Title: Detection of treatment-induced early cardiac injury with PET/MR to enable treatment adaptation to reduce side-effects in patients with lymphoma
Funder: Health Education England

Abstract: BackgroundLymphomas are blood cancers that develop from lymphocytes (a type of white blood cell). There are 16,000 new lymphoma cases each year in the UK and Hodgkin lymphoma (HL), a subtype of lymphoma, is the commonest cancer in teenagers and young adults. Prognosis is generally good, and patients can expect to live many years after treatment. The usual treatment for lymphoma is chemotherapy (anthracyclines) and/or chest radiotherapy. Both increase the risk of cardiovascular disease (CVD) because they can cause heart damage, known as cardiotoxicity. The risk of dying from CVD is more than 10 times higher amongst cancer patients than the general population.Currently, late CVD (>5 years after treatment) in lymphoma survivors is detected too late to reverse it. Treatment-related late CVD in lymphoma patients is a well-researched field. However, research into acute cardiotoxicity during and after ( Aim and objectives: To use simultaneous PET/MR imaging to detect treatment-related acute cardiotoxicity to enable treatment adaptation to reduce side-effects in patients with lymphoma. To detect acute cardiotoxicity and differentiate the effects of chemotherapy and radiotherapy on the heart and cardiac substructures. To understand the chemotherapy and radiotherapy dose-effect relationship. To develop radiation dose constraints for risk reduction from acute cardiotoxicity and to optimise treatment planning for future patients. To examine associations between routine blood biomarkers and ECG with imaging results to inform future work on the use of simple and cheap tests to detect early cardiotoxicity and reverse it. Methods24 lymphoma patients will have PET/MRI scans to detect heart damage at four timepoints: Before treatment After chemotherapy After radiotherapy Six months after treatmentElectrocardiograms and blood tests that can show heart damage (Troponin, N-terminal prohormone brain natriuretic peptide and myosin-binding proteinC) will also be performed at these four timepoints. Between the timepoints, changes in the imaging and blood test parameters that indicate acute cardiotoxicity will be compared using paired-t-tests and within-patient multilevel regression. Regression methods will explore whether there is a dose-response relationship between cardiac radiation/chemotherapy doses and the indicators of acute cardiotoxicity. Milestones for delivery 1: Set up of imaging methodology and ethics and regulatory approvals (Before this study commences - during my prior pilot study) 2: International visits to other experienced centres (Months 1 or 2)3: Patient recruitment and data collection (Months 1-30)4: Data analysis and dissemination (Months 30-36) Anticipated impact and dissemination The patients in this study will benefit from a unique cardiac monitoring programme. If signs of acute cardiotoxicity are found, patients will be referred for cardio-oncology follow-up. For future lymphoma patients, results of this study will help us adapt radiation treatment planning to stop or minimise, treatment-related risk of CVD. The results can be used in other patient groups who receive chest radiotherapy, for example, patients with breast, lung and oesophagus cancers. This work will also provide initial groundwork for further research into chemotherapy dose adaptation and the use of blood biomarkers to predict treatment-related cardiotoxicity.

Lay abstract: What is the health problem? Patients with lymphoma (cancer of the lymph glands) receive treatment with chemotherapy and radiotherapy. Treatment is usually successful, and most lymphoma patients survive many years. However, chemotherapy drugs have ingredients that damage the heart, and when radiotherapy is used to treat a tumour near the heart, it also damages it. This damage can cause serious heart disease, which usually happens five years, or more, after treatment. There are about 16,000 new lymphoma cases each year in the UK. Heart disease is the leading non-cancer cause of death in cancer survivors and a significant source of anxiety. Physical and mental health care for these patients represents a considerable burden and cost to the NHS. My research intends to find ways to reduce the risk of heart disease in lymphoma survivors.Aims of the researchCurrently, heart disease in cancer survivors is detected too late to reverse it. My study aims to: Detect early heart damage during and soon after treatment (six months) in lymphoma patients. Identify treatment characteristics that might be causing early heart damage to the whole heart or parts of it. Propose ways to adapt treatment for future patients to reduce the risk of early heart damage.Methods24 patients will have scans using advanced medical imaging - combined positron emission tomography and magnetic resonance imaging (PET/MRI) to detect heart damage at four timepoints: Before treatment (to establish first if the heart is healthy or diseased) After chemotherapy (to understand how chemotherapy affects the heart) After radiotherapy (to understand how radiotherapy affects the heart and separate the effect from that of chemotherapy, and find which areas of the heart are more sensitive to radiation) Six months after treatment (to understand how early damage progresses)We will also perform electrocardiograms (tracing of the heart's rhythm) and blood tests that can show heart damage and relate these to the findings from imaging at these four timepoints. Benefits to patients The patients in this study will benefit from a unique cardiac monitoring programme. If we find signs of early heart damage, we will refer them for cardiology follow-up. For future lymphoma patients, results of this study will help us adapt treatment to stop, or minimise, treatment-related risk of heart disease, improving life expectancy and quality of life. The results on radiation damage can be used in other patient groups who receive chest radiotherapy, for example, for breast, lung and oesophagus cancers. Patient and public involvement (PPI)Patients and the public are involved in all stages of my research. I have sought advice from the 'South East London Consumer Research Panel for Cancer' (SELCRP) and the only lymphoma-dedicated charity in the UK, 'Lymphoma-Action'. Both reviewed and helped me shape my application. I have set up a Patient Advisory Group, including two SELCRP members and one representative from Lymphoma-Action, who will be actively involved in the PPI activities throughout the study. We will meet every six months to review progress.Communication I will present my findings to patient and carer groups and charities including Lymphoma-Action, British Heart foundation and Cancer-Research UK. I will present at national and international oncology meetings and the UK Lymphoma Radiotherapy Group which formulates national clinical guidelines chaired by my mentor GM. I will publish my research in peer reviewed journals with open-access. I will co-author plain English versions of my papers with members of the Patients Advisory Group to ensure that the patient perspective is captured and publish them in charity blogs Twitter and lymphoma survivors' Facebook pages to achieve a wider reach.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR