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Imaging the Force of Cancer

Periodic Reporting for period 2 - FORCE (Imaging the Force of Cancer)

Reporting period: 2017-07-01 to 2018-12-31

“Force, Imaging the Force of Cancer,” is a large-scale Horizon 2020 project, whose aim is to address a fundamental need in planning and monitoring of cancer treatment by measuring the forces active in cancer.

The mechanical forces on a primary cancer tumour – such as tumour Interstitial Fluid Pressure (IFP) and Cell Traction Force (CTF) at the tumour border zone – are thought to be key indicators of whether cancer therapy is working as well as the likelihood of the cancer spreading to other organs. However, being able to measure these forces non-invasively is currently not possible but is paramount for therapy planning and evaluating treatment efficacy. While the treatment of primary tumour sites is vital, gauging the metastatic potential for cancer spread is increasingly important for ensuring appropriate therapy is given.

The FORCE project will tackle these needs by integrating fundamental developments in engineering and Magnetic Resonance Imaging to develop Magnetic Resonance Force Imaging (MRFI) – a novel non-invasive modality for directly measuring Interstitial Fluid Pressure and cell traction forces. We believe that MRFI derived imaging biomarkers will allow for patient stratification prior to therapy and therapy efficacy control during therapy. This has the potential to result in improved patient outcomes at reduced costs. Clinical trials will be conducted for breast cancer, liver cancer, and brain tumours in three major European clinical centers.

The participation of major industrial and pharmaceutical partners in the project accelerates the time to market and encourages a prompt implementation.
The aim of this project is to measure the forces exerted by a tumour onto its surroundings and quantify the diagnostic impact of this physical parameter in the domain of oncology for breast cancer, liver cancer, and brain tumours. So far, we have demonstrated in simulations and phantom experiments the feasibility to quantify those forces noninvasively via nonlinear tissue mechanics. Our initial results from 25 breast cancer patients show that those lesions that exhibit the largest pressure do show lymphovascular space invasion. If confirmed in a larger cohort, this has major impact on patient pathway. A patient that is currently scheduled for tumour surgery would rather first received neoadjuvant chemotherapy if the presence of lymphovascular space invasion were known prior to surgery. Hence, the measurement of tumour forces could have an immediate impact on patient management, which is the aim of this project.

The liver cancer trial in Paris has started and we have collected the first 5 datasets from patients with hepatocellular carcinoma. More data are required to draw any conclusions. Similarly, the brain cancer trial in Basel & Oslo has started as well (Oslo is new associated partner in the consortium). We have so far collected two brain tumours from Oslo and are working on the analysis.

Technically, we have advanced both on the hardware components as well as on the data acquisition and data postprocessing side. Regarding the hardware, we are currently spinning-out our technology to various other research centres (10 sites globally!). Due to this continuous feedback and exposure to different research and clinical environments, the hardware has reached such a high level of maturity, simplicity, and performance that we are close to industrial commercialization. The advances on the data acquisition side led on the one hand to significant improvement of data quality, and on the other hand to shorter acquisition times whereby further improving image quality. The advances in data postprocessing enabled us to see for the first-time shifts in ionic processes within cells at very short timescales, an unexpected research result that will be published in Science Advances this April 2019.

The mechano-signalling part of the project has provided very exciting new insight into the interaction between tumour cell proliferation and migration subject to mechanical shear forces. It appears that there is a mechanical sweet-spot where tumour cell proliferation is suppressed opening the gateway to very new therapeutic concepts. We are currently working on the translation of that concept to preclinical in-vivo experiments. Fundamental, our consortium managed to transplant a small piece of primary breast tumour tissue approximately two hours after operation on top of a pre-stained collagen gel and was able to monitor the active gel deformations over seven days. This allows now to investigate in 3D the force between tumour cells and habitat at unpreceded levels of details.
Our consortium is tightly working together with significant progress demonstrating the feasibility to measure IFP, quantifying cellular forces fundamentally, validating the impact of IFP in preclinical models and the influence of macroscopic forces on tumor biomechanics, to finally translating the technology into clinical reality by completing clinical trials on breast cancer, liver cancer, and brain cancer. The provision of clinical data will allow us to gauge and further develop the method and bring it from bench to bedside. As three major clinical European centers are tightly involved in this project, main focus is put on the patient benefit generated by the provision of the knowledge regarding the forces generated by a tumor. This involves selection of the drug most likely to work given a certain value of IFP, gauging success of therapy or failure during chemo, and finally predicting whether a tumor has already metastasized towards for instance the sentinel lymph node in case of breast cancer.
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