Joseph Nuradh, Cicchetti Alessandro, McWilliam Alan, Webb Adam, Seibold Petra, Fiorino Claudio, Cozzarini Cesare, Veldeman Liv, Bultijnck Renée, Fonteyne Valérie, Talbot Christopher J, Symonds Paul R, Johnson Kerstie, Rattay Tim, Lambrecht Maarten, Haustermans Karin, De Meerleer Gert, Elliott Rebecca M, Sperk Elena, Herskind Carsten, Veldwijk Marlon, Avuzzi Barbara, Giandini Tommaso, Valdagni Riccardo, Azria David, Jacquet Marie-Pierre Farcy, Charissoux Marie, Vega Ana, Aguado-Barrera Miguel E, Gómez-Caamaño Antonio, Franco Pierfrancesco, Garibaldi Elisabetta, Girelli Giuseppe, Iotti Cinzia, Vavassori Vittotorio, Chang-Claude Jenny, West Catharine M L, Rancati Tiziana, Choudhury Ananya
Department of Clinical Oncology, District General Hambantota, Hambantota, Sri Lanka.
Sri Lanka Cancer Research Group, Sri Lanka College of Oncologists, Maharagama, Sri Lanka.
Front Oncol. 2022 Oct 26;12:937934. doi: 10.3389/fonc.2022.937934. eCollection 2022.
We hypothesized that increasing the pelvic integral dose (ID) and a higher dose per fraction correlate with worsening fatigue and functional outcomes in localized prostate cancer (PCa) patients treated with external beam radiotherapy (EBRT).
The study design was a retrospective analysis of two prospective observational cohorts, REQUITE (development, n=543) and DUE-01 (validation, n=228). Data were available for comorbidities, medication, androgen deprivation therapy, previous surgeries, smoking, age, and body mass index. The ID was calculated as the product of the mean body dose and body volume. The weekly ID accounted for differences in fractionation. The worsening (end of radiotherapy versus baseline) of European Organisation for Research and Treatment of Cancer EORTC) Quality of Life Questionnaire (QLQ)-C30 scores in physical/role/social functioning and fatigue symptom scales were evaluated, and two outcome measures were defined as worsening in ≥2 (WS2) or ≥3 (WS3) scales, respectively. The weekly ID and clinical risk factors were tested in multivariable logistic regression analysis.
In REQUITE, WS2 was seen in 28% and WS3 in 16% of patients. The median weekly ID was 13.1 L·Gy/week [interquartile (IQ) range 10.2-19.3]. The weekly ID, diabetes, the use of intensity-modulated radiotherapy, and the dose per fraction were significantly associated with WS2 [AUC (area under the receiver operating characteristics curve) =0.59; 95% CI 0.55-0.63] and WS3 (AUC=0.60; 95% CI 0.55-0.64). The prevalence of WS2 (15.3%) and WS3 (6.1%) was lower in DUE-01, but the median weekly ID was higher (15.8 L·Gy/week; IQ range 13.2-19.3). The model for WS2 was validated with reduced discrimination (AUC=0.52 95% CI 0.47-0.61), The AUC for WS3 was 0.58.
Increasing the weekly ID and the dose per fraction lead to the worsening of fatigue and functional outcomes in patients with localized PCa treated with EBRT.
我们假设，对于接受外照射放疗（EBRT）的局限性前列腺癌（PCa）患者，盆腔积分剂量（ID）增加以及每次分割剂量更高与疲劳加剧和功能结局恶化相关。
本研究设计为对两个前瞻性观察队列REQUITE（开发队列，n = 543）和DUE - 01（验证队列，n = 228）进行回顾性分析。可获取合并症、用药情况、雄激素剥夺治疗、既往手术史、吸烟情况、年龄和体重指数的数据。ID通过平均体部剂量与体部体积的乘积计算得出。每周ID考虑了分割方式的差异。评估了欧洲癌症研究与治疗组织（EORTC）生活质量问卷（QLQ）- C30在身体/角色/社会功能和疲劳症状量表中放疗结束时与基线相比的恶化情况，并将两个结局指标分别定义为在≥2个（WS2）或≥3个（WS3）量表中恶化。每周ID和临床风险因素在多变量逻辑回归分析中进行检验。
在REQUITE队列中，28%的患者出现WS2，16%的患者出现WS3。每周ID的中位数为13.1 L·Gy/周[四分位间距（IQ）范围为10.2 - 19.3]。每周ID、糖尿病、调强放疗的使用以及每次分割剂量与WS2显著相关[AUC（受试者工作特征曲线下面积）= 0.59；95%CI 0.55 - 0.63]以及WS3（AUC = 0.60；95%CI 0.55 - 0.64）。在DUE - 01队列中，WS2（15.3%）和WS3（6.1%）的发生率较低，但每周ID的中位数较高（15.8 L·Gy/周；IQ范围为13.2 - 19.3）。WS2模型的验证显示其判别能力降低（AUC = 0.52，95%CI 0.47 - 0.61），WS3的AUC为0.58。
对于接受EBRT治疗的局限性PCa患者，每周ID增加和每次分割剂量增加会导致疲劳加剧和功能结局恶化。
