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Pancreastatin predicts survival in neuroendocrine tumors.

ABSTRACT: Serum neurokinin A, chromogranin A, serotonin, and pancreastatin reflect tumor burden in neuroendocrine tumors. We sought to determine whether their levels correlate with survival in surgically managed small bowel (SBNETs) and pancreatic neuroendocrine tumors (PNETs).Clinical data were collected with Institutional Review Board approval for patients undergoing surgery at one center. Progression-free (PFS) and overall (OS) survival were from the time of surgery. Event times were estimated by the Kaplan-Meier method. Preoperative and postoperative laboratory values were tested for correlation with outcomes. A multivariate Cox model adjusted for confounders.Included were 98 SBNETs and 78 PNETs. Median follow-up was 3.8 years; 62 % had metastatic disease. SBNETs had lower median PFS than PNETs (2.0 vs. 5.6 years; p < 0.01). Median OS was 10.5 years for PNETs and was not reached for SBNETs. Preoperative neurokinin A did not correlate with PFS or OS. Preoperative serotonin correlated with PFS but not OS. Higher levels of preoperative chromogranin A and pancreastatin showed significant correlation with worse PFS and OS (p < 0.05). After multivariate adjustment for confounders, preoperative and postoperative pancreastatin remained independently predictive of worse PFS and OS (p < 0.05). Whether pancreastatin normalized postoperatively further discriminated outcomes. Median PFS was 1.7 years in patients with elevated preoperative pancreastatin versus 6.5 years in patients with normal levels (p < 0.001).Higher pancreastatin levels are significantly associated with worse PFS and OS in SBNETs and PNETs. This effect is independent of age, primary tumor site, and presence of nodal or metastatic disease. Pancreastatin provides valuable prognostic information and identifies surgical patients at high risk of recurrence who could benefit most from novel therapies.

SUBMITTER: Sherman SK

PROVIDER: S-EPMC4125469 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Pancreastatin predicts survival in neuroendocrine tumors.

Sherman Scott K SK Maxwell Jessica E JE O'Dorisio M Sue MS O'Dorisio Thomas M TM Howe James R JR

Annals of surgical oncology 20140422 9

<h4>Background</h4>Serum neurokinin A, chromogranin A, serotonin, and pancreastatin reflect tumor burden in neuroendocrine tumors. We sought to determine whether their levels correlate with survival in surgically managed small bowel (SBNETs) and pancreatic neuroendocrine tumors (PNETs).<h4>Methods</h4>Clinical data were collected with Institutional Review Board approval for patients undergoing surgery at one center. Progression-free (PFS) and overall (OS) survival were from the time of surgery. ...[more]

PMID: 24752611

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Project description:IntroductionNeuroendocrine neoplasms (NENs) are a rare group of tumors exceptionally heterogeneous, with clinical presentation ranging from well differentiated more indolent tumors to poorly differentiated very aggressive forms. Both are often diagnosed after the metastatic spread and require appropriate medical treatment. A high priority need in the management of this disease is the identification of effective therapeutic strategies for advanced and metastatic patients. The recent TALENT trial demonstrated the efficacy of lenvatinib, a multi-tyrosine kinase inhibitor, in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with no other treatment indication. Further development of this drug in advanced NETs is warranted.MethodsWe investigated potential clinical and molecular determinants of lenvatinib response in human primary cultures derived from patients with GEP-NET of different grades and sites of origin. We correlated response to treatment with patient clinical characteristics, with the mutational status of 161-cancer associated genes and with the expression levels of MKI-related genes.ResultsLenvatinib exerted a significant antitumor activity in primary GEP-NET cells, with median survival inhibitions similar or higher than those of standard frontline treatments. Of the 11 primary cultures analyzed in our case series, 6 were classified as responder showing a significant survival inhibition, and 5 as non-responder. We observed that the overexpression of HRAS in the original tumor tissue compared to the matched healthy tissue significantly correlated with responsiveness of primary cells to lenvatinib (p=.048). All 5 non-responder cultures showed normal HRAS expression, while of the 6 responder cultures, 4 had HRAS overexpression. Overexpression of HRAS was not associated with gene mutation. None of the other evaluated clinical variables (grade, Ki67, site of origin and syndromic disease) or molecular markers correlated with response.DiscussionLenvatinib appears to be a highly effective drug for the treatment of NETs. The evaluation of HRAS expression in the tumor tissue might improve patient selection and optimize therapeutic outcome.

Project description:ImportanceThe number of patients with small nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is increasing. However, the role of surgery for small NF-PanNETs remains unclear.ObjectiveTo evaluate the association between surgical resection for NF-PanNETs measuring 2 cm or smaller and survival.Design, setting, and participantsThis cohort study used data from the National Cancer Database and included patients with NF-pancreatic neuroendocrine neoplasms who were diagnosed between January 1, 2004, and December 31, 2017. Patients with small NF-PanNETs were divided into 2 groups: group 1a (tumor size, ≤1 cm) and group 1b (tumor size, 1.1-2.0 cm). Patients without information on tumor size, overall survival, and surgical resection were excluded. Data analysis was performed in June 2022.ExposuresPatients with vs without surgical resection.Main outcomes and measuresThe primary outcome was overall survival of patients in group 1a or group 1b who underwent surgical resection compared with those who did not, which was evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Interactions between preoperative factors and surgical resection were analyzed with a multivariable Cox proportional hazards regression model.ResultsOf the 10 504 patients with localized NF-PanNETs identified, 4641 were analyzed. These patients had a mean (SD) age of 60.5 (12.7) years and included 2338 males (50.4%). The median (IQR) follow-up time was 47.1 (28.2-71.6) months. In total, 1278 patients were in group 1a and 3363 patients were in group 1b. The surgical resection rates were 82.0% in group 1a and 87.0% in group 1b. After adjustment for preoperative factors, surgical resection was associated with longer survival for patients in group 1b (hazard ratio [HR], 0.58; 95% CI, 0.42-0.80; P < .001) but not for patients in group 1a (HR, 0.68; 95% CI, 0.41-1.11; P = .12). In group 1b, interaction analysis found that age of 64 years or younger, absence of comorbidities, treatment at academic institutions, and distal pancreatic tumors were factors associated with increased survival after surgical resection.Conclusions and relevanceFindings of this study support an association between surgical resection and increased survival in select patients with NF-PanNETs measuring 1.1 to 2.0 cm who were younger than 65 years, had no comorbidities, received treatment at academic institutions, and had tumors of the distal pancreas. Future investigations of surgical resection for small NF-PanNETs that include the Ki-67 index are warranted to validate these findings.

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Pancreastatin predicts survival in neuroendocrine tumors.

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Pancreastatin predicts survival in neuroendocrine tumors.

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