Clinical and Molecular Risk Factors for Recurrence Following Radical Surgery of Well-Differentiated Pancreatic Neuroendocrine Tumors

Pulvirenti, Alessandra; Pea, Antonio; Chang, David K.; Jamieson, Nigel B.

doi:10.3389/fmed.2020.00385

Cited by 10 publications

(7 citation statements)

References 98 publications

(210 reference statements)

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“…Moreover, overall cancer mortality was found to be higher in patients with abdominal adiposity, independently of BMI, over a mean follow-up of 9.7 years [ 30 ]. Concerning NEN, despite several pathological and molecular tumor features that have been identified to be relevant for prognosis [ 31 , 32 , 33 , 34 , 35 ], data on how extrinsic factors, such as obesity and metabolic diseases influence disease outcomes is very scarce.…”

Section: Discussionmentioning

confidence: 99%

Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia

Santos

Rodrigues

Henrique

et al. 2022

JCM

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The association of well-differentiated gastro-entero-pancreatic neuroendocrine neoplasia (WD GEP-NEN) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. However, whether obesity and metabolic syndrome risk factors are associated with GEP-NEN adverse outcomes and the poorer prognosis was unknown. The present study aimed to evaluate whether the presence of MetS or any of its individual components at WD GEP-NEN diagnosis influenced disease outcomes. A cohort of patients with non-localized WD GEP-NETs (n = 81), was classified according to the primary tumor site (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (3% ≤ Ki67 ≤ 20%) (WHO 2010)), disease extension (loco-regional or metastatic disease), presence of hormonal secretion syndrome (functioning or non-functioning), and evaluated for the presence of MetS criteria at diagnosis. MetS was present in 48 (59.3%) patients. During a median follow-up of 95.0 months (16.8–262.5), 18 patients died of the disease (10 with MetS vs. 8 without MetS). Overall survival (OS) at 5 years was 87.1% (95% CI: 73.6–94.0) for MetS and 90.9% (95% CI: 74.4–97.0) for non-Mets group, while OS at 10 years was 72.5% (95% CI: 55.3–84.0) for MetS, and 76.4% (95% CI: 53.6–89.0) for non-MetS group. Progression-Free Survival (PFS) at 5 years was 45.9% (95% CI: 30.8–59.8) for MetS and 40.0% (95% CI: 21.3–58.1) for non-MetS group, and PFS at 10 years was 18.1% (95% CI: 7.0–33.5) for MetS and 24.4% (95% CI: 9.0–43.7) for non-MetS group. Waist circumference (WC), a surrogate measure for visceral obesity, was associated with significantly shorter PFS (HR = 1.03; 95% CI: 1.01–1.06), although did not influence OS (HR = 1.01; 95% CI: 0.97–1.06). The findings of this study reinforce a potential link between visceral obesity and GEP-NEN and further suggest that obesity could influence disease prognosis.

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Section: Discussionmentioning

confidence: 99%

Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia

Santos

Rodrigues

Henrique

et al. 2022

JCM

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“…After complete resection of a GEP-NET, the risk of recurrence is 57% for panNETs and 53% for siNETs [ 76 ]. The most relevant risk factors for recurrence are grade, vascular invasion, perineural invasion, and stage [ 77 ]. Moreover, after resection of liver metastases, the median time to recurrence is 15.2 months (95% CI: 11.2–19.2 months), and 5- and 10-year overall recurrence rate is 94 and 99%, respectively [ 78 , 79 ].…”

Section: Resultsmentioning

confidence: 99%

Chemotherapy in Well Differentiated Neuroendocrine Tumors (NET) G1, G2, and G3: A Narrative Review

Zappi

Persano

Galvani

et al. 2023

JCM

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Neuroendocrine tumors (NETs) are rare neoplasms with a wide spectrum of clinical behavior, from the long survival of well-differentiated NETs to the dismal prognosis of high-grade neuroendocrine carcinomas (NECs), being G3 NETs a recently recognized intermediate entity. While the role of chemotherapy is well established in NECs, data on NETs mostly derives from small studies, experts’ opinions, and extrapolating results from small-cell lung cancer studies. This narrative review aims to summarize available evidence about the use of chemotherapy in the setting of G1-2 NETs and G3 NETs. We performed literature research in PubMed Library for all articles published up to September 2022 about the efficacy of chemotherapy in NETs. Treatment regimens with STZ-5FU, CAPTEM, and anti-metabolite-based treatment are the most active and tolerated in gastroenteropancreatic NETs (GEP-NETs) G1-G2, while platinum-based regimens (FOLFOX/XELOX) and TEM/CAPTEM showed the best activity in thoracic NETs. Solid evidence about chemotherapy efficacy in G3 NETs is still lacking. Literature data support the use of chemotherapy in low-intermediate grade NETs after the failure of other therapies or if tumor shrinkage is needed. Studies assessing G3 NETs independently from NECs are needed to better understand the role of chemotherapy in this setting.

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“…Also, further steps towards more precise management of those patients are expected to come from new molecular tissue and blood-based biomarkers such as the alanine aminotransferase detection on tissue or the NETest, a multianalyte transcript-based biomarker measured on blood samples. 2,[12][13][14] Local recurrence and intrabdominal nodal recurrence shared a low incidence, estimated at 1.4% (95% CI: 0.8%-2.3%) and 0.8% (95% CI: 0.4%-1.5%) at 5 years, were observed only in grade 1/grade 2 neoplasms, and had the tendency to occur earlier in follow-up postsurgery; cumulative incidence reached a plateau for both sites as time from surgery increased. These findings suggest that these types of recurrence may represent residual disease, the result of non-radical surgery, rather than relapse of disease.…”

Section: Discussionmentioning

confidence: 97%

“…Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms, with heterogeneous biology and clinical behaviors. Surgery is curative in the majority of patients, but in 10% to 15% of cases, recurrent disease develops, with variable patterns and oncological outcomes 1,2 . Clinical and biological predictors of recurrence have been extensively studied and a nomogram to accurately predict recurrence following surgery is now available 1 .…”

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confidence: 99%

Recurring Pancreatic Neuroendocrine Tumor: Timing and Pattern of Recurrence and Current Treatment

et al. 2023

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Objective: The objective of this study was to describe the pattern of recurrence, treatments received, as well the oncological outcomes, of pancreatic neuroendocrine tumors (PanNETs) following curative surgery. Background: PanNETs recur in 10% to 15% of cases following surgery. Information on the natural history and management of recurring disease is lacking. Materials and Methods: Patients with PanNET that underwent curative surgery at 4 institutions between 2000 and 2019 were identified. Patients with poorly differentiated tumors, unknown tumor grade and differentiation, hereditary syndromes, unknown margin or R2 status, metastatic, and those that had neoadjuvant treatment or perioperative mortality were excluded. Clinical variables were assessed including first site of recurrence, treatment received, and survival outcomes. Results: A total of 1402 patients were included: 957 (74%) had grade 1, 322 (25%) had grade 2, and 13 (1%) had grade 3 tumors. Median followup was 4.8 years (interquartile range: 2-8.2 years). Cumulative incidence of recurrence at 5 years was 13% (95% CI: 11%-15.2%) for distant disease, 1.4% (95% CI: 0.8%-2.3%) for locoregional recurrence, and 0.8% (95% CI: 0.4%-1.5%) for abdominal nodal recurrence. Patients who recurred had 2.89 increased risk of death (95% CI: 2-4.1) as compared with patients who did not recur. Therapy postrecurrence included: somatostatin analogs in 111 (61.0%), targeted therapies in 48 (26.4%), liver-directed therapies in 61 (33.5%), peptide receptor radionuclide therapy in 30 (16.5%), and surgery in 46 (25.3%) patients. Multiple treatments were used in 103 (57%) cases. After the first recurrence, 5-year overall survival was 74.6% (95% CI: 67.4%-82.5%). Conclusions: Recurrence following surgery is infrequent but reduces survival. Most recurrences are distant and managed with multiple therapies. Prospective studies are needed to establish strategies for surveillance and the sequence of treatment to control the disease and prolong survival.

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Clinical and Molecular Risk Factors for Recurrence Following Radical Surgery of Well-Differentiated Pancreatic Neuroendocrine Tumors

Cited by 10 publications

References 98 publications

Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia

Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia

Chemotherapy in Well Differentiated Neuroendocrine Tumors (NET) G1, G2, and G3: A Narrative Review

Recurring Pancreatic Neuroendocrine Tumor: Timing and Pattern of Recurrence and Current Treatment

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