Real-World comprehensive genomic profiling data for diagnostic clarity in pulmonary Large-Cell neuroendocrine carcinoma.

BACKGROUND: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is an uncommon subtype of lung cancer believed to represent a spectrum of tumors sharing characteristics of both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Other groups have proposed genomic LCNEC subtypes, including small cell-like, non-small cell-like, and carcinoid-like subtypes. The primary goal of this study was to better define the NSCLC-like subtype with comprehensive genomic profiling (CGP). METHODS: An institutional database was queried to identify tissue specimens (TBx, N = 1,426) and liquid biopsies (LBx, N = 39) submitted for CGP during routine clinical care (8/2014 - 7/2023) with a disease ontology of LCNEC. TBx were profiled with FoundationOne® (F1) or F1CDx, using hybrid-capture technology to detect genomic alterations (GAs). RESULTS: 1,426 LCNEC samples were genomically profiled. The presence of RB1 and TP53 genomic alterations (GAs) were used to define a SCLC-like subtype (n = 557). A carcinoid-like group was defined by the presence of MEN1 mutation in the absence of TP53 GAs (n = 25). The remaining 844 samples were compared to the SCLC-like group and GAs enriched relative to the SCLC-like samples with a false discovery rate (FDR) < 0.0001 were used to define a NSCLC-like group. These NSCLC-like subtype-defining GAs included SMARCA4, KRAS, FGF3/4/19, STK11, CDKN2A/B, MTAP, and CCND1. Under this schema, 530 samples were classified as NSCLC-like and 314 remained unclassified. CONCLUSIONS: Large-scale CGP can better characterize biologically distinct molecular subtypes in LCNEC. Further studies to define how these molecular subtypes may help inform treatment decisions in this complex and challenging malignancy are warranted.

Disparities in Lung Cancer Clinical Trial Discussion and Enrollment at a Safety Net Hospital.

BACKGROUND: In the United States, less than 5% of all adult cancer patients enroll in clinical trials. Few studies explore participation in cancer clinical trials at safety net hospitals, which disproportionately care for minoritized, low-income, uninsured, and underinsured populations. Our study aims to investigate disparities in clinical trial discussions and enrollment among lung cancer patients at Boston Medical Center, the largest safety net hospital in New England. METHODS: We included 1121 patients diagnosed with lung cancer between January 2015 and December 2020. Electronic Medical Records (EMR) were queried, and patients were categorized into three groups: (1) clinical trial discussed and the patient enrolled, (2) clinical trial discussed but the patient not enrolled, and (3) clinical trial not discussed. Sociodemographic variables such as age, gender, race, ethnicity, city, primary language, median household income, medical insurance type, and education level were also collected. Chi-squared,t test, and multivariate regression analysis was done using SPSS version 26.0. RESULTS: Of the 1121 patients, clinical trials were discussed in 141 patients (12.6%), of which 22 (15.6%) were enrolled. Clinical trial discussions were conducted more with younger patients (68.19 vs 71.37, p = .001), but on multivariate analysis there was no significant difference (OR = 1.023; 95% CI 0.998-1.048; p = .068). There was no significant difference in clinical trial discussion or enrollment between the other sociodemographic factors. CONCLUSION: Additional study of barriers to cancer clinical trial discussion and enrollment at safety net institutions can serve as a prerequisite to ameliorating racial disparities observed on a national scale.

Disparities in outcomes between Black and White patients in North America with thoracic malignancies and COVID-19 infection (TERAVOLT).

BACKGROUND: Patients with thoracic malignancies who develop COVID-19 infection have a higher hospitalization rate compared to the general population and to those with other cancer types, but how this outcome differs by race and ethnicity is relatively understudied. METHODS: The TERAVOLT database is an international, multi-center repository of cross-sectional and longitudinal data studying the impact of COVID-19 on individuals with thoracic malignancies. Patients from North America with thoracic malignancies and confirmed COVID-19 infection were included for this analysis of racial and ethnic disparities. Patients with missing race data or races and ethnicities with fewer than 50 patients were excluded from analysis. Multivariable analyses for endpoints of hospitalization and death were performed on these 471 patients. RESULTS: Of the 471 patients, 73% were White and 27% were Black. The majority (90%) were non-Hispanic ethnicity, 5% were Hispanic, and 4% were missing ethnicity data. Black patients were more likely to have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 2 (p-value = 0.04). On multivariable analysis, Black patients were more likely than White patients to require hospitalization (Odds Ratio (OR): 1.69, 95% CI: 1.01-2.83, p-value = 0.044). These differences remained across different waves of the pandemic. However, no statistically significant difference in mortality was found between Black and White patients (OR 1.29, 95% CI: 0.69-2.40, p-value = 0.408). CONCLUSIONS: Black patients with thoracic malignancies who acquire COVID-19 infection are at a significantly higher risk of hospitalization compared to White patients, but there is no significant difference in mortality. The underlying drivers of racial disparity among patients with thoracic malignancies and COVID-19 infection require ongoing investigation.

Disparities in US Lung Cancer Clinical Trial Enrollment.

BACKGROUND: Disparities within clinical trial enrollment are well-documented, reducing the generalizability of results. Although nearly 30 years have passed since Congress passed the NIH Revitalization Act to encourage the participation of minoritized populations in clinical trials, these patients continue to be underrepresented. This study aimed to investigate lung cancer clinical trial enrollment disparities for race/ethnicity, sex, and age. METHODS: We queried the National Institutes of Health: US National Library of Medicine database of clinical trials for all US-based lung cancer clinical trials completed between 2004 and 2021 and collected data on race and ethnicity, gender, and age breakdown. This data was compared to Surveillance, Epidemiology, and End Results (SEER) database data. Independent sample t-tests and Kruskal-Wallis's approach were used to analyze the data. RESULTS: Of 311 eligible trials with exclusive US enrollment, 136 (44%) reported race and ethnicity breakdown for the patient cohort representing 9869 patients. Hispanic, Non-Hispanic American Indian/Alaska Native, Non-Hispanic Black, and Non-Hispanic Unreported participants were underrepresented (p = 0.001, p = 0.005, p = 0.014, p = 0.002, respectively). Non-Hispanic White participants were overrepresented (p = 0.018). Disparities worsened from 2017 to 2021 for Hispanic patients (p = 0.03). No significant differences were found for sex or age. CONCLUSIONS: Disparities for clinical lung cancer trial enrollment have not shown statistically significant improvement since 2004, and representation remains unequal, especially for racial and ethnic minorities.

Association between hospital safety-net burden and receipt of trimodality therapy and survival for patients with esophageal cancer.

BACKGROUND: To examine the relationship between hospital safety-net burden and (1) receipt of surgery after chemoradiation (trimodality therapy) and (2) survival in esophageal cancer patients. METHODS: The National Cancer Database was queried to identify 22,842 clinical stage II to IVa esophageal cancer patients diagnosed in 2004 to 2015. The treatment facilities were categorized by proportion of uninsured/Medicaid-insured patients into percentiles. No safety-net burden hospitals (0-37th percentile) treated no uninsured/Medicaid-insured patients, whereas low (38-75th percentile) and high (76-100th percentile) safety-net burden hospitals treated a median (range) of 8.8% (0.87%-16.7%) and 23.6% (16.8%-100%), respectively. Adjusted odds ratios and hazard ratios with 95% confidence intervals were computed, adjusting for patient, tumor, and treatment characteristics. RESULTS: Compared to no safety-net burden hospital patients, high safety-net burden hospital patients were significantly more likely to be young, Black, and low-income. Age, female sex, Black race, Hispanic ethnicity, nonprivate insurance, lower income, higher comorbidity score, upper esophageal location, squamous cell histology, higher stage, time to treatment, and treatment at a community program or a low-volume facility were associated with lower odds of receiving trimodality therapy. Adjusting for these factors, high safety-net burden hospital patients were less likely to receive surgery after chemoradiation versus no safety-net burden hospital patients (adjusted odds ratio 0.77 [95% confidence interval 0.68-0.86], P < .0001); no difference was detected comparing low safety-net burden hospitals versus no safety-net burden hospitals (adjusted odds ratio 1.01 [0.92-1.11], P = .874). No significant survival difference was noted by safety-net burden (low safety-net burden hospitals versus no safety-net burden hospitals: adjusted hazard ratio 1.01 [0.96-1.06], P = .704; high safety-net burden hospital versus no safety-net burden hospitals: adjusted hazard ratio 0.99 [0.93-1.06], P = .859). CONCLUSION: Adjusting for patient, tumor, and treatment factors, high safety-net burden hospital patients were less likely to undergo surgery after chemoradiation but without significant survival differences.

Timeliness of Lung Cancer Care From the Point of Suspicious Image at an Urban Safety Net Hospital.

BACKGROUND: Timeliness of care is an important metric for lung cancer patients, and care delays in the safety-net setting have been described. Timeliness from the point of the suspicious image is not well-studied. Herein, we evaluate time intervals in the workup of lung cancer at an urban, safety net hospital and assess for disparities by demographic and clinical factors. PATIENTS AND METHODS: We performed a retrospective analysis of lung cancer patients receiving some portion of their care at Boston Medical Center between 2015 and 2020. A total of 687 patients were included in the final analysis. Median times from suspicious image to first treatment (SIT), suspicious image to diagnosis (SID), and diagnosis to treatment (DT) were calculated. Nonparametric tests were applied to assess for intergroup differences in time intervals. RESULTS: SIT, SID, and DT for the entire cohort was 78, 34, and 32 days, respectively. SIT intervals were 87 days for females and 72 days for males (p < .01). SIT intervals were 106, 110, 81, and 41 days for stages I, II, III, and IV, respectively (p < .01). SID intervals differed between black (40.5) and Hispanic (45) patients compared to white (28) and Asian (23) patients (p < .05). CONCLUSION: Advanced stage at presentation and male gender were associated with more timely treatment from the point of suspicious imaging while white and Asian were associated with more timely lung cancer diagnosis. Future analyses should seek to elucidate drivers of timeliness differences and assess for the impact of timeliness disparities on patient outcomes in the safety net setting.

Black Race Remains Associated with Lower Eligibility for Screening Using 2021 US Preventive Services Task Force Recommendations Among Lung Cancer Patients at an Urban Safety Net Hospital.

OBJECTIVE: To evaluate whether the revised US Preventive Services Task Force (USPSTF) criteria reduced inequities in lung cancer screening (LCS) eligibility among a racially diverse sample of patients with lung cancer. METHODS: This is a retrospective analysis of adults diagnosed with primary lung malignancies at an urban safety net hospital. For all patients and exclusively ever-smokers, χ2 tests were used to evaluate differences in LCS eligibility among socio-demographic variables using the 2013 and 2021 USPSTF criteria. Patients who were ineligible for LCS were categorized by reason for exclusion. RESULTS: Among 678 lung cancer patients (46% female, mean age 66 ± 10 years), 51% were White, and 39% were Black. Using the 2013 guidelines, White patients (57%) would have been more likely to be eligible than Black (37%) and other-race patients (35%) (P < 0.0001) at time of cancer diagnosis. Under the 2021 guidelines, White patients (68%) remained more likely to be eligible for LCS than Black (54%) and other-race patients (48%) (P = 0.0002). Among exclusively ever-smoking patients, we did not observe a significant difference in eligibility by race under the 2021 USPSTF guidelines (White [73%], Black [65%], and other-race [65%]; [P = 0.48]). Sex, ethnicity, education level, and insurance type were not associated with differential screening eligibility under either the 2013 or 2021 guidelines. CONCLUSION: The revised 2021 USPSTF LCS guidelines may not be sufficient to eliminate racial inequities in LCS eligibility among patients who go on to be diagnosed with primary lung cancer. Differential rates of lung cancer among never-smokers may contribute to this inequity.

Implementation Challenges and Disparities in Molecular Testing for Patients With Stage IV NSCLC: Perspectives from an Urban Safety-Net Hospital.

The advent of next-generation sequencing (NGS), including both tissue assays and circulating tumor DNA (ct-DNA), has been pivotal in improving outcomes for patients with non-small cell lung cancer (NSCLC). Although molecular testing is standard of care for advanced NSCLC, challenges still exist in its implementation. This Perspective examines barriers to the widespread implementation of NGS from the vantage point of a single urban safety-net institution, with a particular focus on examining racial disparities in NGS completion. We conducted a review of patients at our institution from January 2015 through January 2022 and examined molecular testing patterns before and after the publication of updated molecular testing guidelines from the International Association for the Study of Lung Cancer (IASLC), Association for Molecular Pathology (AMP), and College of American Pathologists (CAP) in March of 2018. While NGS increased over time, we found that 43% of patients in the March 2018 through January 2022 group still did not receive NGS, and the most common reasons for the absence of testing included a lack of physician ordering and insufficient tissue on biopsy. We did not note any racial disparities in completion or time-to-adoption of NGS. Patients with squamous cell carcinoma (SCC) histology were noted to receive liquid NGS markedly less often than patients with non-squamous histology in the March 2018 through January 2022 period. Based on our own data and a review of findings from colleagues in the field, we advocate for additional physician educational programming, increased use of ct-DNA biopsy, automated (reflexive) NGS tissue testing on receipt of biopsy, and consideration for the broader molecular profiling of patients with SCC histology.

The impact of substance use on health care utilization, treatment, and outcomes in patients with non-small cell lung cancer.

Background: Mortality from non-small cell lung cancer (NSCLC) has improved with screening and novel treatments. The substance use epidemic has threatened health outcomes in a variety of diseases, but little is known about how it is associated with NSCLC outcomes. Methods: We performed a retrospective cohort study of 211 patients with NSCLC treated at a safety-net hospital. Sociodemographic data and clinical outcomes were extracted via review of electronic medical records. Patients were stratified based on substance use status. Comparative and multivariable analyses were performed to evaluate baseline characteristics and lung cancer outcomes including survival. Results: Among 193 patients (91.5%) with information available on substance use, 24.9% reported substance use; specifically, alcohol, marijuana, and illicit substances. Patients with substance use were more likely to have increased health care utilization and poor social determinants of health, including safe housing, stable employment, and social support. There were no significant differences in treatment adherence. Only 6.3% of patients with substance use did not receive guideline concordant care (GCC) compared to 24.8% of patients without substance use; due to poor performance status, increased comorbidities, or loss to follow up. On univariable analysis, patients with substance use experienced inferior median overall survival (OS) if they had metastatic disease (0.40 vs. 1.03 years, P=0.01). However, in the multivariable analysis, substance use did not predict for survival. Independent predictors of mortality were sex (male HR, 1.67; 95% CI: 1.04-2.68; P=0.04), smoking status (current smoking HR, 2.63; 95% CI: 1.14-6.08; P=0.02), and stage (stage IV HR, 14.96; 95% CI: 6.28-35.63; P=0.008). Conclusions: Substance use is associated with poor social determinants of health and increased health care utilization. On multivariable analysis, substance use was not independently associated with OS once guideline-concordant care was used. Future studies should focus on improving our understanding of these associations, delineating potential mechanisms, and developing evidence-based strategies to reduce health care utilization and overcome challenges related to poor social determinants of health.

Small cell lung cancer in young patients: trends in sociodemographic factors, diagnosis, treatment, and survival.

Background: Small cell lung cancer (SCLC) in patients <50 years old has unique socioeconomic and clinical implications. We aimed to examine the demographics, treatment patterns, and survival of young patients with SCLC and compared them to older adults. Methods: The National Cancer Database (NCDB) was queried to identify SCLC cases diagnosed from 2004 to 2016. Patients were divided into three age groups: ≥18-<50, ≥50-<70, and ≥70 years. Patient characteristics were evaluated for survival within each age group. Kaplan-Meier and Cox regression analyses were used to assess survival. Results: Of the 172,453 evaluated SCLC patients (median age 66 years), 8,792 were ≥18-<50 years old. Compared to the older groups, patients under 50 were more likely to be Black, uninsured or on Medicaid, have household income <$30,000, and present with stage III or IV disease (P<0.0001 for all). While young patients were more likely to receive guideline-concordant care (GCC), the hazard of death increased to 1.96 (95% CI: 1.80-2.14; P<0.0001) with receipt of nonstandard therapy. Private insurance, female gender, non-White race, Hispanic ethnicity, and higher income were associated with better survival. The youngest cohort had significantly better survival overall when compared to the older patients (P<0.0001), but the survival advantage was reduced with the advancing stage. Conclusions: SCLC patients under 50 years old represent a socioeconomically disadvantaged group with advanced disease at presentation. Despite having fewer comorbidities and being offered guideline-concordant treatment, younger patients with SCLC have only marginally better survival than older patients in advanced stages.

A Definitive Prognostication System for Patients With Thoracic Malignancies Diagnosed With Coronavirus Disease 2019: An Update From the TERAVOLT Registry.

INTRODUCTION: Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far. METHODS: Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics. RESULTS: As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection procedure then identified the following seven major determinants of death: Eastern Cooperative Oncology Group-performance status (ECOG-PS) (OR = 2.47, 1.87-3.26), neutrophil count (OR = 2.46, 1.76-3.44), serum procalcitonin (OR = 2.37, 1.64-3.43), development of pneumonia (OR = 1.95, 1.48-2.58), C-reactive protein (OR = 1.90, 1.43-2.51), tumor stage at COVID-19 diagnosis (OR = 1.97, 1.46-2.66), and age (OR = 1.71, 1.29-2.26). The receiver operating characteristic analysis for death of the selected model confirmed its diagnostic ability (area under the receiver operating curve = 0.78, 95% confidence interval: 0.75-0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90%, and the tree-based model recognized ECOG-PS, neutrophil count, and c-reactive protein as the major determinants of prognosis. CONCLUSIONS: From 73 variables analyzed, seven major determinants of death have been identified. Poor ECOG-PS was found to have the strongest association with poor outcome from COVID-19. With our analysis, we provide clinicians with a definitive prognostication system to help determine the risk of mortality for patients with thoracic malignancies and COVID-19.

The Impact of Residential Racial Segregation on Non-Small Cell Lung Cancer Treatment and Outcomes.

BACKGROUND: Despite decreases in lung cancer incidence, racial disparities in diagnosis and treatment persist. Residential segregation and structural racism have effects on socioeconomic status for black people, affecting health care access. This study aims to determine the impact of residential segregation on racial disparities in non-small cell lung cancer (NSCLC) treatment and mortality. METHODS: Patient data were obtained from Surveillance, Epidemiology, and End Results Program database for black and white patients diagnosed with NSCLC from 2004-2016 in the 100 most populous counties. Regression models were built to assess outcomes of interest: stage at diagnosis and surgical resection of disease. Predicted margins assessed impact of index of dissimilarity (IoD) on these disparities. Competing risk regressions for black and white patients in highest and lowest quartiles of IoD were used to assess cancer-specific mortality. RESULTS: Our cohort had 193,369 white and 35,649 black patients. Black patients were more likely to be diagnosed at advanced stage than white patients, with increasing IoD. With increasing IoD, black patients were less likely to undergo surgical resection than white patients. Disparities were eliminated at low IoD. Black patients at high IoD had lower cancer-specific survival. CONCLUSIONS: Black patients were more likely to present at advanced disease, were less likely to receive surgery for early stage disease, and had higher cancer-specific mortality at higher IoD. Our findings highlight the impact of structural racism and residential segregation on NSCLC outcomes. Solutions to these disparities must come from policy reforms to reverse residential segregation and deleterious socioeconomic effects of discriminatory policies.

Trends of HIV-Related Cancer Mortality between 2001 and 2018: An Observational Analysis.

The burden of AIDS-defining cancers has remained relatively steady for the past two decades, whilst the burden of non-AIDS-defining cancer has increased. Here, we conduct a study to describe mortality trends attributed to HIV-associated cancers in 31 countries. We extracted HIV-related cancer mortality data from 2001 to 2018 from the World Health Organization Mortality Database. We computed age-standardized death rates (ASDRs) per 100,000 population using the World Standard Population. Data were visualized using Locally Weighted Scatterplot Smoothing (LOWESS). Data for females were available for 25 countries. Overall, there has been a decrease in mortality attributed to HIV-associated cancers among most of the countries. In total, 18 out of 31 countries (58.0%) and 14 out of 25 countries (56.0%) showed decreases in male and female mortality, respectively. An increasing mortality trend was observed in many developing countries, such as Malaysia and Thailand, and some developed countries, such as the United Kingdom. Malaysia had the greatest increase in male mortality (+495.0%), and Canada had the greatest decrease (-88.5%). Thailand had the greatest increase in female mortality (+540.0%), and Germany had the greatest decrease (-86.0%). At the endpoint year, South Africa had the highest ASDRs for both males (16.8/100,000) and females (19.2/100,000). The lowest was in Japan for males (0.07/100,000) and Egypt for females (0.028/100,000).

Racial and Other Healthcare Disparities in Patients With Extensive-Stage SCLC.

INTRODUCTION: Systemic treatment with chemotherapy is warranted for patients with extensive-stage SCLC (ES-SCLC). The objective of this study was to determine whether racial and other healthcare disparities exist in receipt of chemotherapy for ES-SCLC. METHODS: Utilizing the National Cancer Database, 148,961 patients diagnosed to have stage IV SCLC from 2004 to 2016 were identified. Adjusted ORs with 95% confidence intervals (95% CIs) were computed for receipt of chemotherapy using multivariate logistic regression modeling. Cox regression modeling was used to perform overall survival analysis, and adjusted hazard ratios were calculated. RESULTS: A total of 82,592 patients were included, among which chemotherapy was not administered to 6557 (7.9%). Higher education, recent year of diagnosis, and treatment at more than one facility were associated with increased odds of receiving chemotherapy. Factors associated with a decreased likelihood of receiving chemotherapy were increasing age, race, nonprivate insurance, and comorbidities. On multivariate analysis, black patients had lower odds of receiving chemotherapy compared with white patients (adjusted OR, 0.85; 95% CI: 0.77-0.93, p = 0.0004). Furthermore, black patients had better survival compared with white patients (adjusted hazard ratio, 0.91; 95% CI: 0.89-0.94, p = 0.91). The 1-year survival (median survival) for black and white patients was 31.7% (8.3 mo) and 28.6% (8 mo), respectively. CONCLUSIONS: Black patients with ES-SCLC were less likely to receive chemotherapy, as were elderly, uninsured, and those with nonprivate insurance. Further studies are required to address underlying reasons for lack of chemotherapy receipt in black patients with ES-SCLC and guide appropriate interventions to mitigate disparities.

c-Cbl Expression Correlates with Human Colorectal Cancer Survival and Its Wnt/ß-Catenin Suppressor Function Is Regulated by Tyr371 Phosphorylation.

The proto-oncogene ß-catenin drives colorectal cancer (CRC) tumorigenesis. Casitas B-lineage lymphoma (c-Cbl) inhibits CRC tumor growth through targeting nuclear ß-catenin by a poorly understood mechanism. In addition, the role of c-Cbl in human CRC remains largely underexplored. Using a novel quantitative histopathologic technique, we demonstrate that patients with high c-Cbl-expressing tumors had significantly better median survival (3.7 years) compared with low c-Cbl-expressing tumors (1.8 years; P = 0.0026) and were more than twice as likely to be alive at 3 years compared with low c-Cbl tumors (P = 0.0171). Our data further demonstrate that c-Cbl regulation of nuclear ß-catenin requires phosphorylation of c-Cbl Tyr371 because its mutation compromises its ability to target ß-catenin. The tyrosine 371 (Y371H) mutant interacted with but failed to ubiquitinate nuclear ß-catenin. The nuclear localization of the c-Cbl-Y371H mutant contributed to its dominant negative effect on nuclear ß-catenin. The biological importance of c-Cbl-Y371H was demonstrated in various systems, including a transgenic Wnt-8 zebrafish model. c-Cbl-Y371H mutant showed augmented Wnt/ß-catenin signaling, increased Wnt target genes, angiogenesis, and CRC tumor growth. This study demonstrates a strong link between c-Cbl and overall survival of patients with CRC and provides new insights into a possible role of Tyr371 phosphorylation in Wnt/ß-catenin regulation, which has important implications in tumor growth and angiogenesis in CRC.

Racial differences in colorectal cancer survival at a safety net hospital.

BACKGROUND: While racial disparity in colorectal cancer survival have previously been studied, whether this disparity exists in patients with metastatic colorectal cancer receiving care at safety net hospitals (and therefore of similar socioeconomic status) is poorly understood. METHODS: We examined racial differences in survival in a cohort of patients with stage IV colorectal cancer treated at the largest safety net hospital in the New England region, which serves a population with a majority (65%) of non-Caucasian patients. Data was extracted from the hospital's electronic medical record. Survival differences among different racial and ethnic groups were examined graphically using Kaplan-Meier analysis. A univariate cox proportional hazards model and a multivariable adjusted model were generated. RESULTS: Black patients had significantly lower overall survival compared to White patients, with median overall survival of 1.9 years and 2.5 years respectively. In a multivariate analysis, Black race posed a significant hazard (HR 1.70, CI 1.01-2.90, p=0.0467) for death. Though response to therapy emerged as a strong predictor of survival (HR=0.4, CI=0.2-0.7, p=0.0021), it was comparable between Blacks and Whites. CONCLUSIONS: Despite presumed equal access to healthcare and socioeconomic status within a safety-net hospital system, our results reinforce findings from previous studies showing lower colorectal cancer survival in Black patients, and also point to the importance of investigating other factors such as genetic and pathologic differences.

c-Cbl mediates the degradation of tumorigenic nuclear ß-catenin contributing to the heterogeneity in Wnt activity in colorectal tumors.

Despite the loss of Adenomatous Polyposis Coli (APC) in a majority of colorectal cancers (CRC), not all CRCs bear hallmarks of Wnt activation, such as nuclear ß-catenin. This underscores the presence of other Wnt regulators that are important to define, given the pathogenic and prognostic roles of nuclear ß-catenin in human CRC. Herein, we investigated the effect of Casitas B-lineage lymphoma (c-Cbl) on nuclear ß-catenin, which is an oncoprotein upregulated in CRC due to loss-of-function APC or gain-of-function CTNNB1 mutations. Despite mechanistic rationale and recent discoveries of c-Cbl's mutations in solid tumors, little is known about its functional importance in CRC. Our study in a cohort of human CRC patients demonstrated an inverse correlation between nuclear ß-catenin and c-Cbl. Further investigation showed that the loss of c-Cbl activity significantly enhanced nuclear ß-catenin and CRC tumor growth in cell culture and a mouse xenograft model. c-Cbl interacted with and downregulated ß-catenin in a manner that was independent of CTNNB1 or APC mutation status. This study demonstrates a previously unrecognized function of c-Cbl as a negative regulator of CRC.

Gastrointestinal symptoms are closely associated with depression in iron deficiency anemia: a comparative study.

BACKGROUND AND OBJECTIVES: Until now, very few studies evaluated the association between gastrointestinal and psychiatric symptoms in iron deficiency anemia (IDA). The study investigated the frequency of functional dyspepsia (FD) in IDA patients and determined its association with depression and somatization. DESIGN AND SETTINGS: The study was conducted at the Hematology Department of Trakya University Medical Faculty, which is a tertiary referral center in northwestern Turkey. It was a case-control study. MATERIALS AND METHODS: A total of 125 consecutive IDA patients and 57 healthy control subjects were included. Patients and controls were questioned about the severity of their gastrointestinal system (GIS)-related symptoms and the presence of constipation and associated symptoms using a visual analog scale. In addition, IDA patients were administered a validated depression scale (Beck Depression Inventory, BDI) and somatization symptoms checklist. RESULTS: IDA patients had more frequent self-reported constipation compared with controls (56% vs 22.8%, P < .001). The mean scores of bloating, dyspepsia, and constipation-related quality of life (QoL) disturbance were significantly higher in the IDA group than in the control group (all P values.