Impact of Specific Bowel Symptoms on Quality of Life in Patients with Midgut Neuroendocrine Tumours

Introduction Patients with midgut neuroendocrine tumours (NETs) suffer from decreased health-related quality of life (HRQoL), in large part due to bowel symptoms. However, it is unknown which bowel symptoms affect HRQoL the most. An enhanced understanding of this is essential to better focus treatment on this aspect of the disease. This study aimed to determine which bowel symptoms affect HRQoL the most in patients with midgut NETs. Methods Consenting patients with midgut NET completed the Memorial Sloan Kettering Bowel Function Instrument and the HRQoL questionnaire (EORTC QLQ-C30). The correlation between bowel symptoms and HRQoL was analysed using multiple linear regression, adjusting for age, Charlson Comorbidity Index score, presence of metastatic disease, chromogranin A, and BMI yielding ß-coefficients with 95% confidence intervals. Results Totally, 119 patients with midgut NET completed the questionnaires and were included in the study. Loose stool and bowel frequency ≥ 3/day were the most common bowel symptoms, reported by 47% and 56% of patients, respectively. However, sensitivity to certain types of food and beverages, a feeling of incomplete emptying of the bowel, and soiling were the symptoms most strongly correlated with decreased HRQoL, especially within domains concerning role and social function, with ß-coefficients for the strongest correlated symptoms of 15.0 and 14.6, respectively. Discussion While symptoms concerning stool consistency and frequency are common in patients with midgut NET, our study suggests that other, more socially stigmatising symptoms affect patients’ HRQoL more. Our findings could help caregivers understand patients’ perceptions of the disease and provide avenues for more directed therapies.

Resection of primary tumor in liver only metastatic midgut neuroendocrine tumors.

446 Background: Surgical management of metastatic midgut neuroendocrine tumors (NET) remains controversial. Resection of primary tumor only without liver resection is advocated only in select patients, frequently for palliation. Additionally, no standard algorithm exists, and the risk profile for these patients is not well documented in the literature. We evaluated these midgut NETs with liver metastasis in the National Cancer Data Base (NCDB) to determine if resection of the primary tumor only affected survival outcomes. Methods: The NCDB was queried to identify patients with liver only metastatic midgut NET tumors between 2010 and 2015. Patients who underwent surgery of their liver metastasis were excluded. The cohort was separated into two groups, those who underwent resection of the primary tumor and those who did not. Patient demographics, year of diagnosis, clinicopathologic tumor characteristics and Charlson/Deyo comorbidity index were compared among the two groups. The primary outcome was overall survival (OS). Kaplan-Meier estimates were used to predict OS. Results: One-thousand nine hundred fifty-two patients with median age of 63 were identified. Median tumor size was 2.4 cm. Of these, 1,295 (66.0%) patients underwent resection of the primary tumor and 667 (34.0%) did not. Patients undergoing resection were younger (median age 63 vs. 65, p < 0.001) and had smaller tumors (median 2.3 cm vs. 3.0 cm, p < 0.001). There was no difference between the groups with respect to sex, year of diagnosis or Charlson/Deyo Comorbidity Score. Median follow up time was 42.8 months (IQR 29.7). A total of 483 deaths occurred in the entire cohort with a 5-year OS of 60.8%. The 5-year OS for patients undergoing resection of the primary tumor was 65.9% and 49.3% for those not undergoing resection (p < 0.001). Conclusions: Patients with liver only metastatic midgut neuroendocrine tumors had an overall survival advantage when the primary tumor was resected. Patients with liver only metastatic midgut NET may benefit from surgical resection and should be evaluated for surgery at the time of diagnosis.

Ovarian metastasis from midgut neuroendocrine tumors: Incidence, clinical implications, and management options—An update.

446 Background: Midgut neuroendocrine tumors (NETs) are rare malignancies that can produce carcinoid syndrome and/or carcinoid heart disease. The incidence of ovarian metastasis, their clinical implications, and the optimal management strategy for these metastasis have not been well studied. We hypothesized that patients with ovarian metastasis will have a high incidence of carcinoid syndrome and carcinoid heart disease. Methods: Charts of 431 female patients seen in our NET clinic between October 2006 and December 2014 with a diagnosis of midgut NET were reviewed. Patients who had a previous bilateral oophorectomy with or without total abdominal hysterectomy were excluded. The incidence of ovarian metastasis, carcinoid syndrome and carcinoid heart disease was calculated. Median survival and 5-year survival rates were determined via the Kaplan-Meier Method. Results: Forty-one (41/431, 10%) patients were found to have ovarian metastasis. Twenty-four (24/41, 59%) patients exhibited carcinoid syndrome and three (3/24, 13%) patients with carcinoid syndrome developed carcinoid-related heart disease. 5-year survival rates for the patients with and without ovarian metastasis were 92% and 87%, respectively. Conclusions: Ovarian metastasis was found in 10% patients with metastatic midgut NET. Fifty-nine percent of these patients exhibited carcinoid syndrome and thirteen percent of which developed carcinoid heart disease, in spite of aggressive somatostatin analog therapy. To improve quality of life, routine therapeutic or prophylactic oophorectomy is recommended for female patients undergoing cytoreductive surgery for their midgut NET, especially for those who are peri- or post-menopausal.

Efficacy of octreotide long-acting repeatable in neuroendocrine tumors: RADIANT-2 placebo arm post hoc analysis

Somatostatin analogues (SSA) have demonstrated antiproliferative activity in addition to efficacy for carcinoid symptom control in functional neuroendocrine tumors (NET). Apost hocanalysis of the placebo arm of the RAD001 In Advanced Neuroendocrine Tumors-2 (RADIANT-2) study was conducted to assess the efficacy of octreotide long-acting repeatable (LAR) on progression-free survival (PFS) and overall survival (OS) estimated using the Kaplan–Meier method. Out of 213 patients randomized to placebo plus octreotide LAR in RADIANT-2, 196 patients with foregut, midgut, or hindgut NET were considered for present analysis. Of these, 41 patients were SSA-treatment naïve and 155 had received SSA therapy before study entry. For SSA-naïve patients, median PFS by adjudicated central review was 13.6 (95% CI 8.2–22.7) months. For SSA-naïve patients with midgut NET (n=24), median PFS was 22.2 (95% CI 8.3–29.5) months. For patients who had received SSA previously, the median PFS was 11.1 (95% CI 8.4–14.3) months. Among the SSA-pretreated patients who had midgut NET (n=119), the median PFS was 12.0 (95% CI 8.4–19.3) months. Median OS was 35.8 (95% CI 32.5–48.9) months for patients in the placebo plus octreotide LAR arm; 50.6 (36.4 – not reached) months for SSA-naïve patients and 33.5 (95% CI 27.5–44.7) months for those who had received prior SSA. Thispost hocanalysis of the placebo arm of the large phase 3 RADIANT-2 study provides data on PFS and OS among patients with progressive NET treated with octreotide therapy.