Inflammation-Based Index and ⁶⁸Ga-DOTATOC PET-Derived Uptake and Volumetric Parameters Predict Outcome in Neuroendocrine Tumor Patients Treated with ⁹⁰Y-DOTATOC.

Abstract

We performed post hoc analyses on the utility of pretherapeutic and early interim ⁶⁸Ga-DOTATOC PET tumor uptake and volumetric parameters and a recently proposed biomarker, the inflammation-based index (IBI), for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor (NET) patients treated with ⁹⁰Y-DOTATOC in the setting of a prospective phase II trial. <b>Methods:</b> Forty-three NET patients received up to 4 cycles of ⁹⁰Y-DOTATOC at 1.85 GBq/m²/cycle with a maximal kidney biologic effective dose of 37 Gy. All patients underwent ⁶⁸Ga-DOTATOC PET/CT at baseline and 7 wk after the first PRRT cycle. ⁶⁸Ga-DOTATOC-avid tumor lesions were semiautomatically delineated using a customized SUV threshold-based approach. PRRT response was assessed on CT using RECIST 1.1. <b>Results:</b> Median progression-free survival and overall survival (OS) were 13.9 and 22.3 mo, respectively. An SUV_mean higher than 13.7 (75th percentile) was associated with better survival (hazard ratio [HR], 0.45; <i>P</i> = 0.024), whereas a ⁶⁸Ga-DOTATOC-avid tumor volume higher than 578 cm³ (75th percentile) was associated with worse OS (HR, 2.18; <i>P</i> = 0.037). Elevated baseline IBI was associated with worse OS (HR, 3.90; <i>P</i> = 0.001). Multivariate analysis corroborated independent associations between OS and SUV_mean (<i>P</i> = 0.016) and IBI (<i>P</i> = 0.015). No significant correlations with progression-free survival were found. A composite score based on SUV_mean and IBI allowed us to further stratify patients into 3 categories with significantly different survival. On early interim PET, a decrease in SUV_mean of more than 17% (75th percentile) was associated with worse survival (HR, 2.29; <i>P</i> = 0.024). <b>Conclusion:</b> Normal baseline IBI and high ⁶⁸Ga-DOTATOC tumor uptake predict better outcome in NET patients treated with ⁹⁰Y-DOTATOC. This method can be used for treatment personalization. Interim ⁶⁸Ga-DOTATOC PET does not provide information for treatment personalization.