title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Treatment with 74-Gy vs 60-Gy RT with concurrent and consolidation carboplatin/paclitaxel with or without cetuximab.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00533949.
authors.affiliation: Henry Ford Hospital, Detroit, Michigan.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Movsas
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania3Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Chen
authors.initials: C
authors.lastname: Hu
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sloan
authors.affiliation: Washington University, St Louis, Missouri.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bradley
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.affiliation: Helen F. Graham Cancer Center, Christiana Care Health System, Newark, Delaware.
authors.forename: Gregory
authors.initials: G
authors.lastname: Masters
authors.affiliation: USON Texas Oncology Cancer Center, Sugar Land.
authors.forename: Vivek
authors.initials: V
authors.lastname: Kavadi
authors.affiliation: Michigan Cancer Research Consortium, Community Clinical Oncology Program (CCOP), Ann Arbor.
authors.forename: Samir
authors.initials: S
authors.lastname: Narayan
authors.affiliation: Washington University, St Louis, Missouri.
authors.forename: Jeff
authors.initials: J
authors.lastname: Michalski
authors.affiliation: Florida Radiation Oncology Group/Baptist Regional Cancer Institute, Jacksonville.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Johnson
authors.affiliation: Helen F. Graham Cancer Center, Christiana Care Health System and Christiana Care CCOP, Newark, Delaware.
authors.forename: Christopher
authors.initials: C
authors.lastname: Koprowski
authors.affiliation: Emory University, Atlanta, Georgia.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Curran
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Yolanda I
authors.initials: YI
authors.lastname: Garces
authors.affiliation: Kansas City CCOP, Prairie Village, Kansas.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Gaur
authors.affiliation: UPMC Cancer Center, Pittsburgh, Pennsylvania.
authors.forename: Raymond B
authors.initials: RB
authors.lastname: Wynn
authors.affiliation: Montana Cancer Consortium CCOP, Billings.
authors.forename: John
authors.initials: J
authors.lastname: Schallenkamp
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Daphna Y
authors.initials: DY
authors.lastname: Gelblum
authors.affiliation: The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada.
authors.forename: Robert M
authors.initials: RM
authors.lastname: MacRae
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Paulus
authors.affiliation: University of Texas Southwestern Medical School, Dallas.
authors.forename: Hak
authors.initials: H
authors.lastname: Choy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002170:Canada; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011788:Quality of Life; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014481:United States
chemical_list: D016190:Carboplatin; D017239:Paclitaxel