Establishing clinical cancer treatments with MR-guided adaptive radiotherapy

The advances in image guided radiotherapy (IGRT) lead to an significant increase in treatment quality of cancer patients. However the guidance of radiotherapy based on X-Ray shows limitations and never translated into online adaptive radiotherapy. Therefore the new concept of MR-guided radiotherapy (MRgRT) was introduced, combining an linear accelerator with a magnetic resonance imaging (MRI). In this hybrid MR-linac system the higher soft tissue contrast of the MRI in combination with an optimization on the anatomy of the day promises increased treatment quality and new standard of practice. However, a MRI has before only supplied additional offline information for the annotation of tumor tissue and an online adaptive workflow was not part of clinical treatments. Therefore the challenges in regard to the magnetic field effect on dose distributions, algorithms and measurement devices as well as the problems due to the online adaptive workflow have not been investigated. In this work, the medical physics basis of MR-guided radiotherapy (MRgRT) was researched and concluded in safe clinical treatments of patients. In a first step the technical drawbacks were researched in a simulation study comparing the possible dose distribution for esophageal cancer between the MR-linac system and a modern state of the art linear accelerator. This simulation study showed the dosimetric drawbacks of the MR-linac system due to loss of conformality and size limitations. In addition we showed, that greater focus has to be put on mid- and low-dose areas and that the corresponding OARs must be included into optimization. However, we showed as well that by adaptation of the optimization, the clinical parameters can be fulfilled leading to feasibility of treatment plans. In a second step the only existing algorithm for calculation of dose distributions at the 1.5 T MR-Linac was compared to a detailed research Monte Carlo (MC) system, due to possible approximations on behalf of the magnetic field and attenuating layers of the MRI. In this investigation the detailed MC-simulation was designed to incorporate the material specific information of the accelerator and MRI and their corresponding cross sections for an exact dose calculation. With an iterative comparison to experimental data the linac specific free parameters were derived and the independent accelerator head model finalized for a validation of patient treatments. This validation showed, with gamma criterion of 3 mm and 3% a passing rate of 99.83 % and therefore validated that the approximations do not correspond to a significant change in dose distribution. In a third step new quality assurances were developed to allow treatment of patients on the MR-linac system. For an experimental measurement of dose deposition a novel workflow was developed and integrated, as the conventional systems showed high influences by the static magnetic field. Based on the characterization, a 2D ionization chamber inside a hexagonal phantom can accurately measure the applied dose and, by comparison with the respective simulation, assure correct machine calibration. For an comprehensive check of online adaptive plans within a treatment workflow an independent secondary dose calculation was established. Based on an independent build Monte Carlo accelerator head and a 3D comparison of dose distributions this secondary dose calculation can verify clinical plans in a median time of 1:23 min. In this comparison of dose distributions a gamma criterion validates the machine parameters and assures correct dose over the full patient anatomy. In the final step the acquired knowledge from the previous studies and developed quality assurances allowed first treatments of patients with online adaptive MRguided radiotherapy. In this dissertation the first worldwide MR-guided treatment of partial breast stands representative to the multitude of different tumor entities initiated at the MR-linac system. Equivalent to the investigations on ERE, ESE and geometric distortion in partial breast, further tumor specific magnetic field effects were evaluated for an assessment of potential risks. With this work the basis for a safe treatment with MR-guided radiotherapy (MRgRT) was developed. Therefore, as methods and respective handling of magnetic field effects are now established, new clinical concepts are being developed starting the next phase of MRgRT improving patient treatments in radiotherapy by deviating from current clinical practice

Local control and patient reported outcomes after online MR guided stereotactic body radiotherapy of liver metastases

IntroductionStereotactic body radiotherapy (SBRT) is used to treat liver metastases with the intention of ablation. High local control rates were shown. Magnetic resonance imaging guided radiotherapy (MRgRT) provides the opportunity of a marker-less liver SBRT treatment due to the high soft tissue contrast. We report herein on one of the largest cohorts of patients treated with online MRgRT of liver metastases focusing on oncological outcome, toxicity, patient reported outcome measures (PROMs), quality of life.Material and methodsPatients treated for liver metastases with online MR-guided SBRT at a 1,5 T MR-Linac (Unity, Elekta, Crawley, UK) between March 2019 and December 2021 were included in this prospective study. UK SABR guidelines were used for organs at risk constraints. Oncological endpoints such as survival parameters (overall survival, progression-free survival) and local control as well as patient reported acceptance and quality of life data (EORTC QLQ-C30 questionnaire) were assessed. For toxicity scoring the Common Toxicity Criteria Version 5 were used.ResultsA total of 51 patients with 74 metastases were treated with a median of five fractions. The median applied BED GTV D98 was 84,1 Gy. Median follow-up was 15 months. Local control of the irradiated liver metastasis after 12 months was 89,6%, local control of the liver was 40,3%. Overall survival (OS) after 12 months was 85.1%. Progression free survival (PFS) after 12 months was 22,4%. Local control of the irradiated liver lesion was 100% after three years when a BED ≥100 Gy was reached. The number of treated lesions did not impact local control neither of the treated or of the hepatic control. Patient acceptance of online MRgSBRT was high. There were no acute grade ≥ 3 toxicities. Quality of life data showed no significant difference comparing baseline and follow-up data.ConclusionOnline MR guided radiotherapy is a noninvasive, well-tolerated and effective treatment for liver metastases. Further prospective trials with the goal to define patients who actually benefit most from an online adaptive workflow are currently ongoing

Impact of MRI on target volume definition in head and neck cancer patients

Abstract Background Target volume definition for curative radiochemotherapy in head and neck cancer is crucial since the predominant recurrence pattern is local. Additional diagnostic imaging like MRI is increasingly used, yet it is usually hampered by different patient positioning compared to radiotherapy. In this study, we investigated the impact of diagnostic MRI in treatment position for target volume delineation. Methods We prospectively analyzed patients who were suitable and agreed to undergo an MRI in treatment position with immobilization devices prior to radiotherapy planning from 2017 to 2019. Target volume delineation for the primary tumor was first performed using all available information except for the MRI and subsequently with additional consideration of the co-registered MRI. The derived volumes were compared by subjective visual judgment and by quantitative mathematical methods. Results Sixteen patients were included and underwent the planning CT, MRI and subsequent definitive radiochemotherapy. In 69% of the patients, there were visually relevant changes to the gross tumor volume (GTV) by use of the MRI. In 44%, the GTV_MRI would not have been covered completely by the planning target volume (PTV) of the CT-only contour. Yet, median Hausdorff und DSI values did not reflect these differences. The 3-year local control rate was 94%. Conclusions Adding a diagnostic MRI in RT treatment position is feasible and results in relevant changes in target volumes in the majority of patients