Lung cancer screening for Hodgkin lymphoma survivors

Background

In some people lung cancer can be caused by treatment for a previous cancer. Hodgkin lymphoma, a blood cancer that affects white blood cells called lymphocytes, is the most common cancer in children. For survivors of Hodgkin lymphoma, ‘second’ breast and lung cancers are the leading cause of death. Most lung cancers in Hodgkin lymphoma survivors are diagnosed at a later stage when they are incurable.

We know that lung cancer screening using low-dose CT scans saves lives by detecting the disease at an early stage, when surgery with curative intent is possible. In England, the NHS is rolling out Targeted Lung Health Checks in certain areas as we await the implantation of a full national lung cancer screening programme.

Unfortunately, Hodgkin lymphoma survivors don’t currently qualify for the Targeted Lung Health Check programme. Furthermore, most survivors of Hodgkin lymphoma are unaware that they’re at a higher risk of developing lung cancer.

This study developed a patient-centred approach to promote the uptake of screening in these high-risk cancer survivors and better awareness of their risk factors, and to encourage them to follow advice about not smoking.

Most survivors of Hodgkin lymphoma are unaware that they’re at a higher risk of developing lung cancer.

What is the problem to be addressed?

Developing the best ways to prevent people who have survived Hodgkin lymphoma (HL) from developing lung cancer and encouraging such survivors to take part in early detection programmes and follow no-smoking advice. 

Findings and outcomes

• Completion of the largest pilot of lung cancer screening for HL survivors to date (102 participants were screened) during which two patients who showed no symptoms were diagnosed with lung cancer
• Validation of the use of a novel decision aid within the pilot to help HL survivors decide about whether to take part in lung cancer screening
• Collection of saliva from around 90 participants for genetic analysis to work out their lung cancer polygenic risk score (a way to measure the risk of developing the disease due to genetic factors)

There were some changes to the original design of this project:

1. It was not possible to address population-based questions as University of Birmingham collaborators were unable to contribute within the time frame of the study, so instead subjects for the study were identified from The Christie ADAPT database.
2. The pilot lung cancer screening study was re-designed as single-arm study as this was deemed more appropriate and feasible to deliver than the original randomised study.

The project was delayed for six months due to the Covid-19 pandemic. The PhD project component was extended to accommodate for this. Study delays relating to the collaboration with the University of Birmingham were mitigated by finding an alternative source of participants from the ADAPT database. There will be a follow-on project at the Biomedical Research Centre Manchester.

Benefits of the project

While this project does not directly benefit a person already diagnosed with lung cancer, it has established the feasibility of lung cancer screening for people diagnosed with Hodgkin lymphoma which could lead to better outcomes for this group of people through early diagnosis.

In the pilot screening study, two asymptomatic patients were diagnosed with small cell lung cancer, one with early stage disease who underwent potentially curative surgical resection and one with advanced stage disease who was treated with chemotherapy. The first patient directly benefitted from this study as their participation led to early diagnosis and a significantly improved prognosis.

Is this RCLCF funded work (or aspects of it) being continued with new funding?

NIHR BRC funding has been secured to continue work into the development of a national lung screening programme in HL survivors.

Part 1 of this study will explore the utility of a population-based approach to create a centrally coordinated national register of HL patients for future late effects research and evaluate the feasibility of developing a lung cancer risk calculator for HL survivors using risk data collected from NHS digital databases and NHS treatment centres, including the bias and power of this approach.

Depending on results and the need for further research at the time, Part 2 will run a multi-centre single-arm screening study through the NCRI. Further research may not be necessary if results from Part 1 are deemed sufficient to include HL survivors as a high-risk subset with established lung cancer screening programmes, as is the case for HL people at increased risk of breast cancer. There may also be scope to develop ands publish lung-cancer-specific patient education and support literature in partnership with Lymphoma Action.

Have any important collaborations resulted from this RFCLCF-funded project?

This study contributed to the successful multi-million-pound award of renewal funding for the Manchester BRC and the establishment of a new BRC theme: Living with and Beyond Cancer.  The team has engaged in new collaborations with researchers at the Institute for Cancer Research and the University of Oxford, to contribute to the follow-on study.

Has this project resulted in changes in practice or benefits to patients?

• Participants are now better informed of their risks of developing lung cancer; of the symptoms to look out for and the importance of following no-smoking advice.
• Education materials have been developed to communicate late effects and lung cancer risks to the wider Hodgkin Lymphoma survivor population.
• Two cases of early- stage lung cancer were diagnosed within the study population; the patients were referred for further treatment within the NHS.
• Participants will continue to be followed up for outcomes through to July 2023 with ongoing access to support as required.

Has this research resulted in changes to healthcare policy, education or training?

In June 2022, the team engaged with NHS Screening (Professor Anne Mackie, director of screening for Public Health England and Dr David Fitzgerald, Programme Director, NHS Cancer Programme). They were fully supportive of the concept of a targeted lung cancer screening for high-risk HL survivors and encouraged us that ongoing research in this field would inform future healthcare policy.

About the grant holder:

Dr Kim Linton is regularly invited to chair and participate in advisory boards involved in clinical drug development and licencing of new medicinal products for patients with lymphoma. She holds committee roles for NICE, Lymphoma Action, The Manchester BRC, The National Cancer Research Institute, the European Haematology Association and the international Women in Lymphoma organisation, as well as several global pharmaceutical drug development committees. She provides peer review for manuscripts and grant funding applications, and authors and edits scientific publications, as well as guidelines, patient literature and textbooks. She is a fellow of the Royal College of Physicians.

What degrees/professional qualifications were obtained during this RCLCF grant funding, eg MSc, PhD?

Dr Rachel Broadbent, Clinical Fellow on the project, has been awarded a PhD.

What is the grant holder/researcher doing now?

Dr Kim Linton continues to work as a clinical senior lecturer at The Manchester Cancer Research Centre. She is leading the Second Cancers theme within the NIHR Manchester BRC Living with and Beyond Cancer programme of research and leading a follow-on national lung cancer screening study in HL survivors. She chairs the Christie Lymphoma Group and the NCRI Low Grade Lymphoma Study Group.   

How important has this funding been to the researcher?

The Roy Castle Lung Cancer Foundation funding award enabled the team to deliver key aspects of this research and to secure follow-on funding to continue this work.

This project played a significant role in the successful creation of new Manchester BRC Living With and Beyond Cancer theme, the only NIHR BRC centre dedicated to late effects research in the UK.

Through the BRC, the team secured five years’ funding for follow-on research in this field.  The appointment of a post-doctoral mixed methods researcher provided invaluable support for the PhD student on this project, and BRC funding has been secured for her to continue in post to develop the follow-on national study.

Funding also enabled the appointment of a clinical nurse specialist to support the research and study participants.  The success of this role supported a business case to secure permanent funding for this individual, who will continue a research clinical nurse specialist role within the team.

Lead researcher: Dr Kim Linton / Location: University of Manchester / Type of research: early detection