Prognostic Stratification of Metastatic Gastroenteropancreatic Neuroendocrine Neoplasms by ¹⁸F-FDG PET: Feasibility of a Metabolic Grading System

Abstract

The tumor proliferation marker, Ki-67 index, is a well-established prognostic marker in gastroenteropancreatic neuroendocrine neoplasms (NENs). Noninvasive molecular imaging allows whole-body metabolic characterization of metastatic disease. We investigated the prognostic impact of 18 F-FDG PET in inoperable multifocal disease. Methods: Retrospective, dual-center analysis was performed on 89 patients with histologically confirmed, inoperable metastatic gastroenteropancreatic NENs undergoing 18 F-FDG PET/CT within the staging routine. Metabolic (PET-based) grading was in accordance with the most prominent 18 F-FDG uptake (reference tumor lesion): mG1, tumor-to-liver ratio of maximum standardized uptake value # 1.0; mG2, 1.0-2.3; mG3, .2.3. Other potential variables influencing overall survival, including age, tumor origin, performance status, tumor burden, plasma chromogranin A ($600 μg/L), neuronspecific enolase ($25 μg/L), and classic grading (Ki-67-based) underwent univariate (log-rank test) and multivariate analysis (Cox proportional hazards model), with a P value of less than 0.05 considered significant. Results: The median follow-up period was 38 mo (95% confidence interval [CI], 27-49 mo); median overall survival of the 89 patients left for multivariate analysis was 29 mo (95% CI, 21-37 mo). According to metabolic grading, 9 patients (10.2%) had mG1 tumors, 22 (25.0%) mG2, and 57 (64.8%) mG3. On multivariate analysis, markedly elevated plasma neuron-specific enolase (P 5 0.016; hazard ratio, 2.9; 95% CI, 1.2-7.0) and high metabolic grade (P 5 0.015; hazard ratio, 4.7; 95% CI, 1.2-7.0) were independent predictors of survival. Conclusion: This study demonstrated the feasibility of prognostic 3-grade stratification of metastatic gastroenteropancreatic NENs by whole-body molecular imaging using 18 F-FDG PET.

Prognostic Factors in Patients Treated with 223Ra: The Role of Skeletal Tumor Burden on Baseline 18F-Fluoride PET/CT in Predicting Overall Survival

“…The risk of death after 223 Ra was increased by 76.5% for each unit increase in TLF 10 . Evaluation of target lesions with 18 F-FDG PET/CT have demonstrated strong correlation to OS (17,(23)(24)(25). We were not able to predict OS, PFS, or TTBE by evaluation of a target lesion (hSUV max ), because patients had widespread metastases, whereas target lesions usually were applicable for evaluation of the primary tumor.…”

Identifying Prognostic Factors for Well-Differentiated Metastatic Pancreatic Neuroendocrine Tumours: A Retrospective International Multicentre Cohort Study

“…Furthermore, metabolic activity measured via 18 F-FDG-PET/CT can stratify patients into different prognostic subgroups [34].…”

Molecular Imaging of Gastroenteropancreatic Neuroendocrine Tumors: Current Status and Future Directions

“…18 F-FDG PET/CT seems more sensitive than tumor differentiation or Ki-67 in the early prediction of progressive low-grade NETs. Therefore, metabolic grading based on 18 F-FDG PET/CT has been proposed in patients with metastatic GEP NETs, and this grading has shown a high predictive power for overall survival (55).…”