Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York.
Herbert Irving Comprehensive Cancer Center, Department of Medicine, Columbia University, New York, New York.
Cancer. 2018 Feb 15;124(4):858-864. doi: 10.1002/cncr.31107. Epub 2017 Nov 7.
A summary measure that reflects the global toxicity burden of a treatment is essential for comparing therapies. Current toxicity summaries are ad hoc and do not distinguish among the severities and types of toxicities. Here a clinically feasible method for estimating the toxicity burden, based on a prospective evaluation of the toxicity profile of a randomized clinical trial of 746 prostate cancer patients conducted by SWOG, is proposed.
For 308 patients who experienced severe toxicities, 2 physicians randomly selected from 14 physicians evaluated each toxicity profile and assigned a visual analogue scale score (0-10) based on their impression of the global burden of toxicities. With mixed-effects models, severity scores and a 10-point toxicity burden score (TBS) were derived from 27 predictors accounting for severe (grade 3) and life-threatening (grade 4) toxicities for each organ class of the Common Terminology Criteria for Adverse Events.
For most organ classes, grade 3 toxicities had a TBS of 4.14 (95% confidence interval [CI], 3.65-4.63), but infections, cardiovascular events, and pulmonary events had a higher TBS with differences of 0.87 (95% CI, 0.53-1.21), 0.88 (95% CI, 0.51-1.25), and 0.73 (95% CI, 0.22-1.24), respectively. Moreover, most grade 4 events had a higher TBS than grade 3 events, except for hemorrhaging, pain, metabolic events, and musculoskeletal events. The intrarater and interrater correlations were 0.91 and 0.59, respectively.
The burden of toxicity grades differs with toxicity types. A TBS provides a toxicity burden summary that incorporates physicians' perspectives and differentiates between severe and life-threatening toxicities and organ classes. Cancer 2018;124:858-64. © 2017 American Cancer Society.
反映治疗毒性总负担的综合指标对于比较疗法至关重要。目前的毒性综合指标是特定的，无法区分毒性的严重程度和类型。在这里，我们提出了一种基于 SWOG 对 746 例前列腺癌患者进行的随机临床试验毒性概况的前瞻性评估，用于估计毒性负担的临床可行方法。
对于 308 例出现严重毒性的患者，从 14 位医生中随机挑选的 2 位医生对每个毒性概况进行评估，并根据他们对毒性总负担的印象分配视觉模拟量表评分（0-10）。采用混合效应模型，根据《常见不良事件术语标准》中每个器官类别中严重（3 级）和危及生命（4 级）毒性的 27 个预测因子，得出严重程度评分和 10 分毒性负担评分（TBS）。
对于大多数器官类别，3 级毒性的 TBS 为 4.14（95%置信区间[CI]，3.65-4.63），但感染、心血管事件和肺部事件的 TBS 更高，差异分别为 0.87（95%CI，0.53-1.21）、0.88（95%CI，0.51-1.25）和 0.73（95%CI，0.22-1.24）。此外，除了出血、疼痛、代谢事件和肌肉骨骼事件外，大多数 4 级事件的 TBS 均高于 3 级事件。内部和外部评估者之间的相关性分别为 0.91 和 0.59。
毒性等级的负担因毒性类型而异。TBS 提供了一种毒性负担综合指标，它结合了医生的观点，并区分了严重和危及生命的毒性以及器官类别。癌症 2018;124:858-64。©2017 美国癌症协会。
