Prostate cancer dose-response, fractionation sensitivity and repopulation parameters evaluation from 25 international radiotherapy outcome data sets

Abstract

Objective: This study was undertaken to model the biochemical free survival at 5 years and to evaluate the parameters defining dose-response curve, dose-fractionation radiosensitivity and repopulation. Methods: It was carried out a literature search on Pubmed to retrieve data sets of patients treated with external beam radiation therapy of 1.8-4.0 Gy per fraction and overall treatment time of 3 to 10 weeks. 10 groups were identified, based on risk class and androgen deprivation therapy (ADT). Dose-response curve D50 (dose at 50% probability of control) and g50 (steepness), α/β (dose-fractionation radiosensitivity), and repopulation parameters, dprolif and Tprolif, were calculated. Bootstrap-based cross-validation was performed and median and 95% CI (confidence interval) were evaluated. Results: 25 data sets, including 20,310 patients, were considered. The median (95% CI) D50 and g50 values were 62 (CI 53 - 66) Gy and 1.6 (0.8 - 2.4). ADT patients showed lower values of D50 and g50 (57 ± 5 Gy and 1.1 ± 0.4) compared to no-ADT patients (65 ± 2 Gy and 2.3 ± 0.6), with p < 0.0001 and p = 0.002. If we did not consider any dependence on overall treatment time, the median (95% CI) value of α/β was 1.4 (1.0 - 1.9) Gy with p < 0.0001 for all patients. The median values of dproli f and Tprolif were 0.0 to 0.3 Gy/d and 18-40 days. Conclusion: Dose-response curve resulted dependent on risk class and ADT, with higher steepness for no-ADT patients. Low values of dose-fractionation radiosensitivity were found, supporting the use of moderate hypofractionated radiotherapy in each risk class. A limited dependence on repopulation was observed.