Introduction

Patients with neuroendocrine tumours (NETs) located in the gastroenteropancreatic tract (GEP) are at risk of malnutrition. NETs are rare cancers arising from enterochromaffin cells. They differ from other cancers based on morphology, clinical behaviour, treatment and relatively good prognosis even in the metastatic case. Somatostatin analogues (SSA’s) are the cornerstone of treatment to control symptoms and tumour growth. Previous studies reported the presence of malnutrition, only based on weight loss or low body mass index (BMI). The Global Leadership into Malnutrition (GLIM) criteria diagnose malnutrition if there is 1) weight loss or, 2) low BMI or 3) presence of sarcopenia, in the presence of a disease. Malnutrition based on these GLIM criteria has not been assessed in patients with GEP-NETs. The effect of malnutrition on overall survival has not been explored before.

Aims & Methods

The aim of this study is to describe the presence of malnutrition in patients with GEP-NET based on the GLIM criteria and correlate this with overall survival.
A Cross-sectional study was performed, between August 2018 and February 2019 in a single NET expert centre in the United Kingdom. All patients with GEP-NETs, using an SSA were screened for malnutrition using the GLIM criteria. Anthropometric data (weight, height and BMI), and body composition analysis were performed to assess the presence of sarcopenia. Patients were scored to be malnourished meeting 1 GLIM criterium, meeting 2 GLIM criteria or meeting all 3 GLIM criteria. Additional demographic and histopathologic data were collected from patient records. Stable disease was classified if there was documentation of stable disease or no change in treatment within 3 months of malnutrition screening. Overall survival was calculated from the moment of malnutrition screening and the date of death or data cut-off in June 2022. Uni- and multivariate Cox regression analyses were performed to identify malnutrition as a risk factor for overall survival.

Results

A total of 118 patients 47% male with median age 67 year (IQR 56.8 – 75.0) were included. The primary tumour was located in the small bowel in 91 patients (71%) or pancreas in 25 patients (21%). Metastases were present in 91 patients (77%). In 84 patients (71%) there was stable disease.
Malnutrition was present in 88 patients (75%), based on low BMI in 26 (22%) patients, based on weight loss in 35 (30%) patients and based on sarcopenia in 83 (70%) patients. One GLIM criterium was met in 50 patients (42%), 2 GLIM criteria in 20 patients (17%) and all 3 GLIM criteria in 18 patients (15%). The presence of malnutrition demonstrated a significantly worse overall survival (p-value 0.01). In a multivariate analysis including age (HR 1 95% CI 0.98 – 1.01, p-value 0.43), sex (HR 0.65 95% CI0.27 – 1.59, p-value 0.35), and stable disease versus progressive disease (HR 4.5 95% CI 1.7 – 11.76, p-value 0.002), meeting 2 or 3 GLIM criteria was significantly associated with worse overall survival (HR 2.16 95% CI 1.34 – 3.48, p-value 0.002). Weight loss was the most important risk factor out of the 3 GLIM criteria (HR 3.5 95% CI 1.14 – 10.85, p-value 0.03) for worse overall survival.

Conclusion

A high percentage (75%) of patients with GEP-NETs using an SSA meet the GLIM criteria for malnutrition which influences overall survival. Meeting two or more GLIM criteria, especially if there is weight loss is associated with worse overall survival. Future research should focus on exploring the effect of nutrition support especially in patients with weight loss and its effect on overall survival.

References

Cederholm T, et al. GLIM criteria for the diagnosis of malnutrition Clinical Nutrition. 2019;38:1–9.

Introduction

Until recently lymph node metastases (LNM) in small bowel neuroendocrine tumours (SB-NETs) were classified as absent (N0) or present (N1). However, the American Joint Committee on Cancer (AJCC) updated the classification to N0, N1 < 12 positive LNM and, N2 as ≥ 12 positive LMN and/or a large mesenteric mass (> 2 cm) (1). All patients will be offered the same surveillance strategy with 6-monthly cross-sectional imaging. This updated N-classification has not been explored in a real-life cohort of patients with SB-NETs.

Aims & Methods

Aim to describe the prevalence of N1 and N2 LMN in a cohort of patients with SB-NETs and to explore its association with recurrence-free survival (RFS) and overall survival (OS).
A retrospective study was performed in a single NET expert centre King’s College Hospital. All patients with curative resection of an SB-NET in the absence of metastases between January 2010 and December 2022 and a histology report available were included. All histology reports were reviewed and reclassified according to the new AJCC N-classification. Additional demographic data were collected from patient records. Recurrence-free survival was calculated from the date of the histology report to the date of documentation of disease recurrence in the multidisciplinary tumour board. Overall survival was calculated from the date of the histology report until the date of death due to any cause. Kaplan-Meier curves were plotted, log-rank test and uni- and multivariate Cox regression analysis were performed.

Results

A total of 112 patients, 52% male with a median age 63.5 years (IQR 55 – 72 year) were included. Sixty-seven patients (60%) had N1 disease and 45 patients (40%) had N2 disease. Within the N2 group, 35 patients (79%) had a large mesenteric mass, 7 patients (17%) had ≥ 12 positive LMN and 2 patients met both criteria (4%). The median mesenteric mass size in the N2 group was 30mm (IQR 25 – 40mm). Three quarters of patients had grade 1 disease and 27 patients (24%) had grade 2 disease. Recurrence occurred in 35 patients (31.5%), of which 18 (26.9%) belonged to the N1-group, while 17 (38.6%) were patients with N2. No significant difference (p-value 0.291) was found in the median time to recurrence, which was 83 months in N1-staged patients versus 61 months in N2-staged patients. There was no significant difference (p-value 0.155) in the median overall survival time between the N1-staged patients (134 months), compared to the N2-staged patients (106 months). Patients with a large mesenteric mass had a significantly (p-value 0.006) shorter overall survival of 102 months compared to the patients with a smaller or no mesenteric mass, median not reached. In multivariate analysis a larger mesenteric mass points towards an association with worse overall survival HR 3.71 (0.93 – 14.83), p-value 0.06.

Conclusion

For patients with small bowel NETs, N1 or N2 lymph node metastases do not affect recurrence-free survival or overall survival. However, a larger mesenteric mass is associated with a significantly shorter overall survival. These data could help develop more patient-tailored surveillance strategies, especially for patients with a larger mesenteric mass who could benefit from more frequent surveillance. Future research in a prospective, multi-center setting could help to clarify better the role of N1 and N2 LNM on recurrence-free and overall survival.

References

1) Woltering E, Bergsland E, Beyer D, O'Dorisio T, Rindi G, Klimstra D, et al. Neuroendocrine Tumors of the Jejunum and Ileum. 2017. p. 375-87.

Disclosure

None

Introduction

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of tumors with rising incidence. Despite several available treatments, including somatostatin analogues (SSAs), targeted therapies (everolimus, sunitinib), and chemotherapy (capecitabine-temozolomide, CAPTEM), predicting therapeutic response and disease progression remains difficult. Tumor-related features (e.g., grading, metastatic burden) influence outcomes but whether some patient-related variables (e.g., lifestyle, comorbidities) play a role is poorly explored.

Aims & Methods

This study aimed to identify tumor and patient-related factors associated with progression and survival outcomes in GEP-NENs treated with SSAs, CAPTEM, or targeted therapies. This is a multicenter, retrospective observational cohort study including patients with well-differentiated GEP-NENs treated with SSAs, CAPTEM, or EVE/SUN. Inclusion criteria were age ≥18 years, histologically confirmed GEP-NEN, and at least 6 months of treatment. Exclusion criteria included poorly differentiated tumors, prior radioligand therapy, and MiNENs. Clinical, pathological, therapeutic, and exposome-related variables were collected. The primary endpoint was progression-free survival (PFS); overall survival (OS) was also evaluated. A target sample size of 400 was estimated for adequate power in subgroup analyses. Univariate analyses were conducted using t-tests or chi-square tests as appropriate. Associations with PFS and OS were further assessed through Cox proportional hazards models.

Results

A total of 301 patients (52.2% pancreatic) from four Italian referral centers for neuroendocrine tumors (Itanet centers) were included: 258 (85.7%) received SSAs, 32 (10.6%) CAPTEM, and 17 (5.6%) EVE/SUN. Median age at diagnosis was 59 years; 51.9% were female. Most patients (73.7%) presented with metastatic disease at diagnosis, and the majority were G2 (58%) or G3 (2.3%).
In univariate analysis, patient-related variables were not significantly associated with PFS, except for lower age at diagnosis and shorter duration of metformin use (both p = 0.05). Conversely, tumor-related variables (grading, Ki67 and presence of bone or liver metastases) were significantly associated with PFS. In multivariable Cox analysis, only liver metastases (HR 2.0), bone metastases (HR 2.15), and G3 tumors (HR 3.35) were associated with shorter PFS. For OS, univariate analysis showed worse survival in male patients (p = 0.017), those with a history of alcohol use (p = 0.027), liver disease (p = 0.013), higher tumor grading/Ki67 (p < 0.001), absence of primary tumor resection (p < 0.001), and presence of bone (p = 0.004) or liver metastases (p < 0.001). Cox multivariable analysis confirmed association of OS with male sex (HR 2.73), alcohol use (HR 6.46), G3 tumors (HR 8.26), liver metastases (HR 6.45), and absence of primary tumor resection (HR 6.45). A subgroup analysis restricted to SSA-treated patients and pancreatic NENs patients revealed similar trends.

Conclusion

In this multicenter real-world study, progression and survival outcomes in GEP-NENs were primarily driven by tumor-related variables such as grading and metastatic spread, while patient-related factors played a limited role. However, results are currently underpowered, having reached approximately 75% of the planned sample size. Future efforts will aim to expand the EVE/SUN and CAPTEM groups to enhance subgroup analyses and improve robustness of findings.

Introduction

The obesity paradox, in patients with cancer, is a hypothesis showing patients with obesity have a prolonged overall survival compared to the ones with a normal weight. This paradox is present in different types of cancer, lung cancer, renal cell cancer, and melanoma. For gastrointestinal cancers, there are conflicting results regarding the obesity paradox. Neuroendocrine neoplasms (NENs) are rare cancers arising anywhere in the body but mainly within the gastroenteropancreatic (GEP) tract. NENs differ from other gastrointestinal cancers as they have a relatively good prognosis even in metastatic disease. NENs are classified into three different grades (G1, G2, G3) based on mitotic count and Ki-67 staining. The grades are correlated with overall survival patients with G1 GEP-NENs have significantly better overall survival compared to patients with G2 or G3 GEP-NENs. The presence of the obesity paradox in patients with GEP-NENs is only described in one population-based study from the USA. However real-world data exploring the obesity paradox are lacking.

Aims & Methods

Aim: To explore the presence of the obesity paradox in patients with GEP-NENs in a single centre in the United Kingdom.
A cross-sectional study was performed regarding all patients with GEP-NENs and treatment with monthly somatostatin analogues (SSA’s) between August 2018 and February 2019. During this period all patients weight, height and BMI were collected. Additional demographic and histopathologic data were extracted from the local hospital database. Stable disease was classed as having no change in oncological treatment within 3 months of weight/height screening. Overall survival (OS) was calculated from the moment of weight/height screening until death or the last follow-up appointment (data cut-off June 2022). Kaplan Meier, log-rank tests and Cox regression analysis were performed.

Results

In total 118 patients, n=55 (47%) males with a median age of 67 years (IQR 56.8 – 75) were included. The primary tumour was in the small intestine in n=91 (77%) and pancreas in n=25 (21%) of patients, and grade 1 in n=74 (71%) or grade 2 in n=30 (29%) of patients. In 91 patients (77%) there was stage IV disease. The median period since diagnosis was 40 months (IQR 14 – 84 months) and median period on SSA 23 months (IQR 5.5 – 59 months). The median BMI is 24.8 (IQR 21.7 – 28.7), 7 patients (6%) are underweight (BMI <18.5), 52 patients (44%) had a normal weight (BMI 18.5 – 24.9), 33 patients (28%) were overweight (BMI 25 – 29.9), 26 patients (22%) were obese (BMI >30). There are significant OS differences between BMI categories p-value 0.002. When correcting for age HR 1 (0.97 – 1.05), sex HR 1.3 (0.49 – 3.66), grading 2.06 (0.74 – 5.72), stable disease versus progressive disease HR 5.4 (1.9 – 14.9), the BMI is still significantly associated with OS with HR 0.31 (0.16 – 0.62), p-value 0.002.

Conclusion

This study shows some evidence for the presence of the obesity paradox in a real-world population of patients with GEP-NENs using an SSA. Patients with a low or normal BMI might benefit from extra attention to their nutritional status and nutritional support. Future research should focus on the pathophysiologic mechanism explaining the obesity paradox.

References

DECREASED INPATIENT MORTALITY IN OBESE PATIENTS WITH ABDOMINAL NETS, Evan S. Glazer, Kelley Stanko, Evan S. Ong, Marlon A. Guerrero, ENDOCRINE PRACTICE 2014

Disclosure

Nothing to disclose

Introduction

Background and objectives: Small intestinal neuroendocrine tumours (SI-NETs) are slow growing but have often metastasized at the time of diagnosis. Most patients are operated either with the intention of curation or to prolonged survival. Improved surgical resection, more comprehensive oncological treatment as well as earlier diagnoses may improve survival, but only few studies have examined survival trends. In this study we aimed to examine the trend in overall survival in patients diagnosed with SI-NETs.

Aims & Methods

Patients with a histological and / or imaging-based diagnosis of SI-NET in Central Norway from 2005 to 2021 were identified. Patient, disease and treatment characteristics including histological grade (G), European Neuroendocrine Tumour Society (ENETS) stage, surgical and oncological treatment types and survival were retrospectively recorded. The cohort was divided in those diagnosed in period one (June 2005-November 2012) and period two (November 2012-December 2021), with 121 patients in each sub-cohort. Overall survival was analyzed using the Kaplan Meier method and a Cox multivariate analysis was performed to identify factors independently associated with survival.

Results

The 242 patients had a median age 70 (17-91) years at diagnosis or surgery and 55.8% were males. The majority of patients underwent surgery (n=205, 84.7%) which was considered curative in 137 (66.8%) patients. Median estimated overall survival was 10.1 years (95% CI 8.5-11.7) and the median overall survival for localized, regional and distant disease stage was 10.6 years (95% CI 7.9-13.2), 11.0 years (95% CI 8.8-13.2) and 7.1 years (3.4-10.8), p=0.005, respectively.
Patients diagnosed in period one had a median survival of 9.0 years (95% CI 6.4-11.7), while median survival for period two was significantly longer and was not reached, p = 0.014. Five year survival for period one was vs. period two was 63.5% and 83.5%. The Kaplan-Meier curves for period one and two separated the first year after diagnosis and the difference persisted. For resected patients the median survival was 9.6 years (95% CI 8.4-10.9) in period one, whereas median survival was not reached for period two, p = 0.008. The ENETs disease stage did not differ between period one and two, but a higher proportion had carcinoid heart disease in period one (7.4% vs. 1.7%, p=0.031). A higher proportion of patients who underwent SI-NET resection were considered tumour free after surgery in period two than in period one (74.3% vs 59.6%, p=0.027). There was also a higher proportion of patients with resection of multiple primary SI-NETs in period two (37.6% vs. 24.0%, p=0.049), which was explained by a higher proportion of multifocal tumours being resected during elective surgery (42.9% vs. 21.1%, p 0.005). There was also a higher number of retrieved lymph nodes in period two (p=0.014). Similar proportions of patients received somatostatin analogues, PRRT or transarterial embolization of liver metastases in period one vs. period two. In a Cox proportional hazard regression model age at diagnosis, ENETS stage, tumour resection and diagnosis before November 2012 were independently associated with overall survival, whereas sex and tumour grade were not.

Conclusion

Survival of patients with SI-NET improved over the study period and this seemed related to lower mortality the first year after diagnosis. Disease stage or oncological treatment did not change, but several factors associated with surgical quality improved during the study period.

Introduction

Inflammatory bowel disease patients are at risk of malnutrition due to the nature of the disease, the drugs used, and some dietary restrictions.Several screening tools are available, including the MUST score: the Malnutrition Universal Screening Tool, a simple and an easy-to-use tool.

Aims & Methods

The aim of our study was to assess the frequency of malnutrition risk using MUST score in IBD patients.
We conducted a prospective study that included 142 patients with IBD. All patients with IBD completed a self-administered nutrition screening assessment using the MUST score.Patients with a MUST score of ≥ 2 were concluded as high-risk for malnutrition.

Results

A total of 142 IBD patients were studied over 2 month period. We enrolled a total of 116 ( 82,1%) patients from outpatient and 26 (18,3%) from inpatient . Risk of malnutrition was identified in 21,1 % of patients according to MUST score. Number of hospitalized patients with malnutrition risk was significantly higher than the outpatient ones ( 84,6% vs 6.9 %, p<0.01).The frequency of high malnutrition risk was 36,8.% in ulcerative colitis (UC) patients and 15,4% in Crohn’s disease (CD) patients (p=0.006).
A high MUST score was strongly associated with an elevated Harvey Bradshaw Index score (p<0.01) for patients with Crohn’s disease, and with Partial Mayo Index scores (p<0.01) for patients with ulcerative colitis.

Conclusion

In our study, we found that the risk of malnutrition was high in both CD and UC patients, especially inpatients ,and it correlates to the disease activity.Considering the effect of malnutrition on the prognosis of the disease ,IBD patients should be evaluated in terms of malnutrition risk both during their routine follow-ups and during hospitalizations.