Somatostatin-Receptor Based Tumor Heterogeneity Predicts Survival in Pancreatic Neuroendocrine Tumor Patients Envisaged for Endoradiotherapy

Objectives: Neuroendocrine tumors from pancreatic origin (pNET) are a rare, but heterogeneous tumor entity. Identification of patients at risk for rapid tumor progression under therapy, e.g. endoradiotherapy (ERT), would be of great value. In this multicenter study, we aimed to evaluate the potential of intratumoral heterogeneity assessment as determined by baseline somatostatin receptor (SSTR)-PET/CT prior to ERT.

Methods: 31 patients suffering from pNET were enrolled (14 females, 60 ± 10 y). Prior to ERT with ¹⁷⁷Lu-labelled somatostatin analogs, baseline SSTR-PET/CT was performed. By manual segmentation of 162 (median, 5) metastases, intratumoral textural features as well as conventional PET parameters (SUV) were computed. The impact of imaging-based as well as clinical parameters to predict progression-free (PFS) and overall survival (OS) was evaluated by Cox hazard and subsequent ROC analysis to obtain cut-off values for Kaplan-Meier curves.

Results: Within follow-up of median 4.4 years, tumor progression was detected after a median of 1.6 y in 20 patients; 13 patients deceased after a median of 1.9 y. In Cox analysis, both heterogeneity parameters Entropy and Intensity Variation were independent for prediction of OS (p&#8804;0.04); the clinical parameters Ki67 (PFS, p<0.002) as well as the administered cumulative dose (OS, p<0.05) were also significantly associated with response prediction. In subsequent ROC analysis, only the heterogeneity parameter Entropy demonstrated predictive ability for OS with an AUC of 0.71 (p=0.02). Of note, none of the conventional PET parameters hold the potential of benefit prediction.

Conclusion: In this multicenter analysis investigating pNET envisaged for ERT, the non-invasive assessment of tumor heterogeneity (e.g. Entropy) could be of great value for more intensified risk stratification. Research Support: n/a