Trends in racial and ethnic disparities in health-related quality of life in older adults with lung cancer.

INTRODUCTION: We aimed to quantitatively examine differences in health-related quality of life (HRQOL) by race/ethnicity among older adults with lung cancer. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) data set, we identified two cohorts of patients ≥65 years old with lung cancer diagnosed from 2004 to 2015 who completed the health outcomes survey within 36 months pre- and post-diagnosis. The Physical Component Summary (PCS) and Mental Component Summary (MCS) were used to measure HRQOL. Racial/ethnic groups were White, Black, Asian, and Hispanic. Univariate (UVA) and multivariable (MVA) linear regression analyses with pairwise contrasts assessed disparities among the racial/ethnic groups. MVA models were adjusted for sex, age, marital status, education, income, year diagnosed, comorbidity count, limitations in activities of daily living, national region, histology, and treatment type (post-diagnosis cohort only). RESULTS: We identified 4025 patients in the pre-diagnosis cohort (White = 75.9 %, Asian = 6.3 %, Black = 8.7 %, and Hispanic = 6.1 %; stages I = 28.8 %, II = 8.9 %, III = 21.7 %, IV = 27.8 %, unknown = 12.7 %) and 2465 patients in the post-diagnosis cohort (White = 74.4 %, Asian = 7.8 %, Black = 8.8 %, and Hispanic = 5.8 %; stages I = 40.2 %, II = 14.1 %, III = 17.5 %, IV = 10.7 %, unknown = 17.5 %; treatment type surgery = 0.9 %, radiation = 46.5 %, radiation and surgery = 26.8 %, no radiation or surgery = 25.9 %). Upon pre-diagnosis cohort UVA, White and Asian patients had higher mean MCS scores than Black and Hispanic patients (51.3 and 52.7 vs 47.4 and 47.4, respectively; p < .001 and p < .001), White patients had higher mean PCS scores than Black patients (38.6 vs 36.0; p < .001), and Asian patients had higher mean PCS scores than White, Black, and Hispanic patients (40.7 vs 38.6, 36.0 and 37.5, respectively; p = .008, p < .001, and p = .005). On pre-diagnosis MVA, White and Asian patients had higher mean MCS scores than Hispanic patients (51.2 and 52.0, respectively, vs 47.2; p < .001). On pre-diagnosis MVA, Asian patients had higher mean PCS scores than White patients (52.0 and 51.2; p = .002).On post-diagnosis UVA, White and Asian patients had higher mean MCS scores than Black patients (48.9 and 48.9, respectively, vs 46.3; p = .006 and p = .042), White patients had higher mean MCS scores than Hispanic patients (48.9 vs 46.1; p = .015), White patients had higher mean PCS scores than Black patients (33.8 vs 31.9; p = .018), and Hispanic patients had higher mean PCS scores than Black patients (34.9 vs. 31.9; p = .019). On post-diagnosis MVA, race/ethnicity was no longer associated with differing MCS or PCS. DISCUSSION: Among older patients with lung cancer, those identifying as White or Asian had higher pre-diagnosis mental HRQOL than Hispanic patients. However, HRQOL differences before diagnosis among all racial/ethnic groups were no longer significant after cancer diagnosis and treatment. Understanding these patterns of HRQOL can be used for more pointed initiatives to improve therapeutic strategy, compliance, goals of care, and treatment-related morbidity.

Evaluating the Impact of Race and Ethnicity on Health-Related Quality of Life Disparities in Patients with Esophageal Cancer: A SEER-MHOS National Database Study.

BACKGROUND: It is unclear whether health-related quality of life (HRQOL) disparities exist between racial/ethnic groups in older patients with esophageal cancer, pre- and post-diagnosis. METHODS: Using the SEER-MHOS (Surveillance, Epidemiology, and End Results and Medicare Health Outcomes Survey) national database, we included patients ages 65-years-old or greater with esophageal cancer diagnosed from 1996 to 2017. HRQOL data within 36 months before and after diagnosis were measured by the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the SF-36 and VR-12 instruments. Total combined score (TCS) was reflected by both PCS and MCS. RESULTS: We identified 1,312 patients, with evaluable data on 873 patients pre-diagnosis and 439 post-diagnosis. On pre-diagnosis cohort MVA, the MCS was better for White over Hispanic patients (54.1 vs. 48.6, P = 0.012). On post-diagnosis cohort MVA, PCS was better for Hispanic compared with White (39.8 vs. 34.5, P = 0.036) patients, MCS was better for Asian compared with White (48.9 vs. 40.9, P = 0.034) patients, and TCS better for Asian compared with White (92.6 vs. 76.7, P = 0.003) patients. CONCLUSIONS: In older patients with esophageal cancer, White patients had better mental HRQOL as compared with Hispanic patients pre-diagnosis. However, post-diagnosis, White patients had worse mental and physical HRQOL compared with Asian and Hispanic patients, respectively, suggesting a greater negative impact on self-reported HRQOL in White patients with esophageal cancer. IMPACT: To our knowledge, this study is the first to explore HRQOL differences in patients with esophageal cancer of various racial and ethnic groups and warrants further validation in future studies.

Expression of LDL receptor-related proteins (LRPs) in common solid malignancies correlates with patient survival.

LDL receptor-related proteins (LRPs) are transmembrane receptors involved in endocytosis, cell-signaling, and trafficking of other cellular proteins. Considerable work has focused on LRPs in the fields of vascular biology and neurobiology. How these receptors affect cancer progression in humans remains largely unknown. Herein, we mined provisional databases in The Cancer Genome Atlas (TCGA) to compare expression of thirteen LRPs in ten common solid malignancies in patients. Our first goal was to determine the abundance of LRP mRNAs in each type of cancer. Our second goal was to determine whether expression of LRPs is associated with improved or worsened patient survival. In total, data from 4,629 patients were mined. In nine of ten cancers studied, the most abundantly expressed LRP was LRP1; however, a correlation between LRP1 mRNA expression and patient survival was observed only in bladder urothelial carcinoma. In this malignancy, high levels of LRP1 mRNA were associated with worsened patient survival. High levels of LDL receptor (LDLR) mRNA were associated with decreased patient survival in pancreatic adenocarcinoma. High levels of LRP10 mRNA were associated with decreased patient survival in hepatocellular carcinoma, lung adenocarcinoma, and pancreatic adenocarcinoma. LRP2 was the only LRP for which high levels of mRNA expression correlated with improved patient survival. This correlation was observed in renal clear cell carcinoma. Insights into LRP gene expression in human cancers and their effects on patient survival should guide future research.

Pertussis Toxin Is a Robust and Selective Inhibitor of High Grade Glioma Cell Migration and Invasion.

In high grade glioma (HGG), extensive tumor cell infiltration of normal brain typically precludes identifying effective margins for surgical resection or irradiation. Pertussis toxin (PT) is a multimeric complex that inactivates diverse Gi/o G-protein coupled receptors (GPCRs). Despite the broad continuum of regulatory events controlled by GPCRs, PT may be applicable as a therapeutic. We have shown that the urokinase receptor (uPAR) is a major driver of HGG cell migration. uPAR-initiated cell-signaling requires a Gi/o GPCR, N-formyl Peptide Receptor 2 (FPR2), as an essential co-receptor and is thus, PT-sensitive. Herein, we show that PT robustly inhibits migration of three separate HGG-like cell lines that express a mutated form of the EGF Receptor (EGFR), EGFRvIII, which is constitutively active. PT also almost completely blocked the ability of HGG cells to invade Matrigel. In the equivalent concentration range (0.01-1.0 µg/mL), PT had no effect on cell survival and only affected proliferation of one cell line. Neutralization of EGFRvIII expression in HGG cells, which is known to activate uPAR-initiated cell-signaling, promoted HGG cell migration. The increase in HGG cell migration, induced by EGFRvIII neutralization, was entirely blocked by silencing FPR2 gene expression or by treating the cells with PT. When U87MG HGG cells were cultured as suspended neurospheres in serum-free, growth factor-supplemented medium, uPAR expression was increased. HGG cells isolated from neurospheres migrated through Transwell membranes without loss of cell contacts; this process was inhibited by PT by >90%. PT also inhibited expression of vimentin by HGG cells; vimentin is associated with epithelial-mesenchymal transition and worsened prognosis. We conclude that PT may function as a selective inhibitor of HGG cell migration and invasion.