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.

Aims This observational study characterized cardiovascular disease (CVD) mortality risk for multiple cancer sites, with respect to the following: (i) continuous calendar year, (ii) age at diagnosis, and (iii) follow-up time after diagnosis. Methods and results The Surveillance, Epidemiology, and End Results program was used to compare the US general population to 3 234 256 US cancer survivors (1973–2012). Standardized mortality ratios (SMRs) were calculated using coded cause of death from CVDs (heart disease, hypertension, cerebrovascular disease, atherosclerosis, and aortic aneurysm/dissection). Analyses were adjusted by age, race, and sex. Among 28 cancer types, 1 228 328 patients (38.0%) died from cancer and 365 689 patients (11.3%) died from CVDs. Among CVDs, 76.3% of deaths were due to heart disease. In eight cancer sites, CVD mortality risk surpassed index-cancer mortality risk in at least one calendar year. Cardiovascular disease mortality risk was highest in survivors diagnosed at <35 years of age. Further, CVD mortality risk is highest (SMR 3.93, 95% confidence interval 3.89–3.97) within the first year after cancer diagnosis, and CVD mortality risk remains elevated throughout follow-up compared to the general population. Conclusion The majority of deaths from CVD occur in patients diagnosed with breast, prostate, or bladder cancer. We observed that from the point of cancer diagnosis forward into survivorship cancer patients (all sites) are at elevated risk of dying from CVDs compared to the general US population. In endometrial cancer, the first year after diagnosis poses a very high risk of dying from CVDs, supporting early involvement of cardiologists in such patients.

The incidence of PD-L1 expression in GBM patients is frequent but is confined to a minority subpopulation, similar to other malignancies that have been profiled for PD-L1 expression. Higher expression of PD-L1 is correlated with worse outcome.

Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages. Glioblastoma patients had an elevated number of monocytes relative to healthy donors. Among CD11b+ cells, microglia and MDSCs constituted a higher percentage of GAMs than did macrophages. GAM profiling using flow cytometry studies revealed a continuum between the M1- and M2-like phenotype. Contrary to current dogma, GAMs exhibited distinct immunological functions, with the former aligned close to nonpolarized M0 macrophages.

To clarify the relationships among TML, MMR, and immune checkpoint expression, we profiled the frequency of shared biomarker phenotypes. On the basis of a variety of potential biomarkers of response to immune checkpoints, only small subsets of glioma patients are likely to benefit from monotherapy immune checkpoint inhibition.

IMPORTANCE Minimal residual disease (MRD) refers to the presence of disease in cases deemed to be in complete remission by conventional pathologic analysis. Assessing the association of MRD status following induction therapy in patients with acute lymphoblastic leukemia (ALL) with relapse and mortality may improve the efficiency of clinical trials and accelerate drug development.OBJECTIVE To quantify the relationships between event-free survival (EFS) and overall survival (OS) with MRD status in pediatric and adult ALL using publications of clinical trials and other databases.DATA SOURCES Clinical studies in ALL identified via searches of PubMed, MEDLINE, and clinicaltrials.gov.STUDY SELECTION Our search and study screening process adhered to the PRISMA Guidelines. Studies that addressed EFS or OS by MRD status in patients with ALL were included; reviews, abstracts, and studies with fewer than 30 patients or insufficient MRD description were excluded. CONCLUSIONS AND RELEVANCE The value of having achieved MRD negativity is substantial in both pediatric and adult patients with ALL. These results are consistent across therapies, methods of and times of MRD assessment, cutoff levels, and disease subtypes. Minimal residual disease status warrants consideration as an early measure of disease response for evaluating new therapies, improving the efficiency of clinical trials, accelerating drug development, and for regulatory approval. A caveat is that an accelerated approval of a particular new drug using an intermediate end point, such as MRD, would require confirmation using traditional efficacy end points.

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.