PM.20.044 – Personalized focused MR-guided thermo-chemotherapy for breast conserving surgery (PERFECT-4-BCS)

Route: Personalised medicine: the individual at the centre

Cluster question: 104 How do we develop minimally invasive techniques and interventions for diagnosis, prognosis, and treatment?

Neoadjuvant chemotherapy (NAC) is the standard procedure to shrink breast cancers to make them operable or eligible for breast conserving surgery. The success rate of downstaging varies dramatically between breast cancers subtypes. Moreover, about 80% of the tumors shrink less than 50% in response to NAC, which is associated with worse prognosis, higher relapse rate and higher death rate compared to patients with complete response irrespective of tumor subtype. Given the unsatisfactory results with current treatment for breast cancer, more effective treatment options to enhance downstaging and increase complete response are urgently needed.
The goal of PERFECT-4-BCS is to increase tumor targeted drug delivery by MR-guided adaptive tumor heating. Adaptive tumor heating will enhance vascular permeability and initiate temperature triggered drug release from thermal sensitive liposomes (TSL). Patient-specific temperature-triggered local drug delivery may increase tumor drug concentration up to 30 times, while simultaneously reducing systemic side effects. Furthermore, we will explore the predictive value of pre-treatment MRI and per-treatment monitoring of MR-tracer release from TSL to non-invasively quantify drug concentration and distribution.
Direct benefits of controlled drug delivery will be improved treatment outcome for breast cancer patients. On long-term, the ability to non-invasively identify personal traits, e.g. tumor microenvironment, may allow fine-tuning of drug selection to optimize individual treatment outcome.
Hence, we will develop i) EMF and ultrasound based systems to deliver patient-specific thermal triggered NAC for primary breast cancer, ii) real-time non-invasive MR techniques to monitor temperature and drug distribution, iii) develop drug-nanocarrier combinations for intravascular triggered drug release, iv) methods for image-based patient selection for personalized local thermo-chemotherapy.
Research groups in oncology, thermal therapy, smart drug delivery and radiology are involved.

Keywords

Breast cancer, hyperthermia, image-guided therapy, local drug delivery, nano-carriers

Other organisations

Amsterdam UMC, Eindhoven University of Technology (TU/e), Erasmus Medical Center (EMC), Thermotherapy Nederland (TTNL), UMC Utrecht (UMCU), Utrecht University (UU)

Submitter

Organisation Erasmus MC Cancer Institute (EMC)
Name Prof. dr. G.C. (Gerard) van Rhoon
E-mail g.c.vanrhoon@erasmusmc.nl