UKINETS2018 Poster Presentations (1) (28 abstracts)
Circulating neuroendocrine tumor gene expression is effective in monitoring peptide receptor radionuclide (PRRT) efficacy
Lisa Bodei 1 , Mark Kidd 2 , Wouter van der Zwan 3 , Aviral Singh 4 , Stefano Severi 5 , Ignat Drozdov 2 , Jarowslaw Cwikla 6 , Agnieska Kolasinska-Cwikla 7 , Richard Baum 4 , Giovanni Paganelli 8 , Eric Krenning 3 & Irvin Modlin 9
1Memorial Sloan Kettering Cancer Center, New York, New York, USA; 2Wren Laboratories, Branford, Connecticut, USA; 3Erasmus University Medical Center, Rotterdam, the Netherlands; 4Zentralklinik Bad Berka, Bad Berka, Germany; 5Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; 6University of Warmia and Mazury, Olsztyn, Poland; 7Marie Curie Insitute, Warsaw, Poland; 8Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldoa, Italy; 9Yale University, New Haven, Connecticut, USA.
Background: Predicting and monitoring PRRT is based upon NET overexpression of somatostatin receptor (SSR) to deliver targeted isotope therapy. Imaging SSR expression is ~60% accurate as a predictor of efficacy. However, it and other imaging modalities e.g., CT/MRI, have utility for monitoring response. Specific blood NET gene expression (Positive Predictor Quotient- [PPQ]) is accurate in predicting PRRT response (93–97%, Bodei et al. EJNMMI 2018). The utility of NET transcripts (NETest) as an assessment of treatment efficacy requires evaluation. We examined whether the NETest could monitor PRRT therapy.
Methods: We evaluated three independent, prospective 177Lu-PRRT treatment cohorts from Meldola, Rotterdam, and Bad Berka (total: n=158, – 2–5 cycles PRRT). Blood was prospectively collected. Baseline evaluation included the NETest (qRT-PCR – multianalyte algorithmic analyses). Blood samples were collected prior to the last PRRT cycle and at follow-up (2–9 months after therapy). Imaging (CT/MRI) were used to evaluate treatment response. Responders included disease stabilization and partial responders. Non-responders exhibited demonstrable disease progression. All blood samples were measured and analyzed in a blinded fashion. Statistics: Non-parametric Mann-Whitney U-test, Kaplan-Meier survival analyses.
Results: PRRT cohort (n=158). Median follow-up: 14–16 months. NETest levels pre-PRRT were 58±25. Responders (n=103): Prior to PRRT, NETest was 61±23. At the end of therapy cycles, levels were 38±22 (P<0.0001). The change represented an average decrease in score of -20%. At follow-up, scores continued to drop (29±15, P<0.006 vs end of therapy score). Non-responders (n=55): Prior to PRRT, NETest was 54±28. At therapy termination, levels were 62±28 (P=0.08). The change was an average increase in score of +13%. In 103 patients, the NETest score decreased or exhibited no change (pre-PRRT to end of therapy) and 53 exhibited an increase. Those with a decrease or no change in NETest demonstrated a mPFS of 23 months. In those with a score increase mPFS was 14 months (χ2=27.2, P<0.0001, Hazard ratio: 0.21).
Conclusion: Alterations in the NETest blood levels are effective in monitoring PRRT efficacy. A decrease in score from pre-therapy to the conclusion of therapy identifies responders. NETest monitoring of PRRT will facilitate disease management.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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