Variability of α/ß ratios for prostate cancer with the fractionation schedule: caution against using the linear-quadratic model for hypofractionated radiotherapy.

ABSTRACT

BACKGROUND: Prostate cancer (PCa) is known to be suitable for hypofractionated radiotherapy due to the very low α/ß ratio (about 1.5-3 Gy). However, several randomized controlled trials have not shown the superiority of hypofractionated radiotherapy over conventionally fractionated radiotherapy. Besides, in vivo and in vitro experimental results show that the linear-quadratic (LQ) model may not be appropriate for hypofractionated radiotherapy, and we guess it may be due to the influence of fractionation schedules on the α/ß ratio. Therefore, this study attempted to estimate the α/ß ratio in different fractionation schedules and evaluate the applicability of the LQ model in hypofractionated radiotherapy. METHODS: The maximum likelihood principle in mathematical statistics was used to fit the parameters α and ß values in the tumor control probability (TCP) formula derived from the LQ model. In addition, the fitting results were substituted into the original TCP formula to calculate 5-year biochemical relapse-free survival for further verification. RESULTS: Information necessary for fitting could be extracted from a total of 23,281 PCa patients. A total of 16,442 PCa patients were grouped according to fractionation schedules. We found that, for patients who received conventionally fractionated radiotherapy, moderately hypofractionated radiotherapy, and stereotactic body radiotherapy, the average α/ß ratios were 1.78 Gy (95% CI 1.59-1.98), 3.46 Gy (95% CI 3.27-3.65), and 4.24 Gy (95% CI 4.10-4.39), respectively. Hence, the calculated α/ß ratios for PCa tended to become higher when the dose per fraction increased. Among all PCa patients, 14,641 could be grouped according to the risks of PCa in patients receiving radiotherapy with different fractionation schedules. The results showed that as the risk increased, the k (natural logarithm of an effective target cell number) and α values decreased, indicating that the number of effective target cells decreased and the radioresistance increased. CONCLUSIONS: The LQ model appeared to be inappropriate for high doses per fraction owing to α/ß ratios tending to become higher when the dose per fraction increased. Therefore, to convert the conventionally fractionated radiation doses to equivalent high doses per fraction using the standard LQ model, a higher α/ß ratio should be used for calculation.