A review, published in the Journal of Vascular and Interventional Radiology (JVIR) in August 2013, serves as an introduction to personalised oncology concepts and provides a summary of relevant concepts. “Interventional radiologists have to keep up to date with targeted therapies and biomarkers. The paper’s intent is to underline the importance of personalised medicine. We hope that it can be a starting point for interventional radiologists,” Nadine Abi-Jaoudeh, lead author on the paper, told Interventional News.
Why should interventional radiologists learn about personalised medicine?
Medicine is shifting to the “4P” of care, which stands for predictive, preventive, personalised, and participatory. The rationale being that disease outcomes will improve if the population at risk is identified and screened appropriately; if therapies focus on disease with minimal side-effects and if response to therapy can be predicted.
In past decades, several advances in genomics have enabled identification of driver mutations and subcellular pathways involved in cancer development, growth and metastatic potential. These unique characteristics can be identified and targeted.
As personalised oncology plays a greater role in patient care, interventional radiologists must learn and keep up to date to remain relevant. Indeed, the era of the “all-knowing” physician who can entirely manage a patient has long been over. Medicine is collaborative in nature with multidisciplinary teams involved in patient management.
As such, interventional radiologists have to understand the concepts and different therapeutic options when patient care is discussed at multidisciplinary team meetings.
In your view what are three important terms in genomics and proteomics that interventional radiologists should know about?
Driver mutation
Targeted therapies
Prognostic and predictive biomarkers.
Can you provide an example of multidisciplinary intervention where interventional radiology and imaging specialists were important in defining the efficacy of a targeted therapy?
As discussed in the paper, Annunziata et al (Clinical Cancer Research 16 (2) 664–672) published their trial about Vandetanib. The lack of clinical benefit of the drug was determined by serial biopsies and contrast-enhanced magnetic resonance imaging. In this trial, female patients with recurring ovarian cancer orally received 300mg of Vandetanib. Prior to therapy initiation and six weeks into therapy, a biopsy of the same site and contrast-enhanced MRI were performed. The biopsy specimens were subjected to proteomic tissue analysis that did not demonstrate any increase in VEFG receptor 2 phosphorylation and contrast-enhanced MRI did not reveal any change in enhancement, thus demonstrating the lack of benefit of the drug. The study was stopped at stage I because of lack of response or disease stabilisation. The serial biopsies and contrast MRI explained the lack of the therapy’s efficacy to inform of molecular mechanisms. The paired biopsies and MRI before and after drug administration are a way to search for surrogate predictive and prognostic biomarkers, and predict drug response much faster than awaiting clinical response.
You have said that the role of interventional radiology in the area of personalised medicine is currently limited to tissue procurement, but has the potential to expand further. How can its role be expanded?
Expanding involvement in that area would be starting point ie. by targeting PET-avid or enhancing area of tumour, interventional radiologists may improve specimen quality further assisting referring physicians in determining efficacy of targeted therapies, validity of predictive biomarkers, etc. Certain interventional procedures such as chemoembolization and ablation induce an immune response. Erinjeri et al. (JVIR 2013 vol 24 issue 8 1105–1112) describe an increase of interleukins six and 10 post ablation. Such immune stimulation can be used to modulate immune response induced by systemic therapies. Indeed, clinical trials such as Tremelimumab with chemoembolization or ablation for liver cancer (principal investigator Tim Greten, NCT01853618) conducted at the National Cancer Institute are attempting to examine this point. Local delivery of targeted therapies is another role for interventional radiologists. Sze et al. (JVIR 2013 vol 24 issue 8 1115–1122) discuss oncolytic virotherapy for example, but other targeted therapies might prove more efficient with local delivery. Interventional radiologists should become involved in targeted therapies development and delivery options. Also, certain targeted therapies can be delivered systemically and the drug activated or released locally by applying energy with high-intensity focused ultrasound.
