Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, People's Republic of China.
Department of Radiation Oncology Gastrointestinal and Urinary and Musculoskeletal Cancer, Cancer Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
Radiat Oncol. 2022 Mar 18;17(1):54. doi: 10.1186/s13014-022-02010-9.
Prostate cancer (PCa) is known to be suitable for hypofractionated radiotherapy due to the very low α/β 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/β ratio. Therefore, this study attempted to estimate the α/β ratio in different fractionation schedules and evaluate the applicability of the LQ model in hypofractionated radiotherapy.
The maximum likelihood principle in mathematical statistics was used to fit the parameters: α and β 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.
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/β 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/β 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.
The LQ model appeared to be inappropriate for high doses per fraction owing to α/β 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/β ratio should be used for calculation.
由于前列腺癌（PCa）的 α/β 比值（约 1.5-3 Gy）非常低，因此适用于分割剂量放疗。然而，几项随机对照试验并未显示分割剂量放疗优于常规分割放疗。此外，体内和体外实验结果表明，线性二次（LQ）模型可能不适用于分割剂量放疗，我们猜测这可能是由于分割方案对 α/β 比值的影响。因此，本研究试图估计不同分割方案中的 α/β 比值，并评估 LQ 模型在分割剂量放疗中的适用性。
使用数理统计中的最大似然原理拟合肿瘤控制概率（TCP）公式中的参数：α 和 β 值，该公式来源于 LQ 模型。此外，将拟合结果代入原始 TCP 公式计算 5 年生化无复发生存率进行进一步验证。
从总共 23281 例 PCa 患者中提取了拟合所需的信息。根据分割方案将总共 16442 例 PCa 患者进行分组。我们发现，对于接受常规分割放疗、中度分割放疗和立体定向体部放疗的患者，平均 α/β 比值分别为 1.78 Gy（95%CI 1.59-1.98）、3.46 Gy（95%CI 3.27-3.65）和 4.24 Gy（95%CI 4.10-4.39）。因此，当剂量分割增加时，计算出的 PCa α/β 比值趋于升高。在所有 PCa 患者中，根据不同分割方案接受放疗的 PCa 风险，可将 14641 例患者进行分组。结果表明，随着风险的增加，k（有效靶细胞数的自然对数）和α值降低，表明有效靶细胞数量减少，放射抗性增加。
由于当剂量分割增加时 α/β 比值趋于升高，因此 LQ 模型似乎不适用于高剂量分割。因此，要使用标准 LQ 模型将常规分割剂量转换为等效高剂量分割，计算时应使用更高的 α/β 比值。
