Overall survival results from the NETTER-1 trial in neuroendocrine tumours: an important milestone

2021 ◽  
Author(s):  
Irene Virgolini
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumours ◽  
Important Milestone

scholarly journals Survival and Disease Recurrence in Patients with Duodenal Neuroendocrine Tumours—A Single Centre Cohort

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3985
Author(s):  
Oddry Folkestad ◽  
Hans H. Wasmuth ◽  
Patricia Mjønes ◽  
Reidun Fougner ◽  
Øyvind Hauso ◽  
...  
Keyword(s):  
Overall Survival ◽  
Recurrence Rate ◽  
Surgical Resection ◽  
Endoscopic Treatment ◽  
Neuroendocrine Tumours ◽  
Disease Recurrence ◽  
Tumour Grade ◽  
Single Centre ◽  
Duodenal Neuroendocrine Tumours

Background: Duodenal neuroendocrine tumours (D-NETs) are rare but increasingly diagnosed. This study aimed to assess the overall survival and recurrence rate among patients treated for D-NETs. Methods: Patients with D-NETs were retrospectively reviewed with a median follow-up time of 4.8 years (range 0.0–17.2 years). Results: A total of 32 patients with median age 68.0 years were identified. Fifteen patients underwent surgery while ten patients underwent endoscopic treatment. Mean estimated overall survival for the entire population was 12.1 years (95% CI 9.5–14.7 years), while 5-year overall survival was 81.3%. Tumour grade G1 was associated with longer mean estimated survival compared to G2 tumours (13.2 years versus 4.4 years, p = 0.010). None of the 23 patients who underwent presumed radical endoscopic or surgical resection had disease recurrence during follow-up. Tumours <10 mm could be treated endoscopically whereas a high proportion of patients with tumours 10–20 mm should be considered for surgery. Conclusion: Patients with D-NETs had long overall survival, and mortality was more influenced by other diseases. Both endoscopic and surgical resections were effective as no recurrences were diagnosed during follow-up.

scholarly journals P-P10 The survival benefit of pancreatic enzyme replacement therapy in adult patients undergoing treatment of pancreatic neuroendocrine tumours

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Oscar Thompson ◽  
Lewis Hall ◽  
Keith Roberts ◽  
Tahir Shah ◽  
Elizabeth Bradley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Benefit ◽  
Neuroendocrine Tumours ◽  
Weight Maintenance ◽  
Pancreatic Insufficiency ◽  
Pancreatic Enzyme ◽  
Exocrine Pancreatic Insufficiency ◽  
Enzyme Replacement ◽  
Pancreatic Enzyme Replacement Therapy ◽  
Pancreatic Neuroendocrine Tumours

Abstract Background Patients with pancreatic neuroendocrine tumours (pNETs), treated with somatostatin analogues (SSAs) or pancreaticoduodenectomy, are at risk of exocrine pancreatic insufficiency. This is frequently undiagnosed but can be treated with pancreatic enzyme replacement therapy (PERT). PERT improves survival and nutritional status in other exocrine pancreatic insufficiency-associated conditions such as pancreatic adenocarcinoma. This single-centre retrospective cohort study aimed to establish whether PERT increases survival or weight maintenance in SSA or pancreaticoduodenectomy-treated patients with pNETs. Methods Departmental databases identified patients (n = 82) diagnosed with pNETs between 2009 and 2019 and managed with SSAs and/or pancreaticoduodenectomy. Their baseline characteristics, treatments and outcomes were established from clinical records. Cases (n = 47) received PERT 3 months after either pancreaticoduodenectomy or commencement of SSAs, controls (n = 35) did not. Overall survival was analysed using the Kaplan-Meier method, the log-rank test and multivariable Cox regression. Percentage monthly weight changes were compared using the Mann-Witney U test. The cohort was investigated as a whole and stratified by intervention (pancreaticoduodenectomy or SSAs) as more cases having undergone pancreaticoduodenectomy was a potential confounder. Results Median survival was not reached in either group. Cases experienced significantly greater 5-year overall survival (81% vs 53%, p = 0.010), however, PERT was not independently associated with survival (Hazard ratio 0.47, 95% CI 0.17-1.30, p = 0.143). Cases showed superior median weight maintenance (+0.04% vs -0.10% per month, p = 0.013), but had lower mean baseline weights (70.0kg vs 81.9kg, p = 0.003). Considering SSA-treated patients (n = 55) only, cases (n = 27) showed greater median weight maintenance (+0.04% vs -0.21% per month, p = 0.025) and a trend towards improved median overall survival (55.5, 95% CI 10.3-100.7 vs 47.7, 95% CI 19.1-76.4 months, p = 0.054). Conclusions PERT may improve the maintenance of weight and therefore nutrition in patients with pNETs, treated with SSAs or pancreaticoduodenectomy. PERT may also convey a survival benefit in this same population, however, due to the numerous factors which affect survival, this study appears underpowered to reliably explore this outcome. Further studies are required to accurately define the use and benefits of PERT in this population.

scholarly journals The Ratio of Free Fatty Acids (Ffas) Divided By High-Density Lipoprotein Cholesterol (HDL-C) Is A Promising Pre-Treatment Biomarker For Predicting Worse Overall Survival (OS) of Neuroendocrine Tumours (Nets) In The Colorectum: A Retrospective Study.

2022 ◽  
Author(s):  
Bin Zhu ◽  
Dan Wu ◽  
Yuanyuan Yang ◽  
Pingli Yu ◽  
Haobo Huang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Overall Survival ◽  
High Density Lipoprotein ◽  
Free Fatty Acids ◽  
High Density Lipoprotein Cholesterol ◽  
Neuroendocrine Tumours ◽  
Tumour Size ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Tumour Grade

Abstract Background: free fatty acids (FFAs) and high-density lipoprotein cholesterol (HDL-C) were associated with various malignancy. However, whether FFA, HDL-C and FFA/HDL-C can play a potiential role in predicting patients with colorectal neuroendocrine tumours (NETs) was unclear. Meanwhile, FFA/HDL-C has a superior prognosis ability was unknown, too.Methods: One hundred patients with pathologically diagnosed colorectal NETs in 2011-2017 were enrolled, and the levels of FFA, HDL-C, low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), cholesterol (CHOL), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) between colorectal NET patients and healthy controls matched by age and sex were compared. In addition, the association of clinicopathological characteristics and follow-up data with FFA, HDL-C and FFA/HDL-C was analysed.Results: FFA was overexpressed (0.55±0.23 vs. 0.48±0.11, P= 0.006), and HDL-C was underexpressed (1.31±0.41 vs. 1.41±0.29, P=0.046) in colorectal NETs. FFA ≥0.52 mmol/L predicted lymph node metastasis (LNM) (P=0.015), HDL-C ≤1.0 mmol/L predicted tumour size ≥2 cm (P=0.017), and FFA/HDL-C>0.75 predicted tumour grade (P=0.030), LNM (P=0.014), and tumour size(P=0.018). No significant association was found between FFA and tumour grade (P=0.613) or HDL-C and tumour grade (P=0.594) or FFA and tumour size (P=0.142) or HDL-C and LNM (P=0.443). FFA ≥0.52 mmol/L (P=0.014) and HDL-C ≤1.0 mmol/L predicted worse overall survival (OS) (P=0.019). FFA/HDL-C predicted an even worse prognosis in terms of OS (P<0.001).Conclusion: FFA ≥0.52 mmol/L HDL-C ≤1.0 mmol/L and FFA/HDL-C>0.75 were promising cut-off values in predicting LNM, tumour size and worse OS in colorectal NETs.

Long-term survival and toxicity in patients with progressive advanced neuroendocrine tumors treated with lutetium peptide radiolabelled radiotherapy: A Western Australian long-term follow-up study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16202-e16202
Author(s):  
Kim Robyn Kennedy ◽  
Phillip Claringbold ◽  
William Macdonald ◽  
Glenn Boardman ◽  
David Turner Ransom ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumours ◽  
Progression Free Survival ◽  
Somatostatin Analogue ◽  
Term Survival ◽  
Free Survival ◽  
Follow Up Study ◽  
Long Term Follow Up

e16202 Background: There are limited treatment options for advanced neuroendocrine tumours, and radiolabelled somatostatin analogues have shown favourable safety and efficacy over other existing treatments. Lutetium Octreotate has been shown to be the somatostatin analogue of choice in Peptide Radiolabelled Radiotherapy (PRRT) for advanced neuroendocrine tumours (NETs). Methods: We conducted a retrospective review of the long term safety and survival outcomes of 104 patients prospectively treated on the CLEMENT1, CLEMENT2, NETTLE, and NETT VALuE trials where patients with advanced progressive NETs were treated with Lutetium Octreotate PRRT in Perth, Western Australia. With a median follow-up time of 68 months, this is the longest follow-up study of advanced NETs treated with Lutetium PRRT in the literature to date. Results: Results showed comparable periods of disease stability as other studies, with median progression free survival of 43 months, and superior survival to other series, with a median survival of 71 months. There were patients who had very durable responses, with five year overall survival 61.5%, five year progression free survival 30.1%, 10 year overall survival 30.1%, and 10 year progression free survival of 29.3%, demonstrating Lu 177 can provide a very long duration of response in some patients. PRRT treatment was well tolerated with 1.9% of patients suffering long term renal impairment, and 1% with long term mild thrombocytopenia attributed to PRRT. Importantly, there was a higher rate of MDS and leukaemia in our series (6.7%), which is likely attributed to the longer period of follow-up with all except one case occurring 48 months after PRRT treatment, which is later than the median follow up in most other studies. Conclusions: Overall, this study showed that Lutetium PRRT remains an efficacious and well tolerated treatment in long term follow-up. For clinicians deciding on the timing of PRRT for individual patients the 6.7% long term risk of MDS/leukaemia needs to be balanced against the 29.3% PFS at 10 years. Clinical trial information: ACTRN12610000440022.

scholarly journals Mesenteric fibrosis and palliative surgery in small intestinal neuroendocrine tumours

2018 ◽  
Vol 25 (3) ◽  
pp. 245-254 ◽  
Author(s):  
Anela Blažević ◽  
Wouter T Zandee ◽  
Gaston J H Franssen ◽  
Johannes Hofland ◽  
Marie-Louise F van Velthuysen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumours ◽  
Primary Tumour ◽  
Palliative Surgery ◽  
Ct Imaging ◽  
Prophylactic Surgery ◽  
Imaging Data ◽  
Mesenteric Mass ◽  
Small Intestinal ◽  
Hallmark Feature

Mesenteric fibrosis (MF) surrounding a mesenteric mass is a hallmark feature of small intestinal neuroendocrine tumours (SI-NETs). Since this can induce intestinal obstruction, oedema and ischaemia, prophylactic resection of the primary tumour and mesenteric mass is often recommended. This study assessed the predictors for mesenteric metastasis and fibrosis and the effect of MF and palliative surgery on survival. A retrospective analysis of 559 patients with pathologically proven SI-NET and available CT-imaging data was performed. Clinical characteristics, presence of mesenteric mass and fibrosis on CT imaging and the effect of palliative abdominal surgery on overall survival were assessed. We found that MF was present in 41.4%. Older age, 5-HIAA excretion ≥67 μmol/24 h, serum CgA ≥121.5 μg/L and a mesenteric mass ≥27.5 mm were independent predictors of MF. In patients ≤52 years, mesenteric mass was less often found in women than in men (39% vs 64%,P = 0.002). Corrected for age, tumour grade, CgA and liver metastasis, MF was not a prognostic factor for overall survival. In patients undergoing palliative surgery, metastasectomy of mesenteric mass or prophylactic surgery did not result in survival benefit. In conclusion, we confirmed known predictors of MF and mesenteric mass and suggest a role for sex hormones as women ≤52 years have less often a mesenteric mass. Furthermore, the presence of MF has no effect on survival in a multivariate analysis, and we found no benefit of metastasectomy of mesenteric mass or prophylactic surgery on overall survival.

scholarly journals Treatment of Liver Metastases from Midgut Neuroendocrine Tumours: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 8 (3) ◽  
pp. 403 ◽  
Author(s):  
Enes Kaçmaz ◽  
Charlotte M. Heidsma ◽  
Marc G. H. Besselink ◽  
Koen M. A. Dreijerink ◽  
Heinz-Josef Klümpen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Metastases ◽  
Neuroendocrine Tumours ◽  
Meta Analysis ◽  
Treatment Options ◽  
Unknown Origin ◽  
Cochrane Library ◽  
Case Surgery ◽  
Gastroenteropancreatic Neuroendocrine Tumours ◽  
Meta Analyses

Strong evidence comparing different treatment options for liver metastases (LM) arising from gastroenteropancreatic neuroendocrine tumours (GEP-NET) is lacking. The aim of this study was to determine which intervention for LMs from GEP-NETs shows the longest overall survival (OS). A systematic search was performed in MEDLINE, Embase and the Cochrane Library in February 2018. Studies reporting on patients with LMs of any grade of sporadic GEP-NET comparing two intervention groups were included for analysis. Meta-analyses were performed where possible. Eleven studies, with a total of 1108, patients were included; 662 patients had LM from pancreatic NETs (pNET), 164 patients from small-bowel NETs (SB-NET) and 282 patients of unknown origin. Improved 5-year OS was observed for surgery vs. chemotherapy (OR .05 95% CI [0.01, 0.21] p < 0.0001), for surgery vs. embolization (OR 0.18 95% CI [0.05, 0.61] p = 0.006) and for LM resection vs. no LM resection (OR 0.15 95% CI [0.05, 0.42] p = 0.0003). This is the largest meta-analysis performed comparing different interventions for LMs from GEP-NETs. Despite the high risk of bias and heterogeneity of data, surgical resection for all tumour grades results in the longest overall survival. Chemotherapy and embolization should be considered as an alternative in case surgery is not feasible.

scholarly journals Ki-67 index and response to chemotherapy in patients with neuroendocrine tumours

2016 ◽  
Vol 23 (7) ◽  
pp. 563-570 ◽  
Author(s):  
Alexa Childs ◽  
Amy Kirkwood ◽  
Julien Edeline ◽  
Tu Vinh Luong ◽  
Jennifer Watkins ◽  
...  
Keyword(s):  
Overall Survival ◽  
Likelihood Ratio ◽  
Neuroendocrine Tumours ◽  
Response Rate ◽  
Proliferation Index ◽  
Characteristic Analysis ◽  
Ki 67 ◽  
Disease Response ◽  
Response To Chemotherapy ◽  
Pancreatic Net

Chemotherapy (CT) is widely used for neuroendocrine tumours (NETs), but there are no validated biomarkers to predict response. The Ki-67 proliferation index has been proposed as a means of selecting patients for CT, but robust data are lacking. The aim of this study was to investigate the relationship between response to chemotherapy and Ki-67 in NET. We reviewed data from 222 NET patients treated with CT. Tumours were graded according to Ki-67 index: G1 ≤2%, G2 3–20% and G3 >20%. Response was assessed according to RECIST and survival calculated from start of chemotherapy to death. To explore Ki-67 as a marker of response, we calculated the likelihood ratio and performed receiver operating characteristic analysis. Overall, 193 patients had a documented Ki-67 index, of which 173 were also evaluable for radiological response: 10% were G1, 46% G2 and 43% G3; 46% were pancreatic NET (PNET). Median overall survival was 22.1 months. Overall response rate was 30% (39% in PNET vs 22% in non-PNET) and 43% of patients had stable disease. Response rate increased with grade: 6% in G1 tumours, 24% in G2 and 43% in G3. However, maximum likelihood ratio was 2.3 at Ki-67=35%, and the area under the ROC curve was 0.60. As reported previously, a high Ki-67 was an adverse prognostic factor for overall survival. In conclusion, response to CT increases with Ki-67 index, but Ki-67 alone is an unreliable means to select patients for CT. Improved methods to stratify patients for systemic therapy are required.

scholarly journals Nomogram for individually predicting overall survival in rectal neuroendocrine tumours

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xingyu Feng ◽  
Gengzhou Wei ◽  
Wei Wang ◽  
Yu Zhang ◽  
Yujie Zeng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumours ◽  
Southern China ◽  
Tnm Classification ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Validation Dataset ◽  
Training Set ◽  
Discrimination Power ◽  
Who Grade

Abstract Background This study aimed to develop a nomogram that predicts the overall survival (OS) of rectal neuroendocrine tumours (NETs). Methods We retrospectively analysed 310 patients with rectal neuroendocrine tumours in 5 hospitals in southern China. All of the patients were assigned to the training set. A multivariable analysis using Cox proportional hazards regression was performed using the training set, and a nomogram was constructed. It was validated on a dataset obtained from the Surveillance, Epidemiology, and End Result (SEER) database of America (n = 547). Results In the training set, the nomogram exhibited improved discrimination power compared with the WHO grade guidelines (Herrell’s C-index, 0.872 vs 0.794; p < 0.001) and was also better than the seventh AJCC TNM classification (Herrell’s C-index, 0.872 vs 0.817; p < 0.001). In the SEER validation dataset, the discrimination was also excellent (C-index, 0.648 vs 0.583, p < 0.001 and 0.648 vs 0.603, p = 0.016, respectively, compared with G grade and TNM classification). Calibration of the nomogram predicted individual survival corresponding closely with the actual survival. Conclusions We developed a nomogram predicting 1- and 3-year OS of patients with rectal neuroendocrine tumours. Validation revealed excellent discrimination and calibration, suggesting good clinical utility.

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