Title: Impact on Quality of life from multi-modality treatment for lung cancer: A randomised controlled feasibility trial of surgery versus radiotherapy in addition to systemic anti-cancer therapy in potentially resectable Stage III-N2 NSCLC
Funder: Department of Health and Social Care

Abstract: Research question: What is the feasibility and acceptability of conducting a randomised phase III trial comparing surgery versus radiotherapy, in addition to systemic anti-cancer treatment, for patients with potentially resectable stage III-N2 non-small cell lung cancer (NSCLC), and health-related quality of life (HRQOL) as the primary outcome? Background: Treatment for N2 NSCLC requires multi-modality treatment with a combination of systemic therapy (chemotherapy) and surgery or radiotherapy. Studies have failed to demonstrate clear evidence of superiority for survival of one strategy over another. There is a dearth of evidence in relation to HRQOL and the burden of different treatment pathways for patients and their carers. Aims: to provide pivotal information that will inform the design of a phase III randomised trial of surgery versus radiotherapy in addition to systemic anti-cancer therapy with HRQOL as a primary outcome; and the feasibility of collecting patient/carer HRQOL and burden data. Objectives: 1) test the willingness of clinicians to refer/recruit/consent patients and willingness of patients/carer to consent; 2) describe recruitment pathways and treatment fidelity; 3) determine the primary outcome assessment for the follow-on trial. Methods: patient participants will be randomised to receive 1) surgery OR 2) radiotherapy PLUS chemotherapy. We will apply the Quintet Recruitment Intervention to maximise recruitment and inform the recruitment strategy for the follow-on trial. Inclusion criteria includes patients with potentially resectable N2 NSCLC who have received an MDT recommendation for multi-modality treatment, including the option of surgery or radiotherapy; over the age of 18 years. We aim to recruit 66 patients and their carers over 20 months from eight high-volume UK centres. Patient and carer questionnaires will be administered at baseline, weeks 2, 6, 12 and month 6. Patient-reported outcomes: EORTC-Core 30, EORTC-plus lung module, Short Form-36, anxiety/depression EQ-5D. Caregiver-reported outcomes: Cancer Caregiver QOL, Caregiver Burden Index, anxiety/depression. Data analysis: Statistical analyses will be descriptive, focusing on calculating confidence intervals for key trial parameters and feasibility metrics. Audio-recordings of recruitment/consenting consultations will be conducted and 12-16 patient/caregiver dyads will be interviewed. Qualitative data will be thematically analysed. Project timeline: Total time: 34 months (plus 3 months pre-study set-up) Ethics/HRA/R&D: 3 months (pre-study) Initial site set-up: Months 1-3 Staggered site opening: Months 4-11 Recruitment: Months 4-24 Follow-up: Months 24-30 Qualitative interviews: 4-30 Data analysis and dissemination: Months 30-34 Impact and Dissemination: The results of this study will directly inform whether or not we proceed to a phase III randomised controlled multi-site trial and if so, identify the best strategies to make that trial successful. We will disseminate the result of this study widely including NCRI, EORTC-lung sub-group, National Forum for Lung Cancer Nurses, and BTOG. We have co-applicants that are leaders/members for each of these organisations. Should we move to a phase III trial we will seek collaboration with European partners and across the UK and seek funding from HTA/EORTC and support. The respective chairs of the EORTC Lung Cancer Committees for surgery and radiotherapy are co-applicants on this proposal and have commenced engagement with members for a Europe-wide trial.

Lay abstract: In this project we will explore how lung cancer patients and their family carers are affected by different types of cancer treatment. The information collected will help patients along with their carers in the future to make decisions about the best treatment option for them. We are focusing on a particular type of lung cancer called Stage III N2. N2 means the cancer has spread just outside the lung to the lymph nodes. Around 2500 patients a year in the UK are diagnosed with this type of lung cancer. There are two main treatments available in the UK: Chemotherapy and surgery Chemotherapy and radiotherapy Patients live for a similar length of time with either treatment option so it is difficult for patients and health professionals to know which treatment to choose. Research to date is yet to establish how the two different treatments offered will affect different individuals; together with the daily impact such treatment will have on both patient and carer. It is important to understand the impact of the treatment on: Symptoms Side effects Emotional well-being Day to day activities Other research studies including N2 lung cancer patients have struggled with patient recruitment. This study design will show us if it is possible to run this type of research with this group of patients. Patients will be allocated at random (a process usually done by computer) to receive one of the two treatments options: 1) Chemotherapy and surgery or 2) Chemotherapy and radiotherapy. We will ask patients and carer to complete questionnaires and to take part in interviews. The information collected will help us to understand the impact of the different treatments on their daily lives. Health professionals will also be asked to take part in interviews. These interviews will help us to understand their experience of recruiting patients to this study. The results of this study will help us decide if we should run a larger study in the future. Patients have been involved in the development of this project and provided feedback on the methods used. We have included a patient as co-applicant on this project to support on-going patient involvement during the study. We will tell hospitals, patients and members of the public about our results and will know whether or not it is possible to run a larger trial.

Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES;6.4 SURGERY
Health categories: CANCER AND NEOPLASMS