Predictive and Prognostic Role of Pre-Therapy and Interim 68Ga-DOTATOC PET/CT Parameters in Metastatic Advanced Neuroendocrine Tumor Patients Treated with PRRT

SIMPLE SUMMARY: Although a significant improvement has been achieved in the management of metastatic neuroendocrine tumor (NET), disease progression is observed in 20–30% of patients treated with peptide receptor radionuclide therapy (PRRT). Therefore, the early identification of patients who are at high risk of treatment failure is important to avoid futile therapy toxicities. The aim of this study was to identify biomarkers derived from baseline and interim 68Ga-DOTATOC PET/CT in patients undergoing PRRT. In 46 metastatic NET patients with available baseline and interim PET, only baseline total tumor volume (bTV) was able to discriminate responders to PRRT (partial response or stable disease) vs. non-responders. Patients with high bTV had also the worst overall survival. bTV, an imaging biomarker, integrated in the initial workup of NET patients could improve risk stratification and contribute to a tailored therapy approach. ABSTRACT: Peptide receptor radionuclide therapy (PRRT) is an effective therapeutic option in patients with metastatic neuroendocrine tumor (NET). However, PRRT fails in about 15–30% of cases. Identification of biomarkers predicting the response to PRRT is essential for treatment tailoring. We aimed to evaluate the predictive and prognostic role of semiquantitative and volumetric parameters obtained from the 68Ga-DOTATOC PET/CT before therapy (bPET) and after two cycles of PRRT (iPET). A total of 46 patients were included in this retrospective analysis. The primary tumor was 78% gastroenteropancreatic (GEP), 13% broncho-pulmonary and 9% of unknown origin. 35 patients (76.1%) with stable disease or partial response after PRRT were classified as responders and 11 (23.9%) as non-responders. Logistic regression analysis identified that baseline total volume (bTV) was associated with therapy outcome (OR 1.17; 95%CI 1.02–1.32; p = 0.02). No significant association with PRRT response was observed for other variables. High bTV was confirmed as the only variable independently associated with OS (HR 12.76, 95%CI 1.53–107, p = 0.01). In conclusion, high bTV is a negative predictor for PRRT response and is associated with worse OS rates. Early iPET during PRRT apparently does not provide information useful to change the management of NET patients.