Our analysis indicates that the incidence of SCLC is decreasing in the United States, and only modest improvements have been seen in survival over the last 30 years. Possible explanations for the decreasing incidence include the decrease in the percentage of smokers and the change to low-tar filter cigarettes. Despite trends toward modest improvement in survival, the outcome remains very poor.
ContextPatients with cancer often have other medical ailments, referred to as comorbidity. Comorbidity may impact treatment decision-making, prognosis, and quality of care assessment.Objective To assess whether comorbidity information can provide important prognostic information in a hospital-based cancer registry.Design, Setting, and Participants An observational prospective cohort study using comorbidity data collected by trained hospital-based cancer registrars. Comorbidity was obtained through medical record review using the Adult Comorbidity Evaluation 27, a validated chart-based comorbidity instrument. A total of 17 712 patients receiving care between January 1, 1995, and January 31, 2001, for the primary diagnosis of new cancer of the prostate, lung (nonsmall cell), breast, digestive system, gynecological, urinary system, or head and neck were included.Main Outcome Measure Duration in months of overall survival.Results A total of 19268 patients were included in the study; median duration of follow-up was 31 months. Of these patients, 1556 (8.0%) were excluded due to missing or unknown data. Severity of comorbidity strongly influenced survival in a dosedependent fashion and the impact of comorbidity was independent of cancer stage. Compared with patients without comorbidity, the adjusted hazard ratio associated with mild comorbidity was 1.21 (95% confidence interval [CI], 1.13-1.30), moderate comorbidity was 1.86 (95% CI, 1.73-2.00), and severe comorbidity was 2.56 (95% CI, 2.35-2.81). Adjusted Kaplan-Meier survival curves revealed that at any point in time the patients with more severe levels of comorbidity had worse survival (partial 2 3 due to comorbidity, 523.54; PϽ.001). Model discrimination ranged from 0.71 for head and neck to 0.86 for prostate cancers.
ConclusionsComorbidity is an important independent prognostic factor for patients with cancer. The inclusion of comorbidity in hospital-based cancer registries will increase the value and use of observational research.
Concurrent comorbidities had the greatest prognostic impact among groups with the highest survival rate and the least impact in groups with the lowest survival rate. These findings can be used to help determine the role comorbidity information should play in studies of cancer outcomes.
Renal clear cell carcinoma (RCC) is the most common type of kidney cancer and the 8th most common cancer overall in the US. RCC survival rates drop precipitously with regional and distant spread and recent studies have demonstrated that RCC presents an epithelial-mesenchymal transition (EMT) phenotype linked to increased recurrence and decreased survival. EMT is a key characteristic of tumor stem cells (TSCs) along with chemo-resistance and radio-resistance, which are also phenotypic of RCC. Targeting these factors is key to increasing the survival of RCC patients. Doublecortin-like kinase 1 (DCLK1) marks TSCs in pancreatic and colorectal cancer and regulates EMT and stemness. Analysis of the Cancer Genome Atlas' RCC dataset revealed that DCLK1 is overexpressed and dysregulated on the mRNA and epigenetic level in more than 93% of RCC tumors relative to adjacent normal tissue. Immunohistochemistry using α-DCLK1 antibody confirmed overexpression and demonstrated a major increase in immunoreactivity in stage II-III tumors compared to normal kidney and stage I tumors. Small-interfering RNA (siRNA) mediated knockdown of DCLK1 resulted in decreased expression of EMT and pluripotency factors and significantly reduced invasion, migration, focal adhesion, drug-resistance, and clonogenic capacity. These findings suggest that DCLK1 is a novel, overexpressed factor in RCC progression that may be targeted to suppress EMT, metastasis, and stemness in early-stage and advanced RCC to increase patient survival. Moreover, the possibility that DCLK1 may mark a population of tumor stem-like cells in RCC should be further investigated in light of these findings.
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