Diagnostic Approaches to Neuroendocrine Neoplasms of Unknown Primary Site

Berner, Alison; Pipinikas, Christodoulos P.; Ryan, Anna E.; Dibra, Harpreet; Moghul, Ismail; Webster, A. D. B.; Luong, TuVinh; Thirlwell, Christina

doi:10.1159/000504370

Cited by 29 publications

(50 citation statements)

References 85 publications

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“…The inclusion of patients with diverse types of GEP-NETs, including GI, pancreatic, and unknown primary origin, was a key strength of this study. While the incidence of NETs is increasing overall, the percentage classified as tumors of unknown primary origin is decreasing, which may reflect advances in tumor identification techniques [ 1 , 48 ]. Tumors of unknown primary origin are estimated to account for 10–22% of GEP-NETs [ 48 , 49 ], which is slightly higher than the 9.1% of patients in our study.…”

Section: Discussionmentioning

confidence: 99%

Lanreotide Depot to Treat Gastroenteropancreatic Neuroendocrine Tumors in a US Community Oncology Setting: A Prospective, Observational Study

Paulson

Ray²,

Aranha

et al. 2022

Oncol Ther

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Introduction Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can result in symptoms such as diarrhea, flushing, abdominal pain, and fatigue and are often associated with a significant disease burden and poor prognosis. This non-interventional, prospective, observational study evaluated the real-world safety and effectiveness of lanreotide depot, a somatostatin analog (SSA) used to treat GEP-NETs, in a community setting. Methods In this prospective, non-interventional study (NCT02730104), adult patients with locally advanced (inoperable), metastatic GEP-NETs treated with lanreotide depot were evaluated by their physician every 6 months from enrollment for 24 months. Clinically defined time to disease progression (TTDP) and overall survival (OS) were estimated for the total population and by primary tumor type (gastrointestinal [GI], pancreatic, unknown origin), and an exploratory analysis determined the rate of progression-free survival (PFS) at 12 and 24 months. Patient satisfaction was evaluated via the Treatment Satisfaction Questionnaire for Medication (TSQM-9), and safety information was recorded. Results Of 99 patients, the 24-month PFS rate was 73.7% (95% confidence interval [CI] 63.1–81.7) and 24-month OS rate was 84.2% (95% CI 74.0–90.7). Median TTDP was not reached because few patients experienced disease progression during the study period. The majority of responding patients expressed satisfaction with treatment on each domain of the TSQM-9. Treatment-related adverse events (AEs) occurred in 19.2% of patients, while no serious AEs (SAEs) were related to the study drug. Conclusions Lanreotide depot is an effective and well-tolerated treatment for GEP-NETs in the real-world community setting. Trial registration ClinicalTrials.gov identifier, NCT02730104. Supplementary Information The online version contains supplementary material available at 10.1007/s40487-022-00208-1.

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Section: Discussionmentioning

confidence: 99%

Lanreotide Depot to Treat Gastroenteropancreatic Neuroendocrine Tumors in a US Community Oncology Setting: A Prospective, Observational Study

Paulson

Ray²,

Aranha

et al. 2022

Oncol Ther

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“…Due to the small number of studies, no clear recommendations have been issued for patients with PanNETs of unknown primary site and liver metastases, which would define the advisability of surgery in search of a primary tumour with simultaneous cytoreduction of metastases [122,123].…”

Section: Guidelinesmentioning

confidence: 99%

“…Z powodu małej liczby przeprowadzonych badań nie określono jednoznacznych zaleceń dotyczących pacjentów z PanNET o nieznanym ognisku pierwotnym i przerzutami do wątroby, określających celowość zabiegu operacyjnego w poszukiwaniu ogniska pierwotnego z jednoczasową cytoredukcją przerzutów [122,123].…”

Section: Zaawansowane Pannets/choroba Przerzutowaunclassified

Pancreatic neuroendocrine neoplasms — update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne trzustki — uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polską Sieć Guzów Neuroendokrynych)]

et al. 2022

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This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially gonoma -glucagon-producing tumour, VIPoma -vasoactive intestinal peptide (VIP) producing tumour, GHRHoma -growth hormone-releasing hormone (GHRH)-producing tumour, ACTHoma -adrenocorticotropin hormone (ACTH)-producing tumour,

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“…A major problem with the existing markers is that as single analytes, most lack the capacity to define the various characteristics associated with tumour cells and the origin of the primary site in metastatic disease. The liver is often a common site of secondary lesions in neuroendocrine cancer, thus, knowing the primary origin may assist in prognosis and tumour management [ 15 ]. Hence, there is a requirement for markers to further characterise tumour origin, grade and prognosis [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

EMT Molecular Signatures of Pancreatic Neuroendocrine Neoplasms

Venugopal

Michalczyk

Khasraw

et al. 2022

IJMS

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Neuroendocrine neoplasms (NENs) are relatively rare neoplasms occurring predominantly in the gastrointestinal tract and pancreas. Their heterogeneity poses challenges for diagnosis and treatment. There is a paucity of markers for characterisation of NEN tumours. For routine diagnosis, immunohistochemistry of the NEN-specific markers CgA and synaptophysin and the proliferation marker Ki-67 are used. These parameters, however, are qualitative and lack the capacity to fully define the tumour phenotype. Molecules of epithelial–mesenchymal transition (EMT) are potential candidates for improved tumour characterisation. Using qRT-PCR, we measured mRNA levels of 27 tumour markers, including 25 EMT-associated markers, in tumour tissue and matched non-tumour tissues for 13 patients with pancreatic NENs. Tissue from patients with three different grades of tumour had distinctly different mRNA profiles. Of the 25 EMT-associated markers analysed, 17 were higher in G3 tissue relative to matched non-tumour tissue, including CD14, CD24, CD31, CD44, CD45, CD56, CK6, CK7, CK13, CK20, NSE, CDX2, CgA, DAXX, PCNA, laminin and Ki-67. The differences in levels of seven EMT-associated markers, Ki-67, DAXX, CD24, CD44, vimentin, laminin and PDX1 plus CgA and NSE (neuroendocrine markers) enabled a distinct molecular signature for each tumour grade to be generated. EMT molecules differentially expressed in three tumour grades have potential for use in tumour stratification and prognostication and as therapeutic targets for treatment of neuroendocrine cancers, following validation with additional samples.

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Diagnostic Approaches to Neuroendocrine Neoplasms of Unknown Primary Site

Cited by 29 publications

References 85 publications

Lanreotide Depot to Treat Gastroenteropancreatic Neuroendocrine Tumors in a US Community Oncology Setting: A Prospective, Observational Study

Lanreotide Depot to Treat Gastroenteropancreatic Neuroendocrine Tumors in a US Community Oncology Setting: A Prospective, Observational Study

Pancreatic neuroendocrine neoplasms — update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne trzustki — uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polską Sieć Guzów Neuroendokrynych)]

EMT Molecular Signatures of Pancreatic Neuroendocrine Neoplasms

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