ABSTRACT
BACKGROUND: Brain metastases are associated with considerable morbidity and mortality. Integration of hospice at the end of life offers patients symptom relief and improves quality of life, particularly for elderly patients who are less able to tolerate brain-directed therapy. Population-level investigations of hospice utilization among elderly patients with brain metastases are limited. METHODS: Using the Surveillance, Epidemiology and End Results-Medicare database for primary cancer sites that commonly metastasize to the brain, we identified 50 148 patients (aged 66 years and older) diagnosed with brain metastases between 2005 and 2016. We calculated the incidence, timing, and predictors of hospice enrollment using descriptive techniques and multivariable logistic regression. All statistical tests were 2-sided. RESULTS: The incidence of hospice enrollment was 71.4% (95% confidence interval [CI] = 71.0 to 71.9; P < .001), a rate that increased over the study period (P < .001). The odds of enrollment for black (odds ratio [OR] = 0.76, 95% CI = 0.71 to 0.82; P < .001), Hispanic (OR = 0.80, 95% CI = 0.72 to 0.87; P < .001), and Asian patients (OR = 0.52, 95% CI = 0.48 to 0.57; P < .001) were substantially lower than white patients; men were less likely to be enrolled in hospice than women (OR = 0.78, 95% CI = 0.74 to 0.81; P < .001). Among patients enrolled in hospice, 32.6% (95% CI = 32.1 to 33.1; P < .001) were enrolled less than 7 days prior to death, a rate that was stable over the study period. CONCLUSIONS: Hospice is used for a majority of elderly patients with brain metastases although a considerable percentage of patients die without hospice services. Many patients enroll in hospice late and, concerningly, statistically significant sociodemographic disparities exist in hospice utilization. Further investigations to facilitate targeted interventions addressing such disparities are warranted.
Subject(s)
Brain Neoplasms/secondary , Brain Neoplasms/therapy , Health Resources/statistics & numerical data , Hospices/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Aged , Aged, 80 and over , Brain Neoplasms/epidemiology , Female , Hospice Care/statistics & numerical data , Hospitalization/statistics & numerical data , Humans , Incidence , Male , SEER Program , United States/epidemiologyABSTRACT
UNLABELLED: The excessive metastatic propensity of melanoma makes it the most deadly form of skin cancer, yet the underlying mechanism of metastasis remains elusive. Here, mining of cancer genome datasets discovered a frequent loss of chromosome 19p13.3 and associated downregulation of the zinc finger transcription factor ZBTB7A in metastatic melanoma. Functional assessment of ZBTB7A-regulated genes identified MCAM, which encodes an adhesion protein key to melanoma metastasis. Using an integrated approach, it is demonstrated that ZBTB7A directly binds to the promoter and transcriptionally represses the expression of MCAM, establishing ZBTB7A as a bona fide transcriptional repressor of MCAM. Consistently, downregulation of ZBTB7A results in marked upregulation of MCAM and enhanced melanoma cell invasion and metastasis. An inverse correlation of ZBTB7A and MCAM expression in association with melanoma metastasis is further validated with data from analysis of human melanoma specimens. IMPLICATIONS: Together, these results uncover a previously unrecognized role of ZBTB7A in negative regulation of melanoma metastasis and have important clinical implications.
Subject(s)
DNA-Binding Proteins/metabolism , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Melanoma/metabolism , Skin Neoplasms/metabolism , Transcription Factors/metabolism , Animals , Binding Sites , CD146 Antigen/metabolism , Gene Deletion , HEK293 Cells , Humans , Lentivirus/metabolism , Melanoma/pathology , Mice , Mice, Nude , Mutation , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Transplantation , Oligonucleotide Array Sequence Analysis , Promoter Regions, Genetic , Transcription, Genetic , Zinc FingersABSTRACT
Elevated glycolysis is a common metabolic trait of cancer, but what drives such metabolic reprogramming remains incompletely clear. We report here a novel transcriptional repressor-mediated negative regulation of glycolysis. ZBTB7A, a member of the POK (POZ/BTB and Krüppel) transcription repressor family, directly binds to the promoter and represses the transcription of critical glycolytic genes, including GLUT3, PFKP, and PKM. Analysis of The Cancer Genome Atlas (TCGA) data sets reveals that the ZBTB7A locus is frequently deleted in many human tumors. Significantly, reduced ZBTB7A expression correlates with up-regulation of the glycolytic genes and poor survival in colon cancer patients. Remarkably, while ZBTB7A-deficient tumors progress exceedingly fast, they exhibit an unusually heightened sensitivity to glycolysis inhibition. Our study uncovers a novel tumor suppressor role of ZBTB7A in directly suppressing glycolysis.
