Search

Background : We studied the effect of race and ethnicity on disease characteristics and survival in gastrointestinal neuroendocrine tumors. Methods : The Surveillance, Epidemiology, and End Results database was used to select patients with non-pancreatic gastrointestinal neuroendocrine tumors diagnosed between 2004 and 2015. Trends in survival were evaluated among three groups: Hispanic, non-Hispanic White, and non-Hispanic Black. Kaplan-Meier and Cox regression methods were performed to calculate overall survival and cause-specific survival after adjusting for patient and tumor characteristics. Results: A total of 26,399 patients were included in the study: 65.1% were non-Hispanic White, 19.9% were non-Hispanic Black, and 15% were Hispanic. Non-Hispanic White patients were more likely to be male (50.0%, p < 0.001), older than 60 years (48.0%, p < 0.001), and present with metastatic disease (17.7%, p < 0.001). Non-Hispanic White patients had small intestine neuroendocrine tumors, while Hispanic and non-Hispanic Black patients had rectum neuroendocrine tumors as the most common primary site. Hispanic patients had better overall survival, while non-Hispanic Black patients had better cause-specific survival versus non-Hispanic White patients. This finding was confirmed on multivariable analysis where Hispanic patients had improved overall survival compared to non-Hispanic White patients (Hazard ratio (HR): 0.89 (0.81-0.97)), whereas non-Hispanic Black patients had better cause-specific survival compared to non-Hispanic White patients (HR: 0.89 (0.80-0.98)). Conclusions : Race/ethnicity is an independent prognostic factor in patients with gastrointestinal neuroendocrine tumors.

Background: We aimed to study the effect of socioeconomic differences and molecular characteristics on survival in patients with young-onset pancreatic neuroendocrine tumors (YOPNET) and typical-onset PNET (TOPNET)., Methods: We identified the patients with YOPNET (<50 years) and TOPNET (≥50 years) who underwent definitive surgery diagnosed between 2004 and 2016 using the National Cancer Database. We evaluated overall survival (OS) using the Kaplan-Meier and Cox regression methods before and after propensity score matching. A publicly available genomic dataset was used to compare mutation frequencies among the two groups., Results: A total of 6259 patients with PNET were included, of which 27% were YOPNET. Patients with YOPNET were more likely to be Black, Hispanic, female, and have private insurance versus patients with TOPNET (all p < 0.001). Patients with YOPNET had a lower comorbidity score, but higher stage and tumor size (all p < 0.001). YOPNET was associated with a greater improved OS than TOPNET before and after propensity score matching ( p < 0.001). On multivariable analysis, this survival difference persisted for YOPNET as an independent prognostic factor (unmatched p = 0.008; matched p = 0.01). For genomic analysis, patients with YOPNET had a lower rate of multiple endocrine neoplasia type-1 (MEN-1) mutation than patients with TOPNET (26% vs. 56%, p < 0.001)., Conclusions: YOPNET represents a disease with distinct clinical features. Patients with YOPNET who underwent definitive surgery had better OS than patients with TOPNET despite having higher stage and tumor size. YOPNET also had lower rate of MEN-1 mutation.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but prediction of their benefit is challenging. Neoantigens generated through impaired non-mismatch DNA repair may result in greater ICI activity. By analyzing 1,661 ICI-treated patients, we show that deletions and mutations in nucleotide excision repair (NER) and homologous repair (HR) pathways are predictors of ICI benefit independent of tumor mutation burden and tumor type. NER and HR mutations are also associated with objective response rates to ICIs in esophagogastric and non-small-cell lung cancers. In a cohort of 40,181 unique patients, NER and HR mutations are present in 3.4% and 13.9% of cancers, respectively. These results indicate that NER and HR gene mutations occur in a subpopulation of cancer patients and may aid patient selection for ICI therapy. Assessing NER and HR mutations in the context of other biomarkers may yield powerful predictors of ICI activity across different cancer types., Competing Interests: DECLARATION OF INTERESTS R.M.S. and L.G.T.M. are inventors on a provisional patent application (62/569,053) filed by MSKCC, relating to the use of TMB in cancer immunotherapy. D.E.G. reports advisory or consulting roles for Bristol-Myers Squibb, Karyopharm, and Catalyst and receives research funding from AstraZeneca, Ber-GenBio, Karyopharm, and 3V Biosciences. L.G.T.M. receives laboratory research funding from AstraZeneca. H.Z. owns Ionis Pharmaceuticals stock worth less than $10,000. H.Z. has an active collaboration with Alnylam Pharmaceuticals and Twenty-Eight Seven Therapeutics. All other authors declare no competing interests.

Journal editors are gatekeepers of knowledge, and pharmaceutical industry payments to oncology editors have not been previously characterized. We performed a cross-sectional study of nonresearch industry payments to editors of 26 oncology research journals. A total of 433 editors were eligible for inclusion in the CMS Open Payments database from 2013 to 2018. A total of 80% of eligible editors had nonresearch payments, and the mean value of payments per editor was $106,778, which has increased over time. Only 5 out of 26 journals disclosed editor conflicts of interest and 3 of these journals reported at least one editor with no nonresearch industry payments but were found to have nonresearch payments. There was a positive correlation between journal impact factor and the average payment per editor for each journal. Our study shows the high prevalence and lack of transparency of nonresearch industry payments to oncology editors. Higher impact journals appear to be associated with greater nonresearch industry payments., (© AlphaMed Press 2020.)

Background and Aims: Foreign body ingestions (FoBIs) are a common cause for medical attention. However, trends and patterns of adult FoBIs as well as associations with clinical comorbidities and behavioral attributes have not been elucidated beyond single institutional experiences., Methods: We utilized survey data from the National Electronic Injury Surveillance System to examine fundamental characteristics of adult FoBIs involving consumer products between 2000 and 2017 across the United States. Data regarding the circumstances of FoBIs were abstracted from narrative data. Relationships among time, intent, demographics, and behavioral attributes were assessed using regression analyses, accounting for survey structure., Results: Adult FoBIs have increased in incidence over the past 2 decades from 3 to 5.3 per 100,000 persons. Examination of consumer products revealed that jewelry (15.4%), nails (7.2%), and toothpicks (6.9%) were the most commonly ingested products. The most common products ingested varied over time, and the number of unique consumer product categories ingested increased from 103 to 143 in the time period studied. Intentional ingestions accounted for 14% of adult FoBIs and frequently involved plastic bagging (13.6%), batteries (13%), nails (10.1%), and desk supplies (6.8%). Adjusted regression analyses demonstrated that compared with accidental FoBIs, intentional FoBIs have increased over time. Intentional FoBIs were more frequently associated with younger age, substance abuse, police custody, and mental and cognitive illnesses relative to accidental FoBIs., Conclusions: Our results indicate that adult FoBIs are an increasing burden of disease in the United States with social, psychiatric, and behavioral contributors to this trend., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. All rights reserved.)

Importance: Toxic effects of conventional chemotherapy and molecularly targeted cancer therapies are generally well defined and occur at predictable points. By contrast, owing to their heterogeneous manifestations, unpredictable timing, and clinical overlap with other conditions, immune-related adverse events (irAE) may be more difficult to diagnose and characterize., Objective: To determine concordance of algorithm-driven medical record review by medical oncologists for the characterization of 8 irAE in patients treated with immune checkpoint inhibitors., Design, Setting, and Participants: Cross-sectional study of patients treated with immune checkpoint inhibitors at a National Cancer Institute-designated comprehensive cancer center from November 30, 2015, to March 7, 2018. A sample size of 52 patients provided 80% power to distinguish substantial agreement (κ = 0.85) from poor agreement (κ = 0.5) based on the Cohen κ., Main Outcomes and Measures: Interrater agreement of 2 observers in the occurrence and grade of irAE., Results: Of 52 patients (32 [61.5%] male; mean [SD] age, 69 [9] years) analyzed, 42 (80.8%) had non-small cell lung cancer and all received anti-programmed cell death 1 or anti-programmed cell death ligand 1 antibodies, with 3 patients (5.8%) receiving combinations with anti-cytotoxic T-lymphocyte antigen 4 antibodies. A median (interquartile range) of 82 (47-180) documents were reviewed per case. There was limited or poor interrater agreement on irAE occurrence (Cohen κ, 0.37-0.64), with the exception of hypothyroidism (κ = 0.8). Weighted κ similarly showed limited or poor agreement for irAE grade (κ = 0.31-0.75). Differences in assessed time of onset ranged from 5 to 188 days. As a control for data availability and access, observers had a high degree of agreement for the exact start date (98%) and end date (96%) of immunotherapy administration, suggesting that information interpretation rather than identification largely accounted for assessment differences. In multivariable analysis, therapy duration (adjusted odds ratio, 4.80; 95% CI, 1.34-17.17; P = .02) and Charlson Comorbidity Index (adjusted odds ratio, 4.09; 95% CI, 1.10-15.18; P = .03) were significantly associated with discordant irAE assessment., Conclusions and Relevance: These findings underscore critical challenges in assessing the occurrence, type, timing, and severity of irAE. Apart from hypothyroidism (a condition that has a discrete diagnostic laboratory test and few other likely etiologies during immunotherapy treatment), interobserver agreement was poor. Given the importance of accurate and timely assessment of toxic effects for clinical trials and real-world disease management, efforts to improve irAE diagnosis and characterization are needed.

Importance: Underrepresentation of female authors in research publications is prevalent, but it is unclear whether this is attributable to sex disparities in research conduct or authorship practices. Case reports are a poorly understood component of the biomedical corpus, and the production of anecdotal observations is not confounded by factors associated with disparities in female representation in research publications. Whether female authorship disparities exist in nonresearch publications of clinical information is unknown., Objectives: To examine the authorship of case reports and elucidate factors associated with sex disparity., Design and Setting: Cross-sectional study of all case reports published by US authors in 2014 and 2015 indexed in PubMed performed from July 2015 to July 2018., Main Outcomes and Measures: The primary outcome measure was the proportion of female first authors. The secondary outcome measures were the proportion of female last authors and female authorship representation among different clinical specialties., Results: Bibliometric data was abstracted from 20 427 case reports published across 2538 journals. A total of 7252 (36%) and 4825 (25%) case reports had a female first and last author, respectively. In comparison, 44% and 34% of US trainees and physicians, respectively, were female in 2015. Among adult case reports, female authorship was more prevalent in academic environments compared with community settings (34.0% vs 28.2% for female first authors and 23.4% vs 19.7% for female last authors). Across states, the proportions of female first authors and last authors were universally less than the proportions of female trainees and active female physicians, respectively. Female first authorship was associated with larger author teams (odds ratio [OR], 1.02; 95% CI, 1.01-1.03), an academic affiliation (OR, 1.16; 95% CI, 1.06-1.27), and a female last author (OR, 1.58; 95% CI, 1.47-1.70). Relative to general internal medicine, specialties dominated by male clinicians were less frequently associated with female first authors. Several exceptions displaying a relatively equivalent tendency for male and female first authorship included oncology (OR, 0.97; 95% CI, 0.81-1.16), ophthalmology (OR, 0.87; 95% CI, 0.72-1.05), and radiation oncology (OR, 0.94 95% CI, 0.56-1.56)., Conclusions and Relevance: The underrepresentation of women among first and last authors in publications of case reports underscores the pervasiveness of sex disparities in medicine. Collaboration and female mentors may be critical instruments in upsetting longstanding practices associated with sex bias. Not all clinical specialties were associated with lower-than-expected female authorship, and further exploration of specialty-specific norms in publication and mentorship may elucidate specific barriers to female authorship.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease associated with immunocompromised states. We describe a case of PML, which developed after prolonged ibrutinib use and a low burden of chronic lymphocytic leukemia disease. The delay in diagnosis of the patient despite multiple presentations to medical providers across different facilities suggests that there is a lack of awareness of PML as a potential complication of ibrutinib. Treatments with postulated anti-John Cunningham polyomavirus agents and IL-2 were ineffective, likely due to the advanced state of the patient's disease. Although recent evidence indicates that ibrutinib may enhance cell-mediated immunity, consistent with elevated CD4+ and CD8+ T cells and appropriate T-cell response to mitogens in the patient, ibrutinib-mediated inhibition of the humoral function may contribute to PML pathogenesis. As the duration of ibrutinib use is often indefinite, and the number of indications for ibrutinib continues to grow, recognition and further evaluation of the link between PML and ibrutinib is warranted., (© 2018 S. Karger AG, Basel.)

Background: Clinical guidelines are commonly based on inadequate evidence, suggesting deficiencies in the present portfolio of clinical research., Aims: To investigate characteristics of clinical trials examining gastrointestinal (GI) diseases registered in ClinicalTrials.gov., Methods: A cross-sectional analysis of 13,647 GI trials and 111,535 non-GI trials initiated between January 1997 and September 2013 was performed. Entries were sorted by operational status, purpose, interventions, trial design, and epochs to identify trends and interactions in trial properties., Results: The global production of GI trials has remained static in recent years and a majority of research efforts are focused on a few diseases. While GI trials are generally produced by highly populated US states and countries, they are also seldom larger than 500 patients. The likelihood of using data monitoring committees, randomization, and double blinding in GI trials has increased over time, though a substantial fraction of GI trials still do not employ rigorous trial designs. While levels of GI trials correlate with disease burden, the explained variance of GI trials by disease burden worldwide is poor., Conclusion: GI trials are chiefly concentrated in few diseases and highly populated regions, exhibit heterogeneous trends and methodologies, and are sensitive to disease burdens, though more so within North America than worldwide., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Collaborative research has become the mainstay in knowledge production across many domains of science and is widely promoted as a means of cultivating research quality, enhanced resource utilization, and high impact. An accurate appraisal of the value of collaborative research efforts is necessary to inform current funding and research policies. We reveal contemporary trends in collaborative research spanning multiple subject fields, with a particular focus on interactions between nations. We also examined citation outcomes of research teams and confirmed the accumulative benefits of having additional authors and unique countries involved. However, when per capita citation rates were analyzed to disambiguate the effects of authors and countries, decreasing returns in citations were noted with increasing authors among large research teams. In contrast, an increasing number of unique countries had a persistent additive citation effect. We also assessed the placement of foreign authors relative to the first author in paper bylines of biomedical research articles, which demonstrated a significant citation advantage of having an international presence in the second-to-last author position, possibly occupied by foreign primary co-investigators. Our analyses highlight the evolution and functional impact of team dynamics in research and suggest empirical strategies to evaluate team science.

The scale and nature of cooperative efforts spanning geopolitical borders in clinical research have not been elucidated to date. In a cross-sectional study of 110,428 interventional trials registered in Clinicaltrials.gov, we characterized the evolution, trial demographics, and network properties of multinational clinical research. We reveal that the relative growth of international collaboratives has remained stagnant in the last two decades, although clinical trials have evolved to become much larger in scale. Multinational clinical trials are also characterized by higher patient enrollments, industry funding, and specific clinical disciplines including oncology and infectious disease. Network analyses demonstrate temporal shifts in collaboration patterns between countries and world regions, with developing nations now collaborating more within themselves, although Europe remains the dominant contributor to multinational clinical trials worldwide. Performances in network centrality measures also highlight the differential contribution of nations in the global research network. A city-level clinical trial network analysis further demonstrates how collaborative ties decline with physical distance. This study clarifies evolving themes and highlights potential growth mechanisms and barriers in multinational clinical trials, which may be useful in evaluating the role of national and local policies in organizing transborder efforts in clinical endeavors.