Title: PET-CT guided, symptom-based, patient-initiated surveillance versus clinical follow-up in advanced head neck cancer (PET NECK 2)
Funder: Department of Health and Social Care

Abstract: Research question Does PETCT-guided, patient-initiated follow-up result in similar overall survival compared to current post-treatment routine surveillance for head and neck cancer (HNC) patients? Background HNC poses a considerable global health burden, with rapidly increasing incidence, severe morbidity, ~40% recurrence, and high mortality. International guidelines recommend regular routine follow-up, aiming to detect recurrences early and enable successful re-treatment. This regimen is effective at detecting recurrences. However, because detection rates are low in asymptomatic patients attending routine consultations, this routine surveillance regimen is inefficient, resource-intensive and increasingly unsustainable. Patients also report that follow-up schedules are too frequent, and may exacerbate fear of recurrence. In contrast, detection rates increase dramatically when patients initiate earlier review because of developing new symptoms. Additionally, small retrospective studies now show that PETCT scanning at 1-year post-treatment demonstrates high, but variable sensitivity (77-97%) and specificity (77-98%) for the detection of recurrent disease, and may be cost-effective. Hence, PETCT at 12 months may select the patients at very low recurrence risk to undergo patient-initiated follow-up. There is, however, conflicting poor-quality literature on (i) the efficacy of PETCT-guided follow-up in improving overall survival, and (ii) the efficacy of patient-initiated follow-up in HNC. Recently, NICE recommended evaluation of effectiveness and cost-effectiveness of PETCT in HNC follow-up as a priority research area. Aim and Objectives: With patients and clinicians, develop a patient-centred, evidenced-based and theoretically-informed complex intervention and information and support resource for PETCT-guided, patient-initiated follow-up for HNC. Compare the efficacy and cost-effectiveness of experimental follow-up (PETCT-guided and patient-initiated) versus current routine clinical follow-up in a randomised controlled trial. Assess differences in fear of recurrence, patient experience, and quality of life between the two follow-up regimens. Develop a recurrence and survival predictive model, based only on clinical factors, as an alternative, especially in low-resource settings. Concurrently collect samples to test future cancer surveillance technologies (future proofing). Methods and timelines for delivery (months): WS1: Establish a Patient Advisory Group to guide and deliver patient and public involvement (month 1-72). WS2: Undertake systematic reviews of barriers to self-referral and predictive clinical models of recurrence (1-12). WS3: Develop the experimental intervention through patient collaboration (1-13). 3a: Evaluate acceptability of the proposed intervention to patients and clinicians using qualitative interviews (1-12). 3b: Develop the intervention and information and support resource, through qualitative focus groups (1-13). WS4: Test feasibility of the developed intervention, with iterative qualitative evaluation and refinement (10-21). WS5: Randomised trial of PETCT-guided, patient-initiated follow-up versus routine clinical follow-up (22-72); with internal pilot; nested qualitative recruitment evaluation (24-41); mixed methods assessment of patient experience and fear of cancer recurrence (24-53), and cost-effectiveness assessment. WS6: Develop and validate a clinical predictive model for recurrence and survival (13-72). Anticipated Impact and Dissemination We expect our findings to have practice-changing impact for the 12,000 UK and the 640,000 world-wide patients diagnosed annually with HNC, as well as clinicians, the NHS, and international guidelines. Dissemination of findings will be undertaken by a multi-modal, multi-faceted, proactive approach, aided by our strong collaborations with patient-support groups and HNC professional bodies.

Lay abstract: Background Head and neck cancer is increasing rapidly, with 12,000 patients diagnosed in the UK each year. Currently, people finishing treatment attend a clinic review every 2-6 months for 5 years to check if the cancer has come back (called recurrence). If caught early, there is a better chance of successful treatment. However, most patients feel they are seen too frequently, which increases their worry about cancer recurrence. It is also inefficient because few cancers are found this way, and clinical services struggle with increasing demand. Recurrent cancers are much more likely to be found when patients ask to be seen because their symptoms have changed. Studies also show that a new type of scan, called PETCT, done 1-year after treatment can identify patients who are unlikely to get recurrence and could therefore be followed up less frequently. Aim We will develop a new way to follow-up patients, guided by their symptoms, and compare it to the current way. We propose patients have a PETCT scan 1-year after finishing treatment. If no cancer is detected, they will be educated, by a nurse, about what symptoms of recurrent cancer to look out for. The information will also be given in print and online. An open urgent appointment guarantees review by their clinical team within 2 weeks if they develop worrying symptoms, instead of regular clinic visits. Programme design We will run a clinical study, comparing the new PETCT guided, patient-initiated follow-up with the current routine follow-up. We aim to find out: a. which is better at detecting cancer recurrence, b. what effects these two ways have on patients experience, worry about recurrence and quality-of-life, c. which costs less, although this is not the main reason for running this study There are knowledge gaps that need answering before running this study. We will look at the existing evidence (systematic review), and do studies to ask patients and clinicians about the following: Will patients/doctors accept the new follow-up way? What information do patients need to help them understand which symptoms to look out for and how to ask for follow-up? Is it possible to implement the new way of follow-up in clinical practice (a feasibility study)? Patient and Public Involvement Eight patients helped design this project from start, and ten will be involved in designing, running, overseeing and analysing it. Team Our multidisciplinary team of doctors, nurses, researchers, and patients are highly experienced and international leaders at running complex clinical trials and the treatment of head and neck cancer. Expected output/dissemination This research will affect the care of all head and neck cancer patients, nationally and internationally. We will publish the results, present them at conferences and directly inform clinicians and patient groups.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS