Periodic Reporting for period 1 - THERMOGUIDE (Optimizing delivery and effectiveness of chemotherapy in breast cancer patients using thermotherapy under image-guidance)
Período documentado: 2019-07-16 hasta 2021-07-15
Breast cancer is the most common cancer and the leading cause of cancer death among women worldwide. Most patients with breast cancer undergo chemotherapy before or after surgery. Chemotherapy is generally applied as a systemic therapy, only a small part of the administered drugs actually reach the tumour. This causes severe side-effects in normal tissue, and often prevents the administration of sufficient dose for effective cure.
Heating the tumour to a temperature of 40-43°C helps to increase the drug concentration in the tumour and hence treatment efficacy via increased blood perfusion, extravasation and membrane fluidity. Furthermore, heating above 41°C inhibits DNA double strand break damage repair and induces an anti-cancer immune response. Despite the potential benefit of combining chemotherapy with thermotherapy, current state-of-the-art commercial and academic systems for thermotherapy of tumours located in the intact breast only provide suboptimal technical solutions for adequately heating the total tumour volume.
Therefore, the primary objective of this MSCA is to develop the first conformal MR-compatible device for MR-guided thermotherapy for patients with primary breast cancer. The novel thermotherapy system should enable high quality thermotherapy in patients with breast cancer in order to enhance drug delivery and hence more effective chemotherapy.
Beyond the aforementioned objective, this MSCA has facilitated the researcher to form a multidisciplinary work group of experts in breast cancer and successfully establish a new line of investigation with the aim of giving continuity to the project and making this new treatment a reality.
Heating the tumour to a temperature of 40-43°C helps to increase the drug concentration in the tumour and hence treatment efficacy via increased blood perfusion, extravasation and membrane fluidity. Furthermore, heating above 41°C inhibits DNA double strand break damage repair and induces an anti-cancer immune response. Despite the potential benefit of combining chemotherapy with thermotherapy, current state-of-the-art commercial and academic systems for thermotherapy of tumours located in the intact breast only provide suboptimal technical solutions for adequately heating the total tumour volume.
Therefore, the primary objective of this MSCA is to develop the first conformal MR-compatible device for MR-guided thermotherapy for patients with primary breast cancer. The novel thermotherapy system should enable high quality thermotherapy in patients with breast cancer in order to enhance drug delivery and hence more effective chemotherapy.
Beyond the aforementioned objective, this MSCA has facilitated the researcher to form a multidisciplinary work group of experts in breast cancer and successfully establish a new line of investigation with the aim of giving continuity to the project and making this new treatment a reality.
The work conducted during this MSCA has been delivered via the successful implementation of 3 work packages (WPs).
WP1: Generation of realistic computational breast models containing tumours and ex-vivo characterization
Magnetic resonance images from patients previously treated with neoadjuvant chemotherapy in Erasmus MC were imported into a specific radiotherapy software for tissue segmentation. Afterwards, patient-specific breast models were generated and patient-specific thermotherapy treatment planning was performed. Additionally, dielectric and thermal properties with the phantoms used during quality assurance procedures were investigated.
WP2: Design and construction of the MR-compatible intact breast thermotherapy applicator
Extensive electromagnetic and thermal modelling was performed with the models developed in WP1 and have proved a unique set of tools to investigate and optimize the breast thermotherapy applicator. As initially planned, the construction of the breast thermotherapy applicator has been based on the development steps of the clinically used Hypercollar, this will facilitate the clinical implementation of the new applicator.
WP3: Construction of breast-specific phantoms and validation of the developed thermotherapy applicator
Breast-specific phantoms derived from the breast models generated in WP1 have been developed. To build the phantoms, a high resolution 3D printer and agar-based mimicking mixtures with human tissue representative properties have been used. Specific MR-sequences have been investigated to obtain non-invasive thermometry.
Results of this MSCA are reported in six journal articles, ten conference papers and two book chapters, with the objective of disseminating the results, promoting thermotherapy as cancer treatment modality, as well as enhancing relevant international collaborations.
WP1: Generation of realistic computational breast models containing tumours and ex-vivo characterization
Magnetic resonance images from patients previously treated with neoadjuvant chemotherapy in Erasmus MC were imported into a specific radiotherapy software for tissue segmentation. Afterwards, patient-specific breast models were generated and patient-specific thermotherapy treatment planning was performed. Additionally, dielectric and thermal properties with the phantoms used during quality assurance procedures were investigated.
WP2: Design and construction of the MR-compatible intact breast thermotherapy applicator
Extensive electromagnetic and thermal modelling was performed with the models developed in WP1 and have proved a unique set of tools to investigate and optimize the breast thermotherapy applicator. As initially planned, the construction of the breast thermotherapy applicator has been based on the development steps of the clinically used Hypercollar, this will facilitate the clinical implementation of the new applicator.
WP3: Construction of breast-specific phantoms and validation of the developed thermotherapy applicator
Breast-specific phantoms derived from the breast models generated in WP1 have been developed. To build the phantoms, a high resolution 3D printer and agar-based mimicking mixtures with human tissue representative properties have been used. Specific MR-sequences have been investigated to obtain non-invasive thermometry.
Results of this MSCA are reported in six journal articles, ten conference papers and two book chapters, with the objective of disseminating the results, promoting thermotherapy as cancer treatment modality, as well as enhancing relevant international collaborations.
This MSCA has been fundamental to the professional development of the fellow, who has been granted with a permanent position in the host institution. Reaching beyond its main objectives, this MSCA has been the cornerstone for the establishment of a new multidisciplinary line of research involving experts from Radiotherapy, Medical Oncology, Surgery, Pathology and Radiology, with the common aim of pioneering thermotherapy for intact breast tumours as a novel treatment solution.
In addition, to further ensure the clinical implementation and commercialization of the developed device, discussions have been initiated with potential commercial partners. The SME Sensius BV has expressed their interest in the breast thermotherapy device as part of their business line. Hence, the work has a good potential in contributing to Europe’s competitiveness for medical equipment.
An important achievement, which is beyond the scope of the MSCA, has been the development of not only the thermotherapy system, but the full specific treatment planning platform for seamless integration into the clinical routine. For this, regular meetings have been held not only with the engineers and researchers, but also with the clinical personnel involved at various levels, from medical doctors who make treatment decisions to technicians and nurses who deliver the treatments. This is considered essential for gradually building up trust and acceptance of all professionals involved for the technology implementation.
In addition, to further ensure the clinical implementation and commercialization of the developed device, discussions have been initiated with potential commercial partners. The SME Sensius BV has expressed their interest in the breast thermotherapy device as part of their business line. Hence, the work has a good potential in contributing to Europe’s competitiveness for medical equipment.
An important achievement, which is beyond the scope of the MSCA, has been the development of not only the thermotherapy system, but the full specific treatment planning platform for seamless integration into the clinical routine. For this, regular meetings have been held not only with the engineers and researchers, but also with the clinical personnel involved at various levels, from medical doctors who make treatment decisions to technicians and nurses who deliver the treatments. This is considered essential for gradually building up trust and acceptance of all professionals involved for the technology implementation.