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Bowman W.A.,Dalhousie University | Robar J.L.,Dalhousie University | Robar J.L.,Nova Scotia Cancer Center | Sattarivand M.,Dalhousie University | Sattarivand M.,Nova Scotia Cancer Center
Medical physics | Year: 2017

PURPOSE: Stereoscopic x-ray image guided radiotherapy for lung tumors is often hindered by bone overlap and limited soft-tissue contrast. This study aims to evaluate the feasibility of dual-energy imaging techniques and to optimize parameters of the ExacTrac stereoscopic imaging system to enhance soft-tissue imaging for application to lung stereotactic body radiation therapy.METHODS: Simulated spectra and a physical lung phantom were used to optimize filter material, thickness, tube potentials, and weighting factors to obtain bone subtracted dual-energy images. Spektr simulations were used to identify material in the atomic number range (3-83) based on a metric defined to separate spectra of high and low-energies. Both energies used the same filter due to time constraints of imaging in the presence of respiratory motion. The lung phantom contained bone, soft tissue, and tumor mimicking materials, and it was imaged with a filter thickness in the range of (0-0.7) mm and a kVp range of (60-80) for low energy and (120,140) for high energy. Optimal dual-energy weighting factors were obtained when the bone to soft-tissue contrast-to-noise ratio (CNR) was minimized. Optimal filter thickness and tube potential were achieved by maximizing tumor-to-background CNR. Using the optimized parameters, dual-energy images of an anthropomorphic Rando phantom with a spherical tumor mimicking material inserted in his lung were acquired and evaluated for bone subtraction and tumor contrast. Imaging dose was measured using the dual-energy technique with and without beam filtration and matched to that of a clinical conventional single energy technique.RESULTS: Tin was the material of choice for beam filtering providing the best energy separation, non-toxicity, and non-reactiveness. The best soft-tissue-weighted image in the lung phantom was obtained using 0.2 mm tin and (140, 60) kVp pair. Dual-energy images of the Rando phantom with the tin filter had noticeable improvement in bone elimination, tumor contrast, and noise content when compared to dual-energy imaging with no filtration. The surface dose was 0.52 mGy per each stereoscopic view for both clinical single energy technique and the dual-energy technique in both cases of with and without the tin filter.CONCLUSIONS: Dual-energy soft-tissue imaging is feasible without additional imaging dose using the ExacTrac stereoscopic imaging system with optimized acquisition parameters and no beam filtration. Addition of a single tin filter for both the high and low energies has noticeable improvements on dual-energy imaging with optimized parameters. Clinical implementation of a dual-energy technique on ExacTrac stereoscopic imaging could improve lung tumor visibility. © 2017 American Association of Physicists in Medicine.


Churchill N.W.,Rotman Research Institute | Churchill N.W.,University of Toronto | Oder A.,Rotman Research Institute | Abdi H.,University of Texas at Dallas | And 10 more authors.
Human Brain Mapping | Year: 2012

Subject-specific artifacts caused by head motion and physiological noise are major confounds in BOLD fMRI analyses. However, there is little consensus on the optimal choice of data preprocessing steps to minimize these effects. To evaluate the effects of various preprocessing strategies, we present a framework which comprises a combination of (1) nonparametric testing including reproducibility and prediction metrics of the data-driven NPAIRS framework (Strother et al. [2002]: NeuroImage 15:747-771), and (2) intersubject comparison of SPM effects, using DISTATIS (a three-way version of metric multidimensional scaling (Abdi et al. [2009]: NeuroImage 45:89-95). It is shown that the quality of brain activation maps may be significantly limited by sub-optimal choices of data preprocessing steps (or "pipeline") in a clinical task-design, an fMRI adaptation of the widely used Trail-Making Test. The relative importance of motion correction, physiological noise correction, motion parameter regression, and temporal detrending were examined for fMRI data acquired in young, healthy adults. Analysis performance and the quality of activation maps were evaluated based on Penalized Discriminant Analysis (PDA). The relative importance of different preprocessing steps was assessed by (1) a nonparametric Friedman rank test for fixed sets of preprocessing steps, applied to all subjects; and (2) evaluating pipelines chosen specifically for each subject. Results demonstrate that preprocessing choices have significant, but subject-dependant effects, and that individually-optimized pipelines may significantly improve the reproducibility of fMRI results over fixed pipelines. This was demonstrated by the detection of a significant interaction with motion parameter regression and physiological noise correction, even though the range of subject head motion was small across the group (≪ 1 voxel). Optimizing pipelines on an individual-subject basis also revealed brain activation patterns either weak or absent under fixed pipelines, which has implications for the overall interpretation of fMRI data, and the relative importance of preprocessing methods. © 2011 Wiley Periodicals, Inc.


Whelan T.J.,McMaster University | Olivotto I.A.,Tom Baker Cancer Center | Olivotto I.A.,Cancer Agency Vancouver Island Center | Parulekar W.R.,Queen's University | And 20 more authors.
New England Journal of Medicine | Year: 2015

Background Most women with breast cancer who undergo breast-conserving surgery receive wholebreast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. Methods We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodalirradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. Results Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P = 0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P = 0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P = 0.01) and lymphedema (8.4% vs. 4.5%, P = 0.001). Conclusions Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. © 2015 Massachusetts Medical Society.


Clemons M.J.,Ottawa Hospital Research Institute | Cochrane B.,McMaster University | Pond G.R.,McMaster University | Califaretti N.,Grand River Regional Cancer Center | And 9 more authors.
Breast Cancer Research and Treatment | Year: 2014

Biomarkers of bone turnover, including urine N-telopeptide (uNTx), have been used as surrogate measures of response to bone-targeted therapies. Vascular endothelial growth factor (VEGF) levels correlate with extent of bone metastases. We assessed whether vandetanib, an inhibitor of VEGF, epidermal growth factor receptor and RET signalling, improved uNTx response when added to fulvestrant (F) in breast cancer patients with bone metastases. Postmenopausal patients with bone predominant, hormone-receptor-positive metastatic breast cancer were randomised to F (500 mg IM days 1, 15, 29, then monthly) with either vandetanib (100 mg PO OD) (FV) or placebo (FP). The primary objective was uNTx response. Secondary objectives included PFS, OS, RECIST response, pain scores and toxicity. Sixty-one patients were allocated to FV and 68 to FP. Out of 127 analyzable patients, an uNTx response occurred in 66 % for FV and 54 % for FP (p = 0.21). No difference was detected between groups for PFS; HR = 0.95 (95 % CI 0.65-1.38) or OS HR = 0.69 (95 % CI 0.37-1.31). For the 62 patients with measurable disease, clinical benefit rates were 41 and 43 %, respectively (p = 0.47). Serious adverse events were similar, 3.3 % for FV versus 5.9 % for FP. Elevated baseline uNTx (>65 nM BCE/mmol Cr) was prognostic for PFS, HR = 1.55 (95 % CI 1.04-2.30) and for OS, HR = 2.32 (95 % CI 1.25-4.33). The addition of vandetanib to fulvestrant did not improve biomarker response, PFS or OS in patients with bone metastases. Baseline bone turnover was prognostic for PFS and OS. © 2014 Springer Science+Business Media.


Lee MacDonald R.,Dalhousie University | Thomas C.G.,Nova Scotia Cancer Center | Thomas C.G.,Dalhousie University
Medical Physics | Year: 2015

Purpose: To investigate potential improvement in external beam stereotactic radiation therapy plan quality for cranial cases using an optimized dynamic gantry and patient support couch motion trajectory, which could minimize exposure to sensitive healthy tissue. Methods: Anonymized patient anatomy and treatment plans of cranial cancer patients were used to quantify the geometric overlap between planning target volumes and organs-at-risk (OARs) based on their two-dimensional projection from source to a plane at isocenter as a function of gantry and couch angle. Published dose constraints were then used as weighting factors for the OARs to generate a map of couch-gantry coordinate space, indicating degree of overlap at each point in space. A couch-gantry collision space was generated by direct measurement on a linear accelerator and couch using an anthropomorphic solid-water phantom. A dynamic, fully customizable algorithm was written to generate a navigable ideal trajectory for the patient specific couch-gantry space. The advanced algorithm can be used to balance the implementation of absolute minimum values of overlap with the clinical practicality of large-scale couch motion and delivery time. Optimized cranial cancer treatment trajectories were compared to conventional treatment trajectories. Results: Comparison of optimized treatment trajectories with conventional treatment trajectories indicated an average decrease in mean dose to the OARs of 19% and an average decrease in maximum dose to the OARs of 12%. Degradation was seen for homogeneity index (6.14% ± 0.67%-5.48% ± 0.76%) and conformation number (0.82 ± 0.02-0.79 ± 0.02), but neither was statistically significant. Removal of OAR constraints from volumetric modulated arc therapy optimization reveals that reduction in dose to OARs is almost exclusively due to the optimized trajectory and not the OAR constraints. Conclusions: The authors' study indicated that simultaneous couch and gantry motion during radiation therapy to minimize the geometrical overlap in the beams-eye-view of target volumes and the organs-at-risk can have an appreciable dose reduction to organs-at-risk. © 2015 American Association of Physicists in Medicine.


Chytyk-Praznik K.,CancerCare Manitoba | Chytyk-Praznik K.,University of Manitoba | Chytyk-Praznik K.,Nova Scotia Cancer Center | Vanuytven E.,CancerCare Manitoba | And 5 more authors.
Medical Physics | Year: 2013

Purpose: Dosimetric verification of radiation therapy is crucial when delivering complex treatments like intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT. Pretreatment verification, characterized by methods applied without the patient present and before the treatment start date, is typically carried out at most centers. In vivo dosimetric verification, characterized by methods applied with the patient present, is not commonly carried out in the clinic. This work presents a novel, model-based EPID dosimetry method that could be used for routine clinical in vivo patient treatment verification. Methods: The authors integrated a detailed fluence model with a patient scatter prediction model that uses a superposition of scatter energy fluence kernels, generated via Monte Carlo techniques, to determine patient scatter fluence delivered to the EPID. The total dose to the EPID was calculated using the sum of convolutions of the calculated energy fluence distribution entering the EPID with monoenergetic dose kernels, specific to the a-Si EPID. Measured images with simple, square fields delivered to slab phantoms were validated against predicted images. Measured and predicted images acquired during the delivery of IMRT fields to slabs and an anthropomorphic phantom were compared using the χ-comparison for 3% dose difference and 3 mm distance-to-agreement criteria. Results: Predicted and measured images of the square fields with slabs in the field agreed within 2.5%. Predicted portal dose images of clinical IMRT fields delivered to slabs and an anthropomorphic phantom agreed with measured images within 3% and 3 mm for an average of at least 97% of the infield pixels (defined as >10% maximum field dose) for each case, over all fields. Conclusions: This work presents the first validation of the integration of a comprehensive fluence model with a patient and EPID radiation transport model that accounts for patient transmission, including complex factors such as patient scatter and the energy response of the a-Si detector. The portal dose image prediction model satisfies the 3% and 3 mm criteria for IMRT fields delivered to slab phantoms and could be used for patient treatment verification. © 2013 American Association of Physicists in Medicine.


Bowes D.,Nova Scotia Cancer Center | Crook J.M.,British Columbia Cancer Agency | Araujo C.,British Columbia Cancer Agency | Batchelar D.,British Columbia Cancer Agency
Brachytherapy | Year: 2013

Purpose: Postplan evaluation is essential for quality assurance in prostate brachytherapy. MRI has demonstrated greater interobserver consistency in prostate contouring compared with CT. Although a valuable tool in postimplant assessment, MRI is costly and not always available. Our purpose is to compare dosimetry obtained using fusion of postimplant CT with preimplant transrectal ultrasound (TRUS) vs. CT-MR fusion. Methods and Materials: Twenty patients receiving permanent 125I seed prostate brachytherapy underwent preimplant TRUS with urethrography, 1-month CT with a Foley catheter, and 1-month MRI. No patient received androgen deprivation therapy or external beam radiotherapy. The prescription dose of 125I implant monotherapy was 144Gy. The preimplant TRUS and postimplant CT images were fused based on urethral position, and the CT-TRUS images were subsequently fused to the MRI using a seed-to-seed match. Dosimetric parameters for the ultrasound- and MR-derived prostate were compared. Results: The mean absolute difference between dosimetry from MRI or CT-TRUS fusion for D90 was 3.2% and in V100 was 1.2%. Only 1 patient had a difference in MR- and ultrasound-derived D90 of more than 10% (11.4%) and only 1 had a difference in V100 of more than 5%. Conclusions: Fusion of preimplant TRUS with 1-month postimplant CT appears to lead to acceptable agreement with MR-based dosimetric parameters in postplan evaluation. TRUS-based volumes may be a reasonable alternative to MRI in settings where MRI is not available. © 2013 American Brachytherapy Society.


Robar J.L.,Dalhousie University | Parsons D.,Dalhousie University | Berman A.,Nova Scotia Cancer Center | MacDonald A.,Dalhousie University
Medical Physics | Year: 2012

Purpose: This is a proof-of-concept study addressing volume of interest (VOI) cone beam CT (CBCT) imaging using an x-ray beam produced by 2.35 MeV electrons incident on a carbon linear accelerator target. Methodology is presented relevant to VOI CBCT image acquisition and reconstruction. Sample image data are given to demonstrate and compare two approaches to minimizing artifacts arising from reconstruction with truncated projections. Dosimetric measurements quantify the potential dose reduction of VOI acquisition relative to full-field CBCT. The dependence of contrast-to-noise ratio (CNR) on VOI dimension is investigated. Methods: A paradigm is presented linking the treatment planning process with the imaging technique, allowing definition of an imaging VOI to be tailored to the geometry of the patient. Missing data in truncated projection images are completed using a priori information in the form of digitally reconstructed radiographs (DRRs) generated from the planning CT set. This method is compared to a simpler technique of extrapolating truncated projection data prior to reconstruction. The utility of these approaches is shown through imaging of a geometric phantom and the head-and-neck section of a lamb. The total scatter factor of the 2.35 MVcarbon beam on field size is measured and compared to a standard therapeutic beam to estimate the comparative dose reduction inside the VOI. Thermoluminescent dosimeters and Gafchromic film measurements are used to compare the imaging dose distributions for the 2.35 MVcarbon beam between VOI and full-field techniques. The dependence of CNR on VOI dimension is measured for VOIs ranging from 4 to 15 cm diameter. Results: Without compensating for missing data outside of truncated projections prior to reconstruction, pronounced boundary artifacts are present, in three dimensions, within 2-3 cm of the edges of the VOI. These artifacts, as well as cupping inside the VOI, can be reduced substantially using either the DRR filling or extrapolation techniques presented. Compared to 6 MV, the 2.35 MVcarbon beam shows a substantially greater dependence of total scatter factor on field size, indicating a comparative advantage of the VOI approach when combined with the low-Z target beam. Dosimetric measurements in the anthropomorphic head phantom demonstrate a dose reduction by up to 15 and 75 inside and outside of the VOI, respectively, compared to full-field imaging. For the 2.35 MVcarbon beam, CNR was shown to be approximately invariant with VOI dimension for bone and lung objects. Conclusions: The low-Z target, VOI CBCT technique appears to be feasible and combines the desirable characteristics of the low-Z target beam with regard to CNR, with the capacity to localize the imaging dose to the anatomy relevant to the image guidance task. © 2012 American Association of Physicists in Medicine.


PubMed | McGill University and Nova Scotia Cancer Center
Type: Journal Article | Journal: Medical physics | Year: 2017

To fabricate organic field effect transistors (OFETs) and evaluate their performance before and after exposure to ionizing radiation. To determine if OFETs have potential to function as radiation dosimeters.OFETs were fabricated on both Si/SiODevices fabricated on Si/SiO2 wafers demonstrated excellent linearity (ROFETs have demonstrated excellent potential in radiation dosimetry applications. A key advantage of these devices is their composition, which can be substantially more tissue-equivalent at low photon energies relative to many other types of radiation detector. In addition, fabrication of organic electronics can employ techniques that are faster, simpler and cheaper than conventional silicon-based devices. These results support further development of organic electronic devices for radiation detection purposes. Funding Support, Disclosures, and Conflict of Interest: This work was funded by the Natural Sciences and Engineering Research Council of Canada.


Hodgson D.C.,University of Toronto | Charpentier A.-M.,University of Toronto | Ng A.,University of Toronto | Bahl G.,Nova Scotia Cancer Center | And 3 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2013

Purpose: Stereotactic radiosurgery (SRS) for brain metastases is a relatively well-studied technology with established guidelines regarding patient selection, although its implementation is technically complex. We evaluated the extent to which local availability of SRS affected the treatment of patients with brain metastases. Methods and Materials: We identified 3030 patients who received whole-brain radiation therapy (WBRT) for brain metastases in 1 of 7 cancer centers in Ontario. Clinical data were abstracted for a random sample of 973 patients. Logistic regression analyses were performed to identify factors associated with the use of SRS as a boost within 4 months following WBRT or at any time following WBRT. Results: Of 898 patients eligible for analysis, SRS was provided to 70 (7.8%) patients at some time during the course of their disease and to 34 (3.8%) patients as a boost following WBRT. In multivariable analyses, factors significantly associated with the use of SRS boost following WBRT were fewer brain metastases (odds ratio [OR] = 6.50), controlled extracranial disease (OR = 3.49), age (OR = 0.97 per year of advancing age), and the presence of an on-site SRS program at the hospital where WBRT was given (OR = 12.34; all P values were <.05). Similarly, availability of on-site SRS was the factor most predictive of the use of SRS at any time following WBRT (OR = 5.98). Among patients with 1-3 brain metastases, good/fair performance status, and no evidence of active extracranial disease, SRS was provided to 40.3% of patients who received WBRT in a hospital that had an on-site SRS program vs 3.0% of patients who received WBRT at a hospital without SRS (P<.01). Conclusions: The availability of on-site SRS is the factor most strongly associated with the provision of this treatment to patients with brain metastases and appears to be more influential than accepted clinical eligibility factors. © 2013 Elsevier Inc. All rights reserved.

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