Award Title: Balancing the Benefits and Risks of Radiotherapy for Lymphoma
Funder: Department of Health and Social Care

Abstract: Background Hodgkin lymphoma (HL) is a malignancy of the lymphatic system that affects approximately 2000 people in the UK annually. More than half of patients are aged under 50 at diagnosis. The prognosis has substantially improved over recent decades. However, there is increasing recognition of the long-term side-effects of treatment, particularly radiotherapy. The optimal use of radiotherapy is therefore under scrutiny. The key to decision making in this context is reliably balancing the benefits and risks.Aims and objectivesMy aim is to develop an online decision support tool that provides individualised estimates of the benefits and risks of radiotherapy used for HL.My objectives are to collate data regarding the benefits and risks of radiotherapy for HL, and to produce a novel dose-response relationship for the risk of stroke. I will also develop methods to estimate radiation doses to organs using pre-chemotherapy PET-CT scans. Data from these studies will be used to formulate statistical models that provide individualised estimates of the benefits and risks of radiotherapy, to be presented as an online decision support tool.MethodsFirstly, I will conduct a systematic review to identify the proportional benefits of radiotherapy from clinical trials, and the relative risks of radiotherapy from epidemiological studies. Secondly, I will perform a population-based cohort study, to determine the absolute rates of HL recurrence and long-term side-effects from radiotherapy. I will investigate whether there is a relationship between the radiation dose received by the carotid arteries and the patient's subsequent risk of stroke using a case-control study nested within a cohort of HL survivors. I will determine correlations between the distribution of HL on pre-chemotherapy PET-CT scans and the radiation dose the organs subsequently receive from radiotherapy.The results of these studies will be used to formulate statistical models that give individualised estimates of the benefits and risks of radiotherapy, based on patient- and disease-specific factors. To enable these estimates to be used in the clinic I will design an online decision support tool, shaped by iterative and formalised qualitative analysis of the views of patients and clinicians.Timelines for deliveryMultiple elements of my work will run concurrently. The systematic review and population-based cohort study will be completed in year 2 to allow development of the statistical models. The studies of stroke risk and radiotherapy dose estimation methods will allow later refinement of the model in year 3. I will commence interviews as part of the decision support tool design in year 1, with surveys in year 2 and focus groups in year 3. The design of the decision support tool will be complete by the end of my fellowship, ready for evaluation in a real-world setting. Anticipated impact and disseminationI will disseminate results at conferences, in peer-reviewed journals and directly with people affected by HL at Lymphoma Action's National Conference and their Lymphoma Matters publication.Ultimately, this research will provide individualised estimates of benefits and risks to facilitate shared decision making regarding radiotherapy that is aligned with an individual's values and preferences.

Lay Abstract: Background and aimsLymphoma is a cancer of the lymphatic system, which is part of the immune system. In Hodgkin lymphoma, the white blood cells in the lymph nodes become cancerous. It is most commonly detected in the lymph nodes in the neck and chest. People of all ages are diagnosed with Hodgkin lymphoma, but it most commonly affects young adults. Around 2,100 people are diagnosed with Hodgkin lymphoma in the UK every year. The usual treatment for Hodgkin lymphoma is chemotherapy, often followed by radiotherapy. Treatment of Hodgkin lymphoma is usually very successful, and 8 in 10 people are cured. These people normally live long after their treatment has finished. There are over 21,000 survivors of Hodgkin lymphoma alive in the UK today.The radiotherapy used to cure Hodgkin lymphoma can result in serious long-term side-effects. These include heart disease, stroke and other new cancers. However, recent research has shown that if radiotherapy isn't used, the chance of cure is significantly lower.The aim of my research is to understand more about the benefits and risks of radiotherapy used to treat Hodgkin lymphoma, and how these vary between individuals. I plan to develop an online tool to give personalised estimates of the benefits and risks. This information will be used by clinicians together with people affected by Hodgkin lymphoma, to come to a shared decision about whether radiotherapy should be used as part of their treatment. Design and methodsI will collect information on the benefits and risks of radiotherapy from published research studies combined with information that has been routinely collected from all patients treated for Hodgkin lymphoma in England over the last 20 years. I will also conduct research studies myself to produce new information about the risk of stroke after radiotherapy. I will use this information to formulate statistical models that will estimate the benefits and risks of radiotherapy for an individual patient with Hodgkin lymphoma. I will develop an online decision support tool which presents these estimates in a clear, accessible way. I will canvas opinion from a range of people affected by lymphoma, and nurses and doctors treating lymphoma, to develop this tool. This will involve interviews, questionnaires and discussion groups.Patient and public involvementI have set up a Project Advisory Group of four people previously treated for Hodgkin lymphoma. I will meet with them regularly to ensure that the questions we ask are directly relevant to patients, and the work has the impact we believe it can. Our initial meeting highlighted that the decision support tool will need to be used by doctors specialising in chemotherapy as well as those specialising in radiotherapy. The group also suggested it will need to be accompanied by information about the role of radiotherapy, and practical advice for patients on how to manage the anxiety associated with the risk of long-term side-effects, what they can do to minimise the risks, and how the potential side-effects can be monitored for following treatment.Communication of results I will present my research to clinicians at national and international conferences, and will publish them in scientific journals. I will also present at the Lymphoma Action National Conference, which is mostly attended by people affected by lymphoma. The Project Advisory Group has agreed to assist with these presentations. I will communicate my findings to a wider audience of people affected by lymphoma through the Lymphoma Matters publication. The decision support tool will be available as an open-access website that will be freely available for use by clinicians before and during consultations with patients.

Research Activity Codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health Categories: CANCER AND NEOPLASMS