Terri S. Armstrong, University of Texas Health Science Center-School of Nursing; Terri S. Armstrong, Jeffrey S. Wefel, Mark R. Gilbert, Tito R. Mendoza, MD Anderson Cancer Center, Houston, TX; Meihua Wang, Minhee Won, Radiation Therapy Oncology Group Statistical Center; Maria Werner-Wasik, Thomas Jefferson University Hospital, Philadelphia, PA; Andrew Bottomley, Corneel Coens, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; David G. Brachman, Arizona Oncology Services Foundation and Barrow Neurological Institute, Phoenix, AZ; Ali K. Choucair, Mayo Clinic, Jacksonville, FL; Minesh Mehta, University of Maryland, Baltimore, MD.
J Clin Oncol. 2013 Nov 10;31(32):4076-84. doi: 10.1200/JCO.2013.49.6067. Epub 2013 Oct 7.
Radiation Therapy Oncology Group trial 0525 tested whether dose-intensifying temozolomide versus standard chemoradiotherapy improves overall survival (OS) or progression-free survival (PFS) in newly diagnosed glioblastoma. Tests of neurocognitive function (NCF) and symptoms (using the MD Anderson Symptom Inventory-Brain Tumor module; MDASI-BT) and of quality of life (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ] -C30/BN20) examined the net clinical benefit (NCB) of therapy.
NCF tests (Hopkins Verbal Learning Test-Revised, Trail Making Test, and Controlled Oral Word Association), MDASI-BT, and EORTC QLQ-C30/BN20 were completed in a subset of patients. Multivariate Cox proportional hazard regression modeling determined the prognostic value of baseline and early change from baseline to cycle 1 for OS and PFS. Two-sample proportional test statistic was used to evaluate differences between treatments (dose-dense v standard-dose) on NCB measures from baseline to cycle 4 in stable patients.
Overall, 182 patients participated in the study. Baseline NCF tests and the physical functioning quality of life scale were associated with OS and PFS. Baseline to cycle 1 in all NCB components were associated with OS and PFS. There was greater deterioration in the dose-dense arm from baseline to cycle 4 in the Global Health and Motor Function subscales (EORTC QLQ-C30/BN20) as well as in overall symptom burden, overall symptom interference, and activity-related symptom interference subscales (MDASI-BT). There were no between-arm differences in NCF.
Longitudinal collection of NCB measures is feasible in cooperative group studies and provides an added dimension to standard outcome measures. Greater adverse symptom burden and functional interference, as well as decreased global health and motor function were observed in patients randomly assigned to the dose-dense arm. Baseline and early change in NCB measures were associated with decreased rates of survival.
放射治疗肿瘤组试验 0525 旨在测试强化替莫唑胺剂量与标准放化疗相比是否能提高新诊断的胶质母细胞瘤患者的总生存期（OS）或无进展生存期（PFS）。神经认知功能（NCF）和症状（使用 MD 安德森症状量表-脑肿瘤模块；MDASI-BT）以及生活质量（欧洲癌症研究与治疗组织生活质量问卷[EORTC QLQ]-C30/BN20）的检测评估了治疗的净临床获益（NCB）。
在患者亚组中完成了 NCF 测试（霍普金斯词语学习测试修订版、连线测试和受控词语联想）、MDASI-BT 和 EORTC QLQ-C30/BN20。多变量 Cox 比例风险回归模型确定了基线和从基线到第 1 周期的早期变化对 OS 和 PFS 的预后价值。采用两样本比例检验统计量评估稳定患者从基线到第 4 周期时两种治疗方法（密集剂量与标准剂量）在 NCB 测量上的差异。
共有 182 名患者参与了该研究。基线 NCF 测试和身体功能生活质量量表与 OS 和 PFS 相关。所有 NCB 成分的基线到第 1 周期均与 OS 和 PFS 相关。在从基线到第 4 周期的过程中，密集剂量组在全球健康和运动功能子量表（EORTC QLQ-C30/BN20）以及总体症状负担、总体症状干扰和与活动相关的症状干扰子量表（MDASI-BT）上的恶化程度更大。NCF 两组之间没有差异。
在合作组研究中，对 NCB 测量值的纵向收集是可行的，并为标准结果测量提供了一个附加维度。在随机分配到密集剂量组的患者中，观察到更大的不良症状负担和功能干扰，以及全球健康和运动功能下降。NCB 测量值的基线和早期变化与生存率降低相关。
