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Assessing guidelines for monitoring cardiotoxicity in patients receiving cardiotoxic systemic therapies: an audit

A 2020/2021 Summer Studentship research project

Student: Tim Bridgman
Supervisors: Professor Bridget Robinson, Dr Kate Gardner
Sponsor: CDHB Oncology Trust

Introduction

The Oncology Service regularly uses systemic therapies which may cause long and short term cardiotoxicity. The anthracyclines are associated with a cumulative irreversible adverse effect on cardiac muscle, which leads to heart failure. This is dose related and the risk increases with higher total doses, but may occur at lower doses in the presence of predisposing cardiac pathology. The newer therapies which target HER2, expressed in about 20% of breast cancers may have a reversible effect on myocardial function, thought due to inhibition of repair mechanisms associated with HER2 function on breast cancer. Many patients with breast cancer receive both anthracyclines and anti-HER2 therapies. The routine use of checking left ventricular function (LVEF ) using cardiac echo has become established, to detect baseline cardiac impairment, and changes on treatment, but is a significant load on the cardiology ECHO service, which is a current resource issue. We wish to explore whether out current guidelines could be adjusted, based on past experience of impact on clinical care, and lessen the burden on the scarce ECHO resource. The main alternative option is a MUGA nuclear medicine scan, but this is invasive and would rapidly reach a similar resource constraint.

Aim

Reduction in the numbers of ECHO tests requested, to lessen the burden on the scarce ECHO resource, without detriment to care.

Method

Patients who receive doxorubicin, epirubicin and/or trastuzumab, pertuzumab or T-DM1 will be sought from Mosaiq diagnosis codes and Pharmacy records, with first treatment starting from January 2017. Cancer types will include breast cancer, including HER2+, high grade lymphoma’s, Hodgkin lymphoma’s, sarcoma’s and upper gastrointestinal cancers. The study will aim to include 200 patients, with at least 10 from each cancer type. Demographic details, concurrent and past health issues such as ischaemic heart, disease, hypertension, diabetes, will be recorded, with current medications. Cancer histology, staging and treatment plan, anticancer medications, doses and dates, weight and height and BSA, and blood pressure will be recorded from mosaiq and HCS electronic records, and ECHO results and dates from HCS. Any treatment changes for LVEF results will be recorded.

Change in LVEF will be correlated with cumulative dose of anthracycline, and with number of doses of anti-HER2 therapy, with both being present in some people with breast cancer. Predictors of fall in LVEF such as comorbidities, age, trend in LVEF over time, cumulative doses, dose changes for other reasons, etc, will be determined using univariate and multivariate multivariate analyses. Where LVEF was determined less frequently than every 12 weeks, the change in LVEF since the previous reading will be assessed for potential for detrimental outcome. Change in LVEF at certain key stages, eg after 4 cycles of anthracycline, or after 12 weeks of anti-HER2 therapy, will be determined and the proportion showing change estimated. Statistical advice will be sought from Prof Chris Frampton, UOC. Recommendations will be formulated for curative and palliative regimens, for anthracycline and for anti-Her2 therapies, and will then be discussed with the cardiology ECHO providers.

Ethics approval will be sought from the Oncology Service Low Risk Ethics Review process.

Maori consultation will also be carried out prior to commencement.

Student researcher’s component of the study

Develop the database of patients receiving anthracyclines and anti-HER 2 therapies, with the help of the supervisors, record patient details form HCS and Mosaiq databases, and create timeline of LVEF results against doses of the potentially cardiotoxic therapies to allow analysis. The student will prepare the report, and with the supervisors, share the results with the Oncology Service. It is hoped the study may be of enough utility for publication in a local journal e.g. NZMJ.

Student prerequisites

Medical student preferred, and if available, 4th or 5th year.

How to apply

Email bridget.robinson@cdhb.health.nz