ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2017) 52 P03 | DOI: 10.1530/endoabs.52.P03

Blood measurements of Neuroendocrine Tumor (NET) transcripts and gene cluster analysis predict efficacy of PRRT

Lisa Bodei1, Wouter van der Zwaan2, Mark Kidd3, Ignat Drozdov3, Richard P Baum4, Dik Kwekkeboom2, Eric Krenning2 & Irvin M Modlin5

1Memorial Sloan Kettering Cancer Center, New York, New York, USA; 2Erasmus Medical Center, Rotterdam, Netherlands; 3Wren Laboratories, Branford, Connecticut, USA; 4Zentraklinik, Bad Berka, Germany; 5Yale University, New Haven, Connecticut, USA.

Background: Peptide receptor radionuclide therapy (PRRT) is based on tumor somatostatin receptor (SSR) overexpression to deliver targeted isotope therapy. Functional imaging of SSR expression (SRE) is used as a predictor of efficacy, but there is no method to objectively predict PRRT efficacy. We report the efficacy of Predictive Quotient Index (PQI) to predict the utility of PPRT. PQI is derived from circulating NET transcript analysis (NETest) integrated with the tumor grade. We validated the utility of this PRRT complementary diagnostic in a prospective, blinded study conducted at Rotterdam.

Methods: NETs (n=42); with progressive disease (74%) were treated with 177Lu-PRRT-treated (29.1±2.2 GBq). Baseline evaluations included clinical status, Grade (Ki67), SRE, CgA (NeoLisa, ULN >108 ng/ml), and NETest (qRT-PCR - multianalyte algorithmic analyses, NETest score: 0–100%; ULN >14%). The PQI (a calculation of ‘omic’ NETest genes regulating metabolism and growth factor signaling) is mathematically integrated with tissue Ki67. The PQI has two prediction outputs: ‘responder’ (R) vs ‘non-responder’ (NR). Disease assessment was by RECIST criteria (Partial Response and Disease Stabilization = Responder vs. Disease Progression = NR). All samples were blinded. Statistics: Cox proportional multiple regression, Kaplan-Meier survival, & McNemar-test.

Results: At restaging, the overall response (disease control rate) was 76%; median PFS not reached (follow-up 5–20 months). Histology: GI: 12; GII: 21; GIII 2; and lung: TC: 2; AC: 4. SRE was Grade 3 (in 80%). NETest was elevated in (NETest score: 61±22%) in all. Predictive accuracies of baseline SRE, clinical status, and CgA ranged from 25 to 54% (not-significant). PQI was the only predictive marker by multivariate analysis (P=0.001). The PQI diagnostic was 95% concordant with response to therapy and significantly more accurate than all other markers (McNemar: P<0.002). Cox-proportional modeling confirmed PQI utility (OR: 9.1, P<0.004). K-MS analysis identified significantly different mPFS between R (not reached) and NR (10.4 months; Hazard Ratio: 92, P<0.0001).

Conclusion: The predictive quotient index comprising blood based ‘omic’ analysis and tissue grading when measured prior to therapy predicts the efficacy of PRRT therapy in GEP and lung NETs in 95%.

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