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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - LIMA (Liquid biopsies and Imaging for improved cancer care)

Teaser

Patients with advanced cancer are typically treated using a combination of methods. If possible, surgical removal is attempted first, followed by chemotherapy to eradicate any remaining disease. Each step increases the chances of patients to survive the disease, but also...

Summary

Patients with advanced cancer are typically treated using a combination of methods. If possible, surgical removal is attempted first, followed by chemotherapy to eradicate any remaining disease. Each step increases the chances of patients to survive the disease, but also increases their risk of severe side effects that may result in poor quality of life or even death.
To strike an appropriate balance between cure and quality of life, it is important to know in advance which individual patients will respond to chemotherapy and who will not. Physicians therefore sometimes switch the order of treatments, performing chemotherapy first, and surgery second. This is called “neoadjuvant chemotherapy”. It allows the tumor to be monitored on medical images during the chemotherapy in order to intervene quickly if the medication is ineffective.
Unfortunately, current methods to measure tumor response have limited accuracy. This is caused in part because medical images cannot visualize microscopic disease and because not all parts of the tumor respond equally well to the same medication.
A consortium of hospitals and industry has joined forces in the LIMA project to tackle this problem. They will develop new methods to increase the chances of cure without compromising quality of life. To allow results to be translated to patients as soon as possible, the study has been designed to follow the current clinical routine of doctors as closely as possible.
In patients with breast cancer and rectal cancer, magnetic resonance imaging (MRI) will be employed to study the biology of the tumor before and during the treatment using state-of-the-art technology. MRI uses magnetic fields and radio waves to create very detailed pictures of the tumor, its functional behaviour and chemical composition. Secondly, blood samples of the same patients will be analysed before and during treatment to automatically look for microscopic tumor cells and their characteristics. Finally, all available information will be combined with clinical information using machine learning techniques to predict as soon as possible after the start of the treatment whether the treatment will eradicate all cancer.
As such the promise of LIMA is that more patients will get the right targeted drugs early on in their therapy, opening the route to more effective treatment.

Work performed

During the first reporting period (M1-M18) the work focused on setting up the workflows for liquid biopsy measurement (ct-DNA and CTCs) as well as setting up the MRI imaging protocols to be used in the two clinical trials which will be run for breast and rectal cancer, respectively. In addition, the protocols for both clinical trials have been drafted and submitted. Some of the key results achieved so far are:
- Panels of DNA mutations, enabling the monitoring of a general patient population for rectal and breast cancer patients, have been developed.
- The multiplexing capabilities of Stilla’s digital droplet PCR system has been increased twofold by the implementation of a 6-colour instrument. (See attached picture of the Naica system.)
- An automated cell-picking instrument for clinical use for picking specific cells from a patient blood draw has been made.

Final results

LIMA will produce a comprehensive database of imaging and corresponding tissue and blood draw information from an unselected series of breast and rectal cancer patients before, during and after their treatment. This dataset will be important for future research in the medical sector, pharmacy, and education. LIMA is also expected to form a basis of new guidelines to standardize the interpretation of treatment response across the EU and worldwide. The current standard of tumor response criteria are based on the RECIST criteria or those from the World Health Organisation, both of which only address changes in the size of the tumor in response to therapy. Although they serve good general purpose, these standards are decades old and do not incorporate information from advanced imaging. Let alone their integration with synchronous information from tissue and blood draws. LIMA offers to interpret and combine this vast expanse of new information on the molecular properties of tumors in a consistent and reproducible manner. Due to this work, it is likely that patients will be diagnosed and treated differently and better across the EU and across the world, in the near future.

If successful, the project will have a considerable impact on the patients and the healthcare systems. For instance, the LIMA project provides the opportunity to both improve disease free and overall survival outcomes. Furthermore, it will result in reduced burden, less side effects for the patients, and increased cost-effectiveness of targeted therapies.

The project has already economic impact, as among the SME’s involved in the project there is a relevant increase in the number of people employed. For instance, during the running of the project, Stilla completed their next funding round of 16 M€, enable further growth of the company.

Website & more info

More info: https://lima-project.eu/.