Department of Bioinformatics and Computational Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77230-1402, USA.
Int J Radiat Oncol Biol Phys. 2011 Oct 1;81(2):600-5. doi: 10.1016/j.ijrobp.2010.11.080. Epub 2011 Mar 4.
To estimate α/β, the parameter ratio from the linear-quadratic (LQ) model, for Grade ≥2 late rectal toxicity among patients treated on Radiation Therapy Oncology Group (RTOG) protocol 94-06; and to determine whether correcting the rectal dose-volume histogram (DVH) for differences in dose per fraction, based on the LQ model, significantly improves the fit to these data of the Lyman-Kutcher-Burman (LKB) normal-tissue complication probability (NTCP) model.
The generalized LKB model was fitted to the Grade ≥2 late rectal toxicity data in two ways: by using DVHs representing physical dose to rectum, and by using a modified approach in which dose bins in the rectal DVH were corrected for differences in dose per fraction using the LQ model, with α/β estimated as an additional unknown parameter. The analysis included only patients treated with the same treatment plan throughout radiotherapy, so that the dose per fraction to each voxel of rectum could be determined from the DVH. The likelihood ratio test was used to assess whether the fit of the LQ-corrected model was significantly better than the fit of the LKB model based on physical doses to rectum.
The analysis included 509 of the 1,084 patients enrolled on RTOG 94-06. The estimate of α/β from the LQ-corrected LKB model was 4.8 Gy, with 68% confidence interval 0.6 Gy to 46 Gy. The fit was not significantly different from the fit of the LKB model based on physical dose to rectum (p = 0.236).
The estimated fractionation sensitivity for Grade ≥2 late rectal toxicity is consistent with values of α/β for rectum found previously in human beings and in rodents. However, the confidence interval is large, and there is no evidence that LQ correction of the rectal DVH significantly changes the fit or predictions of the LKB model for this endpoint.
根据线性二次（LQ）模型，估算接受放射治疗肿瘤协作组（RTOG）94-06 方案治疗的患者中≥2 级晚期直肠毒性的α/β比值，并确定是否可以通过 LQ 模型对直肠剂量-体积直方图（DVH）中每个分次剂量的差异进行校正，从而显著改善 Lyman-Kutcher-Burman（LKB）正常组织并发症概率（NTCP）模型对这些数据的拟合程度。
以两种方式将广义 LKB 模型拟合到≥2 级晚期直肠毒性数据：使用表示直肠物理剂量的 DVH，并使用一种改进的方法，即通过 LQ 模型校正直肠 DVH 中的剂量-bin，以额外未知参数的形式估计α/β。该分析仅包括在整个放射治疗过程中接受相同治疗计划的患者，以便可以从 DVH 中确定直肠每个体素的分次剂量。采用似然比检验评估 LQ 校正模型的拟合度是否显著优于基于直肠物理剂量的 LKB 模型。
该分析纳入了 RTOG 94-06 中 1084 例患者中的 509 例。LQ 校正 LKB 模型的α/β估计值为 4.8 Gy，95%置信区间为 0.6 Gy 至 46 Gy。该拟合与基于直肠物理剂量的 LKB 模型的拟合没有显著差异（p=0.236）。
对于≥2 级晚期直肠毒性的分次敏感性估计值与人类和啮齿动物中之前发现的直肠α/β值一致。然而，置信区间较大，没有证据表明 LQ 校正直肠 DVH 会显著改变 LKB 模型对该终点的拟合程度或预测值。
