Treatment planning and evaluation system for brachytherapy of uveal melanoma

RATIONALE A possible treatment modality of uveal melanoma is brachytherapy applying episcleral plaques with sources such as 106Ru, 125I, 103Pd or 192Ir. In contrast to external beam radiotherapy (EBRT) very few computational, three dimensional (3D) treatment planning tools exist and in addition have considerable limitations with regard to pre- as well as post planning on the basis of the computed dose distribution to the tumor and the adjacent critical structures of the eye. This project aims to develop a 3D treatment planning system for brachytherapy which can handle both gamma- as well as beta-radiation emitting nuclides. Furthermore a software platform for review of uveal melanoma radiotherapy is to be generated that converts the data of all currently available treatment techniques (i.e. brachytherapy and EBRT) to the same radio-oncologic quantity by means of radiobiological modeling. MATERIAL AND METHODS The designated functional principle of the 3D treatment planning tool consists of following steps: (i) the semi- automatic segmentation of tumor and critical ocular structures on magnetic resonance (MR) images which produces a binary 3D matrix describing the individual structure`s boundaries, (ii) the non-uniform deformation of a predefined ocular SubD model to match individual patient anatomy, producing a digital SubD model that is fully segmented and can be discretized into any voxel dimension and (iii) the inclusion of the episcleral plaques into the computer model and subsequent 3D dose calculation on the transformed SubD model by means of convolution with dose kernels. The latter will be validated with accompanying Monte Carlo simulations and experimental dose measurements. The software platform for review of uveal melanoma radiotherapy will have an interface with the brachytherapy treatment planning tool described above and be able to import and export images, structures, and dosimetric information from other treatment planning modalities like EBRT. Radiobiological modeling then will normalize treatment techniques with different duration, dose per fraction and dose rate to a common fractionation scheme. Finally this review software will be applied on databases of uveal melanoma patients and the dosimetric output of these treatments will be investigated with regard to their correlation with local control, overall survival and normal tissue toxicities. The scientific relevance of this project is the improvement in patient care facilitated by the novel computational treatment planning system that allows for personalized therapy and prognosis with regard to brachytherapy of uveal melanoma. Moreover the review software platform enables a radiobiological assessment of different types of radiotherapies and thereby improves the understanding of dose-response and normal tissue tolerance. Theses insights again will contribute to the optimization of therapy protocols, irrespective of the treatment technique.

Uveal melanoma is the most prominent intraocular malignant tumor with an occurrence of 1 per 100,000 people per year. Regarding clinical outcome brachytherapy using 106Ru eye plaques achieves excellent tumor control and low toxicity rates. However, especially when compared to the recent advancements in image-guided three-dimensional external photon beam therapy on linear accelerators, the level of sophistication in aspects of treatment planning and quality assurance is very basic in eye plaque brachytherapy.To achieve a continuous improvement of the clinical follow-up, it is therefore necessary to improve the eye plaque based therapy, so that this technique can live up to the requirements of a modern 3D guided treatment planning. Volumetric descriptions of the tumor and critical structures and the dose deposited within these volumes are crucial parameters in order to understand the relationship between dose and response. By expanding the knowledge on this relationship, a more individual application of 106Ru eye plaques will become possible.In this project a research version of a treatment planning software for Ruthenium plaque based brachytherapy of uveal melanomas was developed. In order to derive dose volume metrics based on actual delivered doses and a volumetric eye model for each patient, full three-dimensional dose distributions were calculated for different 106Ru plaque models and validated in dosimetric measurements. Further studies investigated the robustness and accuracy of this therapy regarding surgical and dosimetric uncertainties. The obtained data was used to derive concepts for safety margins, which are based on realistic dosimetric measurements. Furthermore, methods for treatment plan optimization were developed and analyzed, which in turn can help to minimize the side effects of this radiotherapeutic therapy. To obtain meaningful recommendations for dose prescriptions in order to reduce adverse effects, a comprehensive analysis of the dose-effect relationship is necessary. The software, that was developed within the scope of the project, is capable of providing a significant contribution on this field. In the last phase of this project, a retrospective patient study was performed based on patients who were treated at the AKH Wien/Medical University of Vienna in the last 20 years. This study allowed to correlate a high dose to the retina to a worse visual outcome for the first time.