Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors.
Eur J Nucl Med Mol Imaging
; 43(5): 839-851, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-26596723
ABSTRACT
BACKGROUND:
Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy.METHODS:
NET patients (n = 54), M F 3717, median age 66, bronchial n = 13, GEP-NET n = 35, CUP n = 6 were treated with (177)Lu-based-PRRT (cumulative activity 6.5-27.8 GBq, median 18.5). At baseline 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 (18)FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations regulatory network, proteinprotein interactome analyses. STATISTICAL ANALYSES chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival.RESULTS:
The disease control rate was 72 %. Median PFS was not achieved (follow-up 1-33 months, median 16). Only grading was associated with response (p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ(2) = 27.4; p = 1.2 × 10(-7)) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0.004) for predicting response (76 % accuracy). Combination with grading reached an AUC 0.90 ± 0.07, irrespective of tumor origin. Circulating transcripts correlated accurately (94 %) with PRRT responders (SD+PR+CR; 97 %) vs. non-responders (91 %).CONCLUSIONS:
Blood NET transcript levels and the predictive quotient (circulating gene clusters+grading) accurately predicted PRRT efficacy. CgA was non-informative.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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Octreotida
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Biomarcadores Tumorais
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Tumores Neuroendócrinos
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Compostos Radiofarmacêuticos
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article