Volumetric Parameters Derived from CXCR4-Directed PET/CT Predict Outcome in Patients with Gastrointestinal Neuroendocrine Carcinomas

Abstract

Background Gastro-entero-pancreatic neuroendocrine carcinomas (GEP-NECs) are an aggressive subgroup of neuroendocrine neoplasms (NENs). In patients affected with NEN, there is a growing body of evidence that increased C-X-C motif chemokine receptor (CXCR4) expression is linked to decreasing overall survival (OS) in an ex-vivo setting. Thus, we aimed to determine whether the in-vivo-derived CXCR4-directed whole-body PET signal can also determine GEP-NEC patients with shorter OS. Methods We retrospectively included 16 patients with histologically proven GEP-NEC, who underwent CXCR4-directed PET/CT for staging and therapy planning. We assessed maximum, peak, and mean standardized uptake values as well as whole-body tumor volume (TV) and total-lesion uptake (TLU = SUVmean × TV) using a semi-automatic segmentation tool with a 50% threshold. Association of PET-based biomarkers and OS or radiographic progression-free survival (rPFS; according to RECIST 1.1 criteria) was analyzed using univariable and multivariable cox regression. Results Median OS and rPFS was 7.5 and 7 months, respectively. A significant correlation between TV and TLU was found for OS (TV: hazard ratio (HR) 1.007 95% confidence interval (CI) 1.000–1.014, p = 0.0309; TLU: HR 1.002 95% CI 1.000–1.003, p = 0.0350) and rPFS (TV: HR 1.010 95% CI 1.002–1.021; p = 0.0275; TLU: HR 1.002 95% CI 1.000–1.004, p = 0.0329), respectively. No significant correlation with OS or rPFS was found for non-volumetric parameters (p > 0.4). TV remained a significant predictive marker for OS and rPFS in multivariable analysis (OS: HR 1.012 95%, CI 1.003–1.022, p = 0.0084; rPFS: HR 1.009, 95% CI 0.9999–1.019, p = 0.0491), whereas TLU remained only prognostic for OS (HR 1.009, 95% CI 0.9999–1.019, p = 0.0194) but narrowly failed significance for rPFS (p = 0.0559). Conclusion In-vivo assessment of CXCR4 PET-derived volumetric parameters is predictive for outcome of patients with GEP-NEC and could be used as a risk stratification tool, which detects patients prone to early progression.