Department of Radiation Oncology, Rigshospitalet, University of Copenhagen, Denmark.
Int J Radiat Oncol Biol Phys. 2013 Jan 1;85(1):89-94. doi: 10.1016/j.ijrobp.2012.03.004. Epub 2012 May 30.
To present a novel method for meta-analysis of the fractionation sensitivity of tumors as applied to prostate cancer in the presence of an overall time factor.
A systematic search for radiation dose-fractionation trials in prostate cancer was performed using PubMed and by manual search. Published trials comparing standard fractionated external beam radiation therapy with alternative fractionation were eligible. For each trial the α/β ratio and its 95% confidence interval (CI) were extracted, and the data were synthesized with each study weighted by the inverse variance. An overall time factor was included in the analysis, and its influence on α/β was investigated.
Five studies involving 1965 patients were included in the meta-analysis of α/β. The synthesized α/β assuming no effect of overall treatment time was -0.07 Gy (95% CI -0.73-0.59), which was increased to 0.47 Gy (95% CI -0.55-1.50) if a single highly weighted study was excluded. In a separate analysis, 2 studies based on 10,808 patients in total allowed extraction of a synthesized estimate of a time factor of 0.31 Gy/d (95% CI 0.20-0.42). The time factor increased the α/β estimate to 0.58 Gy (95% CI -0.53-1.69)/1.93 Gy (95% CI -0.27-4.14) with/without the heavily weighted study. An analysis of the uncertainty of the α/β estimate showed a loss of information when the hypofractionated arm was underdosed compared with the normo-fractionated arm.
The current external beam fractionation studies are consistent with a very low α/β ratio for prostate cancer, although the CIs include α/β ratios up to 4.14 Gy in the presence of a time factor. Details of the dose fractionation in the 2 trial arms have critical influence on the information that can be extracted from a study. Studies with unfortunate designs will supply little or no information about α/β regardless of the number of subjects enrolled.
提出一种新的方法，用于分析存在总体时间因素时肿瘤的分割敏感性，以前列腺癌为例。
使用 PubMed 和手动搜索对前列腺癌的放射剂量分割试验进行了系统搜索。合格的试验比较了标准分割外照射与替代分割。从每个试验中提取 α/β 比值及其 95%置信区间（CI），并通过每个研究的逆方差加权对数据进行综合。分析中包含了一个整体时间因素，并研究了其对 α/β 的影响。
共有 5 项涉及 1965 例患者的研究被纳入α/β 的荟萃分析。假设没有总治疗时间影响的综合α/β 为-0.07 Gy（95%CI-0.73-0.59），如果排除一个高度加权的研究，则增加至 0.47 Gy（95%CI-0.55-1.50）。在单独的分析中，共有 2 项基于总共 10808 例患者的研究允许提取一个综合的时间因素估计值，为 0.31 Gy/d（95%CI0.20-0.42）。时间因素使α/β 估计值增加至 0.58 Gy（95%CI-0.53-1.69）/1.93 Gy（95%CI-0.27-4.14），同时包括/不包括高度加权的研究。对α/β 估计值不确定性的分析表明，当低分割臂与常规分割臂相比剂量不足时，信息会丢失。
目前的外照射分割研究与前列腺癌的非常低的α/β比值一致，尽管在存在时间因素的情况下，CI 包括高达 4.14 Gy 的α/β 比值。2 个试验臂的剂量分割细节对从研究中提取信息具有关键影响。无论纳入的受试者数量多少，设计不佳的研究都将提供很少或没有关于α/β 的信息。
