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• W4366543669 abstract "Sir — Mistry [ [1] Mistry H.B. Radiosensitivity index is not fit to be used for dose adjustments: a pan-cancer analysis. Clin Oncol. 2023; 35 Google Scholar ] recently analysed the correlation of the radiosensitivity index (RSI) with, in vitro, the survival fraction at 2 Gy (SF2) and, in clinical treatment, with survival. He found that the RSI had a negative correlation with SF2 and had no correlation with survival. This may not be a problem with the RSI, but with the tumour population being measured. The RSI analysed the untreated cancer for prediction of the outcome with fractionated radiation therapy. It is well established that treatment of a cell line with radiotherapy induces radiation resistance in the surviving cell culture clone. Our previous modelling of the effect of introducing a normal distribution of heterogeneity into the radioresistance of a cancer cell line showed that the radiosensitivity of the initial cancer population has little correlation with the radiosensitivity of the remaining tumour clones after fractionated radiation therapy [ [2] Alfonso J.C.L. Berk L. Modeling of the effect of intratumoral heterogeneity of radiosensitivity on tumor response over the course of fractionated radiation therapy. Radiat Oncol. 2019; 14: 88 Crossref PubMed Scopus (26) Google Scholar ]. It is the sensitivity of this remaining clone that predicts local control and potentially survival. In our paper, we used published pre- and post-radiation therapy cell culture dose-response curves to model the evolution of the clonogen populations. For example, in Figure 3 of our paper, as more sensitive tumour cells are eliminated with 35 daily radiation therapy treatments, the alpha/beta ratio of the majority clonogen decreases from about 21 to 13 and the corresponding SF2 increases from 0.42 to 0.57. These data would explain the poor and overall negative correlation of the RSI with the SF2. The response of the radiosensitivity-heterogeneous tumour would be controlled by two factors: the mean of the initial radiosensitivity distribution and the distribution of the radiosensitivity around the mean. The ultimate control is only dependent on the radiosensitivity of the most resistant clones. Thus, any assay measuring the mean radiosensitivity of an untreated tumour will not predict the final outcome after fractionated radiotherapy. Radiosensitivity Index is Not Fit to be Used for Dose Adjustments: A Pan-Cancer AnalysisClinical OncologyPreviewTo explore the preclinical and latest clinical evidence of the radiation sensitivity signature termed ‘radiosensitivity index’ (RSI), to assess its suitability as an input into dose-adjustment algorithms. Full-Text PDF" @default.
• W4366543669 created "2023-04-22" @default.
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• W4366543669 date "2023-04-01" @default.
• W4366543669 modified "2023-10-17" @default.
• W4366543669 title "Response to Mistry: Radiosensitivity Index is Not Fit to be Used for Dose Adjustments: A Pan-Cancer Analysis" @default.
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• W4366543669 doi "https://doi.org/10.1016/j.clon.2023.04.002" @default.
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