Dose escalation to combat hypoxia in prostate cancer: a radiobiological study on clinical data

Earlier studies have demonstrated that hypoxic regions exist in human prostate cancer and the degree of hypoxia correlates with the treatment outcome of radiotherapy. Using the concept of the clinical oxygen enhancement ratio (COER), the linear-quadratic (LQ) model was extended to account for the effect of tumour hypoxia. The clinical data collected at the Fox Chase Cancer Center for prostate cancer were analysed based on the LQ model as well as the tumour control probability (TCP) model. The LQ and TCP parameters (alpha = 0.15 Gy (-1), alpha/beta = 3.1 Gy and the number of clonogens K = 10(6) approximately 10(7) cells) determined in earlier studies were used to derive the COER for prostate cancer: COER = 1.4 with a standard confidence interval (CI) of (1.2, 1.8). The result is consistent with the in vitro OER measurements of human tumour cell lines under chronic hypoxia conditions. This implies that a higher dose is needed to overcome tumour hypoxia. For prostate tumours, the prescription dose required to overcome tumour hypoxia is 165 Gy (CI: 153 approximately 186 Gy) for permanent 125I implants and 88 Gy (CI: 74 approximately 118 Gy) in 2 Gy fractions for external-beam radiotherapy. The impact of LQ parameters on the calculations of COER and dose escalation was discussed. This study provides a preliminary estimate of the dose escalation needed to overcome tumour hypoxia based on clinical data. More clinical data with better statistics and longer follow-up time are required to further tune the radiobiological modelling of hypoxia for prostate cancer.