing human OVSAHO, OVCAR8, COV362, and OVCAR3 cells cultured in T-25 and T-75 flasks were exposed to different single physical doses of photons, protons, and carbon ion (CIRT) irradiation. We assessed ovarian cells’ in vitro response using clonogenic survival (fitted using LQ model), migration by Boyden chamber assay, and invasion through BioCoat Matrigel invasion assay.Results Following photon irradiation, OVCAR3 was the most radioresistant and OVCAR8 the most radiosensitive cell line. OC cell migration decreased in a dose-dependent manner after irradiation, with CIRT showing the strongest effect, evident by the α/β ratio. The number of invading cells decreased following irradiation with all types. However, the greatest reduction was seen in CIRT, particularly at higher α/β ratios. Proton irradiation demonstrated similar potential to photons but did not match the effects of carbon ions in terms of survival, migration, and invasion. Conclusion: CIRT markedly reduced survival, migration, and invasion of OC cells, particularly in BRCA wild-type OVCAR3 emphasizing its potential to improve local control and lower metastasis risk. This preliminary study serves as a foundation for developing personalized clinical radiation strategies to treat oligometastatic OCs.

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