Ebert Martin A, Foo Kerwyn, Haworth Annette, Gulliford Sarah L, Kennedy Angel, Joseph David J, Denham James W
Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; School of Physics, University of Western Australia, Perth, Western Australia, Australia.
Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Int J Radiat Oncol Biol Phys. 2015 Mar 1;91(3):595-603. doi: 10.1016/j.ijrobp.2014.11.015. Epub 2015 Jan 13.
To use a high-quality multicenter trial dataset to determine dose-volume effects for gastrointestinal (GI) toxicity following radiation therapy for prostate carcinoma. Influential dose-volume histogram regions were to be determined as functions of dose, anatomical location, toxicity, and clinical endpoint.
Planning datasets for 754 participants in the TROG 03.04 RADAR trial were available, with Late Effects of Normal Tissues (LENT) Subjective, Objective, Management, and Analytic (SOMA) toxicity assessment to a median of 72 months. A rank sum method was used to define dose-volume cut-points as near-continuous functions of dose to 3 GI anatomical regions, together with a comprehensive assessment of significance. Univariate and multivariate ordinal regression was used to assess the importance of cut-points at each dose.
Dose ranges providing significant cut-points tended to be consistent with those showing significant univariate regression odds-ratios (representing the probability of a unitary increase in toxicity grade per percent relative volume). Ranges of significant cut-points for rectal bleeding validated previously published results. Separation of the lower GI anatomy into complete anorectum, rectum, and anal canal showed the impact of mid-low doses to the anal canal on urgency and tenesmus, completeness of evacuation and stool frequency, and mid-high doses to the anorectum on bleeding and stool frequency. Derived multivariate models emphasized the importance of the high-dose region of the anorectum and rectum for rectal bleeding and mid- to low-dose regions for diarrhea and urgency and tenesmus, and low-to-mid doses to the anal canal for stool frequency, diarrhea, evacuation, and bleeding.
Results confirm anatomical dependence of specific GI toxicities. They provide an atlas summarizing dose-histogram effects and derived constraints as functions of anatomical region, dose, toxicity, and endpoint for informing future radiation therapy planning.
利用高质量的多中心试验数据集，确定前列腺癌放射治疗后胃肠道（GI）毒性的剂量-体积效应。有影响的剂量-体积直方图区域将被确定为剂量、解剖位置、毒性和临床终点的函数。
可获得TROG 03.04 RADAR试验中754名参与者的计划数据集，并对正常组织晚期效应（LENT）进行主观、客观、管理和分析（SOMA）毒性评估，中位随访时间为72个月。采用秩和方法将剂量-体积切点定义为3个胃肠道解剖区域剂量的近似连续函数，并进行全面的显著性评估。使用单变量和多变量有序回归评估每个剂量下切点的重要性。
提供显著切点的剂量范围往往与显示显著单变量回归优势比的范围一致（代表每百分比相对体积毒性等级单一增加的概率）。直肠出血显著切点的范围验证了先前发表的结果。将下消化道解剖结构分为完整的肛管直肠、直肠和肛管，显示了中低剂量对肛管的影响，包括急迫感和里急后重、排便完整性和大便频率，以及中高剂量对肛管直肠的影响，包括出血和大便频率。推导的多变量模型强调了肛管直肠和直肠高剂量区域对直肠出血的重要性，中低剂量区域对腹泻、急迫感和里急后重的重要性，以及低中剂量对肛管的大便频率、腹泻、排便和出血的重要性。
结果证实了特定胃肠道毒性的解剖学依赖性。它们提供了一个图谱，总结了剂量直方图效应和作为解剖区域、剂量、毒性和终点函数的推导约束条件，以指导未来的放射治疗计划。
