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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

14.12.2019 | Original Article

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

verfasst von: Lisa Bodei, Mark S. Kidd, Aviral Singh, Wouter A. van der Zwan, Stefano Severi, Ignat A. Drozdov, Anna Malczewska, Richard P. Baum, Dik J. Kwekkeboom, Giovanni Paganelli, Eric P. Krenning, Irvin M. Modlin

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 4/2020

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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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Titel: PRRT neuroendocrine tumor response monitored using circulating transcript analysis: the NETest
verfasst von: Lisa Bodei
Mark S. Kidd
Aviral Singh
Wouter A. van der Zwan
Stefano Severi
Ignat A. Drozdov
Anna Malczewska
Richard P. Baum
Dik J. Kwekkeboom
Giovanni Paganelli
Eric P. Krenning
Irvin M. Modlin
Publikationsdatum: 14.12.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 4/2020
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-019-04601-3

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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