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.

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.

Risk factors for lymph node metastasis and prognosis in colorectal neuroendocrine tumours

Purpose The detection rate of colorectal neuroendocrine tumours (CR-NETs) is increasing, but their treatment is still controversial. Lymph node metastasis is an important reference index for the selection of treatment. The aim of our study was to investigate the factors associated with lymph node metastasis and prognosis of CR-NETs. Methods The case characteristics of patients with colorectal neuroendocrine tumours from January 2011 to December 2020 were retrospectively analysed, including age, gender, tumour size, tumour location, lymph node metastasis, pathological grade and follow-up. Results A total of 195 cases of CR-NETs were included in this study. When 15 mm was used as the cut-off value, the sensitivity, specificity and area under the curve (AUC) of lymph node metastases were 95.9%, 95.2% and 0.986, respectively. Multivariate analysis suggested that tumour size ≥ 15 mm (OR: 30.517, 95% CI: 1.250 ~ 744.996, p = 0.036) and lymphovascular invasion (OR: 42.796, 95% CI: 2.882 ~ 635.571, p = 0.006) were independent risk factors for lymph node metastasis. Age ≥ 56 (HR: 7.434, 95% CI: 1.334 ~ 41.443, p = 0.022) and distant metastasis (HR: 24.487, 95% CI: 5.357 ~ 111.940, p < 0.001) were independent prognostic factors in multivariable analyses. Conclusions When the size of a CR-NET is ≥ 15 mm, the risk of lymph node metastasis is higher, and it is recommended to choose the surgical method carefully. Tumour size and lymphovascular invasion were independent risk factors for lymph node metastasis. Age ≥ 56 and distant metastasis were independent prognostic factors.

[177Lu]Lu-DOTA-TATE versus standard of care in adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs): a cost-consequence analysis from an Italian hospital perspective

Purpose To assess and compare clinical outcomes and costs, to the Italian healthcare system, of three therapeutic options approved in the management of adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs). Methods We compared the efficacy, safety, and costs of [177Lu]Lu-DOTA-TATE, everolimus (both originator and generic products), and sunitinib in patients with advanced GEP-NETs (NET G1 and G2) that had progressed following treatment with somatostatin analogs (SSAs). A cost-consequence model was developed and validated by a panel of clinical experts from three NET reference centres in Italy. The clinical outcomes included in the model were median progression-free survival and the incidence of grade 3 or 4 adverse events (AEs), as reported in pivotal clinical trials. The costs for acquisition and administration of each treatment, and of managing AEs, were calculated from the perspective of the Italian national health service. Treatment costs per progression-free month were calculated separately for patients with NETs of pancreatic (PanNETs; all three treatments) and gastrointestinal (GI-NETs; [177Lu]Lu-DOTA-TATE and everolimus only) origin. Results In patients with PanNETs, total costs per progression-free month were €2989 for [177Lu]Lu-DOTA-TATE, €4975 for originator everolimus, €3472 for generic everolimus, and €5337 for sunitinib. In patients with GI-NETs, total costs per progression-free month were €3189 for [177Lu]Lu-DOTA-TATE, €4990 for originator everolimus, and €3483 for generic everolimus. Conclusions [177Lu]Lu-DOTA-TATE was associated with lower costs per progression-free month versus relevant treatment options in patients with GI-NETs or PanNETs (NET G1–G2; progressed following SSA treatment), although acquisition and administration costs are higher. These findings provide further economic arguments in the overall context of treatment decision-making.

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

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.

P-P17 Casting a Wider NET: Defining PEI in patients with Neuroendocrine Tumours using the 13C-MTG breath test

Background Somatostatin-analogues (SSAs) are the first-line treatment of unresectable, symptomatic neuroendocrine tumours (NETs). However, SSAs inhibit pancreatic secretions which could lead to pancreatic exocrine insufficiency (PEI). There is, however, very limited data regarding the physiologic link between SSAs and PEI. PEI negatively impacts patient quality of life (QoL), nutritional status, and clinical outcomes. This is a prospective, observational, cohort study to establish the impact of SSAs on pancreatic exocrine function in patients with NETs, using the 13C-Mixed-Triglyceride (13C-MTG) breath test. Methods Adult patients commencing SSA therapy for NETs, were recruited from December 2020. Patients were excluded if they had a diagnosis of other pancreatic disease, history of upper-gastrointestinal surgery that may alter pancreatic function, or already on SSA therapy. The impact of SSAs on exocrine function was assessed using the 13C-MTG breath test. A quotient of 13CO2/12CO2 was measured by mass spectrometry and the cumulative percent dose recovered at 6 hours (cPDR) is reported. Secondary endpoints investigated were changes in patient weight and Vitamin D levels. Results Exocrine function reduced in all patients (n = 7) following SSA therapy (median reduction from baseline: -22.2%, range: -5.6- -42.1%; p = 0.018) (Figure 1). Vitamin D levels decreased in all but one patient (median decrease from baseline: -11.7%, range: -29.3-10%; p = 0.126). Change in patient weight did not show any significant change (median decrease from baseline: -0.69%, range: -4.26 – 3.6%, p = 0.933). Conclusions SSA therapy appears to have a consistent impact on exocrine function from early in the treatment course. This suggests that there is a widespread underestimation of PEI in this setting. Whether such decrease in exocrine function leads to weight loss remains to be seen. Further studies are required to confirm this work, determine the clinical relevance of this observation, and optimise medical therapy of PEI in this cohort. The 13C-MTG breath test is a feasible and acceptable measure of pancreatic exocrine function in patients treated with SSA therapy for NETs.

P-L13 Proposed sampling methodology for improved accuracy of hepatic burden assessment in neuroendocrine tumours

Background Hepatic burden is a significant confounder in the assessment of impact of primary tumour resection in metastatic small bowel neuroendocrine tumours (SI-NET). For SI-NET metastatic hepatic burden &gt;10% disease replacement or &gt; 5 hepatic metastases are known prognostic markers, though nomograms and scores do not adequately account for this. Most trials do not adequately account for hepatic burden when assessing the survival difference between SI-NET primary tumour resection and no resection. We propose a sampling methodology to more accurately assess metastatic liver burden in SI-NET and correlate with delayed resection vs. upfront primary tumour resection at a specialist NET surgical unit. Methods Patients referred for metastatic SI-NET between January 2003 and February 2020 were identified from a prospective dataset. The earliest CT scan after diagnosis was used. The axial, coronal and sagittal slice position limits of the whole liver were recorded. These limits allowed equitable slice position of the liver, with 8 equally distributed axial, 4 equally distributed coronal and 4 equally distributed sagittal slices. Each slice was used to define the liver and metastatic area as assessed using liver CT windows. Liver burden was estimated as percentage total metastatic area summed from all 8 axial, 4 coronal and 4 sagittal slices. Results 157 total patients were on the collated data base and 46 patients were identified with an appropriate CT. Liver burden was positively skewed. Liver burden was significantly higher for delayed resection vs. upfront resection in all planes of assessment (axial: 11.61% vs. 0.14%, p = 0.003; coronal: 13.46% vs. 0.33%, p = 0.006; sagittal: 10.46% vs. 0.16%, p = 0.008). All planar assessments correlated well with one another (all Kendall’s tau ≥0.851, all p &lt; 0.001). Liver metastatic burden correlated with total liver volume (Kendall’s tau 0.549-0.573, all p &lt; 0.001). Conclusions Hepatic burden differs between resection groups in a small sample at our centre, highlighting the unmeasured confounders favouring primary tumour resection via positive bias. Therefore, hepatic burden needs quantifying in prospective studies that assess primary tumour resection in SI-NET. This is to ensure comparable groups after randomisation. Our method provides an assessment of this metastatic SI-NET liver burden.