Dosimetry and radiobiology of ultrahigh dose-rate radiotherapy delivered with low-energy x-rays and very high-energy electrons

Date

2024

Authors

Hart, Alexander

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Abstract

Radiotherapy is a powerful tool in oncology, from curative treatments to pain relief in palliative care. However, the efficacy of radiotherapy is limited by side effects caused by damage to healthy tissues. Ultrahigh dose-rate radiotherapy (UHDR-RT) has emerged as a possible method of reducing damage to normal tissues while maintaining the ability to control the progression of cancer. UHDR treatments are delivered three orders of magnitude faster than conventional dose-rate radiotherapy (CDR-RT). To reach the dose rates associated with UHDR-RT, novel radiation sources have been developed, spanning a wide range of radiation types, energies, and time structures of delivery. These include kilovoltage x-rays produced by a shutter-controlled x-ray tube, and very high energy electrons (VHEE) accelerated to 200 MeV at high energy physics laboratories. Testing the capability of these sources requires specialized dosimeters and radiobiological models which are not commonly used in traditional radiotherapy. In this work, plastic scintillation detectors (PSDs) of various compositions were used to measure dose from both 120 kVp x-rays and 200 MeV electrons. Experiments with the shutter-controlled x-ray tube demonstrated that lead-doped polystyrene PSDs can be used as accurate dosimeters for dose-rates of up to 40.1 Gy/s and for pulse widths of 1 - 100 ms. At the CERN linear electron accelerator for research (CLEAR) the ability of PSDs to respond linearly with dose and independent of dose rate with 200 MeV electrons was assessed as well as the radiation hardness of the probes. Polystyrene-based PSDs maintained linear light output with dose up to 125.2 Gy per pulse. After receiving tens of kGy within one day, PSDs showed reduced light output. However, they exhibited dose-dependent recovery, and maintained linearity of output with dose per pulse. To explore the radiobiological effects of the same radiation sources, Drosophila melanogaster were irradiated as larvae and were monitored for effects on their development. It was shown that UHDR 120 kVp x-rays are capable of reducing normal tissue damage in flies compared to CDR treatments. At 22 Gy, the UHDR irradiated flies had a longer median lifespan, while at 24 Gy they survived to adulthood at higher rates than the corresponding CDR groups. Irradiations of D. melanogaster with 200 MeV and 9-20 MeV over a range of doses from 10 - 45 Gy at both UHDR and CDR were also performed. The dose response curves allowed for an in vivo determination of the relative biological effectiveness (RBE) of VHEE beams, cal- culated to be between 0.97 and 1.01. This work establishes that PSDs and D. melanogaster are useful platforms for characterizing the physical and radiobiological properties of novel UHDR-RT sources.

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Keywords

Ultrahigh dose-rate radiotherapy, Radiobiology, Dosimetry, Very high energy electrons, Drosophila melanogaster, Plastic scintillator detectors

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