The relationship between abdominal fat and change in left ventricular ejection fraction in cancer patients.

OBJECTIVES: Prior studies have identified a relationship between body mass index (BMI) and intraperitoneal (IP) fat with heart failure; however, in prior studies of cancer patients receiving potentially cardiotoxic chemotherapy, elevations in BMI have not necessarily been associated with decrements in heart function. This study tested the hypothesis that IP fat may be associated with left ventricular ejection fraction (LVEF) decline among cancer patients receiving potentially cardiotoxic chemotherapy. METHODS: In this prospective study of 61 cancer patients (23 breast cancer, 32 lymphoma, and 6 sarcoma), IP fat and other assessments of body composition, and changes in LVEF from pre- to postcancer treatment using noninvasive magnetic resonance imaging was ascertained. RESULTS: After accounting for age, baseline LVEF, and confounding variables, pre- to 24-month post-treatment LVEF changes were inversely correlated with IP fat (r = -0.33; p = 0.02) and positively correlated with measures of subcutaneous (SQ) fat (r = 0.33; p = 0.01). These LVEF changes were not correlated with BMI (r = 0.12; p = 0.37). CONCLUSION: Among patients receiving potentially cardiotoxic chemotherapy, pretreatment IP fat was associated with subsequent declines in LVEF. There was no association between BMI and LVEF decline. These findings may be related to a potential protective effect of SQ fat.

Cardiovascular Assessment Tool for Breast Cancer Survivors and Oncology Providers: Usability Study.

BACKGROUND: Cardiovascular health is of increasing concern to breast cancer survivors and their health care providers, as many survivors are more likely to die from cardiovascular disease than cancer. Implementing clinical decision support tools to address cardiovascular risk factor awareness in the oncology setting may enhance survivors' attainment or maintenance of cardiovascular health. OBJECTIVE: We sought to evaluate survivors' awareness of cardiovascular risk factors and examine the usability of a novel electronic health record enabled cardiovascular health tool from the perspective of both breast cancer survivors and oncology providers. METHODS: Breast cancer survivors (n=49) recruited from a survivorship clinic interacted with the cardiovascular health tool and completed pre and posttool assessments about cardiovascular health knowledge and perceptions of the tool. Oncologists, physician assistants, and nurse practitioners (n=20) who provide care to survivors also viewed the cardiovascular health tool and completed assessments of perceived usability and acceptability. RESULTS: Enrolled breast cancer survivors (84% White race, 4% Hispanic ethnicity) had been diagnosed 10.8 years ago (SD 6.0) with American Joint Committee on Cancer stage 0, I, or II (45/49, 92%). Prior to viewing the tool, 65% of survivors (32/49) reported not knowing their level for one or more cardiovascular health factors (range 0-4). On average, only 45% (range 0%-86%) of survivors' known cardiovascular health factors were at an ideal level. More than 50% of survivors had ideal smoking status (45/48, 94%) or blood glucose level (29/45, 64%); meanwhile, less than 50% had ideal blood pressure (12/49, 24%), body mass index (12/49, 24%), cholesterol level (17/35, 49%), diet (7/49, 14%), and physical activity (10/49. 20%). More than 90% of survivors thought the tool was easy to understand (46/47, 98%), improved their understanding (43/47, 91%), and was helpful (45/47, 96%); overall, 94% (44/47 survivors) liked the tool. A majority of survivors (44/47, 94%) thought oncologists should discuss cardiovascular health during survivorship care. Most (12/20, 60%) oncology providers (female: 12/20, 60%; physicians: 14/20, 70%) had been practicing for more than 5 years. Most providers agreed the tool provided useful information (18/20, 90%), would help their effectiveness (18/20, 90%), was easy to use (20/20, 100%), and presented information in a useful format (19/20, 95%); and 85% of providers (17/20) reported they would use the tool most or all of the time when providing survivorship care. CONCLUSIONS: These usability data demonstrate acceptability of a cardiovascular health clinical decision support tool in oncology practices. Oncology providers and breast cancer survivors would likely value the integration of such apps in survivorship care. By increasing awareness and communication regarding cardiovascular health, electronic health record-enabled tools may improve survivorship care delivery for breast cancer and ultimately patient outcomes.

Simultaneous Left Ventricular Volume and Strain Changes During Chemotherapy Associate With 2-Year Postchemotherapy Measures of Left Ventricular Ejection Fraction.

Background Although changes in left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume, and global circumferential strain occur during cancer treatment, the relationship of these changes to the 2-year post-cancer-treatment measures of left ventricular ejection fraction (LVEF) are unknown. Methods and Results In a prospective, continuously recruited cohort of 95 patients scheduled to receive potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or soft tissue sarcoma, measures of left ventricular end-diastolic volume, LVESV, global circumferential strain, and LVEF were acquired via cardiac magnetic resonance imaging before and then 3 and 24 months after initiating treatment by individuals blinded to all patient identifiers. Participants had an average age of 54±15 years; 68% were women, and 82% were of white race. LVEF declined from 62±7% to 58±9% over the 24 months (P<0.0001), with 42% of participants experiencing a >5% decline in LVEF at 24 months. Predictors of a 24-month >5% decline in LVEF included the following factors from baseline to 3 months into treatment: (1) >3-mL increases in LVESV (P=0.033), (2) >3-mL increases in LVESV or 10-mL declines in left ventricular end-diastolic volume with little change in LVESV (P=0.001), or (3) ≥10% deteriorations in global circumferential strain with little change in LVESV (P=0.036). Conclusion During receipt of potentially cardiotoxic chemotherapy, increases in LVESV, the absence of its deterioration during decreases of left ventricular end-diastolic volume, or the deterioration of global circumferential strain without a marked decrease in LVESV help identify those who will develop more permanent 2-year declines in LVEF.

Association between glycemic control, age, and outcomes among intensively treated patients with acute myeloid leukemia.

PURPOSE: To investigate the impact of hyperglycemia and glycemic variability during intensive acute myeloid leukemia therapy (AML) on outcomes by age. METHODS: Retrospective study of 262 consecutive patients with newly diagnosed AML hospitalized for intensive induction. Hyperglycemia was assessed by mean blood glucose (BG) (mg/dL) during hospitalization and glycemic variability was determined by the standard deviation (SD) of mean BG. Outcomes were complete remission ± incomplete count recovery (CR + CRi), and overall survival (OS). We used logistic regression to evaluate CR + CRi, and Cox proportional hazard models for OS, stratified by age (< 60 vs ≥ 60 years). RESULTS: Older patients (N = 138, median age 70) had higher baseline comorbidity (CCI > 1 60.1% vs 25.8%) and prevalence of diabetes (20.3% vs 7.3%) compared to younger (N = 124, median age 47). The mean ± SD number of BG values obtained per patient during hospitalization was 61 ± 71. The mean (± SD) glucose (mg/dL) during hospitalization was 121.7 (25.9) in older patients (≥ 60 years) versus 111.6 (16.4) in younger. In older patients, higher mean glucose and greater glycemic variability were associated with lower odds of remission (OR 0.80, 95% CI 0.69-0.93 and OR 0.73, 95% CI 0.61-0.88 respectively, per 10-unit increase) and higher mortality rates (HR 1.13, 95% CI 1.05-1.21 and HR 1.17, 95% CI 1.09-1.26, respectively, per 10-unit increase) in multivariate analyses. CONCLUSIONS: Our observations that hyperglycemia and increased glycemic variability were associated with lower remission rates and increased mortality in older patients suggest glycemic control may be a potentially modifiable factor to improve AML outcomes.

Hyperglycemia during first-line R-CHOP or dose adjusted R-EPOCH chemotherapy for non-Hodgkin lymphoma is prevalent and associated with chemotherapy alteration - a retrospective study.

High-dose glucocorticoids such as prednisone are combined with cytotoxic chemotherapy in the R-CHOP or dose adjusted R-EPOCH regimens used for non-Hodgkin lymphoma (NHL). In this retrospective study, our primary objective was to evaluate the incidence of hyperglycemia during first-line R-CHOP or DA-EPOCH-R. The secondary objectives were to evaluate the incidence of chemotherapy alteration and overall survival in those with and without hyperglycemia. One hundred and sixty patients were eligible. We found that 47% of all patients had at least one hyperglycemic episode and hyperglycemia was associated with chemotherapy alteration (p = .028). Multivariate analysis revealed international prognostic index (IPI) ≥ 3 (p = .045) and chemotherapy alteration (p = .001) were associated with decreased overall survival. We conclude that hyperglycemia is common during first-line NHL treatment with R-CHOP or DA-EPOCH-R, even in the absence of known diabetes and is associated with alterations of chemotherapy. Baseline pre-PET scan fasting blood glucose of 100 mg/dL or higher may predict hyperglycemia during therapy.

A Phase II Clinical Trial of CPI-613 in Patients with Relapsed or Refractory Small Cell Lung Carcinoma.

BACKGROUND: Small cell lung cancer (SCLC) is a common lung cancer which presents with extensive stage disease at time of diagnosis in two-thirds of patients. For treatment of advanced disease, traditional platinum doublet chemotherapy induces response rates up to 80% but with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibits the altered form of mitochondrial energy metabolism in tumor cells. METHODS: We evaluated CPI-613 with a single-arm, open-label phase II study in patients with relapsed or refractory SCLC. CPI-613 was given at a dose of 3,000 mg/m2 on days 1 and 4 of weeks 1-3 of 4 week cycle. The primary outcome was response rate as assessed by CT imaging using RECIST v1.1 criteria. Secondary outcomes were progression-free survival (PFS), overall survival (OS), and toxicity. Twelve patients were accrued (median age 57yo) who had previously received between 1 and 4 lines of chemotherapy (median 1) for SCLC with a treatment-free interval of less than 60 days in 9 of the 12 patients. RESULTS: No complete or partial responses were seen. Ten patients (83%) progressed as best response and 2 (17%) were not evaluable for response. Median time to progression was 1.7 months (range 0.7 to 1.8 months). Eleven patients (92%) died with median overall survival of 4.3 months (range 1.2 to 18.2 months). The study was closed early due to lack of efficacy. Of note, three out of three patients who progressed after CPI-613 and were subsequently treated with standard topotecan then demonstrated treatment response with survival for 18.2, 7.4, and 5.1 months. We conducted laboratory studies which found synergy in-vitro for CPI-613 with topotecan. CONCLUSIONS: Single agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combination with a topoisomerase inhibitor is warranted.

Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (EPOCH) With or Without Rituximab as First-Line Therapy for Aggressive Non-Hodgkin Lymphoma.

INTRODUCTION: Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) was developed in an effort to overcome inadequate drug concentrations and compensate for increased drug clearance. The goal of the present study was to examine the risk factors and outcomes of patients with aggressive non-Hodgkin lymphoma (aNHL) treated with DA-EPOCH. PATIENTS AND METHODS: We report the data from 136 patients with previously untreated aNHL who received infusional DA-EPOCH chemotherapy with or without rituximab from 2005 to 2013. Overall survival was estimated using Kaplan-Meier methods. Univariate and multivariate logistic regression was used to determine the factors associated with death, progression, or relapse at 2 years. RESULTS: The overall response rate was 82%. The relapse-free survival rate at 1, 3, and 5 years was 68%, 63%, and 52% with 95% confidence intervals (CIs) of 0.59% to 0.85%, 0.54% to 0.70%, and 0.31% to 0.70%, respectively. Patients with T-cell aNHL had an increased risk of death, progression, or relapse (Odds Ratio, 3.5; 95% CI, 1.4-8.8) compared with those with B-cell aNHL. In multivariate analysis, current smoking, disease in the bone marrow, and the number of cycles completed were independent predictors of death and relapse. CONCLUSION: Our data suggest that EPOCH with or without rituximab is active in both B- and T-cell aNHL. Toxicity did not significantly affect timing of treatment delivery or treatment outcomes. Dose adjustment by hematopoietic nadir similarly had no effect. The effect of smoking during chemotherapy should be evaluated further.

Relation of Pre-anthracycline Serum Bilirubin Levels to Left Ventricular Ejection Fraction After Chemotherapy.

Myocardial injury because of oxidative stress manifesting through reductions in left ventricular ejection fraction (LVEF) may occur after the administration of anthracycline-based chemotherapy (A-bC). We hypothesized that bilirubin, an effective endogenous antioxidant, may attenuate the reduction in LVEF that sometimes occurs after receipt of A-bC. We identified 751 consecutively treated patients with cancer who underwent a pre-A-bC LVEF measurement, exhibited a serum total bilirubin level <2 mg/dl, and then received a post-A-bC LVEF assessment because of symptomatology associated with heart failure. Analysis of variance, Tukey's Studentized range test, and chi-square tests were used to evaluate an association between bilirubin and LVEF changes. The LVEF decreased by 10.7 ± 13.7%, 8.9 ± 11.8%, and 7.7 ± 11.5% in group 1 (bilirubin at baseline ≤0.5 mg/dl), group 2 (bilirubin 0.6 to 0.8 mg/dl), and group 3 (bilirubin 0.9 to 1.9 mg/dl), respectively. More group 1 patients experienced >15% decrease in LVEF compared with those in group 3 (p = 0.039). After adjusting for age, coronary artery disease/myocardial infarction, diabetes mellitus, hematocrit, and the use of cardioactive medications, higher precancer treatment bilirubin levels and lesser total anthracycline doses were associated with LVEF preservation (p = 0.047 and 0.011, respectively). In patients treated with anthracyclines who subsequently develop symptoms associated with heart failure, pre-anthracycline treatment serum bilirubin levels inversely correlate with subsequent deterioration in post-cancer treatment LVEF. In conclusion, these results suggest that increased levels of circulating serum total bilirubin, an intrinsic antioxidant, may facilitate preservation of LVEF in patients receiving A-bC for cancer.

Higher Risk of Severe Drug-Induced Liver Injury among Hispanic HIV-Infected Patients after Initiation of Highly Active Antiretroviral Therapy.

BACKGROUND: Little is known about differences across ethnicities in the development of drug-induced liver injury (DILI) after highly active antiretroviral therapy (HAART) initiation. METHODS: This is a retrospective, longitudinal, comparative, pilot study. DILI within the first year of HAART was evaluated in 50 HIV-infected Hispanics without viral hepatitis who initiated HAART between 2000 and 2009. It was compared to white and black patients (1:1:1) matched by age and CD4 counts. RESULTS: HAART-related DILI of any grade occurred in 30 of 150 (20%) patients and was associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) use (OR 4.49 [95%CI 1.5-13.8]). Severe DILI was significantly more frequent among Hispanics compared to other groups (6% vs. 0%; P = .04). Of the 3 patients with severe DILI, 2 underwent liver imaging and had hepatic steatosis. CONCLUSIONS: Severe DILI within the first year of HAART initiation was infrequent and restricted to Hispanics. Additional studies are needed to determine if fatty liver is involved in the excess of severe DILI observed in this group.