Description of workpackages
The ARTFORCE partner, NKI, is host of the Management Office.
Rachel Tjoa (Project Office Manager) and Paula Hoekstra(Project Finance Officer) are based at the NKI in the Department of Radiotherapy (RT) and the Finance and Information Service (DIF) respectively.
The Management Office is responsible for:
• Organising and coordinating meetings of the Project Steering Committee and consortium meetings
• Coordinating and ensuring administrative information dissemination to partner members
• Preparation of the consortium agreement
• Keeping regular contact with the Project Coordinator, the Project Steering Committee and other parties
• Identifying and reporting to the Project Steering Committee potential problems arising in the project
• Coordinating practical aspects regarding the exchange of personnel
• Establishing good operating practice for financial management
• Preparation of the appropriate documents for signature and forwarding to the host institution
• Producing reports on behalf of the Project Steering Committee
• Setting up a plan for payments and checking partner financial statements
• Distributing project funds and monitoring/reporting project finances to the Project steering Committee and the Executive Committee
• Coordinating financial audits of the partners, to comply with necessary EC regulations.
Workpackage 2 – Development of adaptive radiotherapy techniques to optimally account for the temporally variant patient model.
Geometrical uncertainties such as patient setup variability and (respiration-induced) organ motion limit the precision of radiotherapy delivery. Consequently, the actually delivered dose does not equal the planned dose (what you see is not what you get). Recent developments in image guided radiotherapy allow visualizing the target and OAR just prior to treatment, assessing geometrical discrepancies between planning and delivery, and aligning the target to the planned position using a couch shift to increase the precision of radiotherapy. However, in the case of more complex changes such as relative position changes of tumour and involved lymph nodes, posture changes, e.g. neck flex and tumour response, such a correction is inadequate to increase the precision of RT delivery.
Adaptive radiotherapy, where 1) repetitive imaging of the patient is employed to characterize the patient-specific variabilities and longitudinal changes and 2) these changes are accounted for in a adaptive plan modification, has the potential to correct for complex geometrical variability. In this work package we will develop adaptive radiotherapy techniques for head-and-neck and lung cancer patients and implement these techniques in the clinical trials of this project to maximize their efficacy and safety.
The NKI (Amsterdam) and RaySearch (Stockholm) are collaborating on this workpackage.
Partners Karolinska Institute (Stockholm) and RaySearch (Stockholm) are collaborating in this workpackage in which algorithms for biologically optimised treatment planning will be developed aimed at tumour eradication with minimal normal tissue damage. These algorithms will be based on interim PET scans and recurrence patterns in the two clinical trials which will be carried out during this project on lung cancer and cancer of the head and neck. The algorithm will be an add-on module in a treatment planning system, estimating the accumulated dose and patient-specific treatment response, making it possible to replan and where necessary biologically adapt the treatment.
Three-dimensional (3-D) in vivo dosimetry as an integrated quality assurance (QA) procedure will be implemented making possible accurate verification of the dose delivery applicable on all major brands of radiotherapy treatment equipment within the EU. 3-D in vivo dosimetry will be applied at the start of treatment and again during the treatment, adapting if necessary to changes in the patient anatomy.
Maastro Innovations has developed this QA tool.
Workpackage 5 – Biological markers to predict the response of head and neck tumours to Cetuximab or cispla
At the partner Institut Gustave Roussy in Villejuif, France, specific biological markers which have shown to have predictive or prognostic potential in head and neck as well as lung cancer will be evaluated in relation to the treatment outcome. These biomarkers will aid the selection of patients who will benefit from either the combined treatment with RT and Cetuximab or with RT and cisplatin so that further individualisation of these treatments can be validated.
Clinical trials in lung and head and neck cancer will be carried out among the partners NKI (Amsterdam), Karolinska Institutet (Stockholm), the Institute Gustave Roussy (Villejuif) , Vall d’Hebron (Barcelona), The Christie (Manchester), UMCU (Utrecht) and Erasmus MC (Rotterdam) while the laboratory research will be carried out at INSERM (Paris).
In this workpackage, innovative imaging modalities to allow better prediction of outcome and the individualisation of treatment will be assessed in a multicentric setting. Firstly, standardisation and quality control of imaging will be undertaken from imaging production, data acquisition through to the data analysis process. In the two clinical trials mentioned in Workpackage 5, (functional) imaging of patients will be undertaken followed by the evaluation of metabolic response three months after treatment.
In the head and neck cancer trial, non-invasive imaging of EGFR expression with Cetuximab- labelled Zirconium-89 will be undertaken to evaluate the uptake and biodistribution of the drug on an individual basis. At the start of 2014 the protocol had to be amended. The protocol now exists of two arms, randomizing between standard dose (70Gy in 35 fx) and dose redistribution (64-84 Gy in 35 Fx) based on FDG-PET uptake, with adaptive RT.
In the lung cancer trial, non-invasive imaging of hypoxia with fluorodinated HX4 will be undertaken to identify areas of the tumour where high dose treatment can be delivered
This work will be undertaken at the MAASTRO Clinic, Maastricht, The Netherlands
Workpackage 7 – Dose escalation by boosting radiation with the primary tumour based on a pre-treatment FDG-PET scan.
Partners NKI (Amsterdam) and MAASTRO (Maastricht) will be collaborating in the phase II clinical trial in lung cancer patients in which PET imaging will be applied to identify areas of the tumour which show high uptake of FDG (showing resistance to treatment). These areas of the tumour can then receive a higher radiation dose while sensitive areas (and normal tissue) can be spared.
Workpackage 8 – Increasing the therapeutic ratio for head and neck cancers by pre-treatment selection and dose redistribution.
Within the proposed head and neck cancer trial, it is aimed with the help of pre-treatment information to evaluate the impact of dose redistribution within the tumour on loco-regional control and disease-free survival. For all patients, Zr89-Cetuximab uptake in the primary tumour will be determined, showing or not prediction for Cetuximab-RT efficacy.
At the start of 2014 the protocol had to be amended. The protocol now exists of two arms, randomizing between standard dose (70Gy in 35 fx) and dose redistribution (64-84 Gy in 35 Fx) based on FDG-PET uptake, with adaptive RT.
The NKI (Amsterdam) is the lead for this study and the study will also provide biopsy material for Workpackage 5 and also FDG-PET data for biological optimisation in the future (Workpackage 3). Furthermore, there will be close cooperation with Workpackage 2 as dose redistribution (adaptive treatment) is described.
The European Society of Therapeutic Radiology and Oncology (ESTRO) is a partner in this project and will be mainly responsible for the distribution of the knowledge and expertise gained within the course of this project to the scientific and lay community by way of provision of travel/educational grants, technology exchange programs, top level scientific meetings, publication of results in peer reviewed scientific journals and development of the ARTFORCE and ESTRO websites.