BACKGROUND Neuroendocrine tumors (NETs) can secrete bioactive amines into the bloodstream causing carcinoid syndrome (CS), with symptoms including flushing and diarrhea. However, CS frequency in the NET population has never been rigorously evaluated, nor has its relationship to presenting characteristics. This analysis assessed the proportion of NET patients with CS and associated clinical factors. METHODS We identified patients diagnosed 4/2000–12/2011 from the SEER-Medicare database, excluding those with pancreatic tumors or small cell/large cell lung cancer, as well as those without complete data. The incidence of patients with at least two claims of flushing (782·62), diarrhea (564·5, 787·91), or carcinoid syndrome (259·2) during the three months before and after NET diagnosis was assessed. We compared demographic and clinical characteristics between patients with and without CS using chi-squared tests. We used the Cochran-Armitage trend test to identify trends in CS incidence and cox regression to assess the relationship between CS and survival. FINDINGS Among 9,512 NET patients, 1,922 (19%) had CS. The proportion of NET patients with CS reported increased from 10·8% (50 of 465 patients) in 2000 to 18·6% (159 of 854 patients) in 2011 (p<0·0001). Patients with CS more likely had regional/distant than localized disease, grade 1/2 than grade 3/4 histology, and small bowel or cecal primary tumors rather than lung or colon. Female (p=0·00030) and non-Hispanic white patients (and p < 0·0001) more likely reported CS. CS was associated with shorter survival (HR 1·1, p = 0·017). Age and patient location were not correlated with the incidence of CS. Use of octreotide was more common in patients with CS, while use of chemotherapy and radiation were used more frequently in patients without CS and use of surgery was not significantly associated with the presence of CS at diagnosis. INTERPRETATION This population-based analysis reveals that CS is significantly associated with grade, stage, primary site, and shorter survival. An improved understanding of the heterogeneity of presenting syndromes among patients with NETs may permit more tailored evaluation and management, and enables future research regarding the impact of CS control on patient survival. FUNDING Supported by Ipsen, which sponsored purchasing SEER-Medicare data and funded analytical support. The company was not involved in data collection, analysis, or interpretation. This study was not directly funded by NIH.

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The calibrated Bayesian hierarchical model provides a practical approach to design basket trials with more flexibility and better controlled type I error rates than the Bayesian hierarchical model. The software for implementing the proposed design is available at http://odin.mdacc.tmc.edu/~yyuan/index_code.html.

Summary The basket trial refers to a new type of phase II cancer trial that evaluates the therapeutic effect of a targeted agent simultaneously in patients with different types of cancer that involve the same genetic or molecular aberration. Although patients who are enrolled in the basket trial have the same molecular aberration, it is common for the targeted agent to be effective for patients with some types of cancer, but not others. We propose a Bayesian latent subgroup trial (BLAST) design to accommodate such treatment heterogeneity across cancer types. We assume that a cancer type may belong to the sensitive subgroup, which is responsive to the treatment, or the insensitive subgroup, which is not responsive to the treatment. Conditionally on the latent subgroup membership of the cancer type, we jointly model the binary treatment response and the longitudinal biomarker measurement that represents the biological activity of the targeted agent. The BLAST design makes the interim go–no‐go treatment decision in a group sequential fashion for each cancer type on the basis of accumulating data. The simulation study shows that the BLAST design outperforms existing trial designs. It yields high power to detect the treatment effect for sensitive cancer types that are responsive to the treatment and maintains a reasonable type I error rate for insensitive cancer types that are not responsive to the treatment.

The incidence and prevalence of neuroendocrine tumors (NETs) are continually increasing. While it is known that NET symptoms often predate diagnosis, their prevalence and impact on resource utilization and costs are largely unknown. We identified 9,319 elderly patients diagnosed with NETs between 1/2003 and 12/2011 from the Surveillance, Epidemiology and End Results (SEER)-Medicare. We examined the patients’ conditions potentially associated with NET, resource utilization and costs during the year before diagnosis. We found that NET patients were more likely to have diagnoses of hypertension (63.8% vs. 53.3%), abdominal pain (22.2% vs. 7.6%), heart failure (11.7% vs. 8.0%), diarrhea (5.8% vs. 1.8%), peripheral edema (5.4% vs. 3.8%) and irritable bowel syndrome (1.2% vs. 0.5%) compared to the non-cancer control group. They also had much higher resource utilization including number of outpatient visits (mean: 22.1 vs. 17.2), percentage with ER visits (20.9% vs. 11.6%), and hospitalizations (28.4% vs. 17.0%). Similarly, NET patients incurred significantly higher total (mean: $14602 vs. $9464), outpatient (mean: $5987 vs. $4253), and inpatient costs (mean: $8615 vs. $5211). This first population-based study on the pre-diagnosis symptoms and healthcare utilization found that NET patients were more likely to have certain conditions and incur higher resource utilizations and costs.