1. To learn about the role of liquid biopsy in cancer detection and tumour surveillance.
2. To become familiar with advances of imaging in cancer detection and characterisation.
3. To understand the revised role of imaging in monitoring of cancer therapy.
4. To explore how combining molecular and imaging metrics could improve clinical decision in cancer patients.
Tumours shed DNA fragments in the bloodstream when undergoing apoptosis. Technology is now available that allows genotyping of circulating tumour DNA (ctDNA) to detect somatic alterations found in tumours by sampling blood, a test commonly described as a liquid biopsy. This technique has shown promise in the detection of cancer in its early stages, in the identification of cancer recurrence following surgery and to monitor antineoplastic treatment longitudinally. Detecting the evolving polyclonal mechanisms of drug resistance hints at what personalised treatment could look like in the future. If liquid biopsy proves up to expectations, the role of imaging in the assessment of cancer will have to be revised. This session will explore the potential impact of liquid biopsy on diagnostic imaging from the perspective of the molecular biologist and of the imaging doctor with the aim of drawing-up a shared view.
1. To explain the principles of liquid biopsy.
2. To review the role of liquid biopsy as a diagnostic tool for early diagnosis.
3. To learn about the role of liquid biopsy as a predictor of cancer recurrence.
4. To explore how liquid biopsy could complement imaging, from a molecular biologist's perspective.
When metastatic colorectal cancers are challenged with targeted agents almost invariably a subset of cells insensitive to the drug emerges. As a result, in most instances, targeted therapies are only transiently effective in patients. Strategies to prevent or overcome resistance are therefore essential to design the next generation of clinical trials. How can we overcome the near-certainty of disease recurrence following treatment with targeted agents? To address this question a deeper understanding of the evolutive nature of cancer cells is necessary. We used colorectal cancer (CRC) as a model system to test the hypothesis that by understanding tumour’s evolution the emergence of drug resistance can be controlled. We find that clonal dynamics can be monitored in real time in the blood of patients, and liquid biopsies can be used to intercept the emergence of resistant clones before relapses are clinically manifest. We discovered that a multistep clonal evolution process driven by progressive increases in drug fitness underlies the development of resistance in cells and patient avatars. To have long-term efficacy, the use of targeted therapies must take into account the continuous evolution of cancer cells, that is to say, therapies must adapt to tumour evolution. One possibility is to anticipate the changes the tumours will make. For example, we propose to use liquid biopsies to know early the mechanisms of resistance to EGFR blockade in individual patients, and devised further rounds of therapy accordingly.
1. To review the modern approach to early diagnosis with imaging.
2. To become familiar with the new imaging biomarkers for tumour characterisation.
3. To envisage how liquid biopsy and imaging could complement each other in cancer diagnostics.
Prognostic and predictive imaging biomarkers are essential for personalised oncology, regarding both, research as well as clinical practice. With the backing of computer assistance, an increased amount and complexity of multiparametric and multimodal imaging data enable to precisely detect cancer including its origin, local infiltration pattern and distant spreading, to gain important functional/biological information about its individual aggressiveness and to monitor or even predict morphologic and functional tumour changes during therapy. Sophisticated image postprocessing tools serve to extract information in a quantitative, objective and reproducible way. Recent research on radiomics, deep learning and artificial intelligence even envisage gaining information, which is otherwise inaccessible to conventional visual image analyses by radiologists. But the potential of imaging is inevitably limited for intrinsic reasons, why in many clinical situations microscopic/molecular tissue analyses are still imperative. The collection and molecular analysis of circulating tumour cells, extracellular vesicles and/or cell-free nucleid acids from fluids, especially blood, is currently object of intensive research. It is even hoped that in certain cases non-invasive/ minimal-invasive, the so-called liquid biopsy may replace tissue biopsy. The integration of imaging with liquid biopsy accordingly opens the door to new diagnostic opportunities. Personalised oncology may significantly benefit from the integration of spatial/functional information from imaging and molecular information from a liquid biopsy. But various scientific and methodological issues have still to be addressed before this concept will become a valuable tool for clinical practice.
1. To explain the rationale of cancer surveillance.
2. To review current cancer surveillance imaging strategies.
3. To become familiar with new imaging tools for surveillance of patients with cancer.
4. To explore how liquid biopsy and imaging could improve detection of minimal residual disease.
Cancer surveillance aims to detect disease recurrence at an early enough stage for further definitive treatment to be a success. Accurate quantification of disease burden & comprehensive localisation of disease sites is required to improve patient stratification for further therapy - definitive or otherwise. This ensures that progression-free survival is improved particularly for patients undergoing definitive therapy. Imaging may be utilised either as the primary surveillance tool or to localise disease sites once other techniques have detected recurrence. A liquid biopsy is a highly sensitive test, and one of the challenges for imaging is to be able to localise small burden disease if further treatment is an option. Ultimately, the choice of imaging modality and strategy for active surveillance has to balance sensitivity with cost-effectiveness. This lecture will explore current surveillance protocols for common cancers and the future role of imaging in the era of liquid biopsy.
1. To explain the basic principles of radiogenomics.
2. To summarise the current clinical applications of radiogenomics.
3. To explore how radiogenomics could guide clinical decisions in the future.
With the genomic revolution in the early 1990s, medical research has been driven to study the basis of human disease on a genomic level and to devise precise cancer therapies tailored to the specific genetic makeup of a tumour. To match novel therapeutic concepts conceived in the era of precision medicine, diagnostic tests must be equally sufficient, multilayered and complex to identify the relevant genetic alterations that render cancers susceptible to treatment. With significant advances in training and medical imaging techniques, image analysis and the development of high-throughput methods to extract and correlate multiple imaging parameters with genomic data, a new direction in medical research has emerged. This novel approach has been termed radiogenomics. Radiogenomics aims to correlate imaging characteristics (i.e., the imaging phenotype) from different imaging modalities with gene expression patterns, gene mutations, and other genome-related characteristics and is designed to facilitate a deeper understanding of tumour biology and capture the intrinsic tumour heterogeneity. Ultimately, the goal of radiogenomics is to develop imaging biomarkers for an outcome that incorporate both phenotypic and genotypic metrics. Due to the non-invasive nature of medical imaging and its ubiquitous use in clinical practice, the field of radiogenomics is rapidly evolving, and initial results are encouraging. In this article, we will briefly discuss the background and then summarise the current role and the potential of radiogenomics in oncology.