DETECTING TREATMENT RESPONSE
Imagine a future where a patient enters a whole body scanner and we can identify their primary tumour, recognise its heterogeneous nature to predict the best treatment, and then track how the tumour responds in a matter of days, all without the patient undergoing invasive biopsies…
Here is a summary of some of the programme's impact to date. We look forward to more exciting developments in the next grant period.
BODY COIL FOR WHOLE BODY IMAGING
Our Programme is taking steps towards whole body imaging through the purchase of a body coil. Compared with our current coils, this will allow imaging of a much greater area in a single session. The new coil will particularly improve imaging for ovarian cancer.
APPLYING RADIOGENOMICS AND METABOLIC IMAGING
Tumours are often heterogeneous, with genetic, transcriptomic and proteomic variations present between tumours of the same type and between regions within individual tumours. This heterogeneity is challenging as sampling the molecular landscape of each of the different tumour regions (known as habitats) via separate biopsies is expensive and invasive for patients. CT/ultrasound fusion uses radiomic habitats to guide physical biopsies from each tumour region, and can be integrated into the clinical routine. Eventually, we may be able to replace physical biopsies with imaging on which radiomic analysis has been performed (Beer et al., European Radiology 2020). The radiogenomics team has also developed and validated novel artificial intelligence and machine learning approaches, for dynamically assessing intra-tumour heterogeneity, both spatially and temporally, in renal clear cell carcinoma and high-grade serous ovarian cancer. The method links MRI and CT images with pathology data by creating a 3D-printed tumour mould, designed using the CT images to orientate the tumour after surgical removal (Ursprung et al., European Radiology 2020). The removed tumour is then sliced and radiomic imaging habitats mapped onto the anatomy (Crispin-Ortuzar et al., JCO Clinical Cancer Informatics 2020; Jiménez-Sánchez et al., Nature Genetics 2020; Martin-Gonzales et al., Insights into Imaging 2020).
NOVEL IMAGING AGENTS TO ASSESS TREATMENT RESPONSE
Our researchers are assessing the use of the protein C2AM in monitoring tumour cell death (both apoptosis and necrosis) in cancer patients undergoing neoadjuvant chemotherapy or cancer treatment, with the aim of establishing the first-in-human study of radiolabelled C2Am using positron emission tomography (PET) and magnetic resonance imaging (MRI). Dr André Neves, a Principal Scientific Associate in Professor Kevin Brindle’s research group, has been studying C2Am’s performance in tumour models for nearly twenty years. He commented: “We have conducted several preclinical studies using C2Am as a novel imaging agent for PET. C2Am has consistently enabled the visualisation of cell death in a tumour during the course of therapy, providing a rapid assessment of treatment response (Bulat et al., EJNMMI Res. 2020). The programme historically funded a Gallium generator, now in clinical use at Cambridge University Hospitals to produce agents locally for PET scans of patients with prostate cancer, an example of our research translating into clinical practice.
HYPER-POLARISED CARBON-13 METABOLIC IMAGING
Presently, clinical assessment of treatment response is based on the Response Evaluation Criteria in Solid Tumours (RECIST), which define partial response as a reduction of at least 30% in the sum of the diameters of the target lesion. Early assessment of patient response with this method is difficult as morphological changes may occur months after the start of treatment, and the criteria fail to detect patient response to cytostatic therapies where tumour growth is stopped but not reversed. Accurately predicting response to treatment early in the treatment pathway is critical in reducing patient exposure to ineffective therapies, ultimately improving patient care and reducing costs to the NHS. Dr Ramona Woitek, ACI Senior Research Associate, said: “We are studying how early in our patients’ cancer treatment HP C13 MRI could make a difference in supporting clinical treatment decisions, giving us a clearer picture of which patients will benefit the most from this powerful imaging technique.” Our Programme is the first to report that patients who completely responded to treatment demonstrated a decrease in the lactate/pyruvate ratio detected by HP C13 MRI. Other imaging techniques did not demonstrate this early distinction between patients who went on to reach, or not reach, a complete response to their treatment (Woitek et al., Radiology: Imaging Cancer 2020). We are grateful to the group of women who are supporting pioneering research that is changing the outcome of ovarian cancer and to all the patients who enrol in our trials.