Range uncertainty reductions in proton therapy and associated benefits for patients with brain or skull base tumors

Tattenberg, Sebastian (2023): Range uncertainty reductions in proton therapy and associated benefits for patients with brain or skull base tumors. Dissertation, LMU München: Fakultät für Physik

Abstract

Conventional radiotherapy for cancer is generally photon-based, but the physical advantages of proton-based treatments, which may allow for superior dose conformality to the tumor and superior normal tissue sparing, have been recognized as early as the mid-1940s. However, only technological advancements in more recent decades rendered proton therapy more feasible, and proton treatments still face considerable hurdles. The possibly most significant of these are uncertainties in the in vivo proton range, which stem from factors such as the images on which treatment plans are created and variations in patient setup between different treatment fractions. Such range uncertainties currently prevent the potential advantages of proton therapy from being fully utilized. Many different approaches to reduce in vivo proton range uncertainties are therefore being investigated. This work aims to quantify the benefits of range uncertainty reductions while simultaneously contributing to methods which aim to achieve them. This includes the quantification of direct benefits of range uncertainty reductions based on a set of ten cancer patients with clival tumors. Normal tissue metrics such as the dose to normal tissues as well as the probability of brainstem necrosis or blindness arising as a result of irradiation were determined as a function of range uncertainty. Patient-specific factors such as target volume, prescription dose, and distance between target and optic chiasm were linked to particularly high range uncertainty reduction benefits. However, proton therapy beam arrangements are currently chosen conservatively in order to minimize the potential effects of uncertainties in the in vivo proton range. Indirect range uncertainty reduction benefits such as the feasibility of novel beam arrangements at lower levels of range uncertainty therefore also have to be considered. Such indirect benefits were quantified based on a data set of treatment plans for ten patients with brain or skull base tumors. This study confirmed the importance of patient-specific factors such as target volume and prescription dose. Indirect range uncertainty reduction benefits were observed to exceed the direct benefits of reductions in proton range uncertainties. The quantified range uncertainty reduction benefits can be achieved in a multitude of different ways. Prompt gamma-ray spectroscopy - i.e., measurements of prompt gamma-rays emitted as a result of proton irradiation - allows proton ranges to be verified in real time. The elemental composition of the irradiated tissue can be determined simultaneously. A prototype for prompt gamma-ray spectroscopy-based proton range verification has been developed at Massachusetts General Hospital (MGH) in Boston. For this thesis, the detector prototype's performance was validated using a variety of tissue-mimicking and porcine samples. The mean measured range error was smaller than or equal to 1.2 mm for all samples, and the system was able to differentiate between samples of different elemental compositions accurately. Proton therapy has experienced rapidly-growing interest in recent years. However, uncertainties in the in vivo proton range remain considerable hurdles. The studies conducted for the purpose of this thesis quantify the benefits and thereby emphasize the importance of reducing proton range uncertainties. At the same time, prompt gamma-ray spectroscopy measurements conducted for this thesis contribute towards eventually achieving the range uncertainty reductions studied.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 530 Physik
• Fakultäten: Fakultät für Physik
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 30. Januar 2023
• 1. Bericht­erstatter:in: Parodi, Katia