Validation of a clinical score (CS) for patients (pts) with well-differentiated neuroendocrine tumors (WD NETs) under consideration for peptide receptor radionuclide therapy (PRRT) with Lu 177 dotatate.
Authors: Das Satya , Chauhan Aman , Du Liping , Thomas Katharine , Jacob Aasems , Schad Aimee , Jain Shikha , Jessop Aaron , Shah Chirayu , Eisner David , Cardin Dana Backlund , Ciombor Kristen Keon , Goff Laura Williams , Bradshaw Marques , Delbeke Dominique , Sandler Martin P. , Berlin Jordan , Ramirez Robert A. 
Published: June 2021

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Background: Questions remain regarding when to sequence PRRT and how to categorize pts being considered for the treatment (tx). We previously developed a CS (comprised of 5 categories: available non-PRRT tx for tumor type, prior systemic tx, pt symptoms, tumor burden in critical organs and peritoneal carcinomatosis presence) at Vanderbilt Ingram Cancer Center (VICC) for pts being considered for PRRT to help answer these questions and demonstrated the score to be associated with progression-free survival (PFS) in pts receiving PRRT. Herein, we present the performance of the CS in a validation cohort (VC) and combined cohort (CC). Methods: Our original cohort (OC) included pts with progressive WD NETs (N = 122) under consideration for PRRT between 3/1/2016-3/17/2020 at VICC while our VC included pts under consideration for PRRT (N = 126) between 1/25/2017-11/18/2019 at Ochsner Medical Center (OMC) (N = 51), Markey Cancer Center (MCC) (N = 51) and Rush Medical Center (RMC) (N = 24). All pts in the OC were prospectively scored while pts in the VC were scored retrospectively, with the CS-assigning investigator blinded to patient outcomes. The primary outcome PFS, was estimated by the Kaplan‐Meier method; a Cox proportional‐hazards model adjusting for primary tumor site, tumor grade and number of PRRT doses administered (0, 1-2 or 3-4) was used to analyze effect of CS. Overall survival (OS) was a key secondary outcome. Results: In our VC, on multivariable (MV) analysis, for each 2-point increase in CS, the hazard ratio (HR) for PFS was 2.58 (95% confidence interval (CI) 1.62-4.11). On MV analysis, for each 2-point increase in CS, the HR for OS was 3.89 (95% CI 1.8-4.83). We combined the OC and VC for this analysis in order to increase the predictive power of our originally developed Cox proportional-hazards models. In our CC, of the 248 total pts, median pt age, CS and number of prior tx were 63.3 years, 4 (range 0-8) and 1 (range 0-7), respectively. The most represented primary tumor sites were small intestinal (N = 136), pancreatic (N = 58), unknown primary (N = 26) and lung (N = 14). A total of 140, 82 and 26 pts received 3-4, 0 or 1-2 doses of PRRT, respectively. On MV analysis, for each 2-point increase in CS, the HR for PFS was 2.52 (95% CI 1.90-3.35). On MV analysis, for each 2-point increase in CS, the HR for OS was 3.48 (95% CI 2.33-5.18). No interaction between PRRT doses administered and CS was observed. Conclusions: Increases in CS were strongly associated with worsening PFS and OS in our VC and CC, validating findings from our OC. Although we cannot determine whether the CS specifically predicts PRRT response or is prognostic based upon these data, it is the first presented clinical metric which can categorize pts with WD NETs under consideration for PRRT and estimate anticipated benefit from PRRT for pts.