Insulin‐Dependence and Survival in Pancreatic Neuroendocrine Tumors: Results From the US‐NTSG Group

IntroductionPNETs are rare pancreatic malignancies originating from islet cells and exhibit a strong co-occurrence with Diabetes Mellitus (DM), associated with worse survival outcomes. However, studies have yet to delineate the impact of insulin dependent (IDDM) and non -insulin dependent (NIDDM) on poor oncological outcomes.MethodsUtilizing the U.S. Neuroendocrine Tumor Study Group database (1999-2016), we performed a retrospective cohort study of adult patients who underwent primary surgical resection of PNETs. Patients were categorized based on preoperative diagnosis into non-DM, NIDDM, and IDDM cohorts. We used the Kaplan-Meier method and log-rank test to study cancer-specific survival (CSS). Cox proportional Hazards models were used to assess the impact of IDDM on CSS.ResultsOf the 1,122 patients included in the analysis, 870 (77%) were non-DM, 168 (15%) were NIDDM, and 84 (8%) were IDDM. The groups were similar in tumor stage and grade. However, they differed in sex, BMI, age, ASA class, tumor location, preoperative HbA1c and serum glucose (p-value <0.05). Patients with IDDM had significantly decreased 5-year CSS compared to patients without IDDM (CSS: IDDM 85%, NIDDM 94%, non-DM 93%, NIDDM + non-DM 93%;P<0.01). On multivariate analysis, IDDM was independently associated with worse CSS (HR 2.27, 95% Confidence Interval 1.15-4.45,P=0.02).ConclusionInsulin dependence is associated with worse cancer-specific survival in PNET patients following surgical resection compared to PNET patients with NIDDM or without DM.

BackgroundAlthough lymph node dissection (LND) has been commonly used for patients with bronchopulmonary carcinoids (PCs), the prognostic values of the positive lymph node ratio (PLNR) and the number of removed nodes (NRN) remain unclear.MethodsPatients with resected PCs were identified in the Surveillance, Epidemiology, and End Results (SEER) database (2010–2015). The optimal cut-off values of the PLNR and NRN were determined by X-tile. The inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare the overall survival (OS) and cancer-specific survival (CSS) of patients in different PLNR and NRN groups.ResultsThe study included 1622 patients. The optimal cut-off values of the PLNR and NRN for survival were 13% and 13, respectively. In both Kaplan-Meier analysis and univariable Cox proportional hazards regression analysis before IPTW, a PLNR ≥13% was significantly associated with worse OS (HR = 3.364, P<0.001) and worse CSS (HR = 7.874, P<0.001). These findings were corroborated by the IPTW-adjusted Cox analysis OS (HR = 2.358, P = 0.0275) and CSS (HR = 8.190, P<0.001) results. An NRN ≥13 was not significantly associated with worse OS in either the Kaplan-Meier or Cox analysis before or after IPTW adjustment. In the Cox proportional hazards analysis before and after IPTW adjustment, an NRN ≥13 was significantly associated with worse CSS (non-IPTW: HR = 2.216, P=0.013; IPTW-adjusted: HR = 2.162, P=0.024).ConclusionA PLNR ≥13% could predict worse OS and CSS in patients with PCs and might be an important complement to the present PC staging system. Extensive LND with an NRN ≥13 might have no therapeutic value for OS and may even have an adverse influence on CSS. Its application should be considered on an individual basis.

326 Background: NET are a group of diverse malignancies observed commonly in the gastrointestinal tract. Pancreatic neuroendocrine tumors (PanNET) have been reported to have worse outcomes as compared to neuroendocrine tumors of the gastrointestinal tract (GNET). Our objective was to compare the clinical characteristics, patterns of treatment and survival in PanNET and GNET. Methods: After IRB approval, we identified 379 patients (pts) from 1996-2011 in the Winship registry. A chart review was done. Patients were categorized in mutually exclusive groups of PanNET and GNET. Results: Demographic information and basic characteristics are listed in the table. Treatment modalities for PanNET included surgery (91%), chemotherapy (14%), biologics (sunitinib or everolimus)(6%) and somatostatin analogues (11%). Liver directed therapies were employed in 30 pts with PanNET. Most common modality was radiofrequency ablation (23 pts) followed by Yttrium-90 embolization (5 pts) and chemoembolization (2 pt).Treatment for GNET included surgery (78%), chemotherapy (11%) and somatostatin analogues (17%). Median survival for GNET (all stage) was 11.6 years and PanNET (all stage) was 10.5 years (p=0.063). Using multivariate analysis, only age at diagnosis (p&lt;0.001 for age cohort of &lt;55 yrs) and clinical stage (p=0.002, for local disease) were found to be significant factors. Conclusions: Pts with NET have good prognosis. In our series, both PanNET and GNET, had comparable survival outcomes even in advanced stage. [Table: see text]

BackgroundPancreatic neuroendocrine tumors (pNETs) are rare neuroendocrine neoplasms (NENs) for which little is known about their clinical features, treatment options, and survival prognosis. The purpose of this study is to evaluate the risk factors affecting the overall survival (OS) and cancer-specific survival (CSS) in patients with grade 1 pNETs (G1 pNETs) and to provide a new theoretical basis for clinical diagnosis and treatment.MethodsA retrospective analysis of individuals with G1 pNETs registered in the Surveillance, Epidemiology, End Results (SEER) database was performed. Risk factors affecting OS and CSS were analyzed using Kaplan-Meier analysis, Cox proportional hazards model, and Fine-Gray competing-risk model.ResultsA total of 751 patients were included, most of whom were white (77.2%) women (53.9%) under the age of 60 years (54.9%), of whom 66 died of pNETs (8.78%) and 34 died of other causes (4.52%). Patients who were older than 60 years at diagnosis (hazard ratio [HR] = 1.866, 95% confidence interval [CI]: 1.242-2.805) had worse OS. And stage in the regional extent (HR = 1.777, 95% CI: 1.006-3.137) or distance extent (HR = 4.540, 95% CI: 2.439-8.453) had worse OS. Patients who delayed treatment after diagnosis had shorter CSS (delayed treatment < 1 month: HR = 1.933, 95% CI: 0.863-4.333; delayed treatment ≥ 1 month: HR = 2.208; 95% CI:1.047-4.654). Patients with lymph node metastasis (HR = 1.989, 95% CI: 1.137-3.479) or distant metastasis (HR = 5.625, 95% CI: 1.892-16.726) had worse CSS. Acceptance of surgery can significantly improve the patient’s OS and CSS. OS (partial pancreatectomy [PP]: HR = 0.350, 95% CI: 0.182-0.672; pancreatectomy and duodenectomy [PD]: HR = 0.426, 95% CI: 0.222-0.815; total pancreatectomy [TP]: HR = 0.495, 95% CI: 0.193-1.267). CSS(PP: HR = 0.148, 95% CI: 0.0054-0.401; PD: HR = 0.332, 95% CI: 0.150-0.730; TP: HR = 0.69, 95% CI: 0.254-1.872).ConclusionAge and stage were identified as independent risk factors for OS. Delayed treatment, N stage and M stage were independent risk factors for CSS. Only surgery was identified as independent protective factors for OS and CSS.

Prognosis based on the revised histological classification by the World Health Organization (2010) for pancreatic neuroendocrine tumors

Diabetes Mellitus as an Independent Predictor of Survival of Patients Surgically Treated for Renal Cell Carcinoma: A Propensity Score Matching Study

MP64-07 DIABETES MELLITUS AS AN INDEPENDENT PREDICTOR OF SURVIVAL OF PATIENTS SURGICALLY TREATED FOR RENAL CELL CARCINOMA: A PROPENSITY SCORE MATCHING STUDY.

The aim of this study was to assess incidence and outcomes of neuroendocrine neoplasms (NENs) arising from primary sites other than digestive organs, lung, or thymic gland. Surveillance, Epidemiology, and End Results database (1975-2016) was accessed, and cases of NENs arising from primary sites other than digestive organs, lung, or thymic gland were reviewed. Overall and cancer-specific survival outcomes for NENs arising from different organs compared with small intestinal NENs were evaluated. A total of 4405 patients were included in the study. Compared with small intestinal NENs, some NENs arising from uncommon sites in the current study have worse cancer-specific survival (hazard ratio [HR] for genitourinary vs small intestinal NENs, 1.80; 95% confidence interval [CI], 1.44-2.25; HR for gynecological vs small intestinal NENs, 1.88; 95% CI, 1.52-2.33). When the analysis was limited for patients with distant stage only, small intestinal NENs have better outcomes compared with genitourinary and gynecological NENs (HR for genitourinary NENs with distant stage vs small intestinal NENs with distant stage, 1.38; 95% CI, 1.01-1.88; HR for gynecological NENs with distant stage vs small intestinal NENs with distant stage, 2.02; 95% CI, 1.54-2.66). Compared with small intestinal NENs, NENs arising from uncommon sites (such as genitourinary, gynecological) have worse survival outcomes.

Cancer-specific and overall survival in African American women with endometrial cancer: a SEER-Medicare study

Neuroendocrine gastroenteropancreatic tumors: ESMO Clinical Recommendation for diagnosis, treatment and follow-up

The objective of this research was to construct and validate prognostic nomograms predicting overall survival (OS) and cancer-specific survival (CSS) in patients with pancreatic neuroendocrine tumors (pNETs). We extracted 3787 patients with pNETs from the Surveillance, Epidemiology and End Results database. Nomograms for estimating 3- and 5-year OS and CSS were first established. Then, we used Harrell's Concordance Index, calibration plots, and the area under receiver operating characteristic curve to evaluate the nomograms. The Kaplan-Meier curve was plotted to evaluate the different survival outcomes. In the multivariate analysis, age, grade, functional status, American Joint Committee on Cancer stage, and surgery were associated with OS and CSS. The established nomograms had good discriminative ability, with a Harrell's Concordance Index of 0.830 for OS and 0.855 for CSS. The calibration plots also revealed good agreement. The area under receiver operating characteristic curve values of the nomograms predicting 3- and 5-year OS and CSS rates were 0.836, 0.816 and 0.859, 0.841, respectively. In addition, Kaplan-Meier curve indicated that patients with higher risk had worse survival outcomes. We have proposed and validated the nomograms predicting OS and CSS of pNETs. They can be convenient individualized tools to facilitate clinical decision making.

Neuroendocrine tumors (NETs) are rare, slow-growing neoplasms characterized by their ability to store and secrete different peptides and neuroamines. 1 Some of these substances cause specific clinical syndromes, 2 whereas other may have elevated plasma or urine levels that are not associated with specific syndromes or symptom complexes Unfortunately, there is no Bideal neuroendocrine tumor marker,[ 3 but according to the presentation, the sensitivity and specificity of each marker vary, and it is generally possible to choose those of greatest value for each clinical syndrome. The biochemical markers are those hormones or amines secreted by the neuroendocrine cells from which these tumors are derived. Some of these are not specific to any tumor, but are produced and secreted by most NETs, whereas other biochemical markers are more specific to the type of tumor and where their quantification can lead to the suspicion or confirmation of the presence of such a tumor. The annual incidence of NETs has risen to 40 to 50 cases per million, perhaps because of better diagnosis and the availability of highly specific and sensitive ways to measure these tumors’ products, improved immunohistochemistry, and enhanced techniques for tumor detection. Thus, the perceived increase in incidence may not be a real change in the incidence of the disease. There are a number of impediments to the diagnosis of these tumors. They are rare, comprising less than 2% of gastrointestinal (GI) malignancies, and are therefore not high on the list of causes of specific symptom complexes. Symptoms themselves are often nonspecific and do not lend themselves readily to identifying the specific underlying tumor. In addition, the manifestations are protean and mimic a variety of disorders. Tumors may be found incidentally on laparoscopy for abdominal pain or during the surgical removal of an appendix or even during a computerized tomographic scan of the abdomen for unexplained symptoms. Lung carcinoids may present with hemoptysis or asthma-like symptoms, and midgut carcinoids may be confused with irritable bowel syndrome (IBS). The natural history of this disease is invariably attended by a long history of vague abdominal symptoms, a series of visits to a primary care practitioner, and referral to a gastroenterologist, often with a misdiagnosis of IBS. These symptoms persist with a median latency to correct diagnosis of 9.2 years by which time the tumor has metastasized, causing symptoms such as flushing and diarrhea and progressing on its slow but relentless course until the patient dies. Clearly, a greater index of suspicion and a carcinoid tumor profile screen are warranted for all patients presenting with Btraditional IBS symptoms.[ Midgut carcinoids are associated with mesenteric fibrosis, which can compress mesenteric vessels and cause bowel ischemia and malabsorption, which may be found in the absence of an abdominal mass. The diagnosis of metastases to the liver is generally more obvious but often still takes place only after a delay of many years. Even then, an incorrect diagnosis is not uncommon. Unless biopsy material is examined for the secretory peptides chromogranin, synaptophysin, or neuron-specific enolase (NSE), tumors may be labeled erroneously as adenocarcinoma, with a negative impact on physician’s attitudes regarding management and underestimation of prospects for survival. 4 The common symptomatic manifestations of patients with carcinoid tumors are illustrated in Tables 1 and 2. Flushing

BackgroundThe association between body composition and survival in rectal cancer patients is still unclear. Therefore, we aimed to evaluate the impact of computed tomography (CT)-measured body composition on survival in rectal cancer patients, stratifying our analyses by sex, tumour location, tumour stage and radiotherapy.MethodsThis retrospective cohort study included 173 patients with rectal adenocarcinoma. CT colonography scans at the time of diagnosis were used to assess the skeletal muscle index (SMI) and the visceral adipose tissue area (VAT). The patients were divided into a low or high SMI group and a low or high VAT group according to previously defined cutoff values. Endpoints included cancer-specific survival (CSS) and overall survival (OS).ResultsIn all patients, low SMI was associated with worse CSS (HR, 2.63; 95% CI, 1.35–5.12; P = 0.004) and OS (HR, 3.57; 95% CI, 2.01–6.34; P < 0.001) compared to high SMI. The differences remained significant after adjusting for potential confounders (CSS: adjusted HR, 2.28; 95% CI, 1.13–4.58; P = 0.021; OS: adjusted HR, 3.17; 95% CI, 1.73–5.82; P < 0.001). Low SMI was still related to a poor prognosis after stratifying by sex, tumour location, stage and radiotherapy (P < 0.05). High VAT was associated with better CSS (HR, 0.31; 95% CI, 0.11–0.84; P = 0.022) and OS (HR, 0.40; 95% CI, 0.17–0.97; P = 0.044) compared to low VAT among men with rectal cancer ≤ 10 cm from the anal verge. High VAT was associated with worse CSS (HR, 4.15; 95% CI, 1.10–15.66; P = 0.036) in women with rectal cancer ≤ 10 cm from the anal verge.ConclusionsLow SMI was associated with worse survival. High VAT predicted better survival in men but worse survival in women. The results suggest that CT-measured body composition is a useful tool for evaluating the prognosis of rectal cancer patients and demonstrate the need to include the sex and the tumour location in the analyses.

Neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas are slow-growing but commonly advanced malignancies with increasing incidence and prevalence. While locoregional disease can be effectively managed with resection, treatment of recurrent, progressive or metastatic disease has until recently been limited to palliative embolization and cytoreducitve surgery, with cytotoxic chemotherapeutic agents being the last resort. However, novel molecular targeted therapies inhibiting malignant cell proliferation and neoangiogenesis, as well as new cytotoxic chemotherapy drugs and somatostatin analogues, are all being investigated for their potential use in advanced neuroendocrine tumors. Long-acting release forms of octreotide have been shown to not only improve symptoms in carcinoid syndrome but to also delay progression of gastrointestinal NETs. On the other hand, phase III trials have demonstrated everolimus (with octreotide) and sunitinib to increase progression-free survival in pancreatic NETs. Use of bevacizumab has also shown promise in a phase II study, and results of an ongoing phase III trial comparing it to interferon are eagerly expected. Use of radiolabeled somatostatin analogues is still under investigation, though several phase II studies are encouraging. New cytotoxic agents, most notably temozolomide and capecitabine, are already in use, but their relative effectiveness compared to streptozocin in pancreatic NETs is yet to be determined.

612 Background: The aim of this study was to examine the impact of diabetes mellitus (DM) on survival in neuroendocrine tumor and the impact of neuroendocrine tumor on glycemic control in DM. Methods: Patients with newly diagnosed neuroendocrine tumor with and without DM were matched 1:1 according to age, gender, and year of cancer diagnosis (2005-2017). The file was linked to the electronic medical record to obtain information on DM and neuroendocrine tumor therapies and laboratory results. There were 59 matched pairs (total 118 patients) included in the analysis. We compared characteristics between cases and controls and assessed survival with the Kaplan-Meier method and Cox proportional hazards model. Mixed models compared hemoglobin A1c and glucose levels over time. Results: Median age of patients at diagnosis was 67 (40-86); 41% had stage IV disease. Women constituted 49% of the study population; 22% had pancreatic neuroendocrine tumor and 45% had another GI primary neuroendocrine tumor. No differences in race/ethnicity, marital status, alcohol or tobacco use were detected between cancer patients with and without DM. Mean BMI was significantly different between DM and non-DM patients (31.0 [7.90] versus 26.4 [5.27]); p = 0.011. Among those with DM, mean HbA1c during the year following cancer diagnosis was 7.3%. Mean glucose was significantly different between DM (159.1 [43.5] versus non-DM pts 117 [31.5]); p &lt; 0.001. Median follow-up time was 32.8 (2.4-165.4) months in alive patients. Three year survival was estimated at 72% (95% CI: 60-86%) for DM patients versus 80% (95% CI: 70-92%) in non-DM patients by Kaplan Meier method (p = 0.82 log rank test). Hazard ratio (stratification for matched pairs) = 1.33 (95% CI: 0.56 – 3.16; p = 0.51). Conclusions: DM did not adversely impact survival in patients with neuroendocrine tumor. Neuroendocrine tumor and its treatment did not affect glycemic control. This should be reassuring to oncologists and endocrinologists who treat patients with neuroendocrine tumors and diabetes.