Emerson Lim

Diabetes, body mass index and outcomes in hepatocellular carcinoma patients undergoing liver transplantation

&NA; For many cancers, features of the metabolic syndrome, such as diabetes and obesity, have been associated with both increased risk of cancer development and poor outcomes. Methods We examined a large retrospective cohort of 342 consecutive patients who underwent liver transplantation for hepatocellular carcinoma between January 1999 and July 2010 at our institution. We evaluated the relationship between diabetes, obesity, hepatocellular carcinoma (HCC) recurrence, and overall survival. Results We found that a body mass index (BMI) higher than 30 was an independent predictor of poor overall survival in a multivariable Cox model, approximately doubling the risk of death after transplantation. A BMI higher than 30 was also a predictor of recurrent HCC, although this was of borderline statistical significance (hazard ratio for recurrence, 1.9; 95% confidence interval, 0.9–4.1). We also found increased BMI to be an independent predictor of microvascular invasion within HCC tumors, lending a possible explanation to these results. Those with diabetes showed worsened overall survival compared with those without diabetes in univariate but not multivariable analysis, possibly related to longer wait times. Conclusions Our findings suggest a relationship between higher BMI, tumor vascular invasion, increased recurrence, and worsened overall survival. These findings may help explain why those with high BMI have worse outcomes from their cancers. A better understanding of the role of obesity and diabetes in patients with cancer should help develop better predictors of outcome and improved treatment options for patients with HCC.

Contraindicated Use of Bevacizumab and Toxicity in Elderly Patients With Cancer

PURPOSE Drugs are approved on the basis of randomized trials conducted in selected populations. However, once approved, these treatments are usually expanded to patients ineligible for the trial. PATIENTS AND METHODS We used the SEER-Medicare database to identify subjects older than 65 years with metastatic breast, lung, and colon cancer, diagnosed between 2004 and 2007 and undergoing follow-up to 2009, who received bevacizumab. We defined a contraindication as having at least two billing claims before bevacizumab for thrombosis, cardiac disease, stroke, hemorrhage, hemoptysis, or GI perforation. We defined toxicity as first development of one of these conditions after therapy. RESULTS Among 16,085 metastatic patients identified, 3,039 (18.9%) received bevacizumab. Receipt of bevacizumab was associated with white race, later year of diagnosis, tumor type, and decreased comorbid conditions. Of patients who received bevacizumab, 1,082 (35.5%) had a contraindication. In multivariate analysis, receipt of bevacizumab with a contraindication was associated with black race (odds ratio [OR] = 2.6; 95% CI, 1.4 to 4.9), increased age, comorbidity, later year of diagnosis, and lower socioeconomic status. Patients with lung (OR = 1.7; 95% CI, 1.1 to 2.4) and colon cancer (OR = 1.4; 95% CI, 1.1 to 1.9) were more likely to have a contraindication. In the group with no contraindication, 30% had a complication after bevacizumab; black patients were more likely to have a complication than were white patients (OR = 1.9; 95% CI, 1.21 to 2.93). CONCLUSION Our study demonstrates widespread use of bevacizumab among patients who had contraindications. Black patients were less likely to receive the drug, but those who did were more likely to have a contraindication. Efforts to understand toxicity and efficacy in populations excluded from clinical trials are needed.

Optical biomarkers for breast cancer derived from dynamic diffuse optical tomography

Abstract. Diffuse optical tomography (DOT) is a noninvasive, nonionizing imaging modality that uses near-infrared light to visualize optically relevant chromophores. A recently developed dynamic DOT imaging system enables the study of hemodynamic effects in the breast during a breath-hold. Dynamic DOT imaging was performed in a total of 21 subjects (age 54±10  years) including 3 healthy subjects and 18 subjects with benign (n=8) and malignant (n=14) masses. Three-dimensional time-series images of the percentage change in oxygenated and deoxygenated hemoglobin concentrations ([HbO2] and [Hb]) from baseline are obtained over the course of a breath-hold. At a time point of 15 s following the end of the breath-hold, [Hb] in healthy breasts has returned to near-baseline values (1.6%±0.5%), while tumor-bearing breasts have increased levels of [Hb] (6.8%±3.6%, p<0.01). Further, healthy subjects have a higher correlation between the breasts over the course of the breath-hold as compared with the subjects with breast cancer (healthy: 0.96±0.02; benign: 0.89±0.02; malignant: 0.78±0.23, p<0.05). Therefore this study shows that dynamic features extracted from DOT measurements can differentiate healthy and diseased breast tissues. These features provide a physiologic method for identifying breast cancer without the need for ionizing radiation.

Racial and Insurance Disparities in the Receipt of Transplant Among Patients With Hepatocellular Carcinoma

Patients with hepatocellular carcinoma (HCC) have a poor prognosis if their tumors are not diagnosed early. The authors investigated factors associated with the receipt of liver transplant among patients with HCC and evaluated the effects of these differences on survival.

¡Cocinar Para Su Salud!: Randomized controlled trial of a culturally-based dietary intervention among Hispanic breast cancer survivors

BACKGROUND There is a need for culturally relevant nutrition programs targeted to underserved cancer survivors. OBJECTIVE Our aim was to examine the effect of a culturally based approach to dietary change on increasing fruit/vegetable (F/V) intake and decreasing fat intake among Hispanic breast cancer survivors. DESIGN Participants were randomized to Intervention and Control groups. Diet recalls, detailed interviews, fasting blood, and anthropometric measures were collected at baseline, 3, 6, and 12 months. PARTICIPANTS/SETTING Hispanic women (n=70) with stage 0 to III breast cancer who completed adjuvant treatment and lived in New York City were randomized between April 2011 and March 2012. INTERVENTION The Intervention group (n=34) participated in ¡Cocinar Para Su Salud!, a culturally based nine-session (24 hours over 12 weeks) intervention including nutrition education, cooking classes, and food-shopping field trips. The Control group (n=36) received written dietary recommendations for breast cancer survivors. MAIN OUTCOME MEASURES Change at 6 months in daily F/V servings and percent calories from total fat were the main outcome measures. STATISTICAL ANALYSES Linear regression models adjusted for stratification factors and estimated marginal means were used to compare changes in diet from baseline to 3 and 6 months. RESULTS Baseline characteristics were the following: mean age 56.6 years (standard deviation 9.7 years), mean time since diagnosis 3.4 years (standard deviation 2.7 years), mean body mass index (calculated as kg/m²) 30.9 (standard deviation 6.0), 62.9% with annual household income ≤

Obesity and Microvascular Invasion in Hepatocellular Carcinoma

15,000, mean daily servings of all F/V was 5.3 (targeted F/V 3.7 servings excluding legumes/juices/starchy vegetables/fried foods), and 27.7% of daily calories from fat. More than 60% in the Intervention group attended seven or more of nine classes, with overall study retention of 87% retention at 6 months. At month 6, the Intervention group compared with Control group reported an increase in mean servings of F/V from baseline (all F/V: +2.0 vs -0.1; P=0.005; targeted F/V: +2.7 vs +0.5; P=0.002) and a nonsignificant decrease in percent calories from fat (-7.5% vs -4.4%; P=0.23) and weight (-2.5 kg vs +3.8 kg; P=0.22). CONCLUSIONS ¡Cocinar Para Su Salud! was effective at increasing short-term F/V intake in a diverse population of Hispanic breast cancer survivors.

Phase 1b Study of Abiraterone Acetate Plus Prednisone and Docetaxel in Patients with Metastatic Castration-resistant Prostate Cancer

ABSTRACT Background: We hypothesized that hepatocellular carcinoma (HCC) patients with higher Body Mass Index (BMI) might have more microvascular invasion (MVI) in their tumors. Methods: Records from 138 consecutive patients who underwent surgery at Columbia University Medical Center from January 1, 2002 to January 9, 2008 were evaluated. Results: 40 patients (29%) had MVI, including 14% with BMI <25, 31% with BMI = 25–30, and 40% with BMI >30 (p = .05). However, only maximum alpha-fetoprotein was significantly associated with overall mortality in a Cox model. Conclusions: MVI was associated with obesity. A better understanding of the mechanism of this association may lead to interventions for the treatment and prevention of HCC.

Long-term diet and biomarker changes after a short-term intervention among Hispanic breast cancer survivors: The ¡Cocinar Para Su Salud! randomized controlled trial

Coadministration of docetaxel and abiraterone acetate plus prednisone (AA + P) may benefit patients with metastatic castration-resistant prostate cancer (mCRPC) because of complementary mechanisms of action. COU-AA-206 was a phase 1b study to determine the safe dose combination of docetaxel and AA + P in three cohorts of chemotherapy-naïve mCRPC patients. Twenty-two patients received escalating doses of docetaxel plus AA + P. The primary endpoint was the proportion of patients with a dose-limiting toxicity (DLT) between weeks 2 and 7. The recommended phase 2 dose (RP2D) was the highest safe combination of docetaxel plus AA + P. Prostate-specific antigen (PSA) changes and intensive pharmacokinetic parameters for each drug were evaluated. Docetaxel 75mg/m2 + AA 1000mg + P 10mg was deemed the RP2D, with DLT in one of six patients. PSA declines from baseline of ≥50% and ≥90% were observed for 85.7% and 66.7% of patients, respectively. During median follow-up of 14.5 mo, eight patients had PSA progression and six had radiographic progression or died. Systemic exposure was comparable for docetaxel and abiraterone when given alone or in combination. Studies are ongoing to confirm the efficacy of potent androgen receptor-targeted therapy plus taxane in early mCRPC. PATIENT SUMMARY The combination of hormonal therapy and chemotherapy may improve outcomes in men with metastatic prostate cancer. This study demonstrates the ability to combine the hormonal therapy agent abiraterone acetate, plus prednisone, and the chemotherapy drug docetaxel with an acceptable side effect profile. A high rate of prostate-specific antigen decline was seen, but the study was small and additional research is needed before this becomes a standard approach.

Increased expression of tumor proliferation genes in Hispanic women with early-stage breast cancer.

Background: Among Hispanic breast cancer survivors, we examined the long-term effects of a short-term culturally based dietary intervention on increasing fruits/vegetables (F/V), decreasing fat, and changing biomarkers associated with breast cancer recurrence risk. Methods: Spanish-speaking women (n = 70) with a history of stage 0–III breast cancer who completed treatment were randomized to ¡Cocinar Para Su Salud! (n = 34), a culturally based 9-session program (24 hours over 12 weeks, including nutrition education, cooking classes, and food-shopping field trips), or a control group (n = 36, written dietary recommendations for breast cancer survivors). Diet recalls, fasting blood, and anthropometric measures were collected at baseline, 6, and 12 months. We report changes between groups at 12 months in dietary intake and biomarkers using 2-sample Wilcoxon t tests and generalized estimating equation (GEE) models. Results: At 12 months, the intervention group compared with the control group reported higher increases in mean daily F/V servings (total: +2.0 vs. −0.4; P < 0.01), and nonsignificant decreases in the percentage of calories from fat (−2.2% vs. −1.1%; P = 0.69) and weight (−2.6 kg vs. −1.5 kg; P = 0.56). Compared with controls, participants in the intervention group had higher increases in plasma lutein (+20.4% vs. −11.5%; P < 0.01), and borderline significant increases in global DNA methylation (+0.8% vs. −0.5%; P = 0.06). Conclusions: The short-term ¡Cocinar Para Su Salud! program was effective at increasing long-term F/V intake in Hispanic breast cancer survivors and changed biomarkers associated with breast cancer recurrence risk. Impact: It is possible for short-term behavioral interventions to have long-term effects on behaviors and biomarkers in minority cancer patient populations. Results can inform future study designs. Cancer Epidemiol Biomarkers Prev; 25(11); 1491–502. ©2016 AACR.

ReCAP: Identifying Severe Adverse Event Clusters Using the National Cancer Institute’s Common Terminology Criteria for Adverse Events

Hispanic women have higher breast cancer mortality compared to non-Hispanic whites. We evaluated for Proliferation Axis Score differences, as determined by Oncotype Dx, in Hispanic and non-Hispanic white women with newly diagnosed breast cancer. We matched 219 women, based upon age, stage, and nodal status. Compared to non-Hispanic whites, Hispanic women with hormone-sensitive, HER2-negative early-stage breast cancer had a higher Proliferation Axis Score. No differences were seen in Recurrence Score, ER, PR, or HER2 by Oncotype DX. CCNB1 and AURKA were significantly higher in Hispanic women. These tumor differences may help explain breast cancer outcome differences between the two ethnicities.