A PET scan can guide cancer treatment in real time, telling doctors whether to intensify therapy, switch drugs, or spare a patient from unnecessary radiotherapy. This matters because current imaging often cannot distinguish between a tumour that is responding and one that is not until it is too late. PET reveals molecular changes weeks before CT or MRI would show any difference. The research targets two specific problems: overtreatment that causes lasting side effects, and undertreatment that allows cancer to return. If successful, PET-guided treatment could become standard practice for lymphoma and head and neck cancers. Patients with early complete metabolic response on PET could safely skip radiotherapy, avoiding long-term damage to healthy tissue. Those whose tumours prove resistant could receive targeted dose boosts or more effective drug combinations. The same approach could be extended to other cancers, reducing the number of patients who endure toxic treatment without benefit. The research also aims to replace subjective visual reading of PET scans with quantitative analysis, reducing observer variation and false positives that can lead to unnecessary interventions.
View original technical description
Background: Positron Emission Tomography (PET) scans show functional changes in cancer at the molecular level. PET can enable earlier and more accurate treatment monitoring than CT and MR with the potential for earlier modification of cancer treatment to minimise toxicity and optimise effectiveness, using a personalised approach. Escalation of treatment may involve more aggressive chemotherapy or boosting radiotherapy dose. New techniques using intensity modulated radiotherapy (IMRT) permit 'dose-painting', to areas that PET suggests may be more resistant to treatment. My proposed research: Will use PET to optimize patients' ongoing treatment based on individual response and risk to side-effects. Maximise the benefit of new radiotherapy treatments, using PET to target the right areas. Will develop quantitative techniques for PET reading to improve on the use of the naked eye. Research will focus on haematological and head and neck cancers but have wider application. Aim 1 We hypothesise that PET can guide treatment to reduce toxicity and/or increase cure in trials: a) in early stage Hodgkin Lymphoma (HL) Patients will receive 3 drugs - doxorubicin, vinblastine, darcarbazine and either bleomycin [standard] or brentuximab vedotin (BV) [experimental] as the 4th drug. BV may be more effective with less toxicity. Patients with early complete metabolic response (CMR) on PET which is the primary endpoint will not receive radiotherapy [1042 patients]. b) in Follicular Lymphoma (FL) Patients with PET-CMR after induction will be randomised to receive rituximab for 2 years or no further treatment. Potential cost savings are ~£50 million annually for the NHS if no further treatment is not inferior. Patients without CMR will receive treatment with rituximab and lenalidomide which may prolong progression free survival. [840 patients]. c) in patients > 60 years with HL or co-morbidities that limit standard treatment. BV and Bendamustine will be compared with standard treatment with CMR as the primary endpoint [120 patients]. We will also explore whether pre-treatment PET predicts patient outcomes, to enable PET-guided treatment from the start. Baseline features including metabolic tumour volume will be tested in cohorts with HL, Diffuse large B cell lymphoma and FL. The combination of imaging and non-imaging biomarkers including gene expression profiling and circulating tumour markers will be evaluated in collaboration with the Precision Medicine for Aggressive Lymphoma Consortium. Aim 2 We hypothesise that PET can be used to response-adapt radiotherapy We will use methodology established by our group using PET-CT and currently being evaluated in PET-MR in a planned multicentre trial. Patients with head and neck cancer will be randomised to receive standard or adaptive intensity-modulated radiotherapy, boosting radiotherapy dose to areas of poor response on PET. We will evaluate PET tracers that image hypoxia with nested studies to explore observer variability in target volume delineation to derive a standard approach for PET-guided radiotherapy. We will explore practicalities of using PET with targeted radiotherapy techniques in lymphoma patients to spare normal tissues, using radiobiological modelling to estimate risk reduction. Aim 3 To evaluate techniques to improve the interpretation of PET response Semi-quantitative analysis will be tested in lymphoma datasets to determine if this reduces observer variation and provides a continuous scale with incremental value. PET has been reported to show 'false positive' uptake with new immunomodulatory agents effective against solid tumours. We will assess PET as an exploratory endpoint in 2 UK trials of novel agents in lymphoma to develop criteria for future response-adapted trials. Benefits include using PET-guided treatment to reduce toxicity and improve survival for patients with cancer cost savings by reducing ineffective therapy translation of new imaging guided RT techniques into clinical practice. This is timely with a £130million NHS investment in IMRT.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know