Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer.

Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow.

Persistence of racial disparities in early-stage lung cancer treatment.

OBJECTIVE: Although the incidence of lung cancer has decreased over the past decades, disparities in survival and treatment modalities have been observed for black and white patients with early-stage non-small cell lung cancer, despite the fact that surgical resection has been established as the standard of care. Possible contributors to these disparities are stage at diagnosis, comorbidities, socioeconomic factors, and patient preference. This study examines racial disparities in treatment, adjusting for clinicodemographic factors. METHODS: The Surveillance, Epidemiology, and End Results-Medicare dataset was queried to identify patients diagnosed with primary stage I non-small cell lung cancer between 1992 and 2009. Multivariable logistic regressions were performed to assess the association between race and treatment modalities within 1 year of diagnosis, adjusted for clinical and demographic factors. Adjusted Cox proportional hazards models were performed to evaluate disparities in survival, accounting for mode of treatment. RESULTS: We identified 22,724 patients; 21,230 (93.4%) white and 1494 (6.6%) black. Black patients were less likely to receive treatment (odds ratio [OR]adj, 0.62; 95% confidence interval [CI], 0.53-0.73) and less likely to receive surgery only when treated (ORadj, 0.70, 95% CI, 0.61-0.79). Although univariate survival for black patients was worse, when accounting for treatment mode, there was no difference in survival (hazard ratioadj, 0.97; 95% CI, 0.90-1.04 for all patients, hazard ratioadj, 0.98; 95% CI: 0.90-1.06 for treated patients). CONCLUSIONS: Treatment disparities persist, even when adjusting for clinical and demographic factors. However, when black patients receive similar treatment, survival is comparable with white patients.

Oxygen Use After Lung Cancer Surgery.

BACKGROUND: There are no published reports on predictors of oxygen (O2) use after lung cancer surgery. The prospect of O2 use after lung cancer surgery may affect a patient's therapy choice. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare data set was queried to identify patients diagnosed with primary lung cancer (stage I/II) who underwent surgical resection from 1994 to 2010. Patients with a second resection within 6 months of their first and those with preoperative O2 use were excluded. Multivariable logistic regression was performed to evaluate the odds ratios and 95% confidence intervals of O2 use (defined as being billed for home O2) after discharge for lung cancer surgery. RESULTS: Of 21,245 eligible patients from 1994 to 2010, 3,255 (15.3%) were billed for O2 use in the first month of discharge. Of these, 13.7% (447 of 3,255) stopped using within 1 month, and 1.47% died. By 6 months, an additional 6.7% died, and 46.27% (1,384 of 2,991) were still alive and using O2. Discharge on O2 was associated with higher odds of death within 6 months (odds ratio, 1.35; 95% confidence interval, 1.17 to 1.55). The significant, independent risk factors for O2 use at discharge were procedure, sex, race, histology, pulmonary comorbidities, obesity, length of stay, pulmonary complications, and discharge mode. CONCLUSIONS: Home O2 use after lung cancer surgery comprises a sizable portion of this population and is correlated with death in the first 6 months. Various predictors significantly increased the risk of O2 use at discharge. However, 49.3% of those originally discharged on O2 were alive and off O2 at 6 months.