Measurement of circulating transcript levels (NETest) to detect disease recurrence and improve follow-up after curative surgical resection of well-differentiated pancreatic neuroendocrine tumors

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

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Predictors of recurrence in patients with surgically resected pancreatic neuroendocrine tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.408 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 408-408

Author(s):

Cynthia Harris ◽

Michelle Kang Kim ◽

Kiwoon Joshua Baeg ◽

Mi Ri Lee ◽

Julie Starr ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Cox Regression ◽

Disease Free Survival ◽

Tumor Grade ◽

Disease Recurrence ◽

Stage Ii ◽

Pancreatic Neuroendocrine Tumors ◽

Cox Regression Analysis ◽

Grade 3

408 Background: Current surveillance guidelines regarding follow up of patients with resected pancreatic neuroendocrine tumors (PNETs) are based on limited data, and there have been few studies evaluating recurrence risk in such patients. We assessed disease-free survival (DFS) in a large, multi-institutional cohort of patients with resected PNETs. Methods: Patients with surgically resected, non-metastatic PNETs between 1990-2017 were identified using institutional databases at three institutions: Mount Sinai Hospital, Dana-Farber Cancer Institute, and University of Pennsylvania. Recurrence date was defined as the imaging date documenting first recurrence (n = 56); if an imaging date was not available, then July 1 of that year was used in calculations (n = 9). Kaplan-Meier analysis was used to estimate DFS; multivariate Cox regression analysis was used to assess DFS adjusted for patient and disease-related characteristics, including tumor stage and grade. Results: We identified a total of 418 patients with surgically resected, non-metastatic PNETs between 1990-2017. Of these patients, 299 patients had complete stage and tumor grade information and were used for subsequent analysis. Patients were 48.6% male with a median age of 57.5 years at time of surgery. The distribution of AJCC stage and grade was as follows: 170 (56.9%) patients were stage I, 129 (43.1%) were stage II; 167 (55.9%) had grade 1, 121 (40.5%) had grade 2, and 11 (3.7%) had grade 3 tumors. Median follow-up was 2.6 years (interquartile range = 4.2); during this time, 65 (21.7%) patients developed disease recurrence. After adjusting for potential confounders, patients with more advanced stage and higher tumor grade were significantly more likely to develop disease recurrence (Hazard Ratio (HR): 6.9, 95% CI: 2.5-19.1 for stage II; HR 4.0 (1.7-9.5) for grade 2; HR 2.6 (0.4-17.8) for grade 3). Both higher stage and tumor grade were associated with decreased DFS (p < 0.0001 for both). Conclusions: In surgically resected PNETs, with a median follow-up time of 2.6 years, both higher stage and higher grade are associated with decreased DFS. Further follow up of this cohort is planned.

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Endoscopic mucosal resection: still a reliable therapeutic option for gastrointestinal neuroendocrine tumors

BMC Gastroenterology ◽

10.1186/s12876-021-01821-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gholam Reza Sivandzadeh ◽

Fardad Ejtehadi ◽

Shima Shoaee ◽

Ladan Aminlari ◽

Ramin Niknam ◽

...

Keyword(s):

Endoscopic Mucosal Resection ◽

Neuroendocrine Tumors ◽

Therapeutic Option ◽

Disease Recurrence ◽

Therapeutic Modalities ◽

Mucosal Resection ◽

Well Differentiated ◽

Pathology Reports ◽

Age Range

Abstract Background Neuroendocrine tumors (NETs), as a rare and heterogeneous category of solid tumors, feature various morphologies and behaviors. In recent years, the incidence of NETs has continued to increase. Endoscopic mucosal resection (EMR) is one of the therapeutic modalities for the treatment of gastric and rectal NETs. Methods We evaluated patients with well-differentiated NETs of the stomach, duodenum, or rectum between 2011 and 2018. In this study, all cases with tumors confined to the mucosal or submucosal layers and smaller than 20 mm were resected using the EMR technique. We used EUS, CT scan, or MRI to exclude patients with advanced disease. All patients were actively monitored for recurrence according to the recommended protocols. Results A total of 36 patients with NETs entered the study; 17 (47.2%) were female and the remaining 19 (52.8%) were male, with a total age range of 20–74 years (mean: 52.47 ± 13.47 years). Among the tumors, 31 cases (86.1%) were G1 and the remaining 5 (13.9%) were G2. Based on the pathology reports, 22 tumors (61.1%) were smaller than 1 cm, while the remaining 14 (38.9%) were between 1–2 cm. Twenty-two patients (61.1%) had a margin of specimen involved with the tumor. No recurrence was observed during the mean follow-up time of 63.5 ± 19.8 months (range: 39–103 months). All 36 cases survived during the study period. Conclusion Conventional EMR procedure provides low chance of R0 (complete resection) achievement in gastrointestinal NETs smaller than 20 mm and limited to the mucosa or sub mucosa. However, it could be an option if patients are closely followed. Postoperative marginal involvement is not a reliable predictor of disease recurrence, which may be explained by the deleterious effect of heat coagulation and cauterization applied during tumor removal.

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Analysis of recurrence after resection of pancreatic neuroendocrine tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.304 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 304-304

Author(s):

Naeem A Newman ◽

Gary N. Mann ◽

Mrinal Shukla ◽

Katrina R Swett ◽

Edward A. Levine ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Hepatic Metastases ◽

Disease Free Survival ◽

Retrospective Chart Review ◽

Disease Recurrence ◽

Pancreatic Neuroendocrine Tumors ◽

Free Survival ◽

Ajcc Stage ◽

Disease Free

304 Background: Outcomes after recurrence of resected pancreatic neuroendocrine tumors (PNETs) are not well described. Our aim is to assess the rate and sites of recurrence and its effect on clinical outcomes. Methods: Retrospective chart review of patients (n= 80) who underwent surgical resection of PNETs at two institutions. Patients were treated from September 2002 to July 2010. Charts were reviewed for disease recurrence, date, site, and treatment of recurrence. Results: There were a total of 14 (17.5%) recurrences. The most common site of recurrence was the liver (10 patients, 71.4%). The most common treatment of recurrences was chemotherapy (5 patients, 35.7%). The 1, 3, and 5 year disease-free survival (DFS) was 90.9%, 82.7%, and 72.5% respectively. Median recurrence free survival (RFS) was 127 months. The median follow-up for all PNET patients was 25.8 months (range 1 to 140 months). Three-year survival was 97%. Local, distant, and combined recurrences occurred in 7.5%, 12.5%, and 5% of all patients, respectively. Multivariate analysis found AJCC stage (p=0.03) to be an independent predictor for DFS. Median follow-up of patients after they were found to have a recurrence was 13.8 months. Three-year survival for those with and without recurrence was 96.3% and 100%, respectively (p=0.36). Conclusions: AJCC stage is a significant predictor of recurrence after resection of PNETs with hepatic metastases being most common. Survival of patients with recurrence is not significantly different from patients without recurrence and is likely due to the indolent nature of the disease.

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Pattern of disease recurrence and treatment after surgery for nonfunctioning well-differentiated pancreatic neuroendocrine tumors

Surgery ◽

10.1016/j.surg.2020.06.034 ◽

2020 ◽

Vol 168 (5) ◽

pp. 816-824

Author(s):

Stefano Partelli ◽

Luca Landoni ◽

Valentina Andreasi ◽

Chiara Nessi ◽

Francesca Muffatti ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Disease Recurrence ◽

Pancreatic Neuroendocrine Tumors ◽

Well Differentiated

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Patterns of Recurrence after Resection for Pancreatic Neuroendocrine Tumors: Who, When, and Where?

Neuroendocrinology ◽

10.1159/000495774 ◽

2018 ◽

Vol 108 (3) ◽

pp. 161-171 ◽

Cited By ~ 6

Author(s):

Giovanni Marchegiani ◽

Luca Landoni ◽

Stefano Andrianello ◽

Gaia Masini ◽

Sara Cingarlini ◽

...

Keyword(s):

Liver Metastases ◽

Neuroendocrine Tumors ◽

Vascular Invasion ◽

Disease Recurrence ◽

Nodal Metastasis ◽

Pancreatic Neuroendocrine Tumors ◽

Kaplan Meier ◽

Few Data ◽

Patterns Of Recurrence

Background/Aims: Pancreatic neuroendocrine tumors (pan-NENs) represent an increasingly common indication for pancreatic resection, but there are few data regarding possible recurrence after surgery. The aim of the study was to describe the frequency, timing, and patterns of recurrence after resection for pan-NENs with consequent implications for postoperative follow-up. Methods: We performed a retrospective analysis of pan-NENs resected between 1990 and 2015 at The Pancreas Institute, University of Verona Hospital Trust. Predictors of recurrence were assessed. Survival analysis was conducted using the Kaplan-Meier and conditional survival (CS) methods. Results: The cohort consisted of 487 patients with a median follow-up of 71 months. Recurrence developed in 12.3%: 54 (11.1%) liver metastases, 11 (2.3%) local recurrence, 10 (2.1%) nodal recurrence, and 8 (1.6%) metastases in other organs. Thirty-one (6.4%) died due to disease recurrence. Size > 21 mm, G3 grade, nodal metastasis, and vascular infiltration were independent predictors of overall recurrence. Recurrence occurred either during the first year of follow-up (n = 9), or after 10 years (n = 4). CS analysis revealed that nonfunctioning G1 pan-NEN ≤20 mm without nodal metastasis or vascular invasion had a negligible risk of developing recurrence. In the present series, after 5 years of follow-up without developing recurrence, tumor recurrence occurred only in the form of liver metastases. Conclusions: Recurrence of pan-NENs is rare and is predicted by tumor size, nodal metastasis, grading, and vascular invasion. Patients with G1 pan-NEN without nodal metastasis and vascular invasion may be considered cured by surgery. After 5 years without recurrence, follow-up should focus on excluding the development of liver metastases.

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