Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: state of the art

Mestier, Louis de; Dromain, Clarisse; d’Assignies, Gaspard; Scoazec, Jean‐Yves; Lassau, Nathalie; Lebtahi, Rachida; Brixi, Hédia; Mitry, Emmanuel; Guimbaud, Rosine; Courbon, F.; d’Herbomez, Michèle; Cadiot, Guillaume

doi:10.1530/erc-13-0365

Cited by 69 publications

(68 citation statements)

References 116 publications

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“…At present, compared with CT or MRI, 111 In-pentetreotide is considered suboptimal, with a sensitivity of less than 60% (12). However, with 111 In-pentetreotide whole-body scintigraphy, the therapeutic strategy is still modified in up to 50% of cases (13). 68 …”

Section: Development Of Targeted Compoundsmentioning

confidence: 99%

Somatostatin Receptor 2–Targeting Compounds

Duijzentkunst

Bodei

2017

J Nucl Med

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The molecular imaging and treatment of neuroendocrine tumors (NETs) with radiolabeled somatostatin analogs represent a milestone in the development of theranostic compounds. Whole-body scintigraphy with 111 In-pentetreotide has revolutionized the diagnosis and staging of NETs and the evaluation of treatment outcomes. At present, diagnostic accuracy with positron-emitting radionuclides is greater than 90%. Peptide receptor radionuclide therapy (PRRT) has become a well-accepted treatment for patients with welldifferentiated inoperable or metastatic NETs and disease progression after first-line treatment. Disease control rates (complete or partial remission or stable disease in patients with formerly progressive disease) of up to 95%, with a low incidence of long-term hematologic and renal toxicity, have been reported. In a recently published randomized trial, compared with intensified treatment of midgut NETs with longacting and repeatable octreotide, PRRT reduced the hazard of disease progression and death by 79%. Upcoming developments in PRRT include the use of somatostatin receptor antagonists and a-emitting radionuclides, which may further enhance treatment outcomes.

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Section: Development Of Targeted Compoundsmentioning

confidence: 99%

Somatostatin Receptor 2–Targeting Compounds

Duijzentkunst

Bodei

2017

J Nucl Med

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“…MDCT can localize the primary tumor, assess the extent of disease, characterize the architectural relationships with the surrounding structures and be used to reassess the disease following treatments [8,32,33,34]. …”

Section: Technique Strengthsmentioning

confidence: 99%

“…The better soft-tissue contrast of MRI, as compared to CT, is particularly useful to detect liver metastases for which MRI represents the most sensitive technique [37,38]. The soft-tissue contrast can be further increased by the use of liver-specific and superparamagnetic contrast media [34,39]. Three-dimensional acquisition allows for viewing in multiple anatomical planes to enable accurate image interpretation.…”

Section: Technique Strengthsmentioning

confidence: 99%

The Status of Neuroendocrine Tumor Imaging: From Darkness to Light?

et al. 2014

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Diagnostic imaging plays a pivotal role in the diagnosis, staging, treatment selection and follow-up for neuroendocrine tumors. The available diagnostic strategies are morphologic imaging, including computed tomography, magnetic resonance imaging (MRI) and ultrasound techniques, and molecular imaging, including scintigraphy with ¹¹¹In-pentetreotide and positron emission tomography with ⁶⁸Ga-DOTA-peptides, ¹⁸F-DOPA and ¹¹C-5-HTP. A combination of anatomic and functional techniques is routinely performed to optimize sensitivity and specificity. The introduction of diffusion-weighted MRI and dynamic contrast-enhanced techniques represents a promising advance in radiologic imaging, whereas new receptor-binding peptides, including somatostatin agonists and antagonists, represent the recent most favorable innovation in molecular imaging. Future development includes the short-term validation of these techniques, but in extension also a more comprehensive multilevel integration of biologic information pertaining to a specific tumor and patient, possibly encompassing genomic considerations, currently evolving as a new entity denoted ‘precision medicine'. The ideal is a diagnostic sequence that captures the global status of an individual's tumor and encompasses a multidimensional characterization of tumor location, metabolic performance and target identification. To date, advances in imagery have focused on increasing resolution, discrimination and functional characterization. In the future, the fusion of imagery with the parallel analysis of biological and genomic information has the potential to considerably amplify diagnosis.

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“…Overall, the current criteria for the assessment of NET progression and therapeutic responses are suboptimal (Faivre et al 2012, Castano et al 2014. As a result, alternative imaging criteria, combining morphological and functional techniques, are under consideration (de Mestier et al 2013). Imaging therefore has limitations in the early identification of NET disease progress and the timely establishment of therapeutic efficacy.…”

Section: Introductionmentioning

confidence: 99%

A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

Modlin

Drozdov

Alaimo

et al. 2014

Endocrine-Related Cancer

102

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A critical requirement in neuroendocrine tumor (NET) management is a sensitive, specific and reproducible blood biomarker test. We evaluated a PCR-based 51 transcript signature (NETest) and compared it to chromogranin A (CgA), pancreastatin (PST) and neurokinin A (NKA). The multigene signature was evaluated in two groups: i) a validation set of 40 NETs and controls and ii) a prospectively collected group of NETs (nZ41, 61% small intestinal, 50% metastatic, 44% currently treated and 41 age-sex matched controls). Samples were analyzed by a two-step PCR (51 marker genes) protocol and ELISAs for CgA, PST and NKA. Sensitivity comparisons included c 2 , non-parametric measurements, ROC curves and predictive feature importance (PFAI) analyses. NETest identified 38 of 41 NETs. Performance metrics were: sensitivity 92.8%, specificity 92.8%, positive predictive value 92.8% and negative predictive value 92.8%. Single analyte ELISA metrics were: CgA 76, 59, 65, and 71%; PST 63, 56, 59, and 61% and NKA 39, 93, 84, and 60%. The AUCs (ROC analysis) were: NETest: 0.96G0.025, CgA: 0.67G0.06, PST 0.56G0.06, NKA: 0.66G0.06. NETest significantly outperformed single analyte tests (area differences: 0.284-0.403, Z-statistic 4.85-5.9, P!0.0001). PFAI analysis determined NETest had most value (69%) in diagnosis (CgA (13%), PST (9%), and NKA (9%)). Test data were consistent with the validation set (NETest O95% sensitivity and specificity, AUC Z0.98 vs single analytes: 59-67% sensitivity, AUCs: 0.58-0.63). The NETest is significantly more sensitive and efficient (O93%) than single analyte assays (CgA, PST or NKA) in NET diagnosis. Blood-based multigene analytic measurement will facilitate early detection of disease recurrence and can predict therapeutic efficacy.

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Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: state of the art

Cited by 69 publications

References 116 publications

Somatostatin Receptor 2–Targeting Compounds

Somatostatin Receptor 2–Targeting Compounds

The Status of Neuroendocrine Tumor Imaging: From Darkness to Light?

A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

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