Risk Factors for Disease Progression in Advanced Jejunoileal Neuroendocrine Tumors

Panzuto, Francesco; Campana, Davide; Fazio, Nicola; Brizzi, Maria Pia; Boninsegna, Letizia; Nori, Francesca; Meglio, Giovanni Di; Capurso, Gabriele; Scarpa, Aldo; Dogliotti, Luigi; Braud, Filippo de; Tomassetti, Paola; Fave, Gianfranco Delle; Falconi, Massimo

doi:10.1159/000334038

Cited by 55 publications

(48 citation statements)

References 62 publications

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“…The discriminant power of the WHO 2010 classification system based on the Ki-67 index has been strongly confirmed by the present findings: in multivariate analysis, the Ki-67 index was significantly associated with risk of death, as recently reported [45]. Of particular interest, however, is the fact that 11 of our patients (9 with digestive and 2 with pancreatic NENs) had a well-differentiated neuroendocrine tumor with a proliferative index >20%, which points to an intrinsic limitation to the WHO 2010 classification, which is based only on the proliferative indexes.…”

Section: Discussionsupporting

confidence: 91%

Chromogranin A in Diagnosing and Monitoring Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Large Series from a Single Institution

et al. 2014

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Background/Aims: Plasma chromogranin A (CgA) is the most widely used biochemical biomarker in the diagnostic workup and follow-up of gastroenteropancreatic neuroendo- crine neoplasms (GEP-NENs). Herein, we assessed the clinical utility of CgA in diagnosing and monitoring a large series of GEP-NENs. Patients and Methods: A total of 181 GEP-NEN patients (87 males, 94 females) with pancreatic (n = 81) and gastrointestinal neoplasms (n = 100) were included; 99 patients had grade (G)1 NENs (Ki-67 ≤2%), 57 G2 NENs (Ki-67 3-20%) and 25 G3 NENs (Ki-67 >20%); 81 patients had tumor-node-metastasis (TNM) stage I, 14 stage II, 17 stage III and 69 stage IV cancer. For every patient, CgA values were assessed at diagnosis and during follow-up. Results: At diagnosis, the CgA values were above the upper reference limit in 148 patients (82%); the median CgA levels were significantly higher in functioning than in nonfunctioning tumors (295 vs. 43 U/l; p = 0.0001) as well as significantly higher in patients with metastases than in those without metastases (324.5 vs. 42 U/l; p = 0.0001). In logistic regression analysis, baseline CgA levels were significantly associated with Ki-67 index (p < 0.0001) and TNM stage (p < 0.0001) independently of the age and sex of the patient and the primary site of the tumor. The overall 5- and 10-year survival rates were 74 and 64.5%, respectively. A low Ki-67 index, the type of treatment and an early CgA decrease after treatment were positively correlated with the survival rate. After radical surgery, 15/95 patients relapsed, and an increase in CgA values anticipated the clinical and objective disease recurrence after a period of 9-12 months. Conclusions: In GEP-NENs, plasma CgA has a significant prognostic relevance.

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Section: Discussionsupporting

confidence: 91%

Chromogranin A in Diagnosing and Monitoring Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Large Series from a Single Institution

et al. 2014

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“…Tumor behavior, and thus patient survival, depends on a number of factors, including primary site, tumor histology, proliferative index Ki-67, and staging [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Real-World Study of Everolimus in Advanced Progressive Neuroendocrine Tumors

et al. 2014

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Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3-4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT andchemotherapy, a12-foldincreased riskforseveretoxicitywas observed, with grade 3-4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS,and OS werereported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs. The Oncologist 2014;19:966-974 Implications for Practice: Data reported outside regulatory trial settings are useful for physicians dealing with neuroendocrine tumors (NETs) and provide understanding of whether the findings obtained in those trials are consistent with clinical practice. In this real-world study of everolimus in advanced, progressive NETs, significantly higher severe toxicity was observed in patients with long-duration disease and in those previously treated with systemic chemotherapy and/or peptide receptor radionuclide therapy. These findings may help physicians to plan an optimal therapeutic strategy for these patients to avoid predictable severe toxicity that may also result in limitations for further treatments.

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“…The most recent European Neuroendocrine Tumor Society (ENETS) [1] and North American Neuroendocrine Tumor Society (NANETS) [7] recommendations for the management of siNETs recommend performing the resection of primary siNETs with LN removal, whenever possible, regardless of the metastatic status. The rational for this approach is mainly based on the fact that in patients with siNETs and synchronous liver metastases, the resection of primary and associated LNs not only offers the opportunity to secondarily focus therapeutic management on the liver metastases, but seems to be independently associated with increased survival and symptom relief [2,4,5,8,15,16,17]. However, none of these studies specified a standardized type of surgery to remove the primary and mesenteric LNs.…”

Section: Discussionmentioning

confidence: 99%

Toward a Preoperative Classification of Lymph Node Metastases in Patients with Small Intestinal Neuroendocrine Tumors in the Era of Intestinal-Sparing Surgery

Lardière-Deguelte¹,

Mestier²,

Appere³

et al. 2015

Neuroendocrinology

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Introduction: In patients with small intestinal neuroendocrine tumors (siNETs), surgical resection of the primary tumor and associated mesenteric lymph nodes (LNs) is recommended, but is not well standardized and can be risky in patients with superior mesenteric vessel involvement. Objective: We aimed to evaluate the correlation between the length of resected small bowel and the number of removed LNs, and to propose a preoperative morphological classification of siNET-associated LNs. Methods: The records of patients operated on for siNETs at two expert centers between August 2005 and November 2013 were analyzed. Two specialist radiologists reviewed the preoperative imaging and classified mesenteric LNs into five stages according to their proximity to the trunk and/or branches of the superior mesenteric artery. Results: 72 patients were included. The mean number of removed LNs was 12 ± 15 and the length of removed small intestine was 53 ± 43 cm. No correlation existed between the length of small bowel resection and the number of removed LNs. Overall, 9 (12%), 13 (18%), 36 (50%), 14 (19%) and 0 patients were classified into LN stages 0, I, II, III and IV. The correlation rate between the two observers was 0.98. Patients with LN stage III (hardly resectable) had more removed LNs than those with LN stages 0, I or II (easily removable). Conclusion: Optimal lymphadenectomy is not always associated with extended small bowel resection. In the era of small bowel-sparing surgery, the preoperative classification of mesenteric LNs could help to standardize the surgical management of patients with siNETs.

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Risk Factors for Disease Progression in Advanced Jejunoileal Neuroendocrine Tumors

Cited by 55 publications

References 62 publications

Chromogranin A in Diagnosing and Monitoring Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Large Series from a Single Institution

Chromogranin A in Diagnosing and Monitoring Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Large Series from a Single Institution

Real-World Study of Everolimus in Advanced Progressive Neuroendocrine Tumors

Toward a Preoperative Classification of Lymph Node Metastases in Patients with Small Intestinal Neuroendocrine Tumors in the Era of Intestinal-Sparing Surgery

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