Science, Irving K. Barber Faculty of (Okanagan)
Computer Science, Mathematics, Physics and Statistics, Department of (Okanagan)
DSpace
UBCO
McKeown, Dakota
Master of Science - MSc
University of British Columbia
Purpose: Clinical brachytherapy is typically performed using TG43 formalism, which assumes a homogeneous water medium and does not account for factors such as interseed attenuation or tissue inhomogeneities. Monte Carlo (MC) model-based dose calculation algorithms (MBDCA) provide improved dosimetric accuracy. The purpose of this work was to quantify the impact of eb_gui, a Canadian developed, user-friendly MC MBDCA, on plan evaluation with 80 low dose rate (LDR) breast brachytherapy patients and 76 LDR prostate brachytherapy patients. Methods: Dosimetry of 80 breast brachytherapy cases treated with Pd-103 seeds (TheraSeed200, 2.3-2.8 U, 90 Gy prescription dose) and 76 prostate cases treated with I-125 seeds (AgX100, 0.354-0.493 U, 144 or 110 Gy prescription doses) were simulated using the MC program and doses were calculated using two methods: 1) water-equivalent MC and 2) material-assigned MC. The clinical dose-volume histogram metrics of the targets and organs at risk (OAR) for both simulations were extracted and compared across the two patient cohorts. Results: Breast target volumes showed a slight overestimation of dose by water-equivalent MC of 1% for the CTV V₁₀₀ and 6% for the ETV V₁₀₀ compared to the median material-assigned MC results (p < 0.05). Water-equivalent MC significantly underestimated the skin D₀ꓸ₂꜀ₘ₃ by 20.3% compared to material-assigned MC (p < 0.05). In prostate patients, water-equivalent MC overestimated CTV V₁₀₀ by 4.4% compared to material-assigned MC (p < 0.05). The only potentially clinical significant result for a prostate OAR is the urethra D₁꜀ₘ₃ , where dose was overestimated by 6.3% by water-equivalent MC (p < 0.05). Conclusion: MC simulation of 80 breast and 76 prostate LDR patients were performed. Slight overestimation of dose in target volumes and prostate OARs and potentially clinically significant underestimation of dose in skin were seen using the standard TG43 calculations when compared to the more accurate MBDCA. These differences motivate the future adoption of eb_gui as a valuable tool for LDR breast and prostate treatments in clinical practices.
INVESTIGATION OF A MONTE CARLO MODEL BASED DOSE CALCULATION FORPD-103 LOW DOSE RATE BREAST BRACHYTHERAPY AND I-125 LOW DOSE RATEPROSTATE BRACHYTHERAPYbyDakota McKeownA THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THEDEGREE OFMASTER OF SCIENCEinTHE COLLEGE OF GRADUATE STUDIES(Medical Physics)THE UNIVERSITY OF BRITISH COLUMBIA(Okanagan)September 2023© Dakota McKeown 2023The following individuals certify that they have read, and recommend to the College of GraduateStudies for acceptance, a thesis/dissertation entitled:INVESTIGATION OF A MONTE CARLO MODEL BASED DOSE CALCULATION FORPD-103 LOW DOSE RATE BREAST BRACHYTHERAPY AND I-125 LOW DOSE RATEPROSTATE BRACHYTHERAPYsubmitted by Dakota McKeown in partial fulfillment of the requirements of the degree of Masterof Science in Medical Physics.Dr. Chistina Haston - Department of Computer Science, Mathematics, Physics and Statistics, TheUniversity of British Columbia – OkanaganSupervisorDr. Yiwen Xu - Department of Medical Physics, BC Cancer – KelownaCo-SupervisorDr. Eric Wright - Department of Medical Physics, BC Cancer – KelownaSupervisory Committee MemberDr. Jeffrey Andrews - Department of Computer Science, Mathematics, Physics and Statistics, TheUniversity of British Columbia – OkanaganSupervisory Committee MemberDr. Elizabeth Huynh - Department of Oncology and Department of Medical Biophysics, WesternUniversityExternal ExamineriiAbstractPurpose: Clinical brachytherapy is typically performed using TG43 formalism, which as-sumes a homogeneous water medium and does not account for factors such as interseed atten-uation or tissue inhomogeneities. Monte Carlo (MC) model-based dose calculation algorithms(MBDCA) provide improved dosimetric accuracy. The purpose of this work was to quantify theimpact of eb_gui, a Canadian developed, user-friendly MC MBDCA, on plan evaluation with 80low dose rate (LDR) breast brachytherapy patients and 76 LDR prostate brachytherapy patients.Methods: Dosimetry of 80 breast brachytherapy cases treated with Pd-103 seeds (TheraSeed200,2.3-2.8 U, 90 Gy prescription dose) and 76 prostate cases treated with I-125 seeds (AgX100, 0.354-0.493 U, 144 or 110 Gy prescription doses) were simulated using the MC program and doses werecalculated using two methods: 1) water-equivalent MC and 2) material-assigned MC. The clinicaldose-volume histogram metrics of the targets and organs at risk (OAR) for both simulations wereextracted and compared across the two patient cohorts.Results: Breast target volumes showed a slight overestimation of dose by water-equivalent MCof 1% for the CTV V100 and 6% for the ETV V100 compared to the median material-assigned MCresults (p< 0.05). Water-equivalent MC significantly underestimated the skin D0.2cm3 by 20.3%compared to material-assigned MC (p< 0.05). In prostate patients, water-equivalent MC overes-timated CTV V100 by 4.4% compared to material-assigned MC (p< 0.05). The only potentiallyclinical significant result for a prostate OAR is the urethra D1cm3 , where dose was overestimatedby 6.3% by water-equivalent MC (p< 0.05).Conclusion: MC simulation of 80 breast and 76 prostate LDR patients were performed. Slightoverestimation of dose in target volumes and prostate OARs and potentially clinically significantunderestimation of dose in skin were seen using the standard TG43 calculations when compared tothe more accurate MBDCA. These differences motivate the future adoption of eb_gui as a valuabletool for LDR breast and prostate treatments in clinical practices.iiiLay SummaryThis thesis investigates a new method to calculate dose to breast and prostate cancer patients.Dose describes the impact of radiation treatments on cancer and the negative side effects on healthytissues. The current standard assumes the patients are completely made of water. The new methodaccounts for tissue heterogeneity. The new method is simulated with computer software and showsdoses for cancerous volumes lower than the current standard. Also, for at-risk breast structures likeskin, heart and lung, the new method shows higher doses. This thesis provides a verification thatthe computer software is working as expected before sharing the dose difference results. Thedifferences in dose between the new method and the current standard motivate the adoption of thenew method in cancer clinics.ivPrefaceThis thesis is based on a Monte Carlo program developed by Randle Taylor in collaborationwith Marc Chamberland, Dave Rogers, and Rowan Thomson of the Carleton Laboratory for Ra-diotherapy Physics and software developed by M. Martinov in collaboration with N. Moghadamand R. Thomson of the Carleton Laboratory for Radiotherapy Physics. Subsection 3.1 was a fur-ther clinical validation based on a previous study by Stephen Deering for the breast patients. I wasthe lead investigator for prostate patients data collection and analysis, as well as manuscript com-position, with guidance from the supervisory committee members, Michelle Hilts, Eric Wright,Yiwen Xu, Christina Haston and Jeffrey Andrews. Concept formation for the project comes fromN. Moghadam and R. Thomson of the Carleton Laboratory for Radiotherapy Physics with col-laboration from Samuel Ouellet and Luc Beaulieu from the Département de physique, de géniephysique et d’optique et Centre de recherche sur le cancer and the Service de physique médicaleet radioprotection, et Axe Oncologie du CRCHU de Québec, and Claire Zhang of the Universityof British Columbia (Okanagan).vContentsAbstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iiiLay Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ivPreface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vContents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . viiList of Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . viiiList of Figures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xNomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiiAcknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.1 Breast and prostate cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2 Thesis objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32.1 Radiation Basics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32.1.1 Dose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32.1.2 Radiation toxicities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42.1.3 Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52.1.4 Types of radiation treatments . . . . . . . . . . . . . . . . . . . . . . . . . 52.2 Brachytherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62.2.1 Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62.2.2 Types . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62.2.3 Sources Specifications . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72.2.4 Source Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72.2.5 Source Dosimetry Parameters . . . . . . . . . . . . . . . . . . . . . . . . 82.2.6 TG43 Dose Calculation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92.2.7 LDR Breast and Prostate Brachytherapy Workflow . . . . . . . . . . . . . 112.3 Model-based dose calculation algorithms . . . . . . . . . . . . . . . . . . . . . . 162.3.1 Monte-Carlo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172.3.2 egs_nrc . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172.3.3 egs++ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172.3.4 egs_brachy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172.3.5 eb_gui . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182.3.6 TG186 Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . 203 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223.1 Verifying eb_gui . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223.2 Dosimetric Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24vi4.1 Verifying eb_gui . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244.2 Dosimetric Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37viiList of Tables1 Specifications of radioactive sources commonly used in brachytherapy [1] . Brachyther-apy treatments differ greatly for different source isotopes. . . . . . . . . . . . . . 72 Example planning goals for target coverage and OARs in LDR brachytherapytreatment of prostate cancer [2] . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 Example planning goals for target cover and the most important OAR, skin, inLDR brachytherapy treatment of breast cancer [3] . . . . . . . . . . . . . . . . . . 134 Example post-operation dosimetry goals for the breast and prostate [2] . In the rarecase that the pass criteria is not met the patient may be eligible for further clinicalintervention. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 Sample contour priorities, with higher contours taking a higher priority in tissueassignment alongside possible assigned tissues . . . . . . . . . . . . . . . . . . . 206 Approximate simulation times for MC calculation of dose. Time scales for historynumber greater than 108 are not clinically applicable. . . . . . . . . . . . . . . . . 267 Breast target metric median and IQR for water-equivalent MC (TG43MC) andmaterial-assigned MC (TG186MC) simulations. All differences were significantin a Wilcoxon test. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298 Breast OAR metric median and IQR for water-equivalent MC (TG43MC) andmaterial-assigned MC (TG186MC) simulations. All differences were significantin a Wilcoxon test. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309 Prostate metric median and IQR for water-equivalent MC (TG43MC) and material-assigned MC (TG186MC) simulations. Metric differences with an * were signifi-cant in a Wilcoxon test. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3210 Prostate OAR metric median and IQR for water-equivalent MC (TG43MC) andmaterial-assigned MC (TG186MC) simulations. Metric differences with an * weresignificant in a Wilcoxon test. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33viiiList of Figures1 An example illustrating how to determine V100 and D30 metrics from a DVH ofthe structures in a LDR prostate brachytherapy treatment with prescription dose of144Gy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 The AgX100 I-Seed is composed of a silver marker (coloured grey) coated inradioactive AgI surrounded by air (white) and encapsulated in titanium (blue). . . 83 The TheraSeed200 is composed of two graphite cores (green) coated in radioac-tive Pd-103 separated by lead (red) surrounded by air (white) and encapsulated intitanium (blue). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 Standardized representation of the cylindrical source geometry use in TG43. . . . 105 A pre-operation US with clinician drawn contours for target and critical structuresin treatment of the prostate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 A pre-operation LDR prostate brachytherapy treatment planned on VariSeed . . . 147 A grid template for interstitial brachytherapy implants . . . . . . . . . . . . . . . 158 Workflow for eb_gui tissue assignment . . . . . . . . . . . . . . . . . . . . . . . 199 Sample breast patient VPM highlighting material assignment, a superimposed Pd-103 seed is shown in large to highlight seed material assignment . . . . . . . . . . 2010 Prostate structure DVHs for one sample patient for all simulated histories and TPScalculated . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2411 Breast structure DVHs for one sample patient for all simulated histories and TPScalculated . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2512 Breast target DVH metrics for verification cohort, TG43 IQR are in black withmedian value in orange. Water-equivalent MC IQR are in blue with median valuein red. No significant differences between TG43 and water-equivalent MC wereobserved. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2613 Breast OAR, skin, DVH metrics for verification cohort. TG43 IQR are in blackwith median value in orange. Water-equivalent MC IQR are in blue with medianvalue in red. No significant differences between TG43 and water-equivalent MCwere observed. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2714 Prostate target DVH metrics for verification cohort. TG43 IQR are in black withmedian value in orange. Water-equivalent MC IQR are in blue with median valuein red. No significant differences between TG43 and water-equivalent MC wereobserved. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2715 Prostate urethra DVH metrics for verification cohort. TG43 IQR are in black withmedian value in orange. Water-equivalent MC IQR are in blue with median valuein red. No significant differences between TG43 and water-equivalent MC wereobserved. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28ix16 Breast target DVH volume metrics. Water-equivalent MC results IQR are in bluewith median value in red. Material-assigned MC results IQR are in purple withmedian value in green. Results with *’s were significantly different in a Wilcoxontest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2917 Breast skin DVH dose metrics. Water-equivalent MC IQR are in blue with medianvalue in red. Material-assigned MC IQR are in purple with median value in green.Results with *’s were significantly different in a Wilcoxon test. . . . . . . . . . . 3018 Prostate target DVH volume metrics. Water-equivalent MC IQR are in blue withmedian in red. Material-assigned MC IQR are in purple with median in green.Results with *’s were significantly different in a Wilcoxon test. . . . . . . . . . . 3119 Prostate urethra DVH dose metrics. Water-equivalent MC IQR are in blue withmedian in red. Material-assigned MC IQR are in purple with median in green.Results with *’s were significantly different in a Wilcoxon test. . . . . . . . . . . 32xNomenclatureAAPM : American Association of Physicists in MedicineCIHR : Canadian Institutes of Health ResearchCT : computed tomographyCTV : clinical target volumeDCIS : ductal carcinoma in situDVH : dose-volume histogramDx : absolute dose received by x% of the structure volumeeb_gui : egs_brachy graphical user interfaceEBRT : external beam radiation therapyETV : evaluation target volumeHDR : high dose rateIQR : inter-quartile rangeLDR : low dose rateMBDCA : model-based dose calculation algorithmMRI : magnetic resonance imagingnrc : National Research Council of CanadaOAR : organ at riskPTV : planning target volumeQUANTEC : quantitative analyses of normal tissue effects in the clinicRx : prescription doseTG186 : Task-group 186TG43 : Task-group 43TPS : treatment planning systemUS : ultrasoundxiVPM : virtual patient modelVx : % volume of a structure receiving x% of the prescription dosexiiAcknowledgmentsI’d like to thank everyone who had a hand in helping this thesis take shape. First, I’d like tothank my community of Tsal’alh for their financial support allowing my pursuit of higher educationand my family, for their emotional and financial support.Thanks to my supervisor, Michelle Hilts, for your support and desire to continue supportingmy project despite ultimately having to leave due to sickness. I greatly value your expertise informulating this project and believing in me. I’d also like to thank my local team of members EricWright and Yiwen Xu for stepping up to supervisory roles suddenly for the continued success inthis project. Further, I’d like to thank Claire Zhang for her immense involvement in this project.Every weekly meeting and comment on my thesis by my local team was imperative.I’d also like to thank Narjes Moghadam and Samuel Ouellet for always answering my questionsand ensuring smooth operation in the project. Finally, I’d like to thank my collaborators in thisproject of Joanna Cygler, Luc Beaulieu, Rowan Thomson, and Martin Martinov and local teamof Felipe Castro Cánovas, Juanita Crook and Deidre Batchelar as well as committee membersChristina Haston and Jeffrey Andrews.xiii1 Introduction1.1 Breast and prostate cancer2 in 5 Canadians are expected be diagnosed with cancer in their lifetimes, with 1 in 4 expectedto die of their disease [4]. The treatment of cancer depends on its stage and grade. Cancer stagingdescribes where a cancer is located, its size, how far it has grown into nearby tissues and if it hasspread to other parts of the body. Cancer grade describes how different the cancer cells look fromnormal cells, how quickly they are growing and dividing, and how likely they are to spread.Breast cancer is the most common cancer among Canadian women accounting for 25% ofall new cancer cases and 14% of all cancer deaths in women in 2021 [4]. The most commonform of breast cancer develops in and around the ducts in the breast, tubes which carry milkfrom glands to the nipple. This cancer is referred to as ductal carcinoma and accounts for 50-70% of invasive breast cancers [5]. When the cancer has not spread to surrounding regions thecancer is referred to as in situ. Breast conserving surgery involves removal of all identified regionsof DCIS while attempting to retain as much healthy tissue as possible for the structure of thebreast to be conserved in a process called lumpectomy. The macroscopic cancerous masses areremoved surgically and evaluated pathologically. If it is determined the surgery did not removeall cancerous cells, these cells are targeted by radiation to prevent recurrence of the cancer. Mostcommonly, external beam radiation therapy is given. One alternative form of radiation treatment isbrachytherapy. Brachytherapy is the use of radioactive sources which can irradiate a lumpectomycavity from within or nearby the area. Brachytherapy has the potential to reduce the stress offrequent radiotherapy treatments through permanent seed implants. These seeds can be surgicallyplaced within a patient without needing to be removed, allowing for a single day of treatment. Thismethod of adjuvant brachytherapy is possible for patients diagnosed with DCIS, who have had alumpectomy, or those who have an early-stage invasive breast cancer.Prostate cancer is the most common cancer among Canadian men accounting for 20% of allnew cancer cases in 2021 and 10% of all cancer deaths in men in 2021 [4]. 95% of all prostatecancers are adenocarcinomas, these cancers start in the gland cells of the prostate. They can bepresent in different areas of the prostate but as long as all cancer is contained within the prostatecapsule, low dose rate brachytherapy can be used for treatment. Low dose rate brachytherapy forthe treatment of early stage prostate cancer will be explored in this thesis [6].1.2 Thesis objectivesDose is a measure of energy deposition by radiation per unit mass. The current standard of clin-ical dose calculation in brachytherapy requires assuming the entire region where dose is depositedis water. This assumption can hold for many clinical applications since many human tissues arewater equivalent materials. However, adipose tissue within the breast is not as water equivalent as1other human tissues in the breast like glandular tissue, and in the prostate there can potentially becalcifications which are also not water equivalent. In addition to these tissue inhomogeneities, theradioactive seeds themselves used in brachytherapy treatments are coated in a metal like titaniumwhich is not water equivalent. These different materials will effect the dose deposited in radiationtreatments. For example, calcium attenuates photons more than the water-equivalent normal tissueof the prostate resulting in higher dose being deposited to these calcified regions. These high doseregions reduce the number of available photons to deposit dose in the other regions of the prostate.This affects the overall dose distributed throughout the prostate and can cause the cancerous re-gion to not be properly irradiated. As such, the current standard of assuming only water may beinadequate in these treatments of the breast and prostate. A dose calculation method accountingfor non-water materials will provide a more accurate description of dose to patients in breast andprostate brachytherapy treatments.The goal of this thesis was to highlight the potential differences in current water-based dosecalculation methods to a more sophisticated simulation based dose calculation method account-ing for tissue inhomogeneities and interseed effects. First, to verify a current standard-like dosecalculation from the new dose calculation method against current clinical calculation methods forbreast and prostate patients. Second, to determine the preferred number of particle histories for thenew dose calculation method to balance accuracy and precision with time considerations. Third, tocompare the new dose calculation method to the current standard for breast and prostate patients.This thesis will cover some background helpful for understanding the results in section 2. First,the effects of radiation on cancerous and normal tissues and how it is quantified as dose is coveredin subsection 2.1. Next, the modality of brachytherapy is described in subsection 2.2. Then,characteristics of brachytherapy, the current standard of dose calculation and low dose rate clinicalworkflows are described. Afterwards, the solution to the dose calculation problem, the Monte-Carlo method, is introduced alongside the computer software used to enact the methodology insubsection 2.3 . Further, the methods of validating the calculation program through comparisonswith current dose calculation methods and finally comparing the new calculation method to thecurrent standard are described in section 3 . The results for both the verification and comparisonand presented in section 4 and discussed in section 5 to urge the adoption of these methods fordose calculation in the conclusive section 6 .22 Background2.1 Radiation BasicsSince the discovery of x-rays by Wilhelm Röntgen in 1895 and radioactivity by Henri Bec-queral in 1896, radiation has played an important role in many fields. Radiation is the transmissionof energy in the form of waves or subatomic particles and is classified into either non-ionizing orionizing radiation depending on the ability of the radiation to induce ionizations of the atoms in theabsorbing medium. Ionizing radiation in medicine is used for diagnostic imaging, the treatment ofcancer, blood irradiation and the sterilization of medical equipment.2.1.1 DoseDose is a measure of the energy deposited from ionizing radiation in matter per unit mass. TheSI unit is the Gy which is 1 Jkg . Dose is deposited in the target and nearby normal tissue structuresover the course of radiation treatments. The dose distributions are complex and clinical analysiscan be time consuming and subjective. As such, different tools and metrics have been developedto assist in assessing complex dose distributions. One such tool is the dose-volume histogram(DVH). The DVH collects all dose information for a structure and condenses it into a single plot.In cumulative form, the DVH shows the percent volume of a structure that receives greater thanor equal to an amount of dose as a function of dose. An example DVH showing the differentstructures of the prostate is shown in figure 1 . This figure highlights two important metrics usedin assessing these DVHs the volume (Vx) and dose (Dx) metrics. The Vx metric represents the %volume of a structure receiving x % of the prescription dose. The Dx metric represents the dosereceived by x % volume of a structure. The D metrics can also by used for absolute volumesof a structure. For example the D1cm3 for the urethra represents the minimum dose received bythe hottest 0.1cm3 of the urethra. The D metric Dmax can be used to represent the maximum dosereceived by a structure. The percentile V and D metrics can be extracted directly from the DVHsthrough knowledge of the prescription doses and the absolute volume D metrics can be acquiredthrough the total volume of the structure.3Figure 1: An example illustrating how to determine V100 and D30 metrics from a DVH of thestructures in a LDR prostate brachytherapy treatment with prescription dose of 144Gy.2.1.2 Radiation toxicitiesRadiation causes damage to tumours but it can also damage surrounding normal tissues. Forbreast treatments, risks of fibrosis or atrophy of the breast developing in the years after treatmentare possible. Risks of developing radiation pneumonitis in the lung are also shown in 1− 5%of patients treated by radiation for breast cancer [7]. Quantitative Analyses of Normal TissueEffects in the Clinic (QUANTEC) recommends mean lung doses < 7Gy with V5 metrics< 60%to prevent radiation pneumonitis. For the heart, acute effects include pericarditis with a myriadof possible late effects including: congestive heart failure, ischemic heart disease, coronary arterydisease and myocordial infraction. Evidence of heart disease correlating with radiation breasttreatments comes from the Early Breast Cancer Trialists’ Collaborative Group meta-analyses ofrandomized clinical trials [8]. Conflicting results are seen with developments of heart failure andcoronary artery disease in breast treatments. QUANTEC recommends minimizing heart doses asmuch as possible in breast treatments with conservative estimates of V25Gy < 10% and V30 < 46%to minimize the chance of cardiac mortalities and pericarditis respectively [9]. The ribs can alsobe irradiated in breast treatments, however adult cortical bone is largely radioresistant. Due tothe short range of brachytherapy dose deposition, dose to the heart and lungs is much lower inbrachytherapy treatments than it is in external beam treatments. The side effects of most concern in4breast brachytherapy are those of the skin. Acute effects (6 weeks post treatment) of erythema anddesquamation are possible with late effects manifesting over 2 years post-treatment of localizedfibrosis, telangiectasia and/or changes in the contour of the breast [10].From prostate treatments acute bladder effects are seen in < 10% of patients [11]. With ra-diation induced side effects of: dysuria, increased urinary frequency and urgency, contracture,spasms, reduced flow, and incontinence possible. Acute rectum effects include softer diarrhea-like stools, pain, cramping and frequency of defecation. Late effects include strictures, decreasedcompliance and storage characterized by smaller, more frequent bowel movements [12]. How-ever, in prostate treatments the most important toxicities are seen in the urethra with shrinkage orulcerations developing months to decades post-treatment and strictures on the scale of months toyears.2.1.3 StatisticsStatistical analysis is necessary to compare dose metrics obtained by different calculation meth-ods. A common test used to compare two data sets is the two-sample t-test. This test is meant tocompare means from two independent populations, that both have normally distributed data withequal variances. However, this test cannot be used if the data cannot be assumed to be normallydistributed. As such a non-parametric test that does not assume the distribution of the data set isrequired, such as the Wilcoxon rank sum test.The Wilcoxon rank sum test assesses the null hypothesis that the two populations have equalmedians. The test requires the populations be independent with equal variance. Resultant of thistest is a p-value which represents the probability of observing a result more extreme than observedunder the assumption that the null hypothesis is true. Values of p > 0.05 are taken as a failureto reject the null hypothesis, meaning there is a lack of evidence to suggest the populations havestatistically equal medians. Values with p < 0.05 are taken as the opposite, meaning there issufficient evidence to suggest the populations have statistically differing medians. These valueswill be considered as statistically significant in reporting of results.In addition to reporting the medians of non-parametric statistical data, the interquartile range(IQR) is reported. The IQR is a measure of the spread of non-parametric data and is defined as thedifference between the 75th and 25th percentiles of the data.2.1.4 Types of radiation treatmentsRadiation therapy can be used to treat patients as a mono-therapy or in conjunction withchemotherapy and/or surgery. Chemotherapy is the use of drugs to kill or radiosensitise tumourcells and surgery is the physical removal of tumours from the patient. Microscopic tumour cellsmay remain post-surgery, these are targeted by radiation to minimize the risk of recurrence. Ex-ternal beam radiation therapy (EBRT) is the use of a beam of ionizing radiation from outside the5body that irradiates a target region. EBRT is the most common form of radiation treatment. Thereare many different specializations such as intensity-modulated radiation therapy, volumetric mod-ulated arc therapy and stereotactic ablative body radiotherapy. Novel research and technologies arecontinually developing for EBRT. Internal radiation therapy is another type of radiation treatmentswhere radioactive sources irradiate a target region from within the body. Brachytherapy will be thetreatment modality discussed in the next section.2.2 BrachytherapyBrachytherapy is a cancer treatment modality where radioactive sources are placed within ornearby the tumour delivering high doses of radiation to shrink and eliminate the cancer. Brachyther-apy is able to administer high doses locally, targeting a specific region of the body and minimizingdose to surrounding structures. Common brachytherapy treatment regions include breast, cervix,eye and prostate.2.2.1 TechniquesThe technique for placing brachytherapy sources depends on the treatment region. Intra-cavitary brachytherapy is where brachytherapy sources are inserted in surgically made or alreadyexisting body cavities, like the vagina for treatment of cervical cancers. This technique is usedin treating gynecological cancers. Surface moulds like eye plaques are also used for placingbrachytherapy sources along the surface of the eye. Eye plaques are used in the treatments ofocular melanoma or other ocular malignancies. Interstitial brachytherapy is where the sourcesare inserted within the tumour. The sources are inserted through the use of catheters which arelong, flexible tubes or larger devices called applicators. This thesis is concerned with interstitialbrachytherapy since this technique is used in treating breast and prostate cancers.2.2.2 TypesThere are two main types of brachytherapy depending on the rate at which is dose delivered,and the duration of treatment. High dose rate (HDR) brachytherapy treats at dose rates > 12Gyhrover the course of 1−7days. In low dose rate (LDR) treatments, dose rates range from 0.4−2Gyhrwith treatment courses dependent on the cancer type. Treatments can be anywhere from twice aday for 2−5days or once a week for 2−5weeks. Permanent seed implantation is a subset of LDRtreatments where the radioactive sources are not removed after implant. In these treatments theradiation emitted by these sources decreases with time.There are advantages and disadvantages for each treatment type. LDR treatments are moretime and cost effective [13], but can cause higher radiation exposure to the staff and public. HDRtreatments cause lower radiation exposure to staff and the workflow allows changes to treatment6plans between fractions. However, HDR treatments have higher costs due to needed shieldingconsiderations in addition to continually maintaining new sources.Choice of treatment type depends foremost on cancer type then on patient preferences, clinicianjudgment on initial evaluation and resource availability. For the treatment of prostate cancer forexample there is not currently direct clinical evidence supporting the superiority of HDR or LDRbrachytherapy with respect to tumor control or reduced toxicity [13].2.2.3 Sources SpecificationsThe radioactive sources used in brachytherapy are characterized by their half-life, specific ac-tivity, photon energy, in addition to their chemical and physical properties. In permanent seedimplants a short half-life (less than three months) is desirable to minimize radiation exposure tothe general public. In temporary treatments a source with a longer half-life may be more desirablesince the source can be re-used as it will not decay as rapidly. Specific activity(Bqkg)is a fixedphysical value of a radionuclide and limits the size a source of a certain activity can be. Activity isinversely proportional to half life, so specific activity is as well. The energy of emitted photons willdictate their range in a medium. Therefore, the treatment region and surrounding structures, in ad-dition to the treatment type, influence desired photon energies. Finally, the chemical and physicalproperties of the source need to be considered. The radiation induced toxicities require consider-ation for manufacturing and handling the sources. Further, some sources may also be chemicallytoxic and/or difficult to contain. For example iodine can sublimate to a gaseous form. To containthese sources then an encapsulation is needed. The encapsulation needs to be both chemically andbiologically inert as well as being structurally resistant. The encapsulation must not significantlyattenuate photons emitted from the radioactive sources nor be able to be radioactively activated.Four commonly used radio-isotopes’ specifications are shown in table 1 .Table 1: Specifications of radioactive sources commonly used in brachytherapy [1] . Brachyther-apy treatments differ greatly for different source isotopes.Isotope Half-life(days)Mean Photon Energy(MeV )Use EncapsulationIridium-192 74 0.38 HDR Platinum orstainless steelIodine-125 60 0.028 LDR TitaniumPalladium-103 17 0.021 LDR TitaniumCesium-131 10 0.029 LDR Titanium2.2.4 Source ModelsBrachytherapy sources are manufactured into different models by a variety of companies.These seeds will have different materials used in their construction as well as different sizes and di-mensions available through the manufacturer. Some common I-125 seed models are BrachySeed,7AgX100, ProstaSeed, and SelectSeed. One Pd-103 seed model is TheraSeed200. The geometryand parameters of specific models is important in quantifying the resultant dosimetry. Schematicsof the structure of the two seeds used in this thesis, the AgX100 I-Seed and the TheraSeed200 aregiven in figures 2 and 3 respectively.Figure 2: The AgX100 I-Seed is composed of a silver marker (coloured grey) coated in radioactiveAgI surrounded by air (white) and encapsulated in titanium (blue).Figure 3: The TheraSeed200 is composed of two graphite cores (green) coated in radioactive Pd-103 separated by lead (red) surrounded by air (white) and encapsulated in titanium (blue).2.2.5 Source Dosimetry ParametersMany different parameters are used to relate the specifications of sources to useful dosimetrymetrics. These parameters are listed below:Air Kerma, Kδ : the kinetic energy released by photons in air per unit mass. The air kermais a commonly measured value since it involves measurement in air at relatively large distancesfrom the brachytherapy sources. This is simpler then measuring in clinically relevant conditions(water equivalent material at relatively short distances from the source). Air Kerma is in unitsof Gray (Gy), which is the same units as absorbed dose. However, kerma accounts for all energytransferred to charged and uncharged particles in the medium. Some of the transferred energy (likebremsstrahlung photons) may escape the medium and not contribute to absorbed dose.Air Kerma Rate, K˙δ : the air kerma per unit time. Air Kerma rate is in units of Gray persecond Gys . The air kerma rate is measured for point sources of given activity.Air Kerma Rate Constant, Γδ : source specific quantity relating the air kerma rate at a dis-tance, d, to the source activity.Γδ =d2AK˙δ (1)The air kerma rate constant is computed for each radionuclide from their emitted radiationspectra. Air kerma rate constant is given in units of Gy·m2s·Bq .8Reference Air Kerma Rate, RAKR: the air kerma rate at a distance of 1m away from thesource in air, corrected for air attenuation and scatter. Reference air kerma rate is in units of Gys at1m.Air Kerma Strength, SK: the air kerma rate at a distance, d, away from the source in vacuum.SK = K˙δ (d)d2 (2)The recommended units areU . Where 1U = 1µGy·m2hr =1cGy·cm2hr . SK is generally measured at adistance of 1m in which case the RAKR and SK are the same. SK will decay alongside the activityof the source by:SK (t) = SK0e−λ t (3)Where λ is the decay constant of the source, SK0 is the initial SK , and t is time (in seconds).2.2.6 TG43 Dose CalculationCurrent calculations of brachytherapy doses follow the recommendations of the American As-sociation of Physicists in Medicine’s (AAPM) Task Group 43 (TG43) protocol [14]. The TG43formalism links measurable source parameters like air kerma strength at 1m to dose to water atclinically relevant distances (on the order of cm). TG43 calculates dose to water which is assumedto be the same as dose to medium in clinical settings. In addition, the formalism assumes aninfinite water medium surrounding the sources. These assumptions were considered appropriatefor clinical settings since most soft tissues are water equivalent materials and radiation emitted bybrachytherapy sources have a relatively short range.2.2.6.1 TG43 Dose Rate in Water, D˙(r,θ)All parameters in the formalism are either measured or simulated for each brachytherapysource model. These parameters account for the effects of scatter, attenuation and absorptionby the source encapsulation and surrounding medium. The parameters use a geometry specifiedby figure 4 and allow calculation of dose rate in water to a point (Q(r,θ) in figure 4 ) for either apoint (equation 4 ) or line source (equation 5 ) by:D˙(r,θ) = SKΛGp (r)Gp (r0)gp (r)φan (r) (4)D˙(r,θ) = SKΛGL (r,θ)GL (r0,θ0)gL (r)F (r,θ) (5)With r0 and θ0 specified by figure 4 , the product of SkΛ giving the dose rate at the dosenormalization point for a source with an air kerma strength of Sk, G adjusts the dose rate for9Figure 4: Standardized representation of the cylindrical source geometry use in TG43.inverse square fall-off, g for scatter and absorption effects, and φ/F for anisotropy. More detail oneach parameter can be found in TG43 [14] .2.2.6.2 TG43 Dose in Water, D(r,θ):The dose in water to a point (Q(r,θ)) is calculated by integrating either equation 4 or 5 withSK specified by equation 3 for either a point (equation 6 ) or line (equation 7 ) source model overthe entirety of the treatment time, T :Dp (r,θ ,T ) =T0SK0e−λ tΛGp (r)Gp (r0)gp (r)φan (r)dt (6)=SK0λ(1− e−λT)ΛGp (r)Gp (r0)gp (r)φan (r)DL (r,θ ,T ) =T0SK0e−λ tΛGL (r,θ)GL (r0,θ0)gL (r)F (r,θ) (7)=SK0λ(1− e−λT)ΛGL (r,θ)GL (r0,θ0)gL (r)F (r,θ)Brachytherapy treatments typically consist of multiple sources. Since the TG43 formalismassumes infinite water medium surrounding each source, the effects of interseed attenuation cannotbe accounted for and instead the total dose to a point, DQ, is calculated by a superposition ofthe dose calculated for each source individually. It is possible for sources to have different SK ,accounted for in the sums below with SK0i.10DQ,p =n∑i=1SK0iλ(1− e−λT)ΛGp (ri)Gp (r0)gp (ri)φan (ri) (8)DQ,L =n∑i=1SK0iλ(1− e−λT)ΛGL (ri,θi)GL (r0,θ0)gL (ri)F (ri,θi) (9)Where n = the number of sources. Equations 8 and 9 are the cumulative doses to a point Qtaking either a point or line model for sources. This calculation is repeated at points of interestaround the sources to construct a dose distribution with values for radial dose and anisotropyparameters interpolated depending on the desired dose resolution. The dose distribution can beadjusted to meet desired clinical goals as we will see in the next section.2.2.7 LDR Breast and Prostate Brachytherapy WorkflowThe clinical workflow for performing LDR breast or prostate brachytherapy will be differentfor centres around the world. However, there are commonalities in the key aspects of the workflowand those will be explained in the following subsections. The workflow will follow a LDR prostatetreatment with specifics or differences in breast LDR treatments mentioned when needed.2.2.7.1 Pre-Operation Imaging and ContouringPrior to any seed implantation, the target volumes as well as any critical structures need tobe determined. For prostate LDR treatments the pre-operation imaging that determines these vol-umes is transrectal ultrasound (US). The structures that are visible on the resulting images arethe prostate, urethra and rectum. In treating prostate cancer, the goal is to irradiate the cancerousvolume of the prostate. However, the urethra is very sensitive to ionizing radiation so dose to thiscritical structure must be minimized. For this reason the prostate and urethra need to be defined onthe US images. Often a clinician defines these structures through drawing their outlines on the im-ages. These lines are referred to as contours. The prostate is contoured in its entirety and becausethis is the target volume for the clinical treatment it is also called the clinical target volume (CTV).There are uncertainties in location of these contoured structures that arise from uncertainty in de-lineating structures from normal surrounding tissue, anatomical variation in positioning, and otherfactors. In order to account for these uncertainties a margin around the CTV is also contoured.This margin is called the planning target volume (PTV) and is the final target that must be covered.The final structure contoured on these US images is the urethra. The resultant pre-operation USwith clinician drawn contours is shown in figure 5. The rectum is visible on US but may not becontoured, the plans are manually optimized so clinicians avoid putting seeds close to it.11Figure 5: A pre-operation US with clinician drawn contours for target and critical structures intreatment of the prostateFor breast treatments a pre-operation computed tomography (CT) scan is conducted as opposedto US although US may be used to aid in contouring the seroma, a cancerous, fluid-filled regionpost-surgical extraction of a cancerous tumour. The seroma is the CTV in breast treatments. ThePTV is similarly a 1.5cm margin around this CTV. In addition to these treatment volumes, organsat risk (OARs) such as the skin, ribs, heart and lung are also contoured. It is important to note thatdifferent clinics will have different names and classifications for the target volumes in addition tousing different margins around these volumes.2.2.7.2 Treatment PlanningAfter contouring an US or CT image of a patient, the amount and coverage of the desired radia-tion to the target volumes needs to be determined. This process is referred to as treatment planningand the computer programs used for this are referred to as treatment planning systems (TPS). For12Table 2: Example planning goals for target coverage and OARs in LDR brachytherapy treatmentof prostate cancer [2] .Structure Standard Goal AcceptableProstate V100 ≥ 99%56%≤V150 ≤ 65%V200 ≤ 22%PTV V100 ≥ 98% V100 ≥ 97%50%≤V150 ≤ 60%V200 ≤ 21%Urethra or central area sparing Dmax ≤ 130%RxLDR prostate brachytherapy patients in this thesis, the TPS VariSeed (version 9.0, Varian MedicalSystems Inc., Palo Alto, CA) was used and MIM Symphony (version 6.9.5, MIM Software Inc.,Cleveland, OH) was used for breast LDR brachytherapy patients in this thesis. For these treatmentsseeds of a known model ( 2.2.4 ) and air kerma strength ( 2.2.5 ) are manually or automaticallydistributed throughout the treatment volume. The dose deposited by these seeds is determinedthrough equation 9 and a resulting dose distribution is created. This dose distribution can be ad-justed for target coverage or critical structure sparing by changing seed numbers, locations, or airkerma strength.The goal of treatment planning is to produce a dose distribution that meets certain dose metrics(sometimes referred to as clinical goals). Priorities can also be assigned for these clinical goalsin creating potential treatment plans. These plans attempt to balance fully covering the targetcancerous volumes with the prescription dose (Rx) while limiting the dose to surrounding healthytissue. Some example planning goals used in LDR prostate and breast brachytherapy treatmentsare shown in tables 2 and 3 respectively.Table 3: Example planning goals for target cover and the most important OAR, skin, in LDRbrachytherapy treatment of breast cancer [3] .Structure Standard GoalCTV V100 = 100%PTV V100 > 95%V150 : 50−70%V200 < 25%Skin D0.5cm3 < 90% RxOnce the clinical goals are achieved within a clinically relevant range, the plan is accepted,the seeds are ordered and ready for surgical insertion. The pre-operation treatment plan on thecontoured US is shown in figure 6 .13Figure 6: A pre-operation LDR prostate brachytherapy treatment planned on VariSeed2.2.7.3 Source InsertionFor LDR prostate treatments, brachytherapy sources are surgically inserted interstitially (see2.2.1) under the guidance of US. The purpose of the realtime surgical US is to align it with the pre-operation US. Once aligned, the doctor begins inserting needles containing the seeds to align asclose as possible to the planned locations. This insertion is done with the assistance of an insertiongrid (see figure 7 ) that is aligned to the US. Through the realtime surgical US, the inserted seed14locations can be seen and, if need be, the treatment plan can be adjusted if deposited seed locationsdiffer from the pre-operation plan. After all seeds have been inserted, the patient may remain in theclinic or hospital for a recovery time. Afterwards, the patients are sent home with the radioactivesources within their prostate. Patients may need to avoid contact with radiosensitive members ofthe public like pregnant women until the sources have sufficiently decayed.Figure 7: A grid template for interstitial brachytherapy implantsFor LDR breast treatments, source insertion is similar to the prostate with insertion grids andUS guidance. However, since treatments are planned on CT instead of US there is a greater degreeof uncertainty in source locations in breast treatments. As such, on the same day of surgery thepatient undergoes a day-zero CT scan to verify the location of inserted seeds. Due to this discrep-ancy in imaging modalities the prospect of 3D US to increase the accuracy of source insertions isbeing investigated but has not yet been put into clinical practice.2.2.7.4 Follow-upOne month after surgical brachytherapy insertion, the patient returns for followup imaging,and dosimetric and clinical assessment. A post-operation CT scan is performed with which theseed locations and the urethra (if a catheter is used) can be visualized, this CT image set is referredto as the day-30 CT scan. CT provides excellent resolution of structures which attenuate photons15(like the radioactive seeds). However, it can be be difficult to resolve soft-tissue structures (likethe urethra if no contrast is used) so the post-operation CT is sometimes supplemented with amagnetic resonance imaging (MRI) scan. MRI has excellent soft-tissue contrast and can used tohelp clinicians contour soft-tissue structures.In order to calculate the dosimetry of the patient, the seed locations relative to target and criticalstructures need to be determined. CT scans can be aligned and fused with MRI images. On thesefused images the clinician can contour prostate, rectum, bladder and urethra (if visible). Withthe seed locations relative to the contoured structures dose distribution is re-calculated and theachieved dosimetry goals are evaluated. Sample post-operation dosimetry goals are summarized intable 4 . Further clinical intervention could be necessary depending on this final dosimetry, but thisis very rare. For prostate, the D90 and V100 of the target are the main criteria in evaluating a post-operation plan, with the other metrics being supplemental. In addition to the dosimetric evaluation,the doctor clinically evaluates the symptoms of the patient. Patients can be subsequently reviewedat certain time periods post-operation.Table 4: Example post-operation dosimetry goals for the breast and prostate [2] . In the rare casethat the pass criteria is not met the patient may be eligible for further clinical intervention.Structure Pass CriteriaBreast ETV V90 > 90%Breast OARs dose as low as possibleProstate 130Gy≤ D90 ≤ 200GyV100 ≥ 100%40%≤V150 ≤ 70%10%≤V200 ≤ 35%For breast LDR treatments the outlined workflow is similar, however, in addition to the day 30post-operation CT scan, a day-0 CT scan is conducted after surgery since the original treatmentis planned on CT instead of US. The 30-day CT images are used to monitor the effects of seeddisplacement of the dosimetry of the treatment. The two CT scans are evaluated dosimetricallyand patient symptoms are as well. All clinics will have different patient follow-ups and clinicalintervention but the general workflow for both LDR prostate and breast brachytherapy has beenoutlined.2.3 Model-based dose calculation algorithmsThe limitations of current dose calculation practices under TG43 recommendations are assum-ing dose deposited to an infinite water medium and neglecting the effects of interseed attenuation.Model-based dose calculation algorithms (MBDCAs) allow for a more accurate calculation of dosethrough remedying these two limitations. A MBDCA utilizing the Monte Carlo method and thebackground of it are outlined below.162.3.1 Monte-CarloThe Monte Carlo (MC) method [15] is the estimation of an expected outcome of a stochasticprocess through sampling the process’s governing probability densities. This project is concernedwith the deposition of dose which arises from the stochastic processes governing photon trans-port through a medium. For the MC method to be applicable, accurate probability densities arerequired. The probability densities governing photon transport have been greatly studied and arereadily available.2.3.2 egs_nrcThe electron gamma shower (egs) MC code developed by the National Research Council ofCanada (nrc) [16] is called egs_nrc. This code contains the cross-sections and interaction andtransport methods required to simulate radiation transport. egs_nrc has an application called gwhich calculates a variable g = average fraction of kinetic energy lost to radiative events for pri-mary photon interactions. Or this application can calculate the radiative yield, Y , for slowing downcharged particles beams. In addition to these g also calculates the kerma, K, collision kerma, Kcol ,energy fluence averaged mass-energy transfer coefficient, µtrρ , and the energy fluence averagedmass-energy absorption coefficient,µenρ .2.3.3 egs++egs++ [16] is an application made for egs_nrc which contains geometry and source packagesin addition to further application making classes. egs++ allows for the use of more complex ge-ometries such as a rectilinear phantom from a CT dataset called an egsphant. This allows for doseor collision kerma to be scored in rectilinear voxels or in spherical or cylindrical shells if thatgeometry is desired. In terms of source packages, egs++ allows for different geometries of theradioactive part of the source, altering the shape of radiation into cone or spherical shapes. Finally,egs++ allows for future geometry or source packages to be created through its application mak-ing classes. One such application is egs_brachy which introduces packages for particle transportspecific to brachytherapy treatments.2.3.4 egs_brachyegs_brachy [17] is a brachytherapy specific application which uses egs++ and egs_nrc to sim-ulate radiation transport from radioactive seeds. egs_brachy includes unique source models, dosescoring mechanisms and simulation run modes.The brachytherapy source models allow source particles to be created at the surface of theseed. This saves time since particles absorbed in the source are skipped. And, if desired, othersources in a medium can be ignored. egs_brachy also includes the application egs_AutoEnvelope.17This application allows placement of copies of source geometries throughout the phantom. Sincebrachytherapy seeds often are all the same model for a given treatment, this application saves gen-erating source models redundantly. Lastly, egs_brachy also allows for particle recycling. Sourceswith the same model do not need to repeat the simulation of particles. Instead, particles generatedin the first simulated source are translated and reinitiated at the other source locations at the samerelative position. Upon multiple recycles of particles, the reinitiation location is optimally rotatedabout the source axis. Particle recycling saves the time required for particle generation.One of the key features egs_brachy employs is the track-length estimator. This estimator usesthe fact that at low photon energies, dose is approximately equal to collision kerma through assum-ing charged particle equilibrium. This allows for the track-length estimator to calculate collisionkerma and subsequently dose, D, by:K jcol =∑iEiti(µenρ)iVj= D j (10)where Ei = energy photon traversing voxel, Vj = voxel volume and ti = track-length of photonthrough voxel, are all known quantities, only leaving(µenρ)i, which can be calculated with egs_nrcapplication ’g’. These can be efficiently calculated when g is low which is true when photon en-ergy is low. The track-length estimator was proven by Williamson in 1987 [18] to be accurate andefficient. The use of the track-length estimator saves time and computing power. If no charged par-ticle equilibrium exists the code can still be run to inefficiently calculate dose through interactionscoring.One of the final unique features of egs_brachy is the variety of simulation run modes. egs_brachyallows for either normal or superposition run modes. Normal mode simulates all source locationsat the same time, which accounts for the effects of interseed attenuation. Superposition mode al-lows only one seed active at a time to ignore interseed effects. Superposition mode is useful forsimulating HDR treatments or TG43-like conditions.2.3.5 eb_guiThe egs_brachy code can be accessed through an open-source program called eb_gui (egs_brachygraphical user interface). eb_gui allows for the fast MC code to interface with clinical TPSs andassociated commissioning procedures. The gui converts DICOM files to egs_nrc formats to runegs_brachy automatically. CT images along with clinician drawn contours (RtStruct) and the seedlocations (RtPlan) build egs_brachy virtual patient models and source locations. Tissue densitiesare taken from CT densities through tissue assignment schemes and CT calibration files. Thisalso allows automatic assignment of calcifications which can be visualized through an applicationcalled egs_view. Finally DVHs and dose distributions can be exported and analyzed. With theeffects of tissue density assignments and interseed attenuation accounted for, the dose calculated18by eb_gui will be different than that calculated currently in TPSs.2.3.5.1 Virtual Patient ModelThe virtual patient model (VPM) created by eb_gui uses the three DICOM inputs alongsidelook-up tables to assign materials to voxels of the model. The workflow for this creation processis displayed in figure 8 .Figure 8: Workflow for eb_gui tissue assignmentThe voxel resolution of the VPM is determined from the resolution of the CT images (generally512 x 512 x number of slices pixels) and each voxel is assigned a material type depending on theCT number of the corresponding pixel as well as the assigned structure of the voxel. For example,in a breast patient the default tissue assignment would assign generic female tissue, air or corticalbone to the treatment area. However, with the presence of the breast contour, the program insteadassigns either adipose, glandular tissue or calcification. Similar assignment schemes can be seenfor certain contours like the ribs. For voxels with overlapping structure contours, priority needs tobe given to which structure the voxel will be assigned. A sample tissue priority chart with possibleassigned tissues is given in table 5 .This CT number based material assignment is able to detect and classify calcifications withinthe patients which can be challenging to do by visual inspection of CT scans.Superimposed on the voxel assignments are the brachytherapy seeds. These seeds have specifi-cations and material assignments extracted from the RtPlan file. For example the Pd-103 wrappedTheraSeed-200 has two graphite cores covered in a thin layer of palladium separated with a leadspacer and surrounded by air before being encapsulated by titanium. The seeds are also wrappedin a thin layer of water in the program (not found physically) to prevent geometry errors that canarise due to the overlap of seeds with voxels. eb_gui also allows for metallic artifact reduction19Table 5: Sample contour priorities, with higher contours taking a higher priority in tissue assign-ment alongside possible assigned tissuesBreast ProstateCTV: adipose, gland, calcification Urethra: urethraETV: adipose, gland, calcification Prostate: prostate, P50C50, calcificationPTVs: adipose, gland, calcification Rectum: rectumSkin: skin, air Bladder: bladderBreast: adipose, gland, calcification others: male soft tissue, cortical bone, airHeart: heartLung: lung, airRibs: cortical bone, red marrow, yellowmarrowChest: adipose, muscle, cortical bone,cartilageBody: female soft tissue, air, cortical boneothers: female soft tissue, air, cortical bonearound the seeds, this reduces shadowing artifacts that would otherwise affect tissue assignmentsbased on CT number. A sample breast patient VPM is shown in figure 9 .Figure 9: Sample breast patient VPM highlighting material assignment, a superimposed Pd-103seed is shown in large to highlight seed material assignment2.3.6 TG186 RecommendationsAAPM Task-group 186 [19] (TG186) provides guidance for the adoption of MBDCAs in thetransition away from TG43 based dose calculations in brachytherapy. TG186 addresses new com-20missioning processes through literature review and recommendations for maintaining uniformityacross different centres and institutions. TG186 also highlights needed areas of research to obtaindata required for full implementation of MBDCAs. The research presented in this thesis addressesthe two-step commissioning process outlined in TG186 of reproducing TG43 dose parameters aswell as testing the advanced capabilities of the MBDCA egs_brachy through eb_gui.213 MethodsThe goal of this project is to investigate the potential differences in current water-based dosecalculation methods to more sophisticated MC simulation based dose calculation methods. A myr-iad of different treatment planning softwares are available for current calculations, however eb_guiallows for water-based MC simulations in addition to MC simulations with tissue assignment andconsidering interseed effects. Simulating the current standard alongside the new methodologyallows for eb_gui to calculate dose distributions, DVHs, and DVH metrics for both in the sameformat allowing for simpler comparisons between them.For clarity three different dose distributions are calculated and compared in this thesis: 1)TPS calculated dose distributions according to TG43, the current standard, will be referred to asTG43TPS 2) eb_gui calculated dose distributions with water assigned voxels ignoring interseedeffects, MC simulation with TG43 conditions, will be referred to as TG43MC 3) eb_gui calculateddose distributions with tissue assigned voxels considering interseed effects, MC simulation withTG186 conditions, will be referred to as TG186MC.Prior to running MC simulation of dose calculation, the accuracy of eb_gui needs to be verified.The verification goals are twofold: 1) for MC calculated dose distributions with TG43 conditions(TG43MC) to not be significantly different than current calculation methods and 2) to find anadequate number of simulated histories for goal 1 to be true. Water-equivalent MC not signif-icantly differing from TG43 in DVHs quantified by their respective DVH metrics would verifythe accuracy of the water-equivalent MC simulation in calculating DVHs. In addition to verifyingeb_gui, an appropriate number of simulated photons (histories) is also determined. This number isdetermined to account for simulation time and through analyzing the clinical DVH results.Verifying the accuracy of the material-assigned MC is outside the scope of this project. Theverification is being performed by other members of this CIHR collaboration group but this hasnot yet been published. The verification methodology involves comparisons of eb_gui calculateddose distributions to those calculated by other MC methods. For full commissioning of eb_gui, thedoses calculated should be verified empirically in the future.After verification of eb_gui, DVH metrics extracted from material-assigned MC are comparedto water-equivalent MC over patient cohorts of 76 and 80 for prostate and breast LDR brachyther-apy treatments.3.1 Verifying eb_guiTen breast patient’s day-0 and ten prostate patient’s day-30 post-operation CT images with thecorresponding DICOM plan, and structures were imported into eb_gui. The creation of the VPMsfor each case was verified through egs_view, a program within eb_gui that allows for visualizationsof VPMs. The verification involved visualizing correct tissue assignments for expected contours.Numbers of histories to be tested were set to[107,108,109,1010]. For the prostate patients the22source model was the wrapped AgX-100 I-Seed(125I) with air kerma strengths ranging from 0.354to 0.493U . For the breast patients the source model was the wrapped TheraSeed-200(103Pd) withair kerma strengths ranging from 2.3 to 2.8U . Water-equivalent MC were calculated for each caseat each history number and the DVHs and dose metrics were extracted. The DVHs were comparedwith a Wilcoxon test. These comparisons were used to determine an adequate number of historiesfor the MC simulation. Then the metrics for the adequate number of histories were compared toTPS calculated values. The DVH metrics were compared for the bladder (D1cm3,D2cm3), CTV(D90,D99,V100,V150,V200), rectum (D0.1cm3,D1cm3,D2cm3) and urethra (D0.1cm3,D1cm3,Dmax) forone sample prostate case against the DVHs calculated by the TPS of VariSeed. For the breast casesthe metrics of breast (D1cm3,V150), CTV (D90,V100,V150,V200), ETV (D90,V90,V100,V150,V200),heart (D1cm3), lung (V5), ribs (Dmax) and skin (D0.2cm3,D0.5cm3,D1cm3) were compared againstMIM Symphony. A Wilcoxon rank sum test was run to compare water-equivalent MC and TG43dose metrics for each treatment location.In order for the urethra to be contoured it needs to be visible on CT scans. This is achievedthrough insertion of a catheter into the urethra prior to scanning the patient. For this patient cohortone patient did not have a catheter inserted, meaning DVH comparisons for the urethra only useda patient cohort of 9.3.2 Dosimetric Analysis76 prostate and 80 breast patients were imported into eb_gui with VPMs verified throughegs_view and number of histories set to 108. All seed models and air kerma strength rangeswere the same as in the verification step. Dose distributions were calculated for each case for twosituations: i) TG43-like conditions, (TG43MC) and ii) considering tissue assignment and interseedeffects (TG186MC). DVHs and dose metrics were extracted for both (using the same metrics asin the verification step). The metrics for the two situations were compared for each structureacross the patient cohorts by calculating median and IQR of the data set. A Wilcoxon ranksumtest was run to test the significance of the differences in the dose metrics for each structure. 21prostate patients did not have a visible urethra on post-operation CT images meaning dose metriccomparisons for the urethra were conducted with a patient cohort of 55. 9 patients had boosttreatments instead of monotherapy meaning the prescription dose for these patients was 110 Gyinstead of 144 Gy. This difference in prescription dose will effect the absolute dose received bythe prostate structures meaning the Dx metrics will be affected. As such the Dx metric calculationswere conducted with a patient cohort of 67 (50 for urethra as 4 boost patients had no visibleurethra).234 Results4.1 Verifying eb_guieb_gui calculated dose distributions with water assigned voxels ignoring interseed effects(TG43MC) and TPS calculated dose distribution (TG43TPS) DVHs are shown for one exampleprostate patient in figure 10 and breast patient in figure 11 .Figure 10: Prostate structure DVHs for one sample patient for all simulated histories and TPScalculated24Figure 11: Breast structure DVHs for one sample patient for all simulated histories and TPS cal-culatedFor the larger volume prostate structures (prostate, bladder and rectum), the water-equivalentMC DVHs do not significantly differ (p> 0.9). Only in zooming in on the DVHs are any devi-ations visualized with the 107 water-equivalent MC simulation. With the small volume structure(urethra) the deviations of the 107 water-equivalent MC simulation are more apparent. Over theentire DVH no significant difference is seen (p= 0.9), however, isolating the deviating regionsgives a significant difference between 107 and 108 histories (p= 0.003). No significant differenceis seen between the 108 and the higher history simulations for these same regions (p> 0.7).For the larger volume breast structures (CTV, ETV), all TG43 calculated DVHs do not signif-icantly differ (p> 0.9). For the small volume structure of the ribs, slight deviations of the 107simulation are seen but not significant (p> 0.9). For the skin, a resolution issue in how DVHsare calculated by eb_gui is shown. eb_gui calculates DVHs for resolution based on volumetricdifferences whereas the TPS, MIM Symphony calculates DVHs based on absolute dose intervals.However, this resolution difference does not impact the standard dose metrics extracted from theDVHs.Based on the quantitative analysis of differences in DVHs of the two sample patients 108 his-tories was selected as adequate for DVH comparison. The adequacy of 108 is important due to the25time required for the MC simulations to run (see table 6 ). For 109 and1010 simulations the timerequired for the MC calculation of dose is on time scales which would be impractical for use in theclinic.Table 6: Approximate simulation times for MC calculation of dose. Time scales for history numbergreater than 108 are not clinically applicable.Histories Time (Breast) Time (Prostate)107 5-15 mins 15-30 mins108 20-40 mins 40-80 mins109 2-4 hrs 3-6 hrs1010 20-40 hrs 1-3 daysSome example water-equivalent MC calculated DVH metrics with 108 histories versus TG43calculated ones are shown in figures 12 and 13 for the breast cohort and in figure 14 and 15 for theprostate cohort. No significant difference is seen for all the volume metrics of the targets nor inthe dosimetric indices of the skin. As such, for determination of clinically relevant DVH extractedparameters eb_gui using 108 histories is equivalent to VariSeed and MIM Symphony.Figure 12: Breast target DVH metrics for verification cohort, TG43 IQR are in black with medianvalue in orange. Water-equivalent MC IQR are in blue with median value in red. No significantdifferences between TG43 and water-equivalent MC were observed.26Figure 13: Breast OAR, skin, DVH metrics for verification cohort. TG43 IQR are in black withmedian value in orange. Water-equivalent MC IQR are in blue with median value in red. Nosignificant differences between TG43 and water-equivalent MC were observed.Figure 14: Prostate target DVH metrics for verification cohort. TG43 IQR are in black with medianvalue in orange. Water-equivalent MC IQR are in blue with median value in red. No significantdifferences between TG43 and water-equivalent MC were observed.27Figure 15: Prostate urethra DVH metrics for verification cohort. TG43 IQR are in black withmedian value in orange. Water-equivalent MC IQR are in blue with median value in red. Nosignificant differences between TG43 and water-equivalent MC were observed.4.2 Dosimetric Analysiseb_gui calculated dose distributions with tissue assigned voxels considering interseed effects(TG186MC) and with water assigned voxels ignoring interseed effects (TG43MC) calculated DVHvolume metrics for the breast target volumes are shown in figure 16. Material-assigned MC andwater-equivalent MC calculated DVH dose metrics for one breast OAR, the skin, are shown infigure 17 . Median and IQR for all tested metrics and structures over the 80 breast patients aresummarized for the target volumes in table 7 and for OARs in table 8 . Results are significantlylower for the material-assigned MC calculated breast target metrics and significantly higher forall material-assigned MC calculated OAR metrics compared to water-equivalent MC simulatedvalues. The largest significant differences in target median values between material-assigned MCand water-equivalent MC is seen in the CTV and ETV V200’s of -37.7 and -56.4% respectively.The largest significant differences in OAR median values is seen in the ribs Dmax of 83.4% and theheart D1cm3 of 85.7%. Also, of note are the skin D0.2cm3 , D0.5cm3 and D1cm3 differences of 20.3,22.1 and 18.5% respectively.28Figure 16: Breast target DVH volume metrics. Water-equivalent MC results IQR are in blue withmedian value in red. Material-assigned MC results IQR are in purple with median value in green.Results with *’s were significantly different in a Wilcoxon test.Table 7: Breast target metric median and IQR for water-equivalent MC (TG43MC) and material-assigned MC (TG186MC) simulations. All differences were significant in a Wilcoxon test.CTV ETVMetrics D90 V100 V150 V200 D90 V90 V100 V150 V200MedianTG43MC125.5 99.9 83.1 42.7 102.3 96.5 94.1 72.3 39.1MedianTG186MC115.6 98.9 74.6 31 87.2 93.2 88.8 56.6 25p-value 0.03 0.003 0.01 0.0006 0.0002 0.001 0.0005 5×10−7 4×10−9Median %difference-8.6 -1 -11.4 -37.7 -17.3 -3.5 -6 -27.7 -56.4IQRTG43MC36.9 4.3 27.9 26.9 33.7 7.9 11.3 23.4 15.8IQRTG186MC33 6 29.8 22.8 25.4 11.5 15 22.4 11.529Figure 17: Breast skin DVH dose metrics. Water-equivalent MC IQR are in blue with medianvalue in red. Material-assigned MC IQR are in purple with median value in green. Results with*’s were significantly different in a Wilcoxon test.Table 8: Breast OAR metric median and IQR for water-equivalent MC (TG43MC) and material-assigned MC (TG186MC) simulations. All differences were significant in a Wilcoxon test.Breast Ribs Skin Heart LungMetrics D1cm3 V150 Dmax D0.2cm3 D0.5cm3 D1cm3 D1cm3 V5MedianTG43MC636.5 4 87.5 44.7 39.4 35.6 0.2 3.4MedianTG186MC449.1 4 527.6 56.1 50.6 44.8 1.4 5.1p-value 1×10−25 6×10−10 5×10−18 0.04 0.02 0.01 2×10−7 0.0001Median %difference-41.7 0 83.4 20.3 22.1 18.5 85.7 33.3IQRTG43MC83.9 1.9 78.4 35.4 30.9 25.7 1.1 2.6IQRTG186MC54.1 1.4 419.1 36.7 31.1 27.3 3.4 4.9Material-assigned MC and water-equivalent MC calculated DVH volume metrics for the prostateare shown in figure 18. Material-assigned MC and water-equivalent MC calculated DVH dose30metrics for one prostate OAR, the urethra, are shown in figure 19 . Median and IQR for all testedmetrics and structures over the 76 prostate patients (55 for the urethra) are summarized for theprostate in table 9 and for OARs in table 10 . All material-assigned MC calculated prostate met-rics except V200 were significantly lower than water-equivalent MC values. For OARs only thematerial-assigned MC calculated urethra D0.1cm3 was significantly lower than the water-equivalentMC values. The largest significant differences in target median values between material-assignedMC and water-equivalent MC is seen in the prostate V150 of -11.9%. The largest significant differ-ences in OAR median values is seen in the urethra D0.1cm3 of -6.3%.Figure 18: Prostate target DVH volume metrics. Water-equivalent MC IQR are in blue with medianin red. Material-assigned MC IQR are in purple with median in green. Results with *’s weresignificantly different in a Wilcoxon test.31Table 9: Prostate metric median and IQR for water-equivalent MC (TG43MC) and material-assigned MC (TG186MC) simulations. Metric differences with an * were significant in a Wilcoxontest.ProstateMetrics D90∗ D99∗ V100∗ V150∗ V200Median TG43MC 157 117.3 94.6 52.5 21.5Median TG186MC 144.7 107.1 90.6 46.9 19.8p-value 0.0005 0.001 6×10−5 0.004 0.1Median % difference -8.5 -9.5 -4.4 -11.9 -8.6IQR TG43MC 21.1 24.2 11.2 41.6 62.2IQR TG186MC 21 22.9 9.3 40.5 58.9Figure 19: Prostate urethra DVH dose metrics. Water-equivalent MC IQR are in blue with medianin red. Material-assigned MC IQR are in purple with median in green. Results with *’s weresignificantly different in a Wilcoxon test.32Table 10: Prostate OAR metric median and IQR for water-equivalent MC (TG43MC) and material-assigned MC (TG186MC) simulations. Metric differences with an * were significant in a Wilcoxontest.Urethra Rectum BladderMetrics D0.1cm3∗ D1cm3 Dmax D0.1cm3 D1cm3 D2cm3 D1cm3 D2cm3MedianTG43MC208.8 136.3 265 147.4 108.5 86.9 86.8 74.2MedianTG186MC196.4 131 254.8 138.5 99.8 80.6 86.2 72.6p-value 0.02 0.2 0.4 0.2 0.08 0.08 0.8 0.8Median %difference-6.3 -4 -4 -6.4 -8.7 -7.8 -0.7 -2.2IQRTG43MC41.6 62.2 98.1 54.1 35.9 33.9 26.8 22.2IQRTG186MC40.5 58.9 109.2 51.3 33.7 30.8 29.1 26.4335 DiscussionIn this retrospective study of LDR brachytherapy for breast and prostate cancer differences indose metrics between current water based and investigated tissue-based calculation methods areseen. These metrics are very important in creating and evaluating clinical treatment plans. Inaddition, the tissue-based calculation program eb_gui was assessed for balancing dose calculationaccuracy with clinical time constraints. The results in this thesis motivate the adoption of tissue-based dose calculation methods in the clinic.The decision for 108 histories was motivated through statistical uncertainties present in thesmall volume structure of the urethra. These uncertainties were not visualized in the breast pa-tients but 108 histories were used for consistency. The statistical uncertainties seen arise fromthe number of histories, the number of brachytherapy sources and the size of voxels in the VPMs.Voxel size comes from CT pixel sizes which for the breast were 0.98×0.98mm and for the prostatewere 0.39×0.39mm. The smaller pixel (and subsequently voxel) sizes of the prostate are what con-tribute to the greater uncertainties per voxel which manifest in the smaller volume structures sincethere are less voxels in these structures. Number of seeds also impacts this statistical uncertaintybecause the same number of photons are simulated repeatedly for each seed. This means that sim-ulations with a larger number of seeds result in larger numbers of photons being simulated whichdecreases statistical uncertainty. For the prostate patients the average number of seeds was 89.7where for breast it was 75.3. The smaller seed number in the breast cases motivate the choice of108 histories, however as no significant difference was seen in the small volume structure of theskin between 107 and 108 histories, 107 may be sufficient in breast simulations.The criteria used evaluating post-operation dosimetry are ETV V90 > 90% and dose to OARsas low as possible. Median material-assigned MC results show a V90 that passes this criteria how-ever all doses to OARs (ribs, skin, heart, and lung) are higher than water-equivalent MC values.The results for the breast target volumes show a slight overestimation of dose by water-equivalentMC to the target volumes of 1% for the CTV V100 and 6% for the ETV V100 compared to the me-dian material-assigned MC results. The main reason for the decrease in target doses by material-assigned MC is due to the mass-attenuation properties of adipose tissue compared to water. Adi-pose tissue has a considerably lower mass-attenuation coefficient at the emission energy of Pd-103(20keV ) than water,(µρ)adipose= 0.5677 cm2g(µρ)water= 0.8096 cm2g [20], meaning less dose wouldbe deposited in equivalent volumes of adipose as compared to water. This results in a potentiallysignificant underestimation of dose by water-equivalent MC results for the skin D0.2cm3 of 20.3%compared to material-assigned MC. Material-assigned MC calculated skin dose is a consequenceof the decreased dose absorption in the target volumes. The unattenuated photons exit the targetvolumes and are either absorbed by the remaining breast tissue, skin, or escape. In addition, anunderestimation of dose to the heart, lungs and ribs are also seen in water-equivalent MC results,however, these findings are not as clinically significant due to the low absolute doses received by34the heart and lungs and the radio-resistant nature of the ribs. The increase in skin dose is of mostpotential clinical significance since adverse skin radiation effects may be more severe due to thehigher doses incurred.Comparing these results to other literature, Miksys et al. [21] using patient-specific MC dosecalculations, material-assigned MC, for Pd-103 permanent implant breast brachytherapy foundthe same underestimation of target dose with overestimation of skin dose compared to water-equivalent MC. The PTV (named ETV in this thesis) D90 difference between water-equivalentMC and material-assigned MC was -11% on average, and the skin D1cm3 difference was 29% onaverage. These findings are lower than those in this thesis due to the paper investigating differentmetallic artifact removal and tissue assignment schemes in creation of VPMs. Afsharpour et al.[22] using different breast modeling schemes calculated dose to medium target values of D90. Twoof the modeling schemes, uniform water breast and segmented breast tissue, are similar to themodels examined in this thesis of water-equivalent MC and material-assigned MC. The differencein the dose to medium, material-assigned MC, D90 was -19.7% compared to water-equivalent MC,slightly larger than that found in this thesis.The main criteria used in evaluating post-operation prostate dosimetry are 130Gy ≤ D90 ≤200Gy and V100 = 100%. Material-assigned MC results show a D90 that passes this criteria how-ever both material-assigned MC and water-equivalent MC results show a V100 that does not pass.The water-equivalent MC results for the prostate target volumes show an overestimation of doseto the target volume of 4.4% for the CTV V100 compared to the material-assigned MC results. Thedecrease in the target doses is most likely due to dose shadowing by the brachytherapy seeds orpotential calcifications within the prostate. These regions absorb more dose in the prostate but de-crease photons available to deposit dose elsewhere in the prostate. If the entire region was water,the dose distributions would be uniform, but the small, highly attenuating regions affect the dosecoverage of the target region. This effect is seen to a greater extent in the prostate than the breastdue to a higher number of brachytherapy sources used and potential for high density calcifiedregions. Decreases in dose metrics for the urethra, bladder and rectum follow the dose shadow-ing decreases in the prostate. The only potentially clinically significant result for an OAR is theurethra D1cm3 showing an overestimation of dose of 6.3% by water-equivalent MC. From these re-sults, better dosimetric target coverage may be possible with tissue-based planning considerationsin material-assigned MC.Comparing these results to other literature, Miksys et al. [23] using patient-specific MC,material-assigned MC, dose calculation through EGSnrc BrachyDose [24] for I-125 permanentimplant prostate brachytherapy found the same underestimation of target dose compared to water-equivalent MC. The CTV D90 difference between water-equivalent MC and material-assigned MCaveraged -5.9% and the V100 difference averaged -2.6%. This patient cohort was identified aswithout visible calcifications. The presence of calcifications was seen to lower the D90 by up to25%. The data found in this thesis combines patients with and without calcifications leading to35the higher average differences in the two simulations. Haidara et al. [25] found CTV D90 and V100lower by 2.9 and 2% respectively with urethra D1cm3 lower by 2.8%. These numbers are lower thanthose found in this thesis which could be as a result of different VPM constructions from differentCT imaging procedures, however, the overall patterns of dose underestimated to the all prostatestructures is seen in this thesis and similar literature.The dosimetric analysis conducted in this thesis is part of a larger collaborative project underthe CIHR. Different centres across Canada conducting this dosimetric analysis will combine theirfindings alongside clinical outcome data for the patients. The dosimetric data may be correlatedwith known patient outcomes to motivate revisions for target doses and OAR thresholds along withthe adoption of MBDCAs in the clinic.366 ConclusionTo quantify the dosimetric effects of MC simulated dose calculation, material-assigned MC,to current water-based calculation methods, water-equivalent MC, a retrospective analysis of 76prostate and 80 breast patients was conducted.The results found in this thesis show a statistically significant underestimation of dose to targetvolumes in LDR brachytherapy treatments of both the breast and prostate in material-assignedMC simulations, dose calculation methods accounting for tissue inhomogeneities and interseedattenuation, compared with current TG43-based calculation methods, water-equivalent MC. Forthe main OAR in breast treatments, the skin, and the OARs of the ribs, heart and lung, a statisticallysignificant overestimation of the dose was seen. Only the main OAR in prostate treatments, theurethra, showed a statistically significant underestimation of dose.These results show a potentially clinically significant underestimation of breast skin dose incurrent TG43-based dose calculations. In addition, an overestimation of dose is seen in the urethraas well as target structures in both the breast and prostate. These results motivate the adoption ofMC dose calculation methods for LDR breast and prostate brachytherapy and the further analysisof their clinical importance.37References[1] Mayer C, Gasalberti DP, and Kumar A. Brachytherapy. StatPearls Publishing, 1 2023.[2] Mira Keyes, William James Morris, Ingrid Spadinger, Cynthia Araujo, Arthur Cheung, NickChng, Juanita Crook, Ross Halperin, Vince Lapointe, Stacy Miller, Howard Pai, and TomPickles. Radiation oncology and medical physicists quality assurance in british columbiacancer agency provincial prostate brachytherapy program. 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Thesis/Dissertation
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Haston, Christina
Xu, Yiwen
Investigation of a Monte Carlo model based dose calculation for Pd-103 low dose rate breast brachytherapy and I-125 low dose rate prostate brachytherapy
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