Background/Objectives: Clinical studies have shown a marked reduction in tumor control in prostate cancer treated with radically hypofractionated high-dose-rate brachytherapy (HDR-BT). The purpose of this study was to analyze the dose–response of prostate cancer treated with HDR-BT, specifically aiming at investigating the potential failure of the linear–quadratic (LQ) model to describe the response at large doses-per-fraction. Methods: We collated a dataset of dose–response to HDR-BT (3239 patients). The analysis was conducted separately for low and intermediate risk, resulting in 21 schedules (1633 patients) and 23 schedules (1606 patients), respectively. Data were fitted to tumor control probability models based on the LQ model, the linear–quadratic–linear (LQL), and a modification of the LQ model to include the effect of reoxygenation during treatment. Results: The LQ cannot fit the data unless theα/βis allowed to be high (∼[20, >100] Gy, 95% confidence interval). If theα/βis constrained to be low (≤8 Gy), the LQ model cannot reproduce the clinical results, and the LQL model, which includes a moderation of radiation damage with increasing dose, significantly improves the fitting. On the other hand, the reoxygenation model does not match the results obtained with the LQL. The clinically observed reduction in tumor control in prostate cancer treated with radical HDR-BT is better described by the LQL model. Using the best-fitting parameters, the BED for a 20 Gy × 1 treatment (128Gyα/β) is far less than that of a conventional 2 Gy × 37 fractionation (196Gyα/β). Conclusions: Our analysis showed that the substantial loss of tumor control observed in extremely hypofractionated HDR-BT trials can only be explained by the LQ model if theα/βis very large (≥100 Gy), in clear disagreement with the limits set in the analysis of external radiotherapy data. It seems more reasonable that there is a moderation of the LQ-predicted effect with increasing dose per fraction. These results may assist in the design of radical HDR-BT treatments.
背景/目的：临床研究表明，采用根治性大分割高剂量率近距离放射治疗（HDR-BT）的前列腺癌肿瘤控制率显著降低。本研究旨在分析HDR-BT治疗前列腺癌的剂量-反应关系，特别探讨线性二次（LQ）模型在描述大分割剂量下反应时可能存在的失效问题。方法：我们整理了HDR-BT剂量-反应数据集（共3239例患者）。针对低危和中危患者分别进行分析，分别得到21个治疗方案（1633例患者）和23个治疗方案（1606例患者）。数据拟合采用基于LQ模型、线性二次线性（LQL）模型以及引入治疗期间再氧合效应的LQ修正模型的肿瘤控制概率模型。结果：除非允许α/β值处于较高水平（约[20, >100] Gy，95%置信区间），否则LQ模型无法拟合数据。若将α/β值限制在较低范围（≤8 Gy），LQ模型无法复现临床结果，而引入辐射损伤随剂量增加而减缓机制的LQL模型则显著改善了拟合效果。另一方面，再氧合模型与LQL模型所得结果不相符。LQL模型能更好地描述根治性HDR-BT治疗前列腺癌中临床观察到的肿瘤控制率下降现象。采用最佳拟合参数计算，20 Gy×1次治疗（α/β=128 Gy）的生物等效剂量（BED）远低于常规2 Gy×37次分割方案（α/β=196 Gy）。结论：我们的分析表明，只有在α/β值极大（≥100 Gy）的情况下，LQ模型才能解释极端大分割HDR-BT试验中观察到的肿瘤控制率显著下降现象，这与外照射放疗数据分析设定的限值明显矛盾。更合理的解释是，随着单次分割剂量的增加，LQ模型预测的效应会出现减缓。这些结果可能有助于根治性HDR-BT治疗方案的设计。
肿瘤(癌症)患者之家