Movsas B, Hu C, Sloan J, Bradley J, Komaki R, Masters G, Kavadi V, Narayan S, Michalski J, Johnson DW, Koprowski C, Curran WJ, Jr., Garces YI, Gaur R, Wynn RB, Schallenkamp J, Gelblum DY, MacRae RM, Paulus R, and Choy H. Quality of life analysis of a radiation dose-escalation study of patients with non-small-cell lung cancer: A secondary analysis of the radiation therapy oncology group 0617 randomized clinical trial. JAMA Oncol 2015:1-9.
IMPORTANCE: A recent randomized radiation dose-escalation trial in unresectable stage III non-small-cell lung cancer (NSCLC) (Radiation Therapy Oncology Group [RTOG] 0617) showed a lower survival rate in the high-dose radiation therapy (RT) arm (74 Gy) than in the low-dose arm (60 Gy) with concurrent chemotherapy.
OBJECTIVE: The primary QOL hypothesis predicted a clinically meaningful decline in quality of life (QOL) via the Functional Assessment of Cancer Therapy (FACT)-Lung Cancer Subscale (LCS) in the high-dose RT arm at 3 months.
DESIGN, SETTING, AND PATIENTS: The RTOG 0617 trial was a randomized phase 3 study (conducted from November 2007 to November 2011) in stage III NSCLC using a 2 × 2 factorial design and stratified by histology, positron emission tomography staging, performance status, and irradiation technique (3-dimensional conformal RT [3D-CRT] vs intensity-modulated RT [IMRT]). A total of 185 institutions in the United States and Canada took part. Of 424 eligible patients with stage III NSCLC randomized, 360 (85%) consented to QOL evaluation, of whom 313 (88%) completed baseline QOL assessments.
INTERVENTION: Treatment with 74-Gy vs 60-Gy RT with concurrent and consolidation carboplatin/paclitaxel with or without cetuximab.
MAIN OUTCOMES AND MEASURES: The QOL data were collected prospectively via FACT Trial Outcome Index (FACT-TOI), calculated as the sum of the following measures: Physical Well Being (PWB), Functional Well Being (FWB), and the LCS. Data are presented at baseline and 3 and 12 months via minimal clinically meaningful changes of 2 points or more for PWB, FWB, and LCS or 5 points or more for TOI.
RESULTS: Of the 313 patients who completed baseline QOL assessments, 219 patients (70%) completed the 3-month QOL assessments, and 137 of the living patients (57%) completed the 12-month assessment. Patient demographics and baseline QOL scores were comparable between the 74-Gy and 60-Gy arms. Significantly more patients in the 74-Gy arm than in the 60-Gy arm had clinically meaningful decline in FACT-LCS at 3 months (45% vs 30%; P = .02). At 12 months, fewer patients who received IMRT (vs 3D-CRT) had clinically meaningful decline in FACT-LCS (21% vs 46%; P = .003). Baseline FACT-TOI was associated with overall survival in multivariate analysis.
CONCLUSIONS AND RELEVANCE: Despite few differences in clinician-reported toxic effects between treatment arms, QOL analysis demonstrated a clinically meaningful decline in QOL in the 74-Gy arm at 3 months, confirming the primary QOL hypothesis. Baseline QOL was an independent prognostic factor for survival.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00533949.
Medical Subject Headings
Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Canada; Carboplatin; Carcinoma, Non-Small-Cell Lung; Dose-Response Relationship, Radiation; Female; Humans; Lung Neoplasms; Male; Middle Aged; Paclitaxel; Quality of Life; Radiotherapy Dosage; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Surveys and Questionnaires; Treatment Outcome; United States