Periodic Reporting for period 1 - HYPERBOOST (Creation of advanced cancer treatment planning to boost the effect of Radiotherapy by combining with hyperthermia, heating the tumor.)
Période du rapport: 2020-12-01 au 2022-11-30
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 3 training weeks and the ESRs followed courses in their own institute and visited congresses. Secondments have been performed and more are planned. All these activities taken together will ensure their development towards the professionals needed to push this field forward (objective 1&5).
Both in vitro and in vivo tumour models were deployed to extend understanding and quantify radio-sensitizing effects of hyperthermia, including effect of re-oxygenation. Studies were performed for clinically used radiation schedules. Large screening studies aimed at identification and exploitation of hitherto unknown or ill-explored hyperthermia effects on pathways relevant for e.g. immunological anti-tumour effects (objective 2).
Progress was achieved in understanding and modelling the combined effect of radiotherapy and hyperthermia, in translating those data in multi-objective radiotherapy-hyperthermia treatment optimisation, in acquisition of 3D temperature distributions using MR-thermometry as feedback for planning during treatment, and finally on the clinical user interface incorporating all these advanced hyperthermia treatment planning tools (objective 3).
Clinical thermal enhancement parameters were analysed in preparation of uniform Quality Assurance guidelines and treatment data reporting for prospective multi-centre clinical trials. Immune phenotyping performed in the HYCAN trial revealed relevant detectable changes in peripheral blood suitable for monitoring in upcoming clinical studies, infrastructure for collecting samples is set up. Dedicated MR imaging methods for monitoring tumour response were successfully tested, a biobank was set up for storing blood samples. Retrospective data analysis of clinical studies was successful and the planning of prospective multi-centre registration studies with good quality control and translational studies is progressing as planned (objective 4). Taken together, all progress works towards development of a new generation of professionals that will work towards objective 6.
Both in vitro and in vivo tumour models were deployed to extend understanding and quantify radio-sensitizing effects of hyperthermia, including effect of re-oxygenation. Studies were performed for clinically used radiation schedules. Large screening studies aimed at identification and exploitation of hitherto unknown or ill-explored hyperthermia effects on pathways relevant for e.g. immunological anti-tumour effects (objective 2).
Progress was achieved in understanding and modelling the combined effect of radiotherapy and hyperthermia, in translating those data in multi-objective radiotherapy-hyperthermia treatment optimisation, in acquisition of 3D temperature distributions using MR-thermometry as feedback for planning during treatment, and finally on the clinical user interface incorporating all these advanced hyperthermia treatment planning tools (objective 3).
Clinical thermal enhancement parameters were analysed in preparation of uniform Quality Assurance guidelines and treatment data reporting for prospective multi-centre clinical trials. Immune phenotyping performed in the HYCAN trial revealed relevant detectable changes in peripheral blood suitable for monitoring in upcoming clinical studies, infrastructure for collecting samples is set up. Dedicated MR imaging methods for monitoring tumour response were successfully tested, a biobank was set up for storing blood samples. Retrospective data analysis of clinical studies was successful and the planning of prospective multi-centre registration studies with good quality control and translational studies is progressing as planned (objective 4). Taken together, all progress works towards development of a new generation of professionals that will work towards objective 6.
Part of the scientific results achieved so far reported in the preceding sections already constitute progress beyond the present state of the art: this relates to our extended knowledge of existing and novel 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), development of a practical clinical infrastructure including monitoring of all relevant treatment parameters including novel tumor markers (objective 4). Further scientific progress is expected until 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 is already leading to a growing collaboration and cross-pollination between the different institutes and disciplines involved, with excellent involvement and integration of the European Industry (objectives 5 and 6).
Major societal and socio-economic impact is expected towards the end of the project, as the project is expected to result in more efficient and more clinically effective combination of radiotherapy and hyperthermia treatment delivery, in turn leading to wider adoption of hyperthermia, better clinical results, and lower healthcare costs by better selection of optimal treatment options for individual patients, more employment of ESRs trained in multidisciplinary research and transferable skills, better economic prospects for companies producing hyperthermia devices and treatment planning software (objectives 1-6).
The project is already leading to a growing collaboration and cross-pollination between the different institutes and disciplines involved, with excellent involvement and integration of the European Industry (objectives 5 and 6).
Major societal and socio-economic impact is expected towards the end of the project, as the project is expected to result in more efficient and more clinically effective combination of radiotherapy and hyperthermia treatment delivery, in turn leading to wider adoption of hyperthermia, better clinical results, and lower healthcare costs by better selection of optimal treatment options for individual patients, more employment of ESRs trained in multidisciplinary research and transferable skills, better economic prospects for companies producing hyperthermia devices and treatment planning software (objectives 1-6).