title: Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235.
abstract: OBJECTIVE
  To determine whether higher pre-treatment metabolic tumor volume (tMTV-pre) is associated with worse overall survival (OS) in patients with inoperable NSCLC treated with definitive chemoradiation (CRT).
  
  
  METHODS
  This is a secondary analysis of the American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group 0235 trial. Pre-treatment PET scans were performed on ACRIN-qualified scanners. Computer-aided MTV measurement was performed using RT_Image. Kaplan-Meier curves and Cox proportional hazards regression models were used to assess the association between tMTV and OS.
  
  
  RESULTS
  Of the 250 patients enrolled on the study, 230 were evaluable for tMTV-pre. Patients with MTV-pre >32 mL (median value) vs. ≤32 mL had worse median OS (14.8 vs. 29.7 months, p < 0.001). As a continuous variable, higher tMTV-pre (per 10-mL increase) remained associated with worse OS (HR = 1.03, p < 0.001) after controlling for other variables. A significant interaction between radiation dose and tMTV-pre occurred for OS (p = 0.002), demonstrating that the negative prognostic impact of tMTV-pre decreased as radiotherapy dose increased. Among patients with tMTV-pre ≤32 mL, there was no difference in survival according to radiotherapy dose delivered (p = 0.694). However, median OS was inferior in patients with tMTV-pre >32 mL who received ≤60 Gy compared with those who received 61-69 Gy or ≥70 Gy (p = 0.001).
  
  
  CONCLUSIONS
  Higher tMTV-pre is associated with significantly worse OS in inoperable stage III NSCLC treated with definitive CRT. Our findings suggest that for patients with large tMTV-pre, achieving a therapeutic radiation dose may help maximize OS. Prospective studies are needed to confirm this finding.
authors.affiliation: Department of Radiation Oncology, The Ohio State University, 460 W. 10th Avenue, Columbus, OH, 43210, USA. jose.bazan2@osumc.edu.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Bazan
authors.affiliation: Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, RI, USA.
authors.forename: Fenghai
authors.initials: F
authors.lastname: Duan
authors.affiliation: Center for Statistical Sciences, Brown University School of Public Health, Providence, RI, USA.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Snyder
authors.affiliation: ECOG-ACRIN Cancer Research Group, Philadelphia, PA, USA.
authors.forename: Dunstan
authors.initials: D
authors.lastname: Horng
authors.affiliation: Department of Radiation Oncology, Stanford Cancer Institute, School of Medicine, Stanford University, 875 Blake Wilbur Drive, Stanford, CA, 94305-5847, USA.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Graves
authors.affiliation: Mallinckrodt Institute of Radiology and the Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Barry A
authors.initials: BA
authors.lastname: Siegel
authors.affiliation: Case Comprehensive Cancer Center and Case Western Reserve University, University Hospitals Seidman Cancer Center, Cleveland, OH, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Machtay
authors.affiliation: Department of Radiation Oncology, Stanford Cancer Institute, School of Medicine, Stanford University, 875 Blake Wilbur Drive, Stanford, CA, 94305-5847, USA. bwloo@stanford.edu.
authors.forename: Billy W
authors.initials: BW
authors.lastname: Loo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality* / Q000628:therapy*; D059248:Chemoradiotherapy / Q000401:mortality; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality* / Q000517:prevention & control; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography / Q000379:methods / Q000706:statistics & numerical data*; D015995:Prevalence; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D014481:United States / Q000453:epidemiology
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: FDG-PET; Metabolic tumor volume; NSCLC; SUV