Clinical trials

A qualitative interview study exploring the patient and provider perspectives on the clinical utility of genetic risk profiling in routine clinical practice. The findings from the study may contribute towards future research and informing clinical practice.

Pain from advanced pancreatic cancer is often difficult to control. This pain commonly occurs when the cancer affects a network of nerves in the abdomen called the coeliac plexus. Even strong pain medicines, including morphine and related drugs, may not give enough relief. Some patients may have a procedure called a coeliac plexus block, but this is invasive, not widely available, and does not always work. Radiotherapy is widely used to relieve cancer-related pain in other cancers, but it is not commonly used in the UK for pancreatic cancer pain. Studies carried out in the United States and Amsterdam have investigated the use of radiotherapy to help control pain in pancreatic cancer and have shown benefit for many patients. However, these studies were not specifically designed to target the coeliac plexus nerve region, which is thought to be an important source of pain in pancreatic cancer. Recent research suggests that radiotherapy directed at this nerve area may reduce pain in many patients with limited side effects. This study is therefore being carried out to investigate whether targeting this nerve area using a short course of radiotherapy can safely and effectively improve pain control in patients with advanced pancreatic cancer. The radiotherapy in this study will be delivered using a widely available technique called Intensity Modulated Radiotherapy (IMRT). IMRT is an advanced form of radiotherapy that allows radiation beams to be shaped very precisely to the treatment area while reducing radiation exposure to nearby healthy tissues and organs. IMRT is routinely used in the NHS to treat many different types of cancer, including prostate, head and neck, lung, and gastrointestinal cancers. In this study radiotherapy is not being given with the intention of treating the cancer itself, but rather to help alleviate pain related to the cancer. The main outcome we will measure is whether pain improves by a meaningful amount using a questionnaire called the Brief Pain Inventory (BPI), which assesses pain severity and its impact on daily life. We will also measure changes in pain medication, treatment side effects, overall survival and patients' overall impression of change after treatment. Participants will be followed up for up to 12 months after radiotherapy treatment. If this study shows a promising signal of benefit, radiotherapy for pancreatic cancer pain could become more widely used across the UK. Because IMRT is available at most radiotherapy centres, many patients could receive treatment closer to home.

ctDNA stands for circulating tumour DNA. As ctDNA is released by tumour cells into the blood stream, taking a blood sample and analysing it for ctDNA, can provide a lot of useful information about a patient's cancer. In certain situations, ctDNA can be used to screen for or detect cancer early, to aid clinical decisions about which treatment to give a patient, to provide information about if a cancer has become resistant to treatment, or provide information about how much cancer may be left after treatment (residual disease). The aim of this trial is to establish the clinical utility of implementing ctDNA testing in cancer patients with a view to enhance the delivery of personalised care within the National Health Service in the United Kingdom (UK). One hundred patients will be recruited, with 20 from each of the following cancer types: * Non-small cell lung cancer * Gastrointestinal stromal tumours * Colorectal cancer * Biliary tract cancer * Ovarian cancer. Patients must be aged 18 or over, must have had progressive disease whilst receiving anti-cancer treatment, and must be being treated at The Royal Marsden. Patients will have a blood sample taken and analysed using the Marsden360 ctDNA test. The results of the test will be looked at by The Royal Marsden Genomic Tissue Advisory Board (GTAB), and for each individual patient, the GTAB will determine if having a ctDNA test helped to personalise their care by: * Aiding the identification of a genomically-matched standard of care therapy * Aiding the identification of a genomically-matched clinical trial (based in the UK) * Offering additional prognostic information not otherwise available through standard of care testing * Negating the need for a tissue biopsy.

The goal of this clinical trial is to assess the safety and feasibility of using a new form of radiotherapy technology, known as CT online-adaptive radiotherapy, to reduce the number of treatment sessions required in post-operative radiotherapy for patients with endometrial cancer, from 25 sessions over 5 weeks to 5 sessions over a week and a half. The main questions it seeks to answer are: * If it is safe to deliver the radiotherapy in a smaller number of treatment sessions with a larger dose per session by utilising the CT online-adaptive technology * If it is feasible for this treatment to be delivered using the CT online-adaptive technology in a clinical trial All participants who enrol in the study would be offered the trial treatment of the radiotherapy being delivered in 5 sessions. Any potential participants who are subsequently found to be ineligible during the radiotherapy planning process would be excluded from the trial treatment of a higher dose over 5 sessions, but would still be offered the CT online-adaptive technology over 25 sessions outside of the trial. Participants would undergo the trial treatment with the radiotherapy being delivered in 5 sessions over a week and a half using the CT online-adaptive technology, with any issues during the treatment delivery recorded, and a questionnaire to complete at the end of treatment to see how the new technology was tolerated by participants. Participants will have their side effects recorded by the trial team before, during and after their treatment for 2 years following the radiotherapy. During this time period participants will also be asked to complete patient questionnaires to assess their perception of side effects and their quality-of-life after undergoing the treatment. Participants will also have blood tests before, during and after the radiotherapy for 3 months to check for any potential problems with blood counts as a result of the trial treatment. During the 2 years of follow-up after the radiotherapy, participants will also have assessments for if the cancer has returned, which will be completed by a combination of clinical examination, and CT scans. Following completion of the 2 years of trial follow-up, participants would remain on general follow-up to assess for if the cancer has returned, or for any longer term side effects for up to 5 years after the treatment, but this follow-up will be outside of the trial without the request for ongoing completion of participant questionnaires.

BELIEVE is a translational research study that aims to collect samples of breast cancer tissue and blood from individuals undergoing breast cancer treatment (such as chemotherapy, targeted therapy and immunotherapy) before surgery. In certain cases, MRI scans and stool samples will also be obtained before and during treatment. The samples collected from this study will be used for molecular and genetic research to understand why some cancers respond very well to anticancer treatments, and some do not, develop novel ways of accurately measuring response during treatment, as well as identify which patients are at a higher risk of the cancer coming back after surgery.

DESTINATION 2 is a multi-centre randomised trial treating intermediate risk localised prostate cancer with 2 fraction Stereotactic Body Radiotherapy (SBRT). All radiotherapy will be delivered in two fractions (sessions) on an MR Linac using daily adaptation. Men will either receive uniform dose radiotherapy or de-escalated dose radiotherapy. The primary endpoint is acute GU CTCAE v5 grade 2+ toxicity. It will also look at late toxicity, patient-reported outcome measures and PSA control.

FORTITUDE is a translational research study that aims to collect serial multi-site needle biopsy samples of tumour tissue and blood from metastatic breast cancer patients. Cancer biopsies are generally performed when cancer is diagnosed and are sometimes repeated when the cancer is suspected to have spread but this is not mandatory. However, studies have shown that cancers change with time and evolve to become resistant to therapy. The purpose of this study is to assess the feasibility of biopsies of multiple cancer sites across different time points during treatment and understand how cancers evolve and change throughout treatment. The findings of this study could pave the way for using cancer biopsies more frequently in the clinic to pick up changes in cancer behaviour that could influence treatment choice. The samples collected from this study will be used for molecular and genetic research to increase our understanding of how metastatic breast cancer changes during treatment and will enable us to develop new cancer treatments and new ways of monitoring response to cancer therapies.

This is a cohort study aimed at developing a stratified medicine approach for personalised neoadjuvant chemotherapy (NCT) in high-risk soft tissue sarcoma (STS) patients with dedifferentiated liposarcoma (DDLPS), leiomyosarcoma (LMS), synovial sarcoma (SS), vascular sarcomas, malignant peripheral nerve sheath tumour (MPNST) or other subtypes. It comprises of both retrospective and prospective tissue collection from patients advancing directly to surgery (control group) and patients receiving NCT and surgery.

IReC is the world's first centre for recurrent head and neck cancers. We have the ambitious aim to create a centre of international excellence and set international standards in the curative treatment of recurrent head and neck cancers. One of IReC's key objectives is to develop a national research tissue bank to support laboratory and translational research. The cornerstone of translational research is a well-annotated biobank of cancer samples to explore and validate key research findings. The purpose of IReC-Bio is to support research into recurrent head and neck cancers. A central repository for the rarer recurrent cancers will allow the concentration of cases required in order to support translational research programmes. The overall aim is to facilitate research into understanding disease biology, identifying potentially curative treatments, and allow detailed investigations into the relationships between clinical, pathological and molecular characteristics and clinical outcomes. Combining the IReC Registry and Biobank gives us a comprehensive data and sample set which has never been created before for recurrent head and neck cancer. The aim is to have a national, and in the future international, resource of the study of recurrent head and neck cancer on a molecular and clinical level to support novel ways of treating rHNC.

The RESCUE study is a combined retrospective and prospective multicentre cohort study investigating the survival and functional outcomes in patients undergoing salvage surgery for recurrent, residual, and new primary head and neck squamous cell carcinoma (SCC). Additionally, the RESCUE study will contain an exploratory molecular analysis of consenting patients to assess the relationship between cancer genomics, previous radiotherapy, and recurrence in head and neck cancer.

Radical radiotherapy for head and neck squamous cell cancer (HNSCC) can be administered to primary disease with curative intent. Residual disease, recurrence or further tumours may subsequently occur in this irradiated field. It is unknown whether these cancers reflect primary resistance or represent the evolution of resistance on treatment. Understanding this could allow stratification of patients to more effective primary treatments, such as transoral robotic surgery, or help tailor systemic therapies for these cancers in previously irradiated fields. RECUT+ is an exploratory molecular analysis study to assess the selective impact of radiation therapy on HNSCC. Participants will be recruited from the Royal Marsden Hospital (RMH), Chelsea, a tertiary referral H\&N cancer unit in London, UK, specialising in transoral robotic surgery. Retrospective participants will be identified from previous Head and neck MDT lists at RMH. Prospective participants will be screened for by the RECUT+ team during the weekly H\&N MDT meetings at the Royal Marsden Hospital (RMH). Blood/saliva samples will be collected pre operatively (prospective participants) and post operatively (retrospective and prospective participants) for germline and circulating tumour DNA analysis. Biopsy samples from the original cancer and resected specimens from the post radiotherapy residual/recurrent/new primary disease will undergo molecular analysis to assess for any selective impact of radiotherapy on these further tumours.

Earlier work explored barriers and facilitators to accessing prostate cancer screening, particularly in underserved communities, and provided valuable insights to build upon. This study will explore perspectives on how genetic risk for prostate cancer is explained and understood through in-depth interviews with members of underserved communities. Findings from this work, alongside earlier results, will be used to co-design clear and accessible digital educational resources in collaboration with community members and relevant charities. Participation in cancer screening programmes in the UK varies, with differences linked to socioeconomic status, ethnicity and health literacy. Similar inequalities are seen in access to prostate cancer genetics services, indicating a need for improved engagement. Successful integration of genetics into prostate cancer care requires clear and inclusive information about genetic testing processes, possible outcomes and interpretation of results. Currently, there are limited resources explaining genetic risk for prostate cancer in an accessible way. Co-production with representatives from underserved communities will ensure that educational materials are understandable, relevant and acceptable to all.

Patients diagnosed with prostate cancer and receiving hormone therapy in conjunction with radiotherapy are likely to suffer from adverse effects caused by ADT treatment either short term or long term. The most common side effects include changes in body composition leading to increased visceral fat and reduced lean muscle mass, increased risk of cardiovascular events and fatigue, which overall lower quality of life. There is strong evidence to support exercise interventions in minimising, and in some cases reversing many ADT -related toxicities, but exercise adherence remains a challenge for people living with prostate cancer, particularly due to logistical barriers to attendance such as cost and travel time, as well as insufficient motivation. The aim of this single centre, phase III randomised controlled trial is to assess the efficacy of a new digital exercise programme with virtual supervised group exercise sessions in improving adherence to exercise guidelines. The trial aims to recruit 160 participants with prostate cancer undergoing ADT, who will be allocated either the standard of care group or standard of care plus participation in the digital exercise intervention on a 1:1 ratio. Adherence to physical activity will be measured using a wearable accelerometer, an exercise diary, self-reported questionnaires and clinic based assessments at 3 months, 6 months and 12 months post radiotherapy treatment. Recruitment will take place at the Royal Marsden NHS Foundation Trust, Chelsea.

A prospective observational cohort study of patients undergoing CPI therapy in which translational research is the fundamental aspect of the study.

Patients who require a removal of a breast (mastectomy) for breast cancer or future risk reduction often have immediate breast reconstruction (IBR). This can be performed using either an implant or the patient's own body fat to recreate the breast shape. Patients can find it difficult to imagine their own post-surgery appearance. Using 3D surface imaging (3D-SI) can change a patient's pictures to show them how they might look after surgery, known as a simulation. Some patients may find 3D-SI and simulation gives them confidence in their expectations and others may not feel it helps much. This study will investigate the following 3 questions: 1. Whether 3D-SI and simulation can improve patient confidence about their likely post-surgery appearance 2. Whether 3D-SI measurement of breast shape helps in surgical planning and reduces the need for later adjustment surgery to improve symmetry, especially in patients having a mastectomy on one side only 3. How much radiotherapy changes breast reconstructions over time using 3D- SI to objectively measure this. For this study the follow up for some women who do and some who do not have radiotherapy after breast reconstruction. 3D surface imaging may improve surgeon understanding of breast shape, prior to surgery. In cases where there is a high risk of breast cancer recurrence patients are offered radiotherapy to the breast, either before or after surgery. Radiotherapy has a negative impact on the reconstructed breast, and may cause it to shrink and change position but the effect of radiotherapy has never been accurately quantified. This study will be investigating the following: 1. Whether 3D-SI measurement of breast shape helps in surgical planning and reduces the need for later adjustment surgery to improve symmetry, especially in patients having a mastectomy on one side only 2. How much radiotherapy changes breast reconstructions over time using 3D- SI to objectively measure this. For this study the follow up some women who do and some who do not have radiotherapy after breast reconstruction.

This is a non-randomised, single-centre Phase 2 study, investigating whether the diagnostic biomarker, prostate-specific membrane antigen (PSMA), can detect melanoma metastases using PSMA PET/ CT.

This study aims to determine if it is feasible to collect samples of blood and viable lung cancer tissue in patients with either: * Stage IV mutation-driven NSCLC * Stage II-III NSCLC undergoing neoadjuvant immunotherapy prior to surgery Viable tissue has been defined by the collaborating pathology department as the presence of viable tumour cells, in accordance with recommendations from the International Association or the Study of Lung Cancer. In patients with stage IV NSCLC, obtaining adequate samples of viable tissue for advanced testing can be challenging, as sites of cancer that are accessible by biopsy are often small, and contain few viable cancer cells. If obtained, however, viable blood and tissue specimens can be utilised for genetic and other analyses aimed at identifying cancer markers that may offer prognostic information, or that may potentially lead to development of therapies that target these markers in the future. In patients with stage II-III NSCLC, the use of immunotherapy prior to surgery has been shown to affect the proportion of viable tumour tissue at the time of surgery, although this needs to be further studied. There is a need to better understand the genetic basis of these tumours to improve response rates to immunotherapy prior to surgery. The study will be open for four years in total. The first three years will consist of recruitment and participant follow up, and the fourth year will consist of follow up only. Data analysis will occur in the fifth year when the study is closed.

A prospective imaging and translational tissue study in CNS lymphoma to enable further disease characterisation and the development of potential predictive and prognostic biomarkers.

Prospective, randomised, feasibility study of patients with localised or metastatic renal cell carcinoma (RCC) comparing standard palliative dose radiotherapy to a high-dose hypofractionated regime. Primary aim • To demonstrate feasibility of a randomised study comparing high-dose hypofractionated radiotherapy versus standard palliative dose radiotherapy in localised or metastatic renal cell carcinoma The aim is to recruit a minimum of 24 patients; 12 to the control arm and 12 to the high-dose regime. 2 treatment arms, no placebo: * Control arm - standard palliative-dose radiotherapy, 30Gy in 10 fractions in 3Gy per fraction over 2 weeks * High-dose arm - high-dose radiotherapy, 30Gy in 5 fractions in 6Gy per fraction on alternate days/2-3 fractions a week over 2 weeks

Intratumour heterogeneity is well recognized in multiple cancer types and ultimately leads to therapeutic resistance. It also limits the ability of small samples to represent the whole tumour, having implications for diagnosis, molecular analysis and understanding of the tumour immune microenvironment. By blending- 'homogenizing'- leftover tumour tissue in excess of that required for diagnosistic purposes, one may create a more representative sample for analysis.

Rapid Diagnostic Centres Rapid Diagnostic Centres (RDC) were built to diagnose patients who have common symptoms that occur in cancer, but it is unclear if they have cancer or not. These symptoms include: * Weight loss * Fatigue * Cough * GP suspicion Only 1 in every 10 patients (10%) referred to an RDC will have cancer. Some of the patients with cancer may have been more likely to develop cancer due to inherited or environmental factors. Some of the patients who don't have cancer may also be at higher risk of developing cancer at another time due to inherited or environmental factors. Aims The goal of this observational study is to develop a new blood or non-blood test that could help doctors at RDC: * detect which patients have cancer through a simple and quick blood or non-blood test * detect patients who are at higher risk of having cancer. This is so they can be monitored or guided towards cancer-screening programmes Main End Points * The study will be considered a success if a test or mixture of tests is developed that can correctly sort patients into cancer or non-cancer groups. * Also, the study will be considered a success if a test or mixture of tests can show what type of cancer a patient has if they have cancer. Tests To create this new blood or non-blood test the study will take the following samples from 1000 patients in the RDC Biomarker Study: * Breath samples (around 300 patients) - People with cancer have different levels of chemicals in their breath than people without cancer. The study hopes to develop a breath test which could show if a patient has cancer or not. * Blood samples ( around 1000 patients) - The study hopes to develop a blood test that could show if a patient has cancer or not * Saliva samples (around 1000 patients) - For many cancers, while there is a genetic component there is no one single gene that causes cancer. Instead, it can be a combination of hundreds of genes that causes the risk of cancer in a person to go up. The study hopes to develop a test which could provide a risk score. This risk score is called a 'polygenic risk score' which would tell doctors how likely a patient is to get cancer. Method Patients who meet the criteria to be able to join the study will be asked either via telephone before their appointment, or face-to-face at an appointment at the RDC if they would like to join the study. If they agree to join the study they will read a patient information sheet and sign a consent form to say they understand what the study requires. The patient will then provide blood and saliva samples and in some cases breath samples at their first appointment. They will be then asked to provide further samples (up to three) at their follow-up appointments. Please see below for samples that will be asked for at each appointment: First appointment: Breath (not all sites), Blood, Saliva (not all sites), Survey Follow-up 1: Any samples that could not be taken at the first appointment Follow-up 2: Any samples that could not be taken at the first appointment The patient will be provided with a Study ID to identify their samples. This is a unique code to identify each person on the study. Only the site that recruited the participant will have access to the personal information that matches which patients is known by which Study ID. All organisations external to the site will only know the patient as the Study ID. An example of the study ID could be RDCRMH001. A trained clinical member of the research team at the RDC will take the sample and ship it to the relevant laboratory for testing. As well as blood and non-blood tests, information about the patients will be collected This includes routinely collected clinical data alongside investigation results. No patient identifiable information such as: * Name * Address * Date of birth * Contact details will be collected, and a Study ID will be used to identify the data. A patient questionnaire will be sent out to patients to complete for each appointment asking questions about the patient's health. The RDC doctors treating the patient will see survey answers before the appointment to allow them to act about anything worrying. For a small group of patients anonymised copies of thier scans from their medical records will also be taken. Study Duration Once the study has recruited 1000 patients, it will close to recruitment. These patients will then be followed up for 12 months following the date they joined the study.

This pilot study will take place in thyroid outpatient clinics. It will have two study arms running in consecutive order: first, a Control arm where standard care will take place without PDA-TC, then a Patient Decision Aid (PDA) arm where the PDA-TC is implemented into the clinical practice. Within each arm, eligible patients will attend two thyroid cancer outpatient clinical consultations during which the patient will make a shared decision with their clinicians regarding surgical treatment between hemithyroidectomy and total thyroidectomy. In the PDA arm, the PDA TC pamphlet will be introduced to study participants after the initial clinical consultation. The participants will be encouraged to read and digest information related to the disease and treatment options on PDA-TC before returning for their second consultation where a treatment decision will be made together with their clinicians. Participants will be asked to complete the Decisional Conflict Scale questionnaire after each consultation in both study arms. The patient will also complete a Satisfaction with Decision Scale questionnaire and a Preparation for Decision Making Scale questionnaire after the second consultation in both arms.

Standard radiotherapy in the UK involves having daily chemotherapy tablets with radiotherapy treatment for 5 weeks at a dose of 52.5Gy to the rectal cancer over 25 fractions. This is the likely treatment participants will be having if they decide not to take part in this study. Increasing the dose to 60Gy is shown to increase the chance that rectal cancer will be treated completely, a term known as "complete pathological response". Patients who have a complete pathological response after their treatment can avoid surgery and enter into a surveillance programme to monitor for early signs of the cancer returning. Surveillance can mean 3-6 months camera tests and MRI scans depending on the local unit. If these patients continue to show signs of complete pathological response then they can avoid long term complications from surgery such as a stoma. Unit studies have shown that that increasing the dose of radiotherapy can cause slightly more bowel and bladder side effects, but using adaptive radiotherapy to limit radiotherapy to normal tissue could keep the rate of bothersome side effects as low, which is similar as standard treatment. All adaptive treatments within this trial will be delivered on a state of the art, radiotherapy machine called an MR-linac (Magnetic Resonance Linear Accelerator). It combines an MRI scanner with a radiotherapy treatment machine called a Linear Accelerator (called a 'linac' for short). The use of the MR-linac means there is no extra radiation dose given when taking daily images to check for the position of participants rectal cancer (unlike CT scans or X-ray). It also enables the investigators to adapt or 'tweak' the radiotherapy plan each day to match the exact position of the rectal cancer and adjacent organs. The non-adaptive fractions can be delivered on either the MR-Linac or CT-linac depending on factors such as treatment machine availability. The investigators will deliver the treatment on the MR-linac using a technique called intensity modulated radiotherapy (precise X-ray treatment, called IMRT for short). IMRT is able to mould radiotherapy treatment according to what the investigators can see, therefore enabling the investigators to give highly targeted treatment. The investigators already have considerable experience in delivering radiotherapy to rectal cancer with this machine and now wish to focus on whether they could increase dose to benefit long term outcome for all rectal cancer patients as well as reducing the side effects of treatment. The purpose of this research is to increase the dose to rectal cancer while adapting to the changes that the investigators can see to the rectal cancer during treatment. This means that if the rectal cancer is seen to reduce in size they will be able to deliver a 'shrinking boost' according to what can be seen. This will enable the investigators to give high dose radiotherapy to the cancer whilst limiting radiotherapy to healthy tissue. Without the ability to adapt to changes that the investigators see to the tumour throughout the entire treatment course, standard treatment delivers dose to a larger area of surrounding healthy tissue to ensure that the tumour is sufficiently targeted. The investigators want to find out if by using this adaptive, shrinking boost approach, they can safely increase radiotherapy dose to rectal cancer, whilst limiting the side effects you experience, in comparison with standard treatment. If this is possible, then this would lead into further clinical trial where the investigators would compare outcomes of higher-dose treatment to standard-of-care. The investigators can't be certain that the side effects will be different, and they don't know if this treatment results in the best chance of cancer cure. However they know from other studies that this is the likely outcome, with surgery being delayed for patients. Patients who have a complete pathological response after combined chemotherapy and radiotherapy treatment enter into a surveillance programme where MRI and camera tests (flexible sigmoidoscopy) are performed at regular intervals looking for early signs of cancer returning. The investigators expect that the chance of participants having a complete pathological response with this technique is higher than with standard dose, although the investigators can't know this for sure until they have completed further studies. It is possible that the cure rate may be lower or higher than the standard dose.

Surveillance for colorectal cancer (CRC) in patients predisposed to develop CRC during their lifetime has been impacted by access to colonoscopy suites and endoscopy specialists in the past couple of years. An alternative method, namely the colon capsule, has been proposed, however this investigation is time consuming for the clinician and the images require up to one hour (30-60 minutes) reading to issue a result. The investigators propose to obtain images from paired colonoscopies and colon capsules with the purpose of developing an AI algorithm which could aid the clinicians in reading the colon and expand access to this investigation. The main aim of the study is to determine whether it is possible to obtain usable paired images from patients with Lynch and other cancer predisposition syndromes. This will depend on the willingness of the patients to take part in the study and the technical ability of obtaining data from paired images of colonoscopies and colon capsule. At recruitment, participants will undergo a colon capsule investigation, followed by a routine colonoscopy as per their normal standard of care. Paired endoscopic images from colonoscopies and colon capsules will be collected and anonymised data will be accessed by the bioinformatician for analysis. If the study will be successful in reaching the primary endpoint, further trials will be opened, allowing for a larger population to be included and to obtain more robust data, which eventually can lead to validated AI algorithms and application of computer-aided video-capsules examination as a screening tool in at-risk population.

Detection of molecular relapse with circulating tumour DNA analysis can identify which patients with ER positive breast cancer are relapsing on adjuvant endocrine therapy. This trial will aim to demonstrate that palbociclib and fulvestrant, can defer or prevent relapse in patients with ctDNA detected molecular relapse. The TRAK-ER trial will have two phases, a ctDNA surveillance phase and a randomised therapy trial in patients with positive ctDNA. The TRAK-ER trial will establish a ctDNA screening programme for patients with ER positive breast cancer receiving adjuvant endocrine therapy with at least a further three years of standard adjuvant endocrine therapy planned. Patients recruited into the TRAK-ER study will have high-risk clinical features to identify patients at higher risk of future relapse. ctDNA assays will be used to identify which people are at very high risk of relapse (i.e. those with a positive ctDNA result), and randomise this high risk population between standard endocrine therapy versus palbociclib plus fulvestrant for up to two years.