Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Gaede, Stewart

Abstract

External beam radiation treatment is often included in standard breast cancer and non-small cell lung cancer patients’ curative management. With the advances in radiation treatment (RT) techniques, such as the development of intensity-modulated radiation therapy and volumetric modulated arc therapy, local and regional control benefits are established. However, both cancer type survivors are prone to develop radiation-induced cardiac disease in their cured life. Furthermore, our laboratory previously demonstrated an inflammatory response in canine models using 18FDG/PET imaging during the initial year following RT.

Hence, the overall goal of this thesis is to assess early functional changes and inflammation response in the heart after irradiation in both animal and patient pilot studies with the use of multi-modality imaging. Additionally, planning studies were undertaken to investigate the potential of reducing dose to the heart and substructure, including the left ventricle and the left anterior descending artery, which are unintentionally subjected to a higher dose during RT. Various RT planning techniques including deep-inspiration breath-hold and 4D Robust optimization, which can be applied to treat breast cancer are also examined. This is aimed to provide clinically feasible alternative options for patients who are non-compliant to breath-hold, without compromising target coverage.

In this thesis, we established a clinically feasible protocol to assess early cardiac functional changes and inflammation response of current radiation treatment techniques that are dedicated to minimizing cardiac dose and radiation-induced cardiac toxicity. This included multi-modality cardiac imaging assessment using hybrid PET/MR and CT perfusion imaging with serial blood work performed. Additionally, from the extensive dosimetric heart sparing treatment planning study, we were able to demonstrate/present clinical feasible free-breathing options for patients who are non-compliant with breath-hold treatment. In the future, the benefits of cardiac dose mitigation strategies can be evaluated with the use of multi-modality imaging techniques.

Summary for Lay Audience

With the advancement in radiotherapy techniques, the benefits of positive tumour biological response and progression in breast cancer and non-small cell lung cancer are observed. However, unintentional radiation-induced cardiac toxicity was reported in both cancer type survivors after their treatment. With the use of multi-modality functional cardiac imaging, the early effects on cardiac blood flow, function and inflammatory responses to radiotherapy were assessed from animal models to patient pilot studies before and after radiation treatment, featured in three chapters of this thesis. The feasibility of the non-invasive imaging assessment that we demonstrated may be useful in developing future patient-specific strategies, including early cardiac toxicity detection to minimize post-radiation risk. Moreover, through an extensive radiation dose distribution comparison among various radiotherapy treatment planning techniques, such as deep-inspiration breath-hold and robust optimization, the clinical feasibility in sparing various aspects of the heart are be compared and evaluated. Therefore, the cardiac exposure in future cancer patients can be minimized without compromising target coverage, especially for patients who are not compliant to heart-sparing techniques. In the future, the benefits of cardiac dose mitigation strategies can be evaluated with the use of multi-modality imaging techniques.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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