Clinical Trials in Gastroesophageal Cancers: An Analysis of the Global Landscape of Interventional Trials From ClinicalTrials.gov.

PURPOSE: To describe the global landscape of clinical research into interventions for gastroesophageal cancers (GECs), with examination of trial characteristics, geographic distribution of trial sites, and factors associated with trial termination. METHODS: We queried ClinicalTrials.gov to identify all completed or terminated phase III interventional studies investigating GECs (esophageal squamous cell carcinoma [ESCC], esophageal adenocarcinoma [EAC], gastroesophageal junctional [GEJ], and gastric adenocarcinoma). Data on all reported trial characteristics were extracted. Pearson's chi-square and Fisher's exact tests were used to compare differences in completed and terminated trials. Multivariate logistic regression evaluated predictors of termination. RESULTS: A total of 179 trials were identified; of these, 90% were therapeutic. Most included sites in Asia (61%) and Europe (32%); few included sites in Africa (4%). Thirty percent included sites in low- and middle-income countries (LMICs). Most (70%) focused on gastric or GEJ adenocarcinoma, 13% on EAC and ESCC, and 9% on ESCC alone. Sixteen percent (n = 29) of trials terminated prematurely. In multivariate analysis, study site number, location of recruitment sites, and patient population emerged as predictors of termination. Trials recruiting from US-based sites were more likely to terminate (odds ratio [OR], 7.22 [95% CI, 1.59 to 32.69]). Trials conducted exclusively in LMICs were less likely to terminate (OR, 0.04 [95% CI, 0.01 to 0.59] v conducted in high-income countries [HICs] alone). Studies on ESCC were more likely to terminate (OR, 17.74 [95% CI, 1.49 to 210.69]). CONCLUSION: Although 80% of GECs occur in LMICs, trial activity disproportionately occurs in HICs. Few trials focus on EAC/ESCC despite being highly fatal, highlighting an unmet need. Overall, this study highlights (1) a missed opportunity to recruit patients from high-incidence regions globally; and (2) a pressing need for increasing funding, infrastructure, and support for GEC trials in LMICs.

Case of Tracheoesophageal Fistula Formation as a Rare Complication of Antiangiogenic Tyrosine Kinase Inhibitor Therapy for Metastatic Hepatocellular Carcinoma.

Treatment with antiangiogenic tyrosine kinase inhibitors (TKIs) has shown longer overall survival (OS) and progression-free survival (PFS) than with placebo in patients with advanced hepatocellular carcinoma (HCC) who have previously received systemic therapy. Unfortunately, TKIs are associated with some rare adverse events such as tracheoesophageal fistula formation (TEF). The common risk factors for TEF formation include radiation therapy, prior instrumentation of the esophagus/airway, surgery, and esophagitis. We present a case of a 64-year-old man with a history of HCC who developed TEF after three months of treatment with cabozantinib. Patients experiencing these events require prompt termination of the antiangiogenic TKI. Urgent intervention should be pursued to prevent respiratory failure. Clinicians should be aware of the potential adverse effects of antiangiogenic TKIs, especially in high-risk patients.

Influence of Race/Ethnicity and Household Median Income on Penile Cancer Mortality.

INTRODUCTION: Penile cancer, while relatively rare in developed nations, presents substantial disparities in outcomes among different demographic groups. Previous research has shown race/ethnicity and socioeconomic status, often proxied by household median income, to be critical determinants of health outcomes across various diseases. OBJECTIVE: This study examines the association of race/ethnicity and household median income with survival among penile cancer patients in the United States. METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) Registry to identify patients with a primary diagnosis of penile malignancies from 2000 to 2019. Our primary outcome of interest was the hazard of death following a diagnosis of penile cancer. We utilized the Cox regression model to explore the association between race/ethnicity and median household income and how this influences survival among these patients. We adjusted for patients' characteristics, disease stage at presentation, and treatment modalities. RESULT: Of the 6,520 penile cancer patients identified, 5,242 (80.4%) had primary malignancies. The distribution of patients was as follows: 64.1% non-Hispanic Whites, 8.9% non-Hispanic Blacks, 20.8% Hispanics, and 6.2% from other racial/ethnic groups. The median diagnosis age was 66 years (interquartile range: 56-74). Survival rates at 5, 10, and 15 years showed racial disparities: 76.4%, 72.5%, and 69.7% for non-Hispanic Whites; 70.6%, 64.1%, and 61.1% for non-Hispanic Blacks; and 70.5%, 67.4%, and 65.6% for Hispanics. Multivariate Cox regression revealed worst survival for Black (HR=1.40; 95% CI=1.08-1.81, p=0.01) and Hispanic patients (HR=1.24; 95% CI=1.01-1.52, p=0.04). No association was found between median household income and survival. Interaction analysis indicated that the poorest Black men had worse outcomes than the poorest Whites did (HR=2.08; 95% CI=1.27-3.41, p=0.003). CONCLUSION: Survival rates for non-Hispanic Black and Hispanic patients are significantly lower than those for non-Hispanic Whites. Furthermore, survival is worse for low-income Black patients than their White counterparts in the same income bracket.