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ERC

BIO-IRT Report Summary

Project ID: 335367
Funded under: FP7-IDEAS-ERC
Country: Germany

Mid-Term Report Summary - BIO-IRT (Biologically individualized, model-based radiotherapy on the basis of multi-parametric molecular tumour profiling)

Modern high precision radiotherapy (RT) allows extremely flexible tumour treatments achieving highly conformal radiation doses in the tumour region while sparing surrounding organs at risk. Nevertheless, failure rates of up to 50% are reported for head-and-neck cancer (HNC) due to radiation resistance induced by varying pathophysiological factors such as hypoxia and other clinical factors as HPV-status, genetic fingerprint of the tumour, stage and tumour volume.
This project aims at developing a multi-parametric model for biologically individualized RT (bio-iRT) dose prescriptions in HNC based on biological markers and functional PET/MR imaging.
In a first part of the project, multi-parametric functional information on HNC before and during RT is measured in a preclinical xenograft model. To achieve this, ten different HNC cell lines (FaDu, XF354, CAL-33, UT-SCC-5, SAS, UT-SCC-8, HSC-14, UT-SCC-14, UT-SCC-45, UT-SCC-15) are investigated. In a pilot study, work-flow and methodology were established for preclinical combined PET/MR imaging to obtain simultaneously functional imaging biomarkers from dynamic FMISO PET, high-resolution anatomical T1- and T2-weighted MRI, diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) MRI. In addition, the animals are treated for two weeks with fractionated RT using a dedicated small animal image guided RT (SAIGRT) machine. Subsequently, a second micro-PET/MRI examination is performed before the tumour tissue is further analysed ex-vivo for intrinsic radiation sensitivity (γH2AX), with gene expression analysis, and also immunohistochemically. After successful implementation of the methodology, analysis of the ten HNC cell lines has started. At this stage, two groups of four animals each (FaDu, CAL-33) were successfully imaged and treated. First results show that HNC tumours are extremely heterogeneous with a large intra- and inter-tumour variation, which may be one reason of the wide spectrum of clinically observed radiation resistance levels.
In a second part of the project, a variety of different mathematical and image processing tools and models were developed in order to accurately and robustly analyse the functional data obtained from preclinical PET/MR imaging as well as from immunohistochemistry. Models were implemented for voxel-based analysis of dynamic FMISO PET data as well as for reproducible estimation of apparent diffusion coefficients (ADC-values) from DWI and accurate analysis of time-resolved DCE-MRI data.
One of the aims of the overall project is to validate the multi-parametric response model that will be generated from data measured in the preclinical setting in a clinical study. Consequently, to prepare for the clinical validation phase of the project, models were implemented to analyse clinical multi-parametric functional imaging data from combined PET/MRI. Furthermore, dedicated hardware tools were implemented and tested, which enable for PET/MR imaging in RT patient positioning. In addition, imaging sequences were developed to guarantee distortion correction of DWI data and thus allow the acquisition of non-deformed and spatially accurate ADC maps in clinical practice.
In conclusion, during the first reporting period of this ERC project, major achievements have been obtained in terms of methodology for preclinical functional multi-parametric imaging, modelling or data analysis and hardware preparation for the clinical validation study. With this, corner stones for the future development of a model for bio-iRT dose prescriptions on the basis of multi-parametric molecular profiling were set. Consequently, the detailed investigation and development of bio-iRT will provide a unique basis for future personalized cancer therapies and thus mark a paradigm shift from anatomy-based to bio-iRT concepts with the ultimate goal of improving cancer cure rates.

Contact

Sebastian Claus, (Administrative Financial Project Manager)
Tel.: +4970712977978
Fax: +497071295784
E-mail
Record Number: 189614 / Last updated on: 2016-10-12