pancreastatin-52 and Neuroendocrine-Tumors

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.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Follow-Up Studies; Humans; Intestinal Neoplasms; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neuroendocrine Tumors; Pancreatic Hormones; Pancreatic Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Tumor Burden; Young Adult

The objective of this study was to investigate the prognostic impact of the biomarker serum pancreastatin in patients with metastatic neuroendocrine tumors (NETs) treated with transarterial chemoembolization (TACE).. Patients with metastatic NET treated with TACE at a single institution from 2000 to 2013 were analyzed. Patient demographics, response to therapy, and long-term survival were compared with baseline pancreastatin level and changes in pancreastatin levels after TACE.. A total of 188 patients underwent TACE during the study period. An initial pancreastatin level greater than 5000 pg/mL correlated with worse overall survival (OS) from time of first TACE (median OS, 58.5 vs. 22.1 months, p < 0.001). A decrease in pancreastatin level by 50% or more after TACE treatment correlated with improved OS (median OS 53.8 vs. 29.9 months, p = 0.032). Patients with carcinoid syndrome were more likely to have a subsequent increase in pancreastatin after initial drop post-TACE (78.1 vs. 55.2%, p = 0.002). Patients with an increase in pancreastatin levels after initial drop post-TACE were more likely to have liver progression on imaging (70.7 vs. 40.7%, p = 0.005) and more likely to need repeat TACE (21.1 vs. 6.7%, p = 0.009).. For patients with liver metastases from NET treated with TACE, pancreastatin measurement may be a useful prognostic indicator. Extreme high levels before TACE can predict poor outcomes, whereas significant drops in pancreastatin after TACE correlate with improved survival. An increase in levels after initial decrease may predict progressive liver disease requiring repeat TACE. As such, pancreastatin levels should be measured throughout the TACE treatment period.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chemoembolization, Therapeutic; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Neuroendocrine Tumors; Pancreatic Hormones; Prognosis; Survival Rate; Young Adult

In this study, we look at the clinical features associated with bone metastasis in patients with well-to-moderately differentiated neuroendocrine tumors (NETs), specifically primary tumor characteristics, complications, elevated hormone levels, and survival.. A retrospective study at the Ohio State University was performed on patients diagnosed with well-to-moderately differentiated NETs from 2000 to 2010 who were found to have bone metastases. A control group of patients with metastatic NETs without bone metastases was matched with regard to demographic and clinical data.. Of 341 patients with well-to-moderately differentiated NETs, 40 patients were found with bone metastases within the 10-year study period. Patients with bone metastases had shorter survival (median, 52 months) compared to the control group (median, 98 months; P = 0.024). Of 26 patients with bone metastases who died, 6 (23%) patients had a cause of death related to their bone metastatic disease. There were 8 patients with spinal cord compression, and 6 with pathologic fractures.. Our study suggests that patients with well-to-moderately differentiated NETs metastatic to bone have larger tumors, more frequently elevated pancreastatin, and shorter survival than patients without bone metastases, with complications of bone metastases significantly contributing to mortality and morbidity.

Topics: Academic Medical Centers; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Cause of Death; Cell Differentiation; Databases, Factual; Female; Fractures, Spontaneous; Humans; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Middle Aged; Neuroendocrine Tumors; Ohio; Pancreatic Hormones; Prognosis; Retrospective Studies; Risk Factors; Spinal Cord Compression; Time Factors; Tumor Burden

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 (n=41, 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 χ(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: 0.96±0.025, CgA: 0.67±0.06, PST 0.56±0.06, NKA: 0.66±0.06. 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 >95% sensitivity and specificity, AUC =0.98 vs single analytes: 59-67% sensitivity, AUCs: 0.58-0.63). The NETest is significantly more sensitive and efficient (>93%) 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.

Topics: Adult; Aged; Biomarkers, Tumor; Chromogranin A; Enzyme-Linked Immunosorbent Assay; Female; Hematologic Tests; Humans; Male; Middle Aged; Neuroendocrine Tumors; Neurokinin A; Pancreatic Hormones; Polymerase Chain Reaction; Reproducibility of Results

To assess the value of pancreastatin as a predictive factor for identifying patients with neuroendocrine tumours (NETs) who respond poorly to somatostatin analogues.. A retrospective study of patients with NETs. Patient records from the Northern Ireland Neuroendocrine Tumour Register were interrogated. Those who had pancreastatin concentrations measured on two or more occasions, before and during somatostatin analogue therapy (within the set time-limits) were selected. Data relating to diagnosis, surgery, somatostatin analogue therapy and survival outcome were noted. Data were subjected to univariate and multivariate analysis using Cox proportional hazard model.. Fifty-nine patients with gastroenteropancreatic NETs fulfilled the inclusion criteria. Factors associated with a poor survival outcome on univariate analysis were primary tumour site (P = 0.006) and rapid rise in pancreastatin during somatostatin analogue treatment (P < 0.001). In multivariate analysis, highly significant clinical prognostic indicators were: tumour location (P < 0.001), pre-treatment pancreastatin (P < 0.001) and pancreastatin change (P < 0.001).. This study endorses the finding that pancreastatin is a useful prognostic indicator of neuroendocrine disease. On commencement of treatment, one-third of the subjects showed an immediate negative pancreastatin response to somatostatin analogues, which was associated with poor survival. This is the first study to document such an association. These findings have significant therapeutic consequences. In the presence of a rapidly rising pancreastatin alternative, treatment modalities should be sought.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Humans; Male; Middle Aged; Multivariate Analysis; Neuroendocrine Tumors; Pancreatic Hormones; Prognosis; Somatostatin; Young Adult