Preview

PDF, English - main document Download (1MB) | Terms of use

Abstract

Gamma Knife (GK) radiosurgery is generally used to treat malignant and benign brain lesions and represents a non-surgical alternative to complex brain surgery. This technique precisely delivers high doses of highly focused ionizing radiation to the target region, producing a high therapeutic effect with low damage to the surrounding healthy tissues. During the GK treatment, multiple collimated radiation beams produced with 192 60Co sources, called “shots”, are sequentially delivered to produce an absorbed dose distribution which meets the prescribed radiation dose in the target region while avoiding excessive radiotoxicity to surrounding organs at risk (OARs). The number of shots as well as the characteristics of every shot (i.e. collimation, dose rate, exposure time and location) are particular for each clinical GK treatment plan. Therefore, the shot sequence for each GK treatment plan will produce a specific dose deposition temporal pattern both in the target and in the OARs. However, the radiobiological effect for the target and the OARs depends on the dose deposition temporal pattern, seen as a variation in the dose rate over time. Therefore, different shot sequences leading to the same absorbed dose distribution will produce different radiobiological effects for the target and for the OARs. Hence, the aim of this thesis was to investigate the effect of different shot sequences in GK radiosurgery to optimize the radiobiological effectiveness of the treatment. In addition, the effect of using GK sources decayed after one half-life (5.26 years for 60Co), which have half the dose rate than the non-decayed sources used in the clinical plan, was also analyzed.

In this thesis, a group of 25 patients with various brain tumors treated with a Gamma Knife® Icon™ unit at the Department of Radiation Oncology, University Medical Centre Mannheim, Germany were retrospectively selected for analysis. The study received the corresponding ethical approval by the Medical Ethics Commission II of the Medical Faculty Mannheim, Heidelberg University. As the dose distribution in GK radiosurgery is intrinsically heterogenous, the overall biologically effective dose (oBED) was used to represent the radiobiological effect produced by the GK therapy both for the target and for the OARs. Moreover, three different models were analyzed to consider the sublethal damage repair after irradiation in the calculation of the oBED values: mono-exponential, reciprocal and bi-exponential.

All possible combinations of shots were analyzed to define the optimal shot sequence. For patients with defined OARs, the shot sequence leading to the maximum therapeutic index (i.e. the ratio between the target oBED and the oBED for the dose-limiting organ) was selected as the optimal shot sequence. For patients with no OAR defined, the shot sequence leading to the highest target oBED was defined as optimal. To simulate the physical decay of the GK sources after one half-life, the dose rate for each shot in the clinical plan was halved while the beam-on time was doubled. All calculations were performed for the three evaluated sublethal repair models.

The results of this study showed that there is an optimal shot sequence for each GK treatment plan that produces better radiobiological characteristics than the actual clinical plan. In addition, when using GK sources decayed after one half-life, the target oBED values decreased considerably. Lastly, the three evaluated sublethal damage repair models produced different oBED values among them. However, there were no considerable differences in the changes of the oBED values between the clinical and the optimal shot sequences, as well as between the clinical plans and the plans with decayed GK sources, when analyzed with each of the evaluated repair models.