title: Metabolic tumor burden as marker of outcome in advanced EGFR wild-type NSCLC patients treated with erlotinib.
abstract: OBJECTIVE
  Accurate estimation of the prognosis of advanced non-small cell lung cancer (NSCLC) patients is essential before initiation of palliative treatment; especially in the second and third-line setting. This study was conducted in order to evaluate tumor burden measured on an 2'-deoxy-2'-[18F] fluoro-D-glucose (F-18-FDG) positron emission tomography/computed tomography (PET/CT) scan as a marker of outcome in advanced epidermal growth factor receptor (EGFR) wild-type patients treated with second or third-line erlotinib.
  
  
  METHODS
  Fifty-one patients were included from a prospectively collected cohort. An F-18-FDG-PET/CT scan was conducted prior to erlotinib treatment and tumor burden was measured in terms of metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Median values of MTV and TLG were used for dichotomization of patients. Survival outcome was compared between groups.
  
  
  RESULTS
  MTV and TLG could be measured in 49 patients. High values of MTV and TLG were significantly correlated with shorter PFS (p<0.001 and p=0.027, respectively) and OS (p<0.001 and p=0.002, respectively). In multivariate analyses, including both clinical and imaging data, high MTV and TLG remained strong independent markers of both shorter PFS (MTV, hazard ratio (HR)=5.44 (95% confidence interval (CI) 2.46-12.02); TLG, HR=2.17 (95% CI 1.11-4.26)) and OS (MTV, HR=4.80 (95% CI 2.08-11.06); TLG, HR=2.76 (95% CI 1.33-5.71)).
  
  
  CONCLUSIONS
  High MTV and TLG are independently correlated with shorter PFS and OS in advanced EGFR wild-type NSCLC patients treated with second or third-line erlotinib. Metabolic tumor burden is a highly promising clinical tool that may allow better patient selection for palliative treatment in the future.
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. Electronic address: anlarsen@rm.dk.
authors.forename: Anne
authors.initials: A
authors.lastname: Winther-Larsen
authors.affiliation: Department of Nuclear Medicine, Herning Regional Hospital, Herning, Denmark.
authors.forename: Joan
authors.initials: J
authors.lastname: Fledelius
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Boe Sandahl
authors.initials: BS
authors.lastname: Sorensen
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Meldgaard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D003131:Combined Modality Therapy; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000072078:Positron Emission Tomography Computed Tomography; D011379:Prognosis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D019788:Fluorodeoxyglucose F18; D000069347:Erlotinib Hydrochloride
keywords: EGFR wild-type; Lung cancer; Metabolic tumor volume; Positron emission tomography; Tyrosine kinase inhibitor