The incidence and prevalence of NETs are steadily rising, possibly owing to detection of early-stage disease and stage migration. Survival for all NETs has improved over time, especially for distant-stage gastrointestinal NETs and pancreatic NETs in particular, reflecting improvement in therapies. These data will help to prioritize future research directions.

IMPORTANCE Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice. OBJECTIVE To evaluate the incidences of treatment-related adverse events of PD-1 and PD-L1 inhibitors and the differences between different drugs and cancer types.

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.

The National Lung Screening Trial (NLST) released its main findings in 2011, 1 concluding that the use of low-dose computed tomography (CT) to screen for lung cancer reduced l u ng c a n c e r d e at h s by 2 0 % c o m p a r e d w it h c h e s t radiography. 1,2 The subsequent publication of new lung cancer screening (LCS) guidelines may raise the public's awareness of the clinical application of lowdose CT in screening, 3,4 leading to increased demand for screening not only by individuals who meet the eligibility criteria recommended for LCS but also by those who do not. The present study documents early experience of LCS in terms of both intended and unintended uptake of low-dose CT at the population level.

BackgroundDepression and anxiety have been reported to be associated with chronic physical conditions. We examined the excess risk of chronic physical conditions associated with depression and/or anxiety within a multivariate framework controlling for demographic and modifiable lifestyle risk factors.MethodsWe used a retrospective cross-sectional study design. Study participants were adults aged 22–64 years from 2007 and 2009 Medical Expenditure Panel Survey. We defined presence of depression-anxiety based on self-reported depression and anxiety and classified adults into 4 groups: 1) depression only; 2) anxiety only; 3) comorbid depression and anxiety 4) no depression and no anxiety. We included presence/absence of arthritis, asthma, chronic obstructive pulmonary disorder, diabetes, heart disease, hypertension, and osteoporosis as dependent variables. Complementary log-log regressions were used to examine the excess risk associated with depression and/or anxiety for chronic physical conditions using a multivariate framework that controlled for demographic (gender, age, race/ethnicity) and modifiable lifestyle (obesity, lack of physical activity, smoking) risk factors. Bonferroni correction for multiple comparisons was applied and p ≤0.007 was considered statistically significant.ResultsOverall, 7% had only depression, 5.2% had only anxiety and 2.5% had comorbid depression and anxiety. Results from multivariable regressions indicated that compared to individuals with no depression and no anxiety, individuals with comorbid depression and anxiety, with depression only and with anxiety only, all had higher risk of all the chronic physical conditions. ARRs for comorbid depression and anxiety ranged from 2.47 (95% CI: 1.47, 4.15; P = 0.0007) for osteoporosis to 1.64 (95% CI: 1.33, 2.04; P < 0.0001) for diabetes. Presence of depression only was also found to be significantly associated with all chronic conditions except for osteoporosis. Individuals with anxiety only were found to have a higher risk for arthritis, COPD, heart disease and hypertension.ConclusionPresence of depression and/or anxiety conferred an independent risk for having chronic physical conditions after adjusting for demographic and modifiable lifestyle risk factors.