Towards Clinical Translation of Microbeam Radiation Therapy (MRT) with a Compact Source

Abstract

MRT is an innovative concept of spatially fractionated radiation therapy that has demonstrated substantially improved normal tissue tolerance while achieving local tumor control in a wealth of preclinical studies. In MRT a collimator shapes a few micrometers wide planar x-ray beams with a spacing of a few 100 µm. MRT has the potential to improve cancer treatment substantially. However, until now, only a few large 3rd generation synchrotrons provide beam parameters that would allow patient treatments and therefore, MRT has not yet become clinically available. For a clinical translation, compact x-ray sources are required, that produce high dose rate orthovoltage x-rays from a micrometer sized emitter. We developed and built a first prototype of a line focus x-ray tube (LFxT) dedicated to preclinical MRT research. By exploiting the heat capacity limit, the LFxT can deliver dose rates above 100 Gy/s from a just 50 µm-wide focal spot without destroying the rapidly (>200 Hz) rotating x-ray target. A bespoke collimator splits the homogeneous x-ray field into 50 µm wide high-dose peaks separated by 350 µm wide low-dose troughs (valleys). While the prototype in our lab is restricted to a power of 90 kW and 10 Gy/s at 300 kVp, we have started the development of the first clinically usable LFxT-2 at 1.5 MW power and >100 Gy/s at 600 kVp beam quality. We investigated the clinical applicability of the LFxT-2 by performing retrospective treatment planning studies. In particular, we were examining, whether 600 kVp photons would suffice to meet clinical dose constraints in MRT treatments treatment scenarios for first clinical use of MRT. We coupled the open source platform 3D Slicer with an in-house developed dose calculation algorithm for MRT treatment planning. For comparability of spatially fractionated MRT doses with conventional broad beam treatments, the MRT dose was converted to equivalent uniform dose (EUD) and equivalent doses in 2-Gy-fractions (EQD2). The 3D Slicer RT toolkit enabled the dosimetric analysis based on dose volume histograms (DVHs). We installed a preclinical prototype of the LFxT that is currently put into operation and commissioned. Simulations show the feasibility of the next generation LFxT-2 with more than 100 Gy/s peak dose rate. Planned MRT dose distributions with the LFxT-2 meet established radiotherapy dose constraints in many of the investigated clinical cases. However, treatment planning procedures are not yet optimal and require improvement. In a next step, we will build the LFxT-2 and aim for first clinical MRT trials at this source. In order to further improve calculated MRT dose distributions, we will implement inverse treatment planning techniques.