Treatment Patterns and Survival among Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumours in Sweden - a Population-based Register-linkage and Medical Chart Review Study

Abstract

Background: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are neoplasms derived from the endocrine system in the gastrointestinal tract and pancreas. Treatment options include surgery; pharmacological treatments like somatostatin analogues (SSA), interferon alpha, molecular targeted therapy and chemotherapy; and peptide receptor radionuclide therapy.The objective of this study was to describe treatment patterns and survival among patients with metastatic GEP-NET grade 1 or 2 in Sweden.Methods: Data was obtained via linkage of nationwide registers. Patients diagnosed with metastatic GEP-NET grade 1 or 2 in Sweden between 2005 and 2013 were included (n=811; National population). In addition, medical chart review was performed for the subpopulation diagnosed at Sahlgrenska University Hospital, Gothenburg (n=127; Regional population). Treatment patterns, including treatment sequences, and overall survival were assessed.Results: Most patients had small intestinal NET (76%). In the regional population, 72% had grade 1 tumours; 50% had functioning tumours. The two most common first-line treatments were surgery (57%) and SSA (25%). After first-line surgery, 46% received SSA, while 40% had no further treatment. After first-line SSA, 52% received surgery, while 27% had no further treatment. Overall median survival time from date of diagnosis was 7.0 years (95% CI 6.2-not reached). Among patients with distant metastases, pancreatic NET (vs. small intestinal NET) was associated with poorer survival (HR 1.9; 95% CI 1.1-3.3), as were liver metastases (HR 3.2; 95% CI 1.5-7.0).Conclusions: First-line surgery was typically followed by SSA or no further treatment. Among patients with distant metastases, pancreatic NET or liver metastases were associated with a poorer survival.

Evaluation of Outcomes Following Surgery for Locally Advanced Pancreatic Neuroendocrine Tumors

“…Further, this aggressive surgery may not improve symptoms and long-term survival compared with newer treatments, such as somatostatin analogues, everolimus, sunitinib, interferon α, and peptide receptor radionuclide therapy (PRRT). 17 , 18 …”

Neuroendocrine Neoplasms in Italy

“…The different survival, compared to other studies, could be linked to the fact that ours is a population-based study and therefore the heterogeneity of NENs and probably the lack of inclusion in the registry data of the subtypes associated with less biological aggressiveness (which are generally followed up in the outpatient setting and so are not registered in the Hospital Discharge Records system or in the pathology databases) may explain this lower survival. Furthermore, as our data refer to an earlier period (1976-2010), the impact of newly available effective treatments, even for metastatic cancer, has not yet been observed (22). In our study, NEN patients had a slight, not signif- icant excess risk of having a second tumour: the standardized incidence ratio was 1.06 (95% CI 0.98-1.15).…”

Survival in Patients with Neuroendocrine Tumours of the Small Intestine: Nomogram Validation and Predictors of Survival

“…Remarkably, liver metastases did not prove to be an independent prognostic predictor for DSS. Many other studies did show this association [7,[49][50][51]. However, we included an unknown primary tumour as a separate variable in our multivariable analysis, which likely influenced this outcome since it overlaps with the presence of (liver) metastases.…”

“…Recent advances in identifying (molecular) prognostic factors and the development of liquid biopsies such as CTC, or circulating tumour transcripts (the NETest ® ), appear to be a valuable addition for individualized prognostication [31,54]. Prognostic studies often focussed either solely on clinical and tumour characteristics [3,4,7,10] or the sole predictive value of a biomarker alone (subsequently abandoning the use of clinical and tumour characteristics) [29,53,55]. Our study confirms the prognostic potential of a nomogram based on clinical and tumour characteristics while underlining the need for improvement.…”

“…The incidence of NETs is increasing, with a reported incidence of 6.61 per 100,000 individuals in 2011 [3,4]. NETs of the small intestine (SI-NETs) are, after pulmonary NETs, the second most common NETs and the most frequent malignancy of the small intestine [4][5][6][7]. Up to 73% of patients have metastases at time of diagnosis, predominantly in the liver [1,3,8,9].…”