1. To be familiar with the concept of immunotherapy.
2. To be aware of the current imaging methods for assessing immunotherapies.
3. To learn about new methods in development for assessing immunotherapies.
Evasion of the immune system plays an important role in the development and progression of cancers. Cancer immunotherapies are a promising class of agents that re-engage the immune system in its fight against cancer cells. Strategies range from activating innate/adaptive immune effector mechanisms to neutralising inhibitory/suppressive mechanisms . For example, treatment with interleukin 2 (IL-2) or interferon-α (IFNα) stimulate effector immune cells; conversely antibodies against immune-checkpoint molecules, e.g., cytotoxic T lymphocyte-associated protein 4 (CTLA4)-targeted antibodies and programmed cell death 1 (PD1)-targeted antibodies neutralise immune suppressor mechanisms. Immunotherapies have been shown to be effective in a number of advanced cancers including melanoma, renal cancer, and non-small cell lung cancer. As immunotherapies generate anti-tumour effects by enhancing tumour-specific T cell responses rather than the direct cell killing, response assessment may be challenging. Response may take longer to be detectable by imaging and standard methods, such as response evaluation criteria in solid tumours (RECIST) may be misleading. In this session the role of imaging will be explored and future directions considered.
1. To be aware of the different types of immunotherapies and to understand their mode of action.
2. To understand the limitations of RECIST and be aware of immune response criteria.
3. To understand the limitations of CT for assessment of immunotherapies.
A wide range of cancer immunotherapy approaches have been developed including non-specific immune-stimulant such as cytokines (Interferon, IL2), cancer vaccines (peptide or dendritic cell-based vaccines), adoptive T-cell therapy (TILs, CAR, TRC) and immune checkpoint inhibitors (anti CTLA-4, anti PD1 and anti PDL1). The most commonly used and intensively studied are the immune checkpoint inhibitors (ICIs). Their mechanism of action signifies a true shift in oncology where instead of targeting the tumor cells, ICIs target the immune system to break the cancer tolerance and stimulate the anti-tumor immune response. These new drugs have, since 2011, received marketing authorisation for melanoma, lung, bladder, renal, and head and neck cancer with remarkable and long-lasting treatment response. The novel mechanism of action of these drugs, with immune and T-cell activation, lead to unusual patterns of response with presence of flare phenomenon or pseudo-progression more pronounced and more frequent than previously described responses. Pseudo-progression, that has been described in about 3-10% of patients treated using ICIs, corresponds to increase of tumor burden and/or appearance of new lesions due to Infiltration of the tumor by activated T cells before the disease responds to treatment. To overcome the limitation of RECIST criteria to assess this specific changes in tumour burden, new criteria so-called irRC and then irRECIST were proposed. The major modification involved the inclusion of the measurements of new target lesions into disease assessments and the need of a 4-week CT re-assessment to confirm progression. More recently (2017) a consensus guideline iRECIST was developed by the RECIST working group.
1. To be aware of the advantages and limitations of MRI for assessment of immunotherapies.
2. To describe the potential role of whole-body MRI and quantitative MRI techniques in follow-up.
3. To consider the potential of integrated MRI/PET for the assessment of immunotherapies.
Drugs that modulate the body immune responses are being utilised to treat a range of cancers, including malignant melanoma, non-small cell lung cancer, hepatocellular and bladder carcinomas. In patients receiving immunotherapies, CT is still the most widely used imaging technique for assessing tumour response to treatment and to identify drug related side-effects. However, anatomical MR imaging can also be effectively applied to evaluate tumour regression with treatment using size measurement criteria (e.g., iRECIST). Like CT, increase in tumour size may be observed on MRI in pseudo-progression, which can confound response assessment. Nonetheless, the superior soft tissue contrast of MRI helps to depict subtle disease (e.g., intracranial) and specific complications (e.g., hypophysitis) that are difficult to visualise on CT. There is great interest in applying quantitative MR imaging, including whole body MRI techniques, to study functional changes in tumour cellularity (diffusion-weighted MRI), vascularity (contrast-enhanced MRI) and macromolecules (magnetisation transfer). These are areas of on-going research. Whole body MRI can provide information about inter-tumoural heterogeneity, thus allowing insights into tumour evolution and differential response to treatment. Active research in molecular probes is being undertaken to develop PET imaging tracers that can identify and predict treatment response, which can be explored alongside multi-parametric MRI measurements on a MRI/PET hybrid system as imaging biomarkers.
1. To be aware of abscopal effects with immunotherapy.
2. To describe how focal therapies can be combined with immunotherapies.
3. To be aware of the challenges of focal treatments for systemic effects.
Although interventional oncologists have traditionally assumed that our local therapies including tumor ablation and chemoembolization have minimal systemic effects, there is increasing compelling animal evidence to back up anecdotal clinical reports suggesting that these therapies can stimulate distant effects and can potentially have more widespread effects than just eliminating a focal tumor. On the positive side, several studies have reported that tumor ablation can, under poorly defined “favorable” conditions, induce systemic immunologic “abscopal” effects that induce distant tumor regression. Thus, several groups are pioneering combining interventional oncologic procedures with immunotherapies with the express goal of stimulating immune anti-cancer responses. Simultaneously and by contrast, we and others have demonstrated that radiofrequency and other therapies can in some cases also cause increased cancerous effects by inducing tumor initiation and progression in non-ablated areas. For liver ablation, this has been linked to an increased inflammatory response including cellular recruitment of neutrophils, macrophages, and activated myofibroblasts to the peri-ablated zone and several pro-tumorigenic cytokines such as IL-6 and HGF that increase following ablation. Thus, in all likelihood, there is a balance between pro-oncogenic and pro-immunogenic effects that differs from patient to patient. Thus, our ultimate goal - achievable only through additional mechanistic study - should be to alter the post-ablation milieu to prevent any untoward tumorigenic effects while simultaneously promoting desired abscopic effects.