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PRRT neuroendocrine tumor response monitored using circulating transcript analysis: the NETest

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Peptide receptor radionuclide therapy (PRRT) is effective for metastatic/inoperable neuroendocrine tumors (NETs). Imaging response assessment is usually efficient subsequent to treatment completion. Blood biomarkers such as PRRT Predictive Quotient (PPQ) and NETest are effective in real-time. PPQ predicts PRRT efficacy; NETest monitors disease. We prospectively evaluated: (1) NETest as a surrogate biomarker for RECIST; (2) the correlation of NETest levels with PPQ prediction.

Methods

Three independent 177Lu-PRRT-treated GEP-NET and lung cohorts (Meldola, Italy: n = 72; Bad-Berka, Germany: n = 44; Rotterdam, Netherlands: n = 41). Treatment response: RECIST1.1 (responder (stable, partial, and complete response) vs non-responder). Blood sampling: pre-PRRT, before each cycle and follow-up (2–12 months). PPQ (positive/negative) and NETest (0–100 score) by PCR. Stable < 40; progressive > 40). CgA (ELISA) as comparator. Samples de-identified, measurement and analyses blinded. Kaplan–Meier survival and standard statistics.

Results

One hundred twenty-two of the 157 were evaluable. RECIST stabilization or response in 67%; 33% progressed. NETest significantly (p < 0.0001) decreased in RECIST “responders” (− 47 ± 3%); in “non-responders,” it remained increased (+ 79 ± 19%) (p < 0.0005). NETest monitoring accuracy was 98% (119/122). Follow-up levels > 40 (progressive) vs stable (< 40) significantly correlated with mPFS (not reached vs. 10 months; HR 0.04 (95%CI, 0.02–0.07).

PPQ response prediction was accurate in 118 (97%) with a 99% accurate positive and 93% accurate negative prediction. NETest significantly (p < 0.0001) decreased in PPQ-predicted responders (− 46 ± 3%) and remained elevated or increased in PPQ-predicted non-responders (+ 75 ± 19%). Follow-up NETest categories stable vs progressive significantly correlated with PPQ prediction and mPFS (not reached vs. 10 months; HR 0.06 (95%CI, 0.03–0.12).

CgA did not reflect PRRT treatment: in RECIST responders decrease in 38% and in non-responders 56% (p = NS).

Conclusions

PPQ predicts PRRT response in 97%. NETest accurately monitors PRRT response and is an effective surrogate marker of PRRT radiological response. NETest decrease identified responders and correlated (> 97%) with the pretreatment PPQ response predictor. CgA was non-informative.

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Correspondence to Lisa Bodei.

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All human participant procedures were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent: Informed consent was obtained from all participants in the study.

Conflict of Interest

LB, RPB, and GP—consultancy fees from Ipsen and Advanced Accelerator Applications unrelated to the submitted work (AAA). EPK and DJK—support from AAA unrelated to the submitted work. RPB—support from Ipsen, ROTOP Pharmaka, and OctreoPharm Sciences unrelated to the work. MK—employed by Wren Laboratories. IMM and IAD—consultants for Wren Laboratories. No conflicts for AS, WAvZ, SS, or AM.

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Bodei, L., Kidd, M.S., Singh, A. et al. PRRT neuroendocrine tumor response monitored using circulating transcript analysis: the NETest . Eur J Nucl Med Mol Imaging 47, 895–906 (2020). https://doi.org/10.1007/s00259-019-04601-3

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