Department of Oncology, Rigshospitalet and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, Baltimore, Maryland; Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland.
Int J Radiat Oncol Biol Phys. 2018 Mar 15;100(4):858-865. doi: 10.1016/j.ijrobp.2017.12.011. Epub 2017 Dec 15.
Randomized trials of altered dose/fractionation for external beam radiation therapy are meta-analyzed with the aim of establishing the dose response and fractionation sensitivity.
Studies were identified through PubMed through April 1, 2017. Studies of any-risk prostate cancer patients and any modification of external beam radiation therapy were included. The outcomes and comparisons collected were hazard ratios for biochemical no evidence of disease (bNED) and overall survival (OS). Trial-by-trial estimates of the steepness of the dose-response curve for bNED were performed for dose-escalation trials, followed by inverse variance weighting. The steepness was used to extract estimates of α/β, which were subsequently synthesized. Both analyses were performed assuming no effect of overall treatment time and were repeated assuming a loss of 0.31 Gy/d for a protracted treatment time. Finally, all trials were included in the analyses of the dose response for fractionation-corrected doses. This analysis was repeated for OS. Finally, the per-trial effect on OS was compared to the effect on bNED.
We identified 13 randomized trials involving 10,184 patients. The dose response for bNED from dose-escalation trials was γ = 0.62 (95% confidence interval [CI] 0.37-0.87) and γ = 0.87 (95% CI 0.53-1.21) without and with the overall treatment time effect, respectively. The corresponding estimates of α/β from 8 fractionation trials (7946 patients) were 1.2 Gy (95% CI 0.8-1.7) and 2.7 Gy (95% CI 1.6-3.8). The heterogeneity in the data can be explained by the shallower dose response for bNED in trials with effective doses in the experimental arm >80 Gy equivalent dose in 2-Gy fractions (EQD2) (P = .04). No indication was found of a dose response for OS or a correlation with improvement in bNED.
The reported data of moderate hypofractionation are consistent with a low α/β value with narrow CIs. Dose-escalation trials have demonstrated a dose response for bNED. Escalating doses to >80 Gy EQD2 might not improve bNED. A correlation between benefit in bNED and OS was not found.
通过对外部束放射治疗的改变剂量/分割的随机试验进行荟萃分析，旨在建立剂量反应和分割敏感性。
通过 PubMed 检索到 2017 年 4 月 1 日之前的研究。包括任何风险前列腺癌患者和任何外部束放射治疗的改变的研究。收集的结果和比较包括生化无疾病证据（bNED）和总生存（OS）的危险比。对 bNED 剂量反应曲线的陡峭度进行了剂量递增试验的试验间估计，然后进行逆方差加权。陡峭度用于提取 α/β 的估计值，随后进行综合。这两种分析均假设总治疗时间没有影响，并重复假设延长治疗时间时每天损失 0.31Gy。最后，所有试验均纳入校正分割剂量的剂量反应分析。对 OS 进行了重复分析。最后，将 OS 的每例试验影响与 bNED 的影响进行了比较。
我们确定了 13 项涉及 10184 名患者的随机试验。来自剂量递增试验的 bNED 剂量反应为 γ=0.62（95%置信区间 [CI] 0.37-0.87）和 γ=0.87（95% CI 0.53-1.21），分别无和有总治疗时间效应。来自 8 项分割试验（7946 名患者）的相应 α/β 估计值分别为 1.2Gy（95%CI 0.8-1.7）和 2.7Gy（95%CI 1.6-3.8）。在实验臂有效剂量 >80Gy 等效剂量 2-Gy 分数（EQD2）的试验中，bNED 的剂量反应较浅，可以解释数据的异质性（P=0.04）。未发现 OS 有剂量反应或与 bNED 改善相关。
报告的中度适形分割数据与低 α/β 值和较窄的置信区间一致。剂量递增试验已经证明了 bNED 的剂量反应。将剂量提高到 >80Gy EQD2 可能不会改善 bNED。在 bNED 和 OS 之间没有发现获益相关性。
