Periodic Reporting for period 3 - MEDIRAD (Implications of Medical Low Dose Radiation Exposure)
Okres sprawozdawczy: 2020-06-01 do 2022-02-28
MEDIRAD aimed to enhance the scientific bases and clinical practice of radiation protection (RP) in the medical field and addressed the need to better understand and evaluate the health effects of low-dose ionising radiation (IR) exposure from diagnostic and therapeutic imaging and from off-target effects in radiotherapy (RT).
Key results include (1) image quality assessment tool, organ dosimetry calculation tool, imaging and dose repositories and guidance for dose evaluation and optimization in CT, fluoroscopy-guided procedures and nuclear medicine; (2) standardised quantitative I-131I imaging for dosimetry in thyroid cancer patients, freeware dosimetry tools for molecular therapy and recommendations for a large-scale epidemiological study; (3) development and validation of a prediction model to assess the risk of acute coronary events after RT in individual breast cancer patients based on 3D cardiac dose distributions (BRACE Study); identification and validation of the most important cardiac imaging and circulating biomarkers of radiation-induced cardiovascular changes after breast RT; development of preclinical models as well as different modelling approaches; (4) extended follow-up of major cohorts from the EPI-CT study of paediatric CT patients, implementation of a nested case-control study of brain and haematological malignancies and identification of potential biomarkers of susceptibility to low dose radiation induced cancer; (5) a set of consensus recommendations, based on MEDIRAD findings, developed in collaboration with a broad range of stakeholders, for the scientific and clinical communities as well as policy makers, to encourage professional/regulatory guidance, follow-up research activities and ensure that the MEDIRAD research findings and tools are taken up in clinical practice and thus benefit Europe’s patients.
To fulfil its objectives, the MEDIRAD project relied on a multi-disciplinary consortium involving 34 partners from 14 European countries.
Key results include (1) image quality assessment tool, organ dosimetry calculation tool, imaging and dose repositories and guidance for dose evaluation and optimization in CT, fluoroscopy-guided procedures and nuclear medicine; (2) standardised quantitative I-131I imaging for dosimetry in thyroid cancer patients, freeware dosimetry tools for molecular therapy and recommendations for a large-scale epidemiological study; (3) development and validation of a prediction model to assess the risk of acute coronary events after RT in individual breast cancer patients based on 3D cardiac dose distributions (BRACE Study); identification and validation of the most important cardiac imaging and circulating biomarkers of radiation-induced cardiovascular changes after breast RT; development of preclinical models as well as different modelling approaches; (4) extended follow-up of major cohorts from the EPI-CT study of paediatric CT patients, implementation of a nested case-control study of brain and haematological malignancies and identification of potential biomarkers of susceptibility to low dose radiation induced cancer; (5) a set of consensus recommendations, based on MEDIRAD findings, developed in collaboration with a broad range of stakeholders, for the scientific and clinical communities as well as policy makers, to encourage professional/regulatory guidance, follow-up research activities and ensure that the MEDIRAD research findings and tools are taken up in clinical practice and thus benefit Europe’s patients.
To fulfil its objectives, the MEDIRAD project relied on a multi-disciplinary consortium involving 34 partners from 14 European countries.
WP1 ensured project governance and management procedures and organised communication and dissemination activities. Risks and quality assurance were continuously monitored
Under WP2, novel optimisation methodologies to reduce patient and staff radiation dose and potential radiation-related risks from X-ray imaging were developed while maintaining diagnostic information. Work focused on state-of-the-art CT, fluoroscopically-guided interventional procedures and hybrid systems.
Under WP3, the first European imaging network for quantitative radioiodine imaging for dosimetry of thyroid cancer patients was set-up and used to calculate radiation doses to target tissues and healthy organs to assess the effects of low dose radiation and plan a large-scale epidemiological study. A bio-kinetic treatment model was developed to personalise treatment. The induction and repair of DNA damage in blood cells during the therapy was assessed
In WP4, the EARLY-HEART and BRACE clinical epidemiological studies were completed and provide data for modelling and in a multivariate NTCP-model for acute coronary for validation (for BRACE). For the biomarkers studies, pre-clinical models have been performed and data analysed. Classical and novel biomarkers were proposed. Networks analysis showed a ‘healthy’ biomarker network which needs to be confirmed after complete data analysis (will continue beyond project’s end).
In WP5, the extended follow-up of over 360 000 patients from the French, Dutch and Spanish EPI-CT cohorts more than doubling the person years of follow-up and the original number of cancer cases. A statistically significant dose-response relationship was observed for all malignant brain tumours. A nested case-control study allowed the collection of information on additional radiological procedures and the analysis of their impact on the dose-response estimates. Analyses of susceptibility to radiation induced cancer suggest that susceptibility may be linked to DNA damage response and identified a number of potential miRNA biomarkers.
Under WP6, 4 Recommendations aiming at enhancing the RP of patients, workers and the general public were developed, based on the outcomes of WP2-5. 21 priorities were addressed and integrated under four major themes: (RECO#1): Consolidating patient data repositories across EU; (RECO#2): Optimisation of ionising radiation-based medical protocols for diagnostics or therapy; (RECO#3): Further optimisation of radiation protection for patients and medical workers; (RECO#4): Future research on medical radiation protection in EU. To facilitate their dissemination, a policy brief and infographics were produced.
Under WP2, novel optimisation methodologies to reduce patient and staff radiation dose and potential radiation-related risks from X-ray imaging were developed while maintaining diagnostic information. Work focused on state-of-the-art CT, fluoroscopically-guided interventional procedures and hybrid systems.
Under WP3, the first European imaging network for quantitative radioiodine imaging for dosimetry of thyroid cancer patients was set-up and used to calculate radiation doses to target tissues and healthy organs to assess the effects of low dose radiation and plan a large-scale epidemiological study. A bio-kinetic treatment model was developed to personalise treatment. The induction and repair of DNA damage in blood cells during the therapy was assessed
In WP4, the EARLY-HEART and BRACE clinical epidemiological studies were completed and provide data for modelling and in a multivariate NTCP-model for acute coronary for validation (for BRACE). For the biomarkers studies, pre-clinical models have been performed and data analysed. Classical and novel biomarkers were proposed. Networks analysis showed a ‘healthy’ biomarker network which needs to be confirmed after complete data analysis (will continue beyond project’s end).
In WP5, the extended follow-up of over 360 000 patients from the French, Dutch and Spanish EPI-CT cohorts more than doubling the person years of follow-up and the original number of cancer cases. A statistically significant dose-response relationship was observed for all malignant brain tumours. A nested case-control study allowed the collection of information on additional radiological procedures and the analysis of their impact on the dose-response estimates. Analyses of susceptibility to radiation induced cancer suggest that susceptibility may be linked to DNA damage response and identified a number of potential miRNA biomarkers.
Under WP6, 4 Recommendations aiming at enhancing the RP of patients, workers and the general public were developed, based on the outcomes of WP2-5. 21 priorities were addressed and integrated under four major themes: (RECO#1): Consolidating patient data repositories across EU; (RECO#2): Optimisation of ionising radiation-based medical protocols for diagnostics or therapy; (RECO#3): Further optimisation of radiation protection for patients and medical workers; (RECO#4): Future research on medical radiation protection in EU. To facilitate their dissemination, a policy brief and infographics were produced.
MEDIRAD aimed to achieve significant progress in the interaction between the RP and medical scientific communities at EU level, leading to cross-fertilisation of research efforts and provision of more consolidated and robust science-based policy recommendations to decision makers in both sectors.
The detailed dosimetric data produced in WP2 will be valuable for optimising radiation protection of patients, as well as for input to epidemiological studies and development of models of radiation-induced risk.
Under WP3, dosimetry for radionuclide therapy could potentially help to personalise treatments for patients. Dosimetry software developed is freely available to the community and the recommendations and protocols developed will help to set up future clinical trials for radiopharmaceuticals. The results of the bio-kinetic treatment planning model and the biodosimetry, to assess induction and repair of DNA damage in blood cells, are important pieces in personalised treatment planning for radionuclide therapy.
In WP 4, the predictive model developed, based on both dose distribution and biomarkers, is unprecedented and needs to be prospectively tested. The developed network analysis and mechanistic modelling tools will have the potential for gaining deeper insights into cardiovascular disease development even beyond radiation-induced disease.
Under WP5 estimation of cancer risk following CT scanning in young people with additional insights was updated, as well as the analyses on factors that may modify this risk, i.e. genetic and epigenetic variants and potential confounders.
In WP6, the development of the four Recommendations represents innovative means to bring together the stakeholder and the research communities.
The detailed dosimetric data produced in WP2 will be valuable for optimising radiation protection of patients, as well as for input to epidemiological studies and development of models of radiation-induced risk.
Under WP3, dosimetry for radionuclide therapy could potentially help to personalise treatments for patients. Dosimetry software developed is freely available to the community and the recommendations and protocols developed will help to set up future clinical trials for radiopharmaceuticals. The results of the bio-kinetic treatment planning model and the biodosimetry, to assess induction and repair of DNA damage in blood cells, are important pieces in personalised treatment planning for radionuclide therapy.
In WP 4, the predictive model developed, based on both dose distribution and biomarkers, is unprecedented and needs to be prospectively tested. The developed network analysis and mechanistic modelling tools will have the potential for gaining deeper insights into cardiovascular disease development even beyond radiation-induced disease.
Under WP5 estimation of cancer risk following CT scanning in young people with additional insights was updated, as well as the analyses on factors that may modify this risk, i.e. genetic and epigenetic variants and potential confounders.
In WP6, the development of the four Recommendations represents innovative means to bring together the stakeholder and the research communities.