Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Dr. Aaron Ward

2nd Supervisor

Dr. Douglas Hoover

Co-Supervisor

Abstract

While prostate cancer is not typically an aggressive disease, it can be lethal for some patients. Treatment of the disease has proven to be effective; however, when the disease recurs locally it does so most commonly at the site of the dominant intraprostatic lesion (DIL). An effective treatment method for prostate cancer is high dose rate brachytherapy (HDR-BT). This is a radiation therapy where a radioactive seed is interstitially inserted into the patient to deliver the radiation dose. It was the goal of this work to utilize preprocedural imaging and pathological data from radical prostatectomy specimens to investigate methods to dose escalate DILs. The first objective was to establish a baseline range of doses that DILs would receive within clinically standard whole-gland HDR-BT treatment plans. To execute this objective, DILs were retrospectively registered within previously implemented HDR-BT plans to analyze DIL dose. The next objective was to investigate targeting mpMRI and PSMA-PET DILs and to determine if this would translate to escalated dose to the pathologically defined cancer. This was performed by retrospectively developing mpMRI and PSMA-PET DIL targeted treatment plans and comparing the doses delivered to co-registered digital histology between targeted and whole-gland plans. The final investigation that was performed aimed to determine an optimal margin to be added to the mpMRI DILs to increase dose to the pathologically confirmed cancer . To do so, we created mpMRI targeted HDR-BT treatment plans with varying margins added to the DIL and analyzed the dose that would have been delivered to the pathologically confirmed cancer. The results of this work demonstrated that while most DILs would receive the prescription dose during HDR-BT, up to 26% may receive less than the intended dose . Secondly, it was shown that by targeting predefined DILs on mpMRI or PSMA-PET with a boost of 130% of the 15-Gy prescription resulted in an average increase of 1.3 Gy to the pathologically defined high-grade disease in comparison to standard whole-gland plans. Lastly, there is the potential to further increase the dose to the pathologically confirmed disease by adding an expansion margin of 1 mm to the mpMRI-defined DILs.

Summary for Lay Audience

Prostate cancer is the most frequently diagnosed non-skin cancer amongst Canadian men. Treatment for prostate cancer has very high rates of success; however, when treatment is unsuccessful and the cancer returns, it most frequently returns within the prostate where the largest tumour was located. One promising treatment option for prostate cancer is called high-dose rate brachytherapy (HDR-BT). HDR-BT is a radiation therapy treatment where a radioactive seed is temporarily inserted into the patient to deliver the radiation dose to the prostate to kill the cancer. Recently, magnetic resonance imaging (MRI) and positron emission tomography have demonstrated the ability to locate prostate cancer tumours. Therefore, recent research has investigated using HDR-BT to target tumours seen on MRI and PET. It is the goal of this thesis to investigate and validate that targeting tumours seen on MRI and PET imaging translates to increased dose to the ground truth location of the cancer as confirmed by pathology. To perform this validation, we started by analyzing how much dose would be delivered to tumours through standard non-targeted HDR-BT (when radiation dose is equally targeted to the entire prostate). Once we established what dose a standard plan would deliver to a tumour, we then targeted tumours that were identified on MRI and PET and determined what dose the pathologically defined cancer would have received with targeted treatment plans. The last objective of this work was to test to see if adding an expansion margin to the tumours would result in further dose increase dose to the pathologically confirmed cancer. To do this we added expansion margins ranging from 1 mm to 5 mm to each of the tumours. This thesis established the dose with which normal HDR-BT treatment plans would treat tumours, determined that targeted treatment plans would increase dose to the pathologically confirmed cancer, and lastly concluded that to deliver the most dose to pathologically confirmed disease a 1 mm expansion margin should be added to MRI tumours before designing the treatment plans.

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