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

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.

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.

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 dprolif and Tprolif were 0.0 to 0.3 Gy/d and 18-40 days.

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.

Prostate cancer response to moderate hypofractionated radiotherapy was reliably quantified considering risk class and androgen deprivation therapy.

The British journal of radiology. 2019 Apr 24 [Epub ahead of print]

Matteo Tamponi, Domenico Gabriele, Angelo Maggio, Michele Stasi, Giovanni B Meloni, Maurizio Conti, Pietro Gabriele

1 ATS, Sardinia Regional Health Service , Sassari , Italy., 2 Institute of Radiological Sciences University of Sassari , Italy., 3 Medical Physics, Candiolo Cancer Institute - FPO , IRCCS, Candiolo (To) , Italy., 5 Radiation Therapy, Candiolo Cancer Institute - FPO , IRCCS, Candiolo (To) , Italy.