Prognostic factors and survival after surgical resection of pancreatic neuroendocrine tumor with validation of established and modified staging systems

Benetatos, Nikolaos; Hodson, James; Marudanayagam, R.; Sutcliffe, Robert P.; Isaac, John; Ayuk, John; Shah, Tahir; Roberts, Keith

doi:10.1016/j.hbpd.2018.03.002

Cited by 19 publications

(10 citation statements)

References 33 publications

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“…We further demonstrated that high tumor grade is a strong, negative predictor of OS. Both tumor stage and grade are widely used for prognostic assessment, and the ENETS classification system for PNET has been evaluated previously (23,(25)(26)(27)(28)(29). In line with Ekeblad et al and Scarpa et al (23,26), we found no significant difference between stage I and II disease (Table 2).…”

Section: Discussionsupporting

confidence: 82%

Predicting Progression, Recurrence, and Survival in Pancreatic Neuroendocrine Tumors: A Single Center Analysis of 174 Patients

et al. 2022

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IntroductionThe European Neuroendocrine Tumor Society, ENETS, reports variables of prognostic significance in pancreatic neuroendocrine tumors (PNET). However, studies have short follow-ups, and the optimal treatment remains controversial. We aimed to determine overall survival (OS), progression-free survival (PFS) after conservative treatment, and recurrence-free survival (RFS) after surgery and further to find predictors of aggressive PNET behavior to support treatment decisions.Methods174 patients with PNET treated at Aarhus University Hospital from 2011 to 2021 were included in a retrospective cohort study. Patients were divided into surgically resected (SUR, n=91) and medically or conservatively treated (MED, n=83). Variables were tested in univariate and multivariate survival analysis. Median follow-up time was 3.4 years in the MED group and 4.5 years in the SUR group.ResultsThe 5-year OS was 95% and 65% for the SUR and MED groups, respectively. The 5-year RFS in the SUR group was 80% whereas the 5-year PFS in the MED group was 41%. Larger tumor size, Ki67 index, tumor grade, and stage were predictive of shorter OS, RFS, and PFS. Further, chromogranin A was a predictor of OS. Larger tumor size was associated with higher stage and grade. Only 1 of 28 patients with stage 1 disease and size ≤2 cm developed progression on a watch-and-wait strategy during a median follow-up of 36 months.ConclusionThis study supported the ENETS staging and grading system to be useful to predict OS, PFS, and RFS in PNET. Further, our data support that small, localized, low-grade PNETS can be followed with active surveillance.

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Section: Discussionsupporting

confidence: 82%

Predicting Progression, Recurrence, and Survival in Pancreatic Neuroendocrine Tumors: A Single Center Analysis of 174 Patients

et al. 2022

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“…GEP-NET histologic evaluation is a key component of clinical management. Tumor grade, as determined by evaluation of Ki-67 immunohistochemical stains and mitotic counts, is currently employed to predict prognosis and determine surgical management (Benetatos et al 2018). This scoring system is time-consuming and hampered by poor reproducibility (Reid et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Evaluating gastroenteropancreatic neuroendocrine tumors through microRNA sequencing

Panarelli

Tyryshkin

Wong

et al. 2019

Endocrine-Related Cancer

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Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can be challenging to evaluate histologically. MicroRNAs (miRNAs) are small RNA molecules that often are excellent biomarkers due to their abundance, cell-type and disease stage specificity and stability. To evaluate miRNAs as adjunct tissue markers for classifying and grading well-differentiated GEP-NETs, we generated and compared miRNA expression profiles from four pathological types of GEP-NETs. Using quantitative barcoded small RNA sequencing and state-of-the-art sequence annotation, we generated comprehensive miRNA expression profiles from archived pancreatic, ileal, appendiceal and rectal NETs. Following data preprocessing, we randomly assigned sample profiles to discovery (80%) and validation (20%) sets prior to data mining using machine-learning techniques. High expression analyses indicated that miR-375 was the most abundant individual miRNA and miRNA cistron in all samples. Leveraging prior knowledge that GEP-NET behavior is influenced by embryonic derivation, we developed a dual-layer hierarchical classifier for differentiating GEP-NET types. In the first layer, our classifier discriminated midgut (ileum, appendix) from non-midgut (rectum, pancreas) NETs based on miR-615 and -92b expression. In the second layer, our classifier discriminated ileal from appendiceal NETs based on miR-125b, -192 and -149 expression, and rectal from pancreatic NETs based on miR-429 and -487b expression. Our classifier achieved overall accuracies of 98.5% and 94.4% in discovery and validation sets, respectively. We also found provisional evidence that low- and intermediate-grade pancreatic NETs can be discriminated based on miR-328 expression. GEP-NETs can be reliably classified and potentially graded using a limited panel of miRNA markers, complementing morphological and immunohistochemistry-based approaches to histologic evaluation.

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“…Several prognostic markers have been suggested in patients with pancreatic NET (PNET), including age at diagnosis, tumor grade and stage [4][5][6]. Indeed, high-grade PNET, lymph node involvement and presence of distant metastases are all associated with reduced disease-specific survival [7,8]. Additional markers have been proposed, some are based on surgical specimens, such as tumor-invading platelet count [9] and composite of pancreatic duct dilatation and neutrophil to lymphocyte ratio [10].…”

Section: Introductionmentioning

confidence: 99%

Plasma Hemoglobin and Red Blood Cell Mass Levels as Dynamic Prognostic Markers for Progression and Survival in Pancreatic Neuroendocrine Tumors

et al. 2021

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There are scarce data on readily available markers enabling immediate risk stratification and personalized management in patients with advanced pancreatic neuroendocrine tumors. This study explores the association of red blood cells-related parameters as prognostic markers in patients harboring pancreatic neuroendocrine tumors. Retrospective analysis of a tertiary medical center database, acquiring data of patients with pancreatic neuroendocrine tumors including demographics, tumor-related parameters and consecutive imaging results, vital status at last follow-up, and red blood cells parameters at baseline, last follow-up, and dynamics (last/baseline ratio). Univariate and multivariable analyses were performed. Sixty-seven patients were identified (mean age at diagnosis of 63±11 years, 56.7% males). Patients with disease progression had lower hemoglobin, red blood cells mass values and hematocrit at the last evaluation (p<0.001 for all comparisons), with red blood cells mass level<3.9 m/μl and a 6% and 9% relative reduction in hemoglobin and hematocrit levels, respectively, associated with an increased risk for disease progression. Similarly, patients deceased during the study period had lower hemoglobin, red blood cells mass values and hematocrit (p<0.03 for all) than those alive, at last follow-up. Eleven percent reduction in hemoglobin level was noted indicating a higher mortality risk (p=0.04). Negative hemoglobin and hematocrit dynamics were independently associated with increased risk for disease progression (p=0.03 and 0.049, respectively). In conclusion, decrease in red blood cells mass, hemoglobin and/or hematocrit levels are all associated with poor prognosis in patients with pancreatic neuroendocrine tumors. We suggest utilizing these parameters as complementary follow-up prognostic markers to radiologic imaging in this patients population.

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Prognostic factors and survival after surgical resection of pancreatic neuroendocrine tumor with validation of established and modified staging systems

Cited by 19 publications

References 33 publications

Predicting Progression, Recurrence, and Survival in Pancreatic Neuroendocrine Tumors: A Single Center Analysis of 174 Patients

Predicting Progression, Recurrence, and Survival in Pancreatic Neuroendocrine Tumors: A Single Center Analysis of 174 Patients

Evaluating gastroenteropancreatic neuroendocrine tumors through microRNA sequencing

Plasma Hemoglobin and Red Blood Cell Mass Levels as Dynamic Prognostic Markers for Progression and Survival in Pancreatic Neuroendocrine Tumors

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