Quic-Concept

Imaging biomarkers extracted from CT, PET and MRI scans are extremely beneficial tools for assessing if a cancer drug is working at an early stage. However, scientists are frustrated that not enough of these tests are validated for use in clinical research.### IMI’s QuIC-ConCePT project seeks to address this challenge by accelerating the validation of existing bioimaging markers so that they can reliably be used in drug research. ‘Our frustration was that there was only a small number of imaging biomarkers that drug developers could trust,’ says deputy project coordinator John Waterton, professor of translational imaging at the UK’s University of Manchester and former head of imaging at the pharmaceutical company AstraZeneca. ‘The genesis of the QuIC-ConCePT project was to add to the number of imaging biomarkers that could be used in drug development. We cherry-picked a few promising tests – and then put them through a vigorous validation process.’  ###

The project focuses on tumour cell proliferation, programmed cell death (apoptosis) and cell death due to injury, disease or lack of blood supply (necrosis) and has concentrated on two imaging biomarkers for measuring these. These include: MRI ADC (Apparent Diffusion Coefficient), a measure of diffusion of water molecules within tissue that gives information about tissue integrity; and FLT (fluorothymidine) PET scan, which measures whether tumour cells are dividing fast. The team has evaluated the two imaging biomarkers, assessing their reproducibility, effectiveness, timing, dose response and imaging in animals and humans. They are now awaiting results from two clinical trials involving a well-known cancer drug for lung and liver cancer patients to see if changes in imaging are reflected in the pathology of the cancer tumours. Results are due to be published in 2018. QuIC-ConCePT also led a consensus group that produced a set of 14 recommendations (or a ‘roadmap’) for accelerating the clinical validation of imaging biomarkers in an influential paper in the medical journal Nature Reviews Clinical Oncology.

• Read the full story

An international team of experts, including scientists from IMI cancer project QuIC-ConCePT, have put forward a framework to improve the way imaging is used in clinical trials of cancer drugs. Writing in The Lancet Oncology, the team explains that improvements in imaging methods are making them increasingly popular in clinical trials of cancer drugs.### Used well, imaging can show whether or not a patient is responding to treatment with days of the treatment starting. However, there are issues with the use of imaging in clinical trials; for example, the quality of data derived from imaging is variable. The researchers propose a practical, risk-based framework and recommendations on the use of imaging as a marker of how well a treatment is working. They recommend carrying out a risk assessment plan before the study starts, and reviewing and updating the risk plan throughout the trial. ‘In cancer clinical trials, we are always trying to strike the right balance between maximising data quality and minimising cost. Here, risk management can be an extremely helpful tool, because it can help us to prioritise, reduce costs, and decrease attrition rates,’ said the lead author of the paper, Dr Yan Liu of the EORTC. ‘In our study, we used a quality risk management approach to help us outline a consensus framework for imaging biomarker driven trials. This approach recognises that other stakeholders such as regulatory bodies, pharmaceutical companies, and patients also play essential roles in the conduct of these trials.’

QuIC-ConCePT is working on validating imaging biomarkers for early-stage cancer drug development. In the past, such biomarkers were widely used by academia in single centre studies, but were difficult for industry to use because results from different imaging centres were not comparable.### Reproducibility is critically dependent on how imaging equipment performs for each different hospital. QuIC-ConCePT currently has 15 separate clinical trials either underway or completed to reach technical assay validation in patients with lung and liver malignancies, mainly coordinated through consortium partner EORTC and in collaboration with US colleagues at the Quantitative Imaging Biomarker Alliance of the Radiological Society of North America (US QIBA). This ground-breaking work includes repeatability, reproducibility, and advanced image analysis to overcome the challenges of scanning living, breathing patients.  QuIC-ConCePT is also working towards a unique standardisation project to ensure that the enabling work in animal models is completely valid. The scope of this work is far beyond the capabilities of even the largest cancer centre and the IMI model has ensured that the focus has remained on the needs of drug development. 

A new technology to analyse scans of cancer patients predicts how their disease will progress. This is the key outcome from a recent study published in Nature Communications that was supported in part by IMI’s QuIC-ConCePT project.### The findings could help to advance personalised treatments for cancer patients and also improve clinical trials of cancer drugs. Cancer patients regularly undergo imaging scans, yet until recently much of the exquisite detail in these scans was lost in the analysis. Recently, a new technique called radiomics has allowed researchers to put numbers to the scans, effectively creating a detailed ‘blueprint’ of the tumour. In this study, researchers used radiomics to analyse 440 aspects of over 1 000 computed tomography (CT) scans from patients with lung or head and neck cancers. Their findings demonstrate that radiomics can be used to predict far more accurately how the disease will progress in a patient, and suggest that it could be used to determine which medicines may be most appropriate for each individual patient. In addition, the results imply that radiomics could be used in clinical trials to identify the patients most likely to benefit from a new medicine and to monitor the impact of the medicine on the disease. QuIC-ConCePT is now working to confirm its findings with additional high quality data from the EFPIA companies in the project. 

Scientific progress in cancer research has substantially increased our understanding of the molecular biology of cancer, paving the way to novel treatments. However, new tools to rapidly and reliably demonstrate the efficacy of novel cancer drugs are lacking.### A new paper by scientists from IMI project QuiC-ConCePT discusses how magnetic resonance imaging (MRI) could be used to assess the efficacy of new drugs. MRI scans are able to highlight differences in the way water moves in different tissues by detecting something called the apparent diffusion coefficient (ADC). This is important because the ADC of healthy tissues is different to that of cancerous tissues. Furthermore, studies have shown that the ADC of cancer cells rises sharply when the cells are killed, for example by chemotherapy. This means that ADC could potentially be used to assess whether a treatment has worked or not. However, more studies are needed before ADC can be used in studies to test the efficacy of new treatments. Writing in the European Journal of Cancer, QuiC-ConCePT scientists set out a roadmap highlighting the steps needed before ADC can be used in drug development.