Predicting the impact of standard and hypofractionated schedules in prostate cancer radiotherapy with a mechanistic model

Prostate cancer has been typically treated with a total radiation dose of 74-80 Gy administered in 2 Gy fractions. However, about 20% of patients suffer biochemical recurrence. Hypofractionated treatments may have a positive effect on tumour control. Nevertheless, the choice of an optimal personalised therapy is still compromised by the limited knowledge of the response of patients to high irradiation fractions. The purposes of this work were i) to predict biochemical recurrence after standard fractionation using our previously developed mechanistic model and ii) to explore the impact of hypofractionated treatments for patients who suffered biochemical failure. A cohort of 279 patients with localised prostate adenocarcinoma was used. Analogous virtual tissues were built from pre-treatment MRIs. The prescribed standard irradiation schedules were simulated using the mechanistic model. Biochemical recurrence was predicted from the in silico number of tumour cells at the end of treatment (AUC = 0.68). Then, alternative 2.5 and 3 Gy fractionations were simulated for patients who suffered biochemical recurrence. Significantly lower numbers of tumour cells at the end of treatment were obtained after these hypofractionated schedules. Significant decreases in total doses assuring tumour control were also observed for these patients (median of -103 and -14.0 Gy for 2.5 and 3 Gy fractionations, respectively).

Automated summary

Prostate cancer is typically treated with a standard radiation dose, but biochemical recurrence is still common. Hypofractionated treatments may have positive effects on tumor control. This study aimed to predict biochemical recurrence after standard fractionation using a mechanistic model and explore the impact of hypofractionated treatments for patients with biochemical failure. The results showed that hypofractionated schedules resulted in lower tumor cell numbers and decreased total doses for tumor control.