10 research outputs found
Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.
The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies
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The Effect of Anemia on Mortality in Indigent Patients With Mild‐to‐Moderate Chronic Heart Failure
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The impact of a standardized disease management program on race/ethnicity and gender disparities in care and mortality
Data on racial and gender differences in mortality in patients followed in a standardized heart failure disease management program (HFDMP) are scarce.
Survival was calculated by race/ethnicity and gender for 837 patients enrolled in a HFDMP. (The patients studied were indigent African American and White outpatients [39% African American, 36% female] enrolled into at Leonard J. Chabert Medical Center in Houma, Louisiana.) The hazard ratio associated with demographic and clinical characteristic individually and as a whole, was estimated for the four groups.
White males had the highest mortality (African American female: HR=0.64, African American male: HR=0.65, White female: HR=0.67, p<.05). Age (HR=1.04, p<.001), ejection fraction (HR=0.97, p<.001), New York Heart Association (NYHA) (HR=1.57, p<.001), systolic blood pressure (HR=0.99, p<.05), hematocrit (HR=0.96, p<.01), diabetes (HR=0.98, p<.05), and body mass index (HR=0.98, p<.05) were significant predictors of mortality in the univariate model. Age (HR=1.04, p<.001), NYHA (HR=1.40, p<.001), diabetes (HR=2.52, p<.001), and White female (HR=.44, p<.01) were significant predictors of mortality in the multivariate model.
With the exception of White females, who demonstrated lower mortality, amongst African American males and females and White males who participated in a HFDMP no difference in survival was observed
Representative sequencing: Unbiased sampling of solid tumor tissue
International audienceAlthough thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias isinherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g., 6 mmbiopsy), which becomes grossly under-powered as tumor volume scales. Here, we demonstrate representative sequencing (Rep-Seq) as a new method to achieve unbiased tumor tissue sampling. Rep-Seq uses fixed residual tumor material, which is homogenized and subjected to next-generation sequencing. Analysis of intratumor tumor mutation burden (TMB) variability shows a high level of misclassification using current single-biopsy methods, with 20% of lung and 52% of bladder tumors having at least one biopsy with high TMB butlow clonal TMB overall. Misclassification rates by contrast are reduced to 2% (lung) and 4% (bladder) when a more representative sampling methodology is used. Rep-Seq offers an improved sampling protocol for tumor profiling, with significant potential for improved clinical utility and more accurate deconvolution of clonal structure