title: Prognostic value of metabolic tumor burden from (18)F-FDG PET in surgical patients with non-small-cell lung cancer.
abstract: OBJECTIVE
  To assess the prognostic value of metabolic tumor burden as measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT), independent of current Union Internacional Contra la Cancrum/American Joint Committee on Cancer tumor, node, and metastasis (TNM) stage; in comparison with that of standardized uptake value (SUV) in surgical patients with non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  This study retrospectively reviewed 104 consecutive surgical patients (47 males, 57 females, median age at PET/CT scan of 67.92 years) with diagnosed stage I to IV NSCLC who had baseline (18)F-FDG PET/CT scans. The (18)F-FDG PET/CT scans were performed in accordance with National Cancer Institute guidelines. The MTV of tumors in the whole body (MTV(WB)), TLG of tumors in the whole body (TLG(WB)), the maximum standardized uptake value of tumors in the whole body (SUV(maxWB)) as well as the mean standardized uptake value of tumor in the whole body (SUV(meanWB)) were measured. The median follow-up among 67 survivors was 42.07 months from the PET/CT (range 2.82-80.95 months). Statistical methods included Kaplan-Meier curves, Cox regression, and C-statistics. The interobserver variability of SUV(maxWB), SUV(meanWB), MTV(WB), and TLG(WB) between two observers was analyzed using concordance correlation coefficients (CCCs).
  
  
  RESULTS
  The interobserver variability of SUV(maxWB), SUV(meanWB), MTV(WB) and TLG(WB) was very low with CCCs greater than 0.882. There was a statistically significant association of stage with overall survival (OS). The hazard ratio (HR) of stage III and stage IV as compared with stage I was 3.60 (P = .001) and 4.00 (P = .013), respectively. The MTV(WB) was significantly associated with OS with a HR for 1-unit increase of ln(MTV(WB)) of 1.40/1.32 (P = .004/.039), before/after adjusting for stage and other prognostic factors including chemoradiation therapy, and surgical procedure, respectively. TLG(WB) had a statistically significant association with OS before and after adjusting for stage and the other prognostic factors. The HR for 1-unit increase in ln(TLG(WB)) was 1.26 (P = .011) and 1.25 (P = .031), before and after the adjustment, respectively. Subjects with conditions that led to pneumonectomy (HR = 2.82, P = .035) or segmental resection (HR = 3.44, P = .044) had significantly worse survival than those needing lobectomy. There was no statistically significant association between OS and age, gender, tumor histology, ln(SUV(maxWB)), and ln(SUV(meanWB)) (all P > .05). There were 37 deaths during follow-up.
  
  
  CONCLUSIONS
  Baseline whole-body metabolic tumor burden as measured with MTV(WB) and TLG(WB) on FDG PET is a prognostic measure independent of clinical stage and other prognostic factors including chemoradiation therapy and surgical procedure with low interobserver variability and may be used to further risk stratify surgical patients with NSCLC. This study also suggests that MTV and TLG are better prognostic measures than SUV(max) and SUV(mean). These results will need to be validated in larger cohorts in a prospective study.
authors.affiliation: Department of Radiology, First Hospital of Lanzhou University, Lanzhou, Gansu, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Kristen
authors.initials: K
authors.lastname: Wroblewski
authors.forename: Shengri
authors.initials: S
authors.lastname: Liao
authors.forename: Rony
authors.initials: R
authors.lastname: Kampalath
authors.forename: Bill C
authors.initials: BC
authors.lastname: Penney
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Pu
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008207:Lymphatic Metastasis; D008297:Male; D064847:Multimodal Imaging; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011013:Pneumonectomy; D049268:Positron-Emission Tomography; D011379:Prognosis; D016016:Proportional Hazards Models; D019275:Radiopharmaceuticals; D012189:Retrospective Studies; D015996:Survival Rate; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden; D051598:Whole Body Imaging
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18