PROGNOSTIC SIGNIFICANCE OF PRIMARY TUMORAL FDG UPTAKE MEASURED BY PET: Systematic Review and Meta-analysis Ben A. Dwamena, MD

BACKGROUND Tumors have increased glucose transporters and thus increased glucose uptake compared with non-cancerous cells Abnormally increased uptake of glucose and radioactive analog, fluorodeoxyglucose = increased proliferative activity

BACKGROUND Increased proliferative activity = aggressiveness = decreased patient survival Quantified on PET scanning by the standardized uptake value (SUV) of FDG

BACKGROUND Several published studies of potential clinical application of FDG uptake on PET as predictor of patient outcome Narrative reviews and cursory evaluation suggest tumoral FDG uptake may be independent marker of overall patient survival

RESEARCH OBJECTIVE Perform a systematic review of published data To validate or refute assertions of independent prognostic value of FDG uptake on PET scanning To ascertain whether such value is dependent on tumor type To evaluate the impact of publication bias and heterogeneity on summary estimates

LITERATURE RETRIEVAL Exhaustive Search Of Multiple Databases : MEDLINE, EMBASE, CURRENT CONTENTS etc Database Search used the OVID search engine and Internet (for PUBMED) Cross-citation of references from retrieved Studies

STUDY SELECTION English Language Publications Evaluated impact of pretreatment FDG uptake on overall survival (OS) Used a specific cutoff SUV for FDG-uptake Performed a multivariate analysis (Cox regression modeling)

META-ANALYSIS RANDOM EFFECTS meta-analysis using Hazard Ratio as Effect size parameter Testing for HETEROGENEITY by homogeneity tests and meta-regression Assessed data for PUBLICATION BIAS by funnel plots and statistical tests

STUDY CHARACTERISTICS

DATA SYNTHESIS Fourteen studies eligible for review: Lung (4) Head/neck (4) Pancreas (3) Breast (1) Hepatocellular (1) Sarcoma (1) Study size: The overall Hazard Ratio (95% CI) was 2.3 ( )

TUMOR-SPECIFIC HAZARD RATIOS BREAST: 4.1( ) HEAD/NECK: 3.3 ( ) PANCREAS: 3.0 ( ) LUNG:2.5 ( ) SARCOMA:1.6 ( ) LIVER:1.5 ( )

FOREST PLOT OF STUDY-SPECIFIC HR

PUBLICATION BIAS: Funnel Plot

CONCLUSIONS Selectively biased estimates suggestive of an independent prognostic impact Cutoff value positively predictive of increased mortality Inadequately powered studies with differing cutoff points Variable follow-up, heterogeneous patient spectrum limits generalizability

RECOMMENDATION Carefully performed, adequately powered, multicenter studies are warranted to Validate findings of systematic review Assess prognostic value of FDG uptake in other settings such as staging and post- neoadjuvant therapy evaluation