use-linear-accelerator-for-conducting-vitro-radiobiology

Use of a Linear Accelerator for Conducting In Vitro Radiobiology Experiments

Radiation therapy remains one of the cornerstones of cancer management. For most cancers, it is the most effective, nonsurgical therapy to debulk tumors. ...

Cleveland Clinic

Using a MatriXX 2D ionization chamber array, we evaluated the detection sensitivity of systematically introduced MLC leaf positioning shifts to test whether the conventional IMRT QA method can be used for quality assurance of an MLC tracking algorithm. Because of finite special resolution, we first tested whether the detection sensitivity was dependent of the locations of leaf shifts and positions of ionization chambers. We then introduced the same systematic leaf shifts in two clinical intensity modulated radiotherapy plans (prostate and head and neck cancer). Our results reported differences between the measured planar doses with and without MLC shifts (errors). Independent of the locations of the leaf position shifts and positions of the detectors, for the simple rectangular fields, the MatriXX was able to detect ±2 mm MLC leaf positioning shifts with Gamma index of 3%/3 mm and ±1 mm MLC leaf position shifts with Gamma index of 2%/2 mm. For the clinical plans, measuring the fields individually, leaf positioning shifts of ±2 mm were detected using Gamma index of 3%/3 mm and a passing rate of 95%. When the fields were measured compositely, the Gamma index exhibited less sensitivity for the detection of leaf positioning shifts than when the fields were measured individually. In conclusion, if more than 2 mm MLC leaf shifts were required, the commercial detector array (MatriXX) is able to detect such MLC positioning shifts, otherwise a more sensitive quality assurance method should be used.

Sensitivity of array detector measurements in determining shifts of MLC leaf positions.

Intensity-modulated radiation therapy (IMRT) has allowed optimization of three-dimensional spatial radiation dose distributions permitting target coverage while reducing normal tissue toxicity. However, radiation-induced normal tissue toxicity is a major contributor to patients' quality of life and often a dose-limiting factor in the definitive treatment of cancer with radiation therapy. We propose the next logical step in the evolution of IMRT using canonical radiobiological principles, optimizing the temporal dimension through which radiation therapy is delivered to further reduce radiation-induced toxicity by increased time for normal tissue recovery. We term this novel treatment planning strategy "temporally feathered radiation therapy" (TFRT).

Temporally feathered intensity-modulated radiation therapy: A planning technique to reduce normal tissue toxicity.

Radiation therapy is an integral part of treatment for patients with glioblastoma. New technological advances in linear accelerators have made extra-high dose rate irradiation possible. This shortens patient treatment time significantly compared to standard dose rate irradiation, but the biologic effects of extra high dose rate irradiation are poorly understood. Glioma stem-like cells (GSCs) are resistant to standard radiation and contribute to tumor progression. Here, we assess the therapeutic effect of extra high dose rate vs. standard dose rate irradiation on GSCs. GSCs were exposed to 2, 4 and 6 Gy X-irradiation at dose rates of 4.2 Gy/min or 21.2 Gy/min (400 monitoring units (MU)/min or 2100 MU/min). We analyzed cell survival with cell growth assays, tumorsphere formation assays and colony formation assays. Cell kill and self-renewal were dependent on the total dose of radiation delivered. However, there was no difference in survival of GSCs or DNA damage repair in GSCs irradiated at different dose rates. GSCs exhibited significant G1 and G2/M phase arrest and increased apoptosis with higher doses of radiation but there was no difference between the two dose rates at each given dose. In a GSC-derived preclinical model of glioblastoma, radiation extended animal survival, but there was no difference in survival in mice receiving different dose rates of radiation. We conclude that GSCs respond to larger fractions of radiation, but extra high dose rate irradiation has no significant biologic advantage in comparison with standard dose rate irradiation.

Article	Year
Sensitivity of array detector measurements in determining shifts of MLC leaf positions. Journal of applied clinical medical physics\| PubMed ID: 28799273	2017
Temporally feathered intensity-modulated radiation therapy: A planning technique to reduce normal tissue toxicity. Medical physics\| PubMed ID: 29786861	2018
The effects of extra high dose rate irradiation on glioma stem-like cells. PloS one\| PubMed ID: 30118510	2018

Andrew Godley

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