Edith Pituskin

Sarcopenia as a Determinant of Chemotherapy Toxicity and Time to Tumor Progression in Metastatic Breast Cancer Patients Receiving Capecitabine Treatment

Purpose: Body composition has emerged as an important prognostic factor in cancer patients. Severe depletion of skeletal muscle (sarcopenia) and, hence, of overall lean body mass may represent an occult condition in individuals with normal or even high body weight. Sarcopenia has been associated with poor performance status, 5-fluorouracil toxicity, and shortened survival in cancer patients. Here, we prospectively studied patients with metastatic breast cancer receiving capecitabine treatment in order to determine if sarcopenia was associated with a higher incidence of toxicity and a shorter time to tumor progression (TTP). Experimental Design: Fifty-five women with metastatic breast cancer resistant to anthracycline and/or taxane treatment were included. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment, and TTP was determined prospectively. Results: Approximately 25% of patients were classified as sarcopenic, and this feature was seen in normal weight, overweight, and obese individuals. Toxicity was present in 50% of sarcopenic patients, compared with only 20% of nonsarcopenic patients (P = 0.03), and TTP was shorter in sarcopenic patients (101.4 days; confidence interval, 59.8-142.9) versus nonsarcopenic patients (173.3 days; confidence interval, 126.1-220.5; P = 0.05). Conclusion: Sarcopenia is a significant predictor of toxicity and TTP in metastatic breast cancer patients treated with capecitabine. Our results raise the potential use of body composition assessment to predict toxicity and individualize chemotherapy dosing.

Cardiovascular risk profile of patients with HER2/neu-positive breast cancer treated with anthracycline-taxane-containing adjuvant chemotherapy and/or trastuzumab

Purpose: To evaluate the cardiovascular risk profile of a subset of patients with early-stage breast cancer treated with adjuvant taxane-anthracycline–containing chemotherapy and/or trastuzumab (Herceptin). Experimental Design: Twenty-six patients with breast cancer (mean, 20 months postchemotherapy) and 10 healthy age-matched women were studied. We measured 14 metabolic and vascular established cardiovascular disease (CVD) risk factors, body mass index, cardiorespiratory fitness, and left ventricular systolic function. All assessments were done within a 14-day period. Results: Cardiac abnormalities were suggested by left ventricular ejection fraction (LVEF) <50% in 8% of patients, LVEF remained >10% below pretreatment values in 38%, whereas 50% presented with resting sinus tachycardia. Brain natriuretic peptide was significantly elevated in 40% of patients and was correlated with LVEF (r = −0.72, P = < 0.001). For the majority of CVD risk factors, similar proportions of patients and controls (35-60%) were classified as “undesirable.” A significantly higher proportion of patients were classified with low cardiorespiratory fitness (46% versus 0%, P < 0.01), being overweight/obese (72% versus 50%, P < 0.05), and having resting sinus tachycardia (50% versus 0%, P < 0.01) compared with controls. Cardiorespiratory fitness and body mass index were correlated with CVD risk factors (r = −0.64 to 0.63, P < 0.05; r = −0.63 to 0.67, P < 0.05, respectively). Exploratory analyses revealed several differences between CVD risk factors based on chemotherapy regimen. Conclusion: Breast cancer survivors treated with adjuvant chemotherapy are at a higher risk of developing late-occurring CVD than age-matched controls due to direct and indirect treatment-related toxicity. (Cancer Epidemiol Biomarkers Prev 2007;16(5):1026–31)

A Uridine Glucuronosyltransferase 2B7 Polymorphism Predicts Epirubicin Clearance and Outcomes in Early-Stage Breast Cancer

BACKGROUND Epirubicin is metabolized by uridine glucuronosyltransferase 2B7 (UGT2B7), an enzyme rich in single nucleotide polymorphisms (SNPs). We studied whether the -161 C > T germline SNP in UGT2B7 was related to epirubicin metabolism and whether differences exist in the toxicity and efficacy of epirubicin-based chemotherapy among patients who were TT homozygotes, CT heterozygotes, and CC homozygotes. PATIENTS AND METHODS A total of 132 women with non-metastatic breast cancer receiving FEC (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)) were prospectively enrolled. Toxicity was assessed in cycle 1 using the National Cancer Institute Common Toxicity Criteria, version 2.0. RESULTS The sequence at -161 was studied in 132 subjects; 37 were TT homozygotes, 63 were CT heterozygotes, 26 were CC homozygotes, and 6 could not be genotyped. The CC genotype patients had decreased epirubicin clearance (median, 103.3 L/hr) compared with the CT/TT genotype patients (median, 134.0 L/hr; P = .002). The CC homozygous patients had an increased risk of grade 3 to 4 leukopenia compared with the TT homozygotes or heterozygotes (P = .038 and P = .032, respectively). TT homozygotes or heterozygotes had an increased risk of early recurrence (P = .039; χ(2) test). CONCLUSION The results of the present prospective pharmacogenetic study suggest that the UGT2B7 -161 C > T SNP correlate with drug metabolism, toxicity, and efficacy in patients receiving epirubicin chemotherapy. Further studies of this UGT2B7 SNP as a predictor of epirubicin toxicity and efficacy are warranted.

Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance

AIM To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer. METHODS Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated. RESULTS During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity). CONCLUSION Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods.

Cardio-oncology interventions in outpatients referred for autologous bone marrow transplantation.

137 Background: Cancer patients (PTS) referred for autologous bone marrow transplantation (autoBMT) are frequently pre-treated with established cardiotoxins and as a result may not have adequate cardiac function to meet eligibility criteria for autoBMT. Furthermore, mobilizing and consolidation chemotherapy result in additional serial exposures with acute and long-term negative cardiac sequelae. Accordingly, these PTS represent a population with a major unmet need for appropriate cardiovascular screening and interventions. AIM to evaluate the need and effectiveness of prospective multidisciplinary cardio-oncology assessment and intervention in an unselected outpatient population referred for autoBMT. METHODS From January 1, 2013 - December 31, 2013, PTS referred for autoBMT were systematically screened for comorbid conditions, cardiovascular risk factors and eligibility for transplant. Physical exam, laboratory (ECG, complete profile) and transthoracic echocardiogram with contrast were performed. Those with EF < 50%, increased IVsd/LVpWd, ECG abnormalities +/- significant cardiac history underwent proBNP and high sensitivity troponin testing. PTS with abnormal findings or decreased left ventricular (LV) function were referred to the Edmonton Cardio-Oncology REsearch (ENCORE) program. RESULTS 73 unique PTS were screened by the Edmonton autoBMT program. Of these, 16 (20%) were reviewed by ENCORE. Reasons for referral included: decreased LV function (n = 6, 38%); increased IVsd (n = 5, 31%); arrhythmia (n = 4, 25%); angina (n = 1, 5%). Pharmacotherapy was initiated for 6 PTS; additional modality or serial cardiac imaging for 12 PTS; urgent stent for 1 PT. 100% proceeded to autoBMT without adverse cardiovascular outcomes or mortality. CONCLUSIONS With systematic screening, a high proportion of PTS referred for autoBMT required cardio-oncology assessment and interventions, with 100% proceeding safely as a result. ENCORE represents a novel approach in the provision of cardio-oncology expertise for autoBMT PTS acutely during the mobilizing and transplantation period. Future examination of our prospective dataset will elucidate the longer term effects of our interventions.

Supporting Patients With Incurable Cancer: Backup Behavior in Multidisciplinary Cross-Functional Teams

Caring for patients with incurable cancer presents unique challenges. Managing symptoms that evolve with changing clinical status and, at the same time, ensuring alignment with patient goals demands specific attention from clinicians. With care needs that often transcend traditional service provision boundaries, patients who seek palliation commonly interface with a team of providers that represents multiple disciplines across multiple settings. In this case study, we explore some of the dynamics of a cross-disciplinary approach to symptom management in an integrated outpatient radiotherapy service model. Providers who care for patients with incurable cancer must rely on one another to secure delivery of the right services at the right time by the right person. In a model of shared responsibilities, flexibility in who does what and when can enhance overall team performance. Adapting requires within-team and between-team monitoring of task and function execution for any given patient. This can be facilitated by a common understanding of the purpose of the clinical team and an awareness of the particular circumstances surrounding care provision. Backup behavior, in which one team member steps in to help another meet an expectation that would otherwise not be fulfilled, is a supportive team practice that may follow naturally in high-functioning teams. Such team processes as these have a place in the care of patients with incurable cancer and help to ensure that individual provider efforts more effectively translate into improved palliation for patients with unmet needs.

Feasibility and acceptability of integrated cardiac rehabilitation in outpatients referred for autologous bone marrow transplantation.

139 Background: High-dose chemotherapy (HDCT) and bone marrow/hematopoietic cell transplantation (BMT) is established therapy for many malignancies. While advances in transplant practise have led to improved cancer-specific outcomes, HDCT negatively impacts healthy organ function via direct effects (ie high-dose cytotoxic injury to organ systems) and indirect effects (i.e., functional disability). The resulting cardiometabolic sequelae such as dyslipidemia, hypertension, diabetes, and weight gain (with lean body mass loss) contribute to the significantly increased rates of cardiovascular (CV) mortality and heart failure (HF) observed in HDCT survivors. Cardiac rehabilitation/secondary prevention (CR/SP) programs are a level 1 recommendation in multiple CV diseases, reducing CV risk and events. Currently, the feasibility of integrating standard CR/SP programs in outpatients (PTS) referred for HDCT is unknown. AIM To prospectively evaluate feasibility and acceptability of routine referral tocardiovascular rehabilitation/secondary prevention (CR/SP) in unselected lymphoma PTSreferred for autologous HDCT/BMT. METHODS Lymphoma PTS referred for HDCT/BMT were screened and referred to the CR/SP program. Baseline exercise testing was performed prior to HDCT/BMT. Upon recovery (6 weeks) testing was repeated, and PTS were invited to participate in a 6-week standard CR/SP program of exercise rehabilitation and CV risk reduction education. RESULTS 20 PTS were referred for HDCT/BMT from January 1, 2015 to July 1, 2015. All were referred to the CR/SP program. 100% underwent exercise testing, and all proceeded to BMT without adverse cardiovascular outcomes or mortality. High levels of satisfaction of CR/SP program components were reported. CONCLUSIONS In unselected PTS, seamless integration of CR/SP within standard HDCT/BMT care is feasible and acceptable. We expect short term measurable impacts including reduced symptom burden and improved quality of life. Longer term impacts will evaluate CV morbidity and mortality. This work will inform patient-centered care and improve supportive and survivorship care across the cancer continuum.

The Role of Cardio-Oncology in the Interprofessional Care of Adult Patients Receiving Cancer Therapy

OBJECTIVE To discuss the toxic effects of therapy to the structure and function of the cardiovascular system and the role of the cardio-oncology team in the interprofessional care of adult patients, including current approaches, research findings, and future endeavors DATA SOURCE: Published articles and international cardiology and oncology association guidance documents. CONCLUSION Although a new field of study, cardio-oncology is a rapidly expanding area of great clinical need. Evidence is only now accumulating, with most guidelines based on opinion or extrapolated from cardiovascular literature. Oncology care providers face complex decisions on a daily basis, whether before, during, or following definitive cancer treatments. IMPLICATIONS FOR NURSING PRACTICE In the era of both traditional and targeted cancer therapies, the long-term side effects to the cardiovascular system and, consequently, the needs of cancer survivors are increasingly complex. Accordingly, oncology nurses must not only be aware of such potential effects, but should conduct careful serial symptom review and consider risk-reduction and cancer rehabilitation strategies across the disease trajectory.

Variability of left ventricular volume and ejection fraction measurements using contrast echocardiography: The influence of the left ventricular length measurements in a large cohort of patients during monitoring cardiotoxic effects of chemotherapy

To investigate the influence of length difference in left ventricular (LV) long axis between the apical four‐chamber and two‐chamber views on measurements of LV volumes and ejection fraction (EF).

What is the minimum change in left ventricular ejection fraction, which can be measured with contrast echocardiography?

Background There are limited data on what is the minimum change that can be detected in cancer patients undergoing treatment with cardiotoxic drugs and are referred for monitoring left ventricular (LV) function. Objective To assess the variability in the measurement of LV volumes and ejection fraction (EF) in contrast echocardiography and to determine the minimum detectable difference (MDD) between two EF measurements that can be deemed significant. Methods A total of 150 patients were divided into three groups according to EF (EF <53, 53–60, and >60%). Each group consisted of 50 randomly selected cancer patients who underwent contrast echocardiography between July 2010 and May 2014. Repeated measurements of LV volumes and EF were performed offline by a sonographer and a cardiologist. Inter-observer variability was assessed by analysis of variance. Measurement error was estimated by standard error of measurement and MDD. Results The 95% confidence interval with a single measurement of EF was 2 percentage points in the groups of patients with EF <53% and EF >60%, and 2.5 percentage points for patients with EF 53–60%. The MDD for EF, end-diastolic volume and end-systolic volume that could be recognized with 95% confidence interval were 4 percentage points, 7 mL and 4 mL, respectively. Conclusion Contrast echocardiography is a reliable tool for serial measurements of EF to monitor cardiotoxicity due to chemotherapy. In a high-volume echocardiography laboratory with experienced staff, the MDD for EF of 4 percentage points on a good-quality recording demonstrates the high reproducibility of the Simpson’s method using contrast echocardiography.