Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
Radiother Oncol. 2010 May;95(2):135-41. doi: 10.1016/j.radonc.2010.02.009. Epub 2010 Mar 24.
The purpose of this review is to evaluate the methodology used in published phase I radiotherapy (RT) dose escalation trials. A specific emphasis was placed on the frequency of reporting late complications as endpoint.
We performed a systematic literature review using a predefined search strategy to identify all phase I trials reporting on external radiotherapy dose escalation in cancer patients.
Fifty-three trials (phase I: n = 36, phase I-II: n = 17) fulfilled the inclusion criteria. Of these, 20 used a modified Fibonacci design for the RT dose escalation, but 32 did not specify a design. Late toxicity was variously defined as > 3 months (n = 43) or > 6 months (n = 3) after RT, or not defined (n = 7). In only nine studies the maximum tolerated dose (MTD) was related to late toxicity, while only half the studies reported the minimum follow-up period for dose escalation (n = 26).
In phase I RT trials, late complications are often not taken into account and there is currently no consensus on the methodology used for radiation dose escalation studies. We therefore propose a decision-tree algorithm which depends on the endpoint selected and whether a validated early surrogate endpoint is available, in order to choose the most appropriate study design.
本综述旨在评估已发表的 I 期放疗（RT）剂量递增试验中使用的方法学。特别强调将晚期并发症作为终点的报告频率。
我们采用预设的搜索策略进行了系统文献回顾，以确定所有报告癌症患者外部放疗剂量递增的 I 期试验。
53 项试验（I 期：n = 36，I 期-II 期：n = 17）符合纳入标准。其中，20 项采用改良 Fibonacci 设计进行 RT 剂量递增，但 32 项未指定设计。晚期毒性的定义各不相同，包括 RT 后 >3 个月（n = 43）或 >6 个月（n = 3）或未定义（n = 7）。仅有 9 项研究将最大耐受剂量（MTD）与晚期毒性相关联，而只有一半的研究报告了剂量递增的最短随访时间（n = 26）。
在 I 期 RT 试验中，晚期并发症往往未被考虑在内，目前对于放射剂量递增研究的方法学尚无共识。因此，我们提出了一个决策树算法，该算法取决于所选的终点以及是否存在经过验证的早期替代终点，以便选择最合适的研究设计。
