Publications

PURPOSE

In a sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer who received at least two cycles of chemotherapy (CTX), the purposes were to evaluate for inter-individual differences in the severity of sleep disturbance and determine which demographic, clinical, and symptom characteristics were associated with initial levels as well as the trajectories of sleep disturbance.

METHODS

A total of 1331 patients completed study questionnaires in their homes, at six time points over two cycles of CTX (prior to CTX administration, approximately 1 week after CTX administration, and approximately 2 weeks after CTX administration). Questionnaires included demographic, clinical, and symptom assessments (i.e., General Sleep Disturbance Scale, Lee Fatigue Scale, Center for Epidemiological Studies-Depression Scale, Spielberger State-Trait Anxiety Inventories, Attentional Function Index). Hierarchical linear modeling based on full maximum likelihood estimation was performed.

RESULTS

Characteristics associated with higher initial levels of sleep disturbance included higher body mass index, poorer functional status, higher trait anxiety, higher depressive symptoms, and higher evening fatigue. Characteristics associated with the worse trajectories of sleep disturbance were higher levels of education and higher sleep disturbance at enrollment. Characteristics associated with both higher initial levels and worse trajectories of sleep disturbance were higher morning fatigue and worse attentional function.

CONCLUSIONS

A large amount of inter-individual variability exists in sleep disturbance during CTX. The modifiable and non-modifiable characteristics found in this study can be used to identify higher risk patients and provide earlier interventions to reduce sleep disturbance.

BACKGROUND

Noninvasive models to predict the presence of coronary artery disease (CAD) may help reduce the societal burden of CAD.

OBJECTIVES

From a prospective registry of patients referred for coronary angiography, the goal of this study was to develop a clinical and biomarker score to predict the presence of significant CAD.

METHODS

In a training cohort of 649 subjects, predictors of ≥70% stenosis in at least 1 major coronary vessel were identified from >200 candidate variables, including 109 biomarkers. The final model was then validated in a separate cohort (n = 278).

RESULTS

The scoring system consisted of clinical variables (male sex and previous percutaneous coronary intervention) and 4 biomarkers (midkine, adiponectin, apolipoprotein C-I, and kidney injury molecule-1). In the training cohort, elevated scores were predictive of ≥70% stenosis in all subjects (odds ratio [OR]: 9.74; p < 0.001), men (OR: 7.88; p <0.001), women (OR: 24.8; p < 0.001), and those with no previous CAD (OR: 8.67; p < 0.001). In the validation cohort, the score had an area under the receiver-operating characteristic curve of 0.87 (p < 0.001) for coronary stenosis ≥70%. Higher scores were associated with greater severity of angiographic stenosis. At optimal cutoff, the score had 77% sensitivity, 84% specificity, and a positive predictive value of 90% for ≥70% stenosis. Partitioning the score into 5 levels allowed for identifying or excluding CAD with >90% predictive value in 42% of subjects. An elevated score predicted incident acute myocardial infarction during 3.6 years of follow up (hazard ratio: 2.39; p < 0.001).

CONCLUSIONS

We described a clinical and biomarker score with high accuracy for predicting the presence of anatomically significant CAD. (The CASABLANCA Study: Catheter Sampled Blood Archive in Cardiovascular Diseases; NCT00842868).

Because of inherent disease heterogeneity, targeted therapies have eluded triple-negative breast cancer (TNBC), and biomarkers predictive of treatment response have not yet been identified. This study was designed to determine whether the mTOR inhibitor everolimus with cisplatin and paclitaxel would provide synergistic antitumor effects in TNBC. Patients with stage II/III TNBC were enrolled in a randomized phase II trial of preoperative weekly cisplatin, paclitaxel and daily everolimus or placebo for 12 weeks, until definitive surgery. Tumor specimens were obtained at baseline, cycle 1, and surgery. Primary endpoint was pathologic complete response (pCR); secondary endpoints included clinical responses, breast conservation rate, safety, and discovery of molecular features associated with outcome. Between 2009 and 2013, 145 patients were accrued; 36% of patients in the everolimus arm and 49% of patients in the placebo arm achieved pCR; in each arm, 50% of patients achieved complete responses by imaging. Higher rates of neutropenia, mucositis, and transaminase elevation were seen with everolimus. Clinical response to therapy and long-term outcome correlated with increased frequency of DNA damage response (DDR) gene mutations, Basal-like1 and Mesenchymal TNBC-subtypes, AR-negative status, and high Ki67, but not with tumor-infiltrating lymphocytes. The paclitaxel/cisplatin combination was well tolerated and active, but addition of everolimus was associated with more adverse events without improvement in pCR or clinical response. However, discoveries made from correlative studies could lead to predictive TNBC biomarkers that may impact clinical decision-making and provide new avenues for mechanistic exploration that could lead to clinical utility. .