Periodic Reporting for period 2 - HYPERBOOST (Creation of advanced cancer treatment planning to boost the effect of Radiotherapy by combining with hyperthermia, heating the tumor.)
Periodo di rendicontazione: 2022-12-01 al 2024-11-30
Hyperthermia (HT), heating tumors to temperatures of 40-44°C, is an oncological treatment used in combination with radiotherapy (RT) and chemotherapy to enhance their efficacy. Clinical effectiveness of HT has been demonstrated in randomised studies and HT is currently applied for many clinical indications, like cervical cancer and recurrent breast cancer. Clinical results can be further improved as application of HT with well-controlled tumor temperatures and optimal timing and sequence realising full synergy of RT+HT is challenging. Optimal HT delivery requires accurate planning, moreover preclinical research has shown that many mechanisms are responsible for the therapeutic effect of HT, all presumably with a different temperature-effect relationship and with different optimal timing between RT and HT. Optimisation of clinical RT+HT treatments therefore requires a quantum leap in understanding and in clinical application. Scientific objective of this multidisciplinary project with contributions from all sectors and disciplines (biology, physics and oncology) is to combine training and research into the synergistic molecular mechanisms responsible for the therapeutic effect of HT on RT with the development of a versatile and innovative planning platform which utilises biological knowledge to achieve optimal patient-specific treatment delivery and ultimately application in a clinical registration study in a network of European centres implementing this treatment planning software to ensure optimal treatment delivery.
The major objective of Hyperboost is therefore to train a new generation of creative and entrepreneurial professionals with the skills and expertise to coordinate, develop, apply and optimise advanced multi-modality cancer treatments. HYPERBOOST will also develop an advanced personalised treatment planning platform for hyperthermia based on extensive (pre)clinical data.
The key aims of the HyperBoost project are to:
1. Train and equip early stage researchers with transferable, multi-disciplinary skills essential in high-end biomedical engineering, clinical hyperthermia and translational oncology (WP2)
2. Obtain and validate new insights into clinical working mechanisms of hyperthermia (WP3)
3. Translate preclinical and clinical results (WP3, WP5) into mathematical relations and treatment planning models (WP4)
4. Apply novel treatment planning models for personalised treatment (WP4) to improve the efficacy of clinical treatments (WP5)
5. Initiate, stimulate and profit from multidisciplinary cross-pollination between the disciplines involved in hyperthermic oncology (WP3-5)
6. Consolidate and expand the European infrastructure and industry for hyperthermia research and clinical application (WP 2-6)
The major objective of Hyperboost is therefore to train a new generation of creative and entrepreneurial professionals with the skills and expertise to coordinate, develop, apply and optimise advanced multi-modality cancer treatments. HYPERBOOST will also develop an advanced personalised treatment planning platform for hyperthermia based on extensive (pre)clinical data.
The key aims of the HyperBoost project are to:
1. Train and equip early stage researchers with transferable, multi-disciplinary skills essential in high-end biomedical engineering, clinical hyperthermia and translational oncology (WP2)
2. Obtain and validate new insights into clinical working mechanisms of hyperthermia (WP3)
3. Translate preclinical and clinical results (WP3, WP5) into mathematical relations and treatment planning models (WP4)
4. Apply novel treatment planning models for personalised treatment (WP4) to improve the efficacy of clinical treatments (WP5)
5. Initiate, stimulate and profit from multidisciplinary cross-pollination between the disciplines involved in hyperthermic oncology (WP3-5)
6. Consolidate and expand the European infrastructure and industry for hyperthermia research and clinical application (WP 2-6)
We organized 2 more training weeks and the ESRs continued following courses in their own institute and visited congresses. Remaining secondments have been completed. All these activities taken together completed training of the professionals needed to push this field forward (objective 1&5).
In vitro and in vivo tumour models were used to better understand and optimize efficacy of radio-sensitizing effects of hyperthermia by combining with heat stress response and immune checkpoint inhibitors. Other studies succeeded in optimizing radiotherapy-hyperthermia time intervals resulting in enhanced benefit with more tumour response and less normal tissue side effects. (objective 2).
The results achieved in understanding and modelling during the first years were applied to optimize the combined effect of radiotherapy and hyperthermia. Multi-objective radiotherapy-hyperthermia treatment optimisation was integrated in clinically used radiotherapy planning systems. Reliable quantitative 3D temperature distributions using MR-thermometry was achieved, and these advanced hyperthermia planning tools were all integrated and used in a new clinical user interface (objective 3).
Retrospective analysis of treatment outcome for different tumour sites revealed clear dose-effect relationships. This clinical evidence, combined with the preclinical evidence thus confirmed the need for high level Quality Assurance in treatment delivery. New guidelines were established and device performance was checked in our network as well as current differences in treatment protocols. The reliability of non-invasive MR-thermometry was improved using AI methods. We also progressed in developing a novel helmet hyperthermia applicator for brain tumours using MR for both heating and thermometry. A Europe-wide multicentre data registry and infrastructure for collecting biomaterials was established. Prospective multi-centre registration studies with good quality control and translational studies are thus progressing as planned (objective 4).
Concluding, all progress achieved succeeded in preparing a new generation of professionals that can work towards objective 6.
In vitro and in vivo tumour models were used to better understand and optimize efficacy of radio-sensitizing effects of hyperthermia by combining with heat stress response and immune checkpoint inhibitors. Other studies succeeded in optimizing radiotherapy-hyperthermia time intervals resulting in enhanced benefit with more tumour response and less normal tissue side effects. (objective 2).
The results achieved in understanding and modelling during the first years were applied to optimize the combined effect of radiotherapy and hyperthermia. Multi-objective radiotherapy-hyperthermia treatment optimisation was integrated in clinically used radiotherapy planning systems. Reliable quantitative 3D temperature distributions using MR-thermometry was achieved, and these advanced hyperthermia planning tools were all integrated and used in a new clinical user interface (objective 3).
Retrospective analysis of treatment outcome for different tumour sites revealed clear dose-effect relationships. This clinical evidence, combined with the preclinical evidence thus confirmed the need for high level Quality Assurance in treatment delivery. New guidelines were established and device performance was checked in our network as well as current differences in treatment protocols. The reliability of non-invasive MR-thermometry was improved using AI methods. We also progressed in developing a novel helmet hyperthermia applicator for brain tumours using MR for both heating and thermometry. A Europe-wide multicentre data registry and infrastructure for collecting biomaterials was established. Prospective multi-centre registration studies with good quality control and translational studies are thus progressing as planned (objective 4).
Concluding, all progress achieved succeeded in preparing a new generation of professionals that can work towards objective 6.
Many of the scientific results achieved in the project reported in the preceding sections already constitute progress beyond the present state of the art: we have extended knowledge and explored novel methods to even better exploit the radio-sensitizing effects of hyperthermia (objective 2), translation of clinical and preclinical data into more advanced biological treatment planning models, improved algorithms, sophisticated planning tools and data acquisition (objective 3) and development of a practical clinical infrastructure including monitoring of all relevant treatment parameters including novel tumor markers (objective 4). Further scientific progress is expected beyond the end of the project, particularly regarding even better understanding and quantification of radio-sensitizing effects of hyperthermia, their incorporation in treatment planning and optimization models, practical and routine clinical application and validation.
The project has led to closer and more effective collaboration and cross-pollination between the different institutes and disciplines involved, with strong involvement and integration of the European Industry, leading to visible expansion in the Radiation Oncology community (objectives 5 and 6).
Major societal and socio-economic impact is expected after the end of the project, as the project is seen to result in more efficient and more clinically effective combination of radiotherapy and hyperthermia treatment delivery. This is already leading to wider adoption of hyperthermia, which is expected to yield better clinical results, and lower healthcare costs by better selection of optimal treatment options for individual patients. In addition it is leading to employment of ESRs trained in multidisciplinary research and transferable skills, and even better economic prospects for companies producing hyperthermia devices and treatment planning software (objectives 1-6).
The project has led to closer and more effective collaboration and cross-pollination between the different institutes and disciplines involved, with strong involvement and integration of the European Industry, leading to visible expansion in the Radiation Oncology community (objectives 5 and 6).
Major societal and socio-economic impact is expected after the end of the project, as the project is seen to result in more efficient and more clinically effective combination of radiotherapy and hyperthermia treatment delivery. This is already leading to wider adoption of hyperthermia, which is expected to yield better clinical results, and lower healthcare costs by better selection of optimal treatment options for individual patients. In addition it is leading to employment of ESRs trained in multidisciplinary research and transferable skills, and even better economic prospects for companies producing hyperthermia devices and treatment planning software (objectives 1-6).