A randomized trial to evaluate the impact of exercise-based cardiac rehabilitation for the prevention of chemotherapy-induced cardiotoxicity in patients with breast cancer: ONCORE study protocol.

BACKGROUND: Anthracyclines and monoclonal antibodies against human epidermal growth factor receptor-2 (HER2) are frequently used to treat breast cancer but they are associated with risk of developing cardiotoxicity. Implementation of cardioprotective strategies as part of breast cancer treatment are needed. To date, a limited number of studies have examined the effectiveness of cardiac rehabilitation programs or exercise programs in the prevention of cardiotoxicity through an integral assessment of cardiac function. The ONCORE study proposes an exercise-based cardiac rehabilitation program as a non-pharmacological tool for the management of chemotherapy-induced cardiotoxicity. METHODS: The study protocol describes a prospective, randomized controlled trial aimed to determine whether an intervention through an exercise-based CR program can effectively prevent cardiotoxicity induced by anthracyclines and/or anti-HER2 antibodies in women with breast cancer. Three hundred and forty women with breast cancer at early stages scheduled to receive cardiotoxic chemotherapy will be randomly assigned (1:1) to participation in an exercise-based CR program (intervention group) or to usual care and physical activity recommendation (control group). Primary outcomes include changes in left ventricular ejection fraction and global longitudinal strain as markers of cardiac dysfunction assessed by transthoracic echocardiography. Secondary outcomes comprise levels of cardiovascular biomarkers and cardiopulmonary function through peak oxygen uptake determination, physical performance and psychosocial status. Supervised exercise program-related outcomes including safety, adherence/compliance, expectations and physical exercise in- and out-of-hospital are studied as exploratory outcomes. Transthoracic echocardiography, clinical test and questionnaires will be performed at the beginning and two weeks after completion of chemotherapy. DISCUSSION: The growing incidence of breast cancer and the risk of cardiotoxicity derived from cancer treatments demand adjuvant cardioprotective strategies. The proposed study may determine if an exercise-based CR program is effective in minimizing chemotherapy-induced cardiotoxicity in this population of women with early-stage breast cancer. The proposed research question is concrete, with relevant clinical implications, transferable to clinical practice and achievable with low risk. Trial registration ClinicalTrials.gov Identifier: NCT03964142. Registered on 28 May 2019. Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03964142.

Clinical Relevance and Therapeutic Application of CTCs in Advanced Breast Cancer.

Precision medicine through liquid biopsy represents an emerging approach in the management of cancer. The CTC count in blood samples from patients with advanced breast cancer is a powerful prognostic factor for both progression free and overall survival. Moreover, high levels of CTCs at any time during the treatment can reliably predict progression before imaging studies and/or tumor markers. Furthermore, there are works on the molecular characterization of the CTCs and their potential ability to guide the treatment in a dynamic way. However, their role remains controversial. Detection and enumeration of CTCs is variable among different tumors and is subjected to biases related mainly to their methodology, which is not completely standardized. In addition, they must demonstrate their clinical value to guide the treatment and a translation on patient's survival.

Exercise-based cardio-oncology rehabilitation for cardiotoxicity prevention during breast cancer chemotherapy: The ONCORE randomized controlled trial.

BACKGROUND: Breast cancer (BC) treatment with anthracyclines and/or anti-human epidermal growth factor receptor-2 (HER2) antibodies is associated with an increased risk of cardiovascular disease complications, including cancer therapy-related cardiac dysfunction (CTRCD). While Cardio-Oncology Rehabilitation (CORe) programs including exercise have emerged to minimize these risks, its role in preventing CTRCD is unclear. OBJECTIVES: We investigated the effectiveness of an exercise-based CORe program in preventing CTRCD [left ventricular ejection fraction (LVEF) drop ≥10% to a value <53% or a decrease >15% in global longitudinal strain (GLS)]. Secondary outcomes examined changes in cardiac biomarkers, physical performance including peak oxygen consumption, psychometric and lifestyle outcomes. Safety, adherence, and patient satisfaction were also assessed. METHODS: This is a randomized controlled trial including 122 early-stage BC women receiving anthracyclines and/or anti-HER2 antibodies, randomized to CORe (n = 60) or usual care with exercise recommendation (n = 62). Comprehensive assessments were performed at baseline and after cardiotoxic treatment completion. The average duration of the intervention was 5.8 months. RESULTS: No cases of CTRCD were identified during the study. LVEF decreased in both groups, but was significantly attenuated in the CORe group [-1.5% (-2.9, -0.1); p = 0.006], with no changes detected in GLS or cardiac biomarkers. The CORe intervention led to significant body mass index (BMI) reduction (p = 0.037), especially in obese patients [3.1 kg/m2 (1.3, 4.8)]. Physical performance and quality-of-life remained stable, while physical activity level increased in both groups. No adverse events were detected. CONCLUSIONS: This study suggests that CORe programs are safe and may help attenuate LVEF decline in BC women receiving cardiotoxic therapy and reduce BMI in obese patients.

Clear-cell adenocarcinoma of vesical origin: a case study of metastatic disease treated with chemotherapy.

Vesical clear cell adenocarcinoma is an uncommon tumour. The description of nearly all published cases focuses on histological issues, providing few clinical particulars and limited followup. The treatment choice is resection. No publications have been found regarding systemic treatments for advanced disease. We present a case of metastatic clear cell adenocarcinoma of the bladder treated with chemotherapy.