Publications by authors named "Don Yee"

36 Publications

Clinical Learning, Didactic Education, and Research Experiences of Radiation Oncology Resident Physicians in Canada.

J Cancer Educ 2020 Jul 4. Epub 2020 Jul 4.

Division of Radiation Oncology, University of Alberta, Edmonton, AB, Canada.

Changes in the field of radiation oncology (RO) impacts residency training. Assessing trainee experiences is essential to inform curriculum development. We aim to explore gaps and strengths in current Canadian RO training, as we move towards competency-based medical education (CBME). An online survey was distributed to residents at all Canadian RO training programs. Surveys consisted of 66 open-ended, Likert-scale, matrix-style, and multiple-choice questions, and assessed clinical exposure, didactic teaching, professional relationships, and research experiences. Statistics were calculated from anonymized, aggregate responses. Out of 128 eligible residents, 53 responded (41% response rate). Of these, 57% were male, and 77% were Canadian medical graduates. Senior residents (PGY-4 to PGY-5) perceived insufficient exposure to lymphoma and ocular malignancies, brachytherapy for breast and esophagus malignancies, and stereotactic radiotherapy of the pancreas, prostate, and adrenal gland. Half (51%) had training on image-guided radiotherapy (IGRT) challenges, and 43% had a formal staff mentor. Most residents presented at least one research project at conferences (77%) and authored ≥ 1 publications (66%) during residency. Canadian RO residents are satisfied with their clinical training and educational experience in high-volume tumor sites and high-volume brachytherapy procedures. Areas identified for potential improvement are (1) low-volume tumor sites; (2) low-volume brachytherapy procedures; (3) low-volume stereotactic radiotherapy sites; (4) IGRT challenges; and (5) mentorship opportunities. These findings will inform future CBME curriculum revisions.
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http://dx.doi.org/10.1007/s13187-020-01799-xDOI Listing
July 2020

Motivations, Well-Being, and Career Aspirations of Radiation Oncology Resident Physicians in Canada.

J Cancer Educ 2020 Mar 6. Epub 2020 Mar 6.

Division of Radiation Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada.

Prior Pan-Canadian surveys of Radiation Oncology (RO) residents reveal a decrease in Canadian RO employment opportunities. Canadian RO resident levels increased from 130 in 2003, peaked at 209 in 2009, then decreased to 130 in 2017. Recognizing that RO has entered another period of transition, we re-examined resident motivations and perspectives on the job market and explored well-being and career aspirations among a contemporary cohort of Canadian RO residents. An online survey was distributed to residents at all Canadian RO training programs. Surveys consisted of 75 open-ended, Likert-scale, matrix-style, and multiple-choice questions. Student's t test compared subgroups, with statistical significance at p ≤ 0.05. Out of 128 eligible residents, 84 completed the survey (66% response rate) with representative sampling from each training year. Demographics reveal 53% male, and 85% Canadian registry-funded. Top training-related stressors were exam performance, job prospects, and physical/psychological demands of residency. Most intend to pursue fellowship post-residency (80%) and practice in Canada (88%). Few believe they can obtain staff positions treating preferred tumor sites (38%) or at preferred geographic locations (28%). Residents view job market being less competitive than 5 years ago (40%) and predict it will be less competitive in 5 years (60%). Canadian RO residents feel adequately trained, and most pursue post-residency fellowships. Current perceptions of the Canadian job market remain guarded, but appear more optimistic about the future. This update provides insights into current RO training and identifies areas that could be addressed by incoming competency-based medical education models for RO.
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http://dx.doi.org/10.1007/s13187-020-01717-1DOI Listing
March 2020

Should Stereotactic Radiosurgery Be Considered for Salvage of Intracranial Recurrence after Prophylactic Cranial Irradiation or Whole Brain Radiotherapy in Small Cell Lung Cancer? A Population-Based Analysis and Literature Review.

J Med Imaging Radiat Sci 2020 03 20;51(1):75-87.e2. Epub 2019 Nov 20.

Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.

Background: Prophylactic cranial irradiation (PCI) improves survival and prevents intracranial recurrence (IR) in limited stage (LS) and extensive stage (ES) small cell lung cancer (SCLC). However, despite PCI, IR affects 12%-45%, and limited data exist regarding salvage brain reirradiation (ReRT). We performed a population-based review of IR in SCLC.

Methods: Demographic, treatment, and outcome data of consecutive patients (N = 371) with SCLC assessed at a tertiary cancer centre (01/2013-12/2015) were abstracted, and summary statistics calculated. Kaplan-Meier estimates and univariate and multivariate analysis (MVA) via the Cox proportional hazard model were performed.

Results: Median age was 66.1 years, and 59.8% were Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Median survival was 24 months (95% CI 18.3-29.7 months) for LS (N = 103) and 7 months (95% CI 6.1-7.9 months) for ES (N = 268). 72 of 103 patients with LS and 97 of 214 of those with ES received PCI. 54 of 268 ES presented with brain metastases (BM) of whom 46 of 54 received whole brain RT (WBRT). 18.9% (32/169) recurred post-PCI (13 LS; 19 ES) and 30.4% (14/46) recurred after WBRT. Of those who recurred/progressed after cranial RT, 56.5% (26/46) had <5 BM, 39.1% had no extracranial disease, and 50% were ECOG 0-2. In retrospect, 17 of 46 would have been candidates for salvage stereotactic radiosurgery: 13 post-PCI and 4 post-WBRT.

Conclusions: This cohort challenges commonly held beliefs that IR is always diffuse, associated with clinical deterioration, and synchronous with systemic failure. Approximately 1 in 3 SCLC patients with IR after PCI or WBRT appear clinically appropriate for salvage stereotactic radiosurgery.
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http://dx.doi.org/10.1016/j.jmir.2019.10.001DOI Listing
March 2020

Informal caregiver quality of life in a palliative oncology population.

Support Care Cancer 2020 Apr 10;28(4):1695-1702. Epub 2019 Jul 10.

Department of Radiation Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada.

Purpose: Many patients with advanced cancer receive primary supports from informal caregivers (IC). As patient health deteriorates, IC assume increasing responsibility, often accompanied by distress. We investigated the quality of life (QOL) of IC of patients referred to a palliative radiotherapy (PRT) program.

Methods: IC accompanying patients to a dedicated PRT clinic completed a survey based on the validated Caregiver Quality of Life Index-Cancer (CQOLC). Demographics, burden, and engagement in support services were evaluated. Summary statistics were calculated, and parameters were assessed for association with CQOLC scores by a generalized linear model.

Results: Two hundred one surveys were analyzed representing 197 unique patients. The mean age was 68.3 years, with predominantly lung (25.0%) and prostate (19.3%) malignancies. 24.4% had been in hospital/long-term care within the previous 7 days. IC were 60.8% female, and 60.6% were the patient's spouse. 69.5% lived with the patient and 38.3% were additionally employed. IC spent a daily mean of 6.6 h (SD 7) assisting with instrumental (72.5%) and basic (37.5%) activities of daily living. Mean CQOLC score was 82.1/140 (SD 20). 63.8% of IC had previously accessed support service(s), most commonly home care (37.2%) and pharmacy (29.1%). 55.9% indicated interest in services not yet accessed. Multivariate analysis revealed additional employment, cohabitation, poor patient performance status, and interest in accessing more support services significantly correlated with higher IC burden.

Conclusions: Employing the CQOLC to screen IC of patients referred to a PRT program permits early identification of vulnerable IC to facilitate linkage with appropriate supports.
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http://dx.doi.org/10.1007/s00520-019-04970-3DOI Listing
April 2020

Initial clinical assessment of "center-specific" automated treatment plans for low-dose-rate prostate brachytherapy.

Brachytherapy 2018 Mar - Apr;17(2):476-488. Epub 2017 Dec 1.

Department of Oncology, University of Alberta, Edmonton, AB, Canada, T6G 1Z2. Electronic address:

Purpose: To report results of an initial pilot study assessing iodine-125 prostate implant treatment plans created automatically by a new seed-placement method.

Methods And Materials: A novel mixed-integer linear programming method incorporating spatial constraints on seed locations in addition to standard dose-volume constraints was used to place seeds. The approach, described in detail elsewhere, was used to create treatment plans fully automatically on a retrospective basis for 20 patients having a wide range of prostate sizes and shapes. Corresponding manual plans used for patient treatment at a single institution were combined with the automated plans, and all 40 plans were anonymized, randomized, and independently evaluated by five clinicians using a common scoring tool. Numerical and clinical features of the plans were extracted for comparison purposes.

Results: A full 51% of the automated plans were deemed clinically acceptable without any modification by the five practitioners collectively versus 90% of the manual plans. Automated plan seed distributions were for the most part not substantially different from those for the manual plans. Two observed shortcomings of the automated plans were seed strands not intersecting the prostate and strands extending into the bladder. Both are amenable to remediation by adjusting existing spatial constraints.

Conclusions: After spatial and dose-volume constraints are set, the mixed-integer linear programming method is capable of creating prostate implant treatment plans fully automatically, with clinical acceptability sufficient to warrant further investigation. These plans, intended to be reviewed and refined as necessary by an expert planner, have the potential to both save planner time and enhance treatment plan consistency.
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http://dx.doi.org/10.1016/j.brachy.2017.10.012DOI Listing
January 2019

Evaluating performance of a user-trained MR lung tumor autocontouring algorithm in the context of intra- and interobserver variations.

Med Phys 2018 Jan 15;45(1):307-313. Epub 2017 Dec 15.

Department of Medical Physics, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada.

Purpose: Real-time tracking of lung tumors using magnetic resonance imaging (MRI) has been proposed as a potential strategy to mitigate the ill-effects of breathing motion in radiation therapy. Several autocontouring methods have been evaluated against a "gold standard" of a single human expert user. However, contours drawn by experts have inherent intra- and interobserver variations. In this study, we aim to evaluate our user-trained autocontouring algorithm with manually drawn contours from multiple expert users, and to contextualize the accuracy of these autocontours within intra- and interobserver variations.

Methods: Six nonsmall cell lung cancer patients were recruited, with institutional ethics approval. Patients were imaged with a clinical 3 T Philips MR scanner using a dynamic 2D balanced SSFP sequence under free breathing. Three radiation oncology experts, each in two separate sessions, contoured 130 dynamic images for each patient. For autocontouring, the first 30 images were used for algorithm training, and the remaining 100 images were autocontoured and evaluated. Autocontours were compared against manual contours in terms of Dice's coefficient (DC) and Hausdorff distances (d ). Intra- and interobserver variations of the manual contours were also evaluated.

Results: When compared with the manual contours of the expert user who trained it, the algorithm generates autocontours whose evaluation metrics (same session: DC = 0.90(0.03), d  = 3.8(1.6) mm; different session DC = 0.88(0.04), d  = 4.3(1.5) mm) are similar to or better than intraobserver variations (DC = 0.88(0.04), and d  = 4.3(1.7) mm) between two sessions. The algorithm's autocontours are also compared to the manual contours from different expert users with evaluation metrics (DC = 0.87(0.04), d  = 4.8(1.7) mm) similar to interobserver variations (DC = 0.87(0.04), d  = 4.7(1.6) mm).

Conclusions: Our autocontouring algorithm delineates tumor contours (<20 ms per contour), in dynamic MRI of lung, that are comparable to multiple human experts (several seconds per contour), but at a much faster speed. At the same time, the agreement between autocontours and manual contours is comparable to the intra- and interobserver variations. This algorithm may be a key component of the real time tumor tracking workflow for our hybrid Linac-MR device in the future.
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http://dx.doi.org/10.1002/mp.12687DOI Listing
January 2018

Unexpected Seed Migration in Prostate Brachytherapy Implants Coincident with Change in Seed Stranding Product.

Cureus 2017 May 12;9(5):e1243. Epub 2017 May 12.

Department of Oncology, University of Alberta.

Purpose: This study was undertaken to determine if significant seed migration occurred when our institution changed seed products by comparing patterns of seed migration in implants containing different stranding material.

Methods And Materials: Day 0 and Day 30 CT scans were registered by the contoured prostate center of mass. An implant reconstruction program identified seeds on CT according to the pre-plan, enabling one-to-one correspondence between Day 0 and Day 30 seeds. Significant seed migration was defined by review of seeds that migrated > 2 cm outside the prostate or appearance in unexpected locations.   Results: Twenty-five (149, 16.8%) new strands displayed movement > 2 cm between Day 0 and Day 30 compared with just 2/118 (1.7%) of the standard strands. Six out of 26 (23%) patients with new strands displayed significant migration compared with 2/13 (14%) of patients with standard strands. In the six patients with new strands and significant migration, a mean of four strands (17%, range: 2-8 per patient) migrated significantly with 65% due to whole strand migration, 25% due to strand breakage, and 10% strand clumping. In the control group, only two strands (2%) migrated significantly, both due to strand breakage. Despite the greater seed movement with the new strands, Day 0 and Day 30 dosimetry was acceptable.

Conclusion: In this short report, we identified that a change to a new strand type was associated with unexpected significant seed movement compared to our typical strands. Since seed movement can arise from unexpected causes, it is important to maintain quality assurance practices when a change in technique or infrastructure is instituted.
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http://dx.doi.org/10.7759/cureus.1243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467979PMC
May 2017

Quantifying I placement accuracy in prostate brachytherapy using postimplant transrectal ultrasound images.

Brachytherapy 2017 Mar - Apr;16(2):306-312. Epub 2017 Feb 1.

Department of Oncology, University of Alberta, Edmonton, AB, Canada. Electronic address:

Purpose: The quality of a prostate brachytherapy implant depends on the accurate placement of sources. This study quantifies the misplacement of I sources from the intended location using intraoperative ultrasound images.

Methods And Materials: I sources were manually identified in the postimplant ultrasound images and compared to the preoperative plan. Due to the subjective nature of the identifying sources, only sources identified with high confidence were included in the analysis. Misplacements from the original intended coordinate were measured along the X, Y, and Z axes and were stratified between overall misplacements and regions of the prostate gland.

Results: A total of 1619 I sources using 357 strands were implanted in 15 patients' prostate glands, with 1197 (74%) confidently identified for misplacement analysis. The overall mean displacement was 0.49 cm and in the X, Y, and Z direction was 0.13, 0.15, and 0.38 cm, respectively. Greater source misplacement occurred in the anterior part of the prostate gland than the posterior part of the prostate gland by a factor 1.33 (p < 0.0001). Comparing sources in the lateral vs. medial regions of the prostate, no statistically significant differences on source misplacement were observed. Comparing misplacement in the base vs. midgland vs. apex identified the greatest difference between the base and midgland by a factor of 1.29 (p < 0.0001).

Conclusions: This study has identified significant misplacement of I sources from their intended locations with the greatest error misplacement occurring in the Z direction. Source misplacement tends to occur more commonly in the anterior gland and in the base of the prostate.
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http://dx.doi.org/10.1016/j.brachy.2016.11.015DOI Listing
June 2017

Does location of prostate cancer by sextant biopsies predict for relapse after (125)I seed implant brachytherapy?

Brachytherapy 2015 Nov-Dec;14(6):788-94. Epub 2015 Aug 3.

Department of Oncology, Faculty of Medicine and Dentistry, Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.

Purpose: To report on the importance of cancer location from diagnostic prostate biopsies in predicting biochemical relapse for patients treated with (125)I seed implant brachytherapy as monotherapy for favorable risk disease; specifically, to assess the clinical significance of potentially underdosing the base region of the prostate gland.

Methods And Materials: Of 1145 consecutive patients, 846 had pretreatment biopsies allowing for sextant analysis and consequent evaluation of biochemical failure tendencies. Biochemical failure was defined as a posttreatment rise in the nadir prostate-specific antigen (PSA) by at least 2 ng/mL. Patient and tumor characteristics, dosimetry, the use of hormone therapy, source strength, and postimplant PSA kinetics were analyzed between sextant subgroups.

Results: Sixty-two patients (7.3%) with sextant pathology had biochemical failure. There was no significant difference between the failure locations. There were 528 patients (62.4%) with some element of base involvement (BI), and 318 patients (37.6%) with no evidence of BI. Of the 62 patients with biochemical failure, 42 (67.7%) showed BI on biopsy and 20 (32.3%) had no BI. The 10-year relapse-free survival rate is 88.2% (95% confidence interval: 84.3%, 92.2%) and 92.0% (95% confidence interval: 88.4%, 95.8%) for the BI and no BI groups, respectively (p = 0.17). The mean D90 delivered to the base, midgland, and apex was 140.8 (±21.8) Gy, 170.8 (±22.5) Gy, and 177.9 (±29.5) Gy, respectively, for all patients.

Conclusions: There are no significantly worse outcomes for patients treated with an (125)I seed implant for favorable risk prostate cancer with some element of BI, despite lower doses of radiation delivered to the base region.
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http://dx.doi.org/10.1016/j.brachy.2015.07.002DOI Listing
July 2016

Distinguishing prostate-specific antigen bounces from biochemical failure after low-dose-rate prostate brachytherapy.

J Contemp Brachytherapy 2014 Oct 5;6(3):247-53. Epub 2014 Sep 5.

Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada.

Purpose: The purpose of this study was to characterize benign prostate-specific antigen (PSA) bounces of at least 2.0 ng/mL and biochemical failure as defined by the Phoenix definition after prostate brachytherapy at our institution, and to investigate distinguishing features between three outcome groups: patients experiencing a benign PSA bounce, biochemical failure, or neither.

Material And Methods: Five hundred and thirty consecutive men treated with low-dose-rate brachytherapy with follow-up of at least 3 years were divided into outcome groups experiencing bounce, failure, or neither. A benign bounce was defined as a rise of at least 2.0 ng/mL over the pre-rise nadir followed by a decline to 0.5 ng/mL or below, without intervention. Patient and tumor characteristics, treatment variables, and PSA kinetics were analyzed between groups.

Results: Thirty-two (6.0%) men experienced benign bounces and 47 (8.9%) men experienced failure. Men experiencing a bounce were younger (p = 0.01), had a higher 6-month PSA level (p = 0.03), and took longer to reach a final nadir (p < 0.01). Compared to the failure group, men with bounce had a lower pre-treatment PSA level (p = 0.01) and experienced a rise of at least 2.0 ng/mL that occurred sooner after the implant (p < 0.01) with a faster PSA doubling time (p = 0.01). Only time to PSA rise independently differentiated between bounce and failure (p < 0.01), with a benign bounce not being seen after 36 months post-treatment. Prostate-specific antigen levels during a bounce reached levels as high as 12.6 ng/mL in this cohort, and in some cases took over 5 years to decline to below 0.5 ng/mL.

Conclusions: Although there is substantial overlap between the features of benign PSA bounces and failure, physicians may find it useful to evaluate the timing, absolute PSA level, initial response to treatment, and rate of rise when contemplating management for a PSA rise after low-dose-rate brachytherapy.
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http://dx.doi.org/10.5114/jcb.2014.45093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200178PMC
October 2014

Dose-escalated Hypofractionated Intensity-modulated Radiation Therapy With Concurrent Chemotherapy for Inoperable or Unresectable Non-Small Cell Lung Cancer.

Am J Clin Oncol 2017 Jun;40(3):294-299

*Department of Oncology, Division of Radiation Oncology †Department of Oncology, Division of Medical Oncology ‡Division of Medical Physics, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, AB, Canada.

Purpose: The local control of inoperable non-small cell lung cancer (NSCLC) using standard radiotherapy (RT) doses is inadequate. Dose escalation is a potential strategy to improve the local control for patients with NSCLC; however, the optimal dose required for local control in this setting is unknown.

Methods And Materials: Patients with unresectable or inoperable stage II/III NSCLC with ECOG≤1 received 48 Gy in 20 daily fractions using intensity-modulated radiotherapy, followed by 1 of 3 boost dose levels: 16.8 Gy/7 (cumulative 2 Gy equivalent dose [EQD2]≅76 Gy/38), 20.0 Gy/7 (EQD2≅84 Gy/42), and 22.7 Gy/7 (EQD2≅92 Gy/46). Two cycles of cisplatin/etoposide chemotherapy were given concurrent with RT. The maximum tolerated dose was defined as the dose at which ≥30% experienced dose-limiting toxicity (any NCIC Common Terminology for Adverse Events V3.0 grade 3 or higher acute toxicity).

Results: Twelve patients completed treatment with a median follow-up of 22 months (range, 7 to 48). The median age was 72 (range, 54 to 80) and 50% of patients had adenocarcinoma. Five, 3, and 4 patients were treated on dose levels 1, 2, and 3, respectively. No dose-limiting toxicity was observed. One-year local progression-free survival and overall survival estimates were 81% and 58%, respectively.

Conclusions: Hypofractionated intensity-modulated radiotherapy was well tolerated and provided meaningful local control for patients with locally advanced inoperable NSCLC. The maximum tolerated dose of RT in this setting lies beyond an EQD2 of 92 Gy/46 and further dose escalation in this setting is warranted.
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http://dx.doi.org/10.1097/COC.0000000000000140DOI Listing
June 2017

Late Toxicity and Outcomes in High-risk Prostate Cancer Patients Treated With Hypofractionated IMRT and Long-term Androgen Suppression Treatment.

Am J Clin Oncol 2017 Apr;40(2):200-206

Divisions of *Radiation Oncology ∥Medical Physics ¶Division of Experimental Oncology, Department of Oncology, Cross Cancer Institute, Edmonton, AB †Department of Radiation Oncology, Cancer Care, Eastern Health, St Johns, NF ‡Radiation Oncology, Saskatoon Cancer Centre, Saskatoon, SK, Canada §Radiation Oncology, UPMC Beacon Hospital, Dublin, Republic of Ireland.

Objective: To assess late toxicity and outcomes in high-risk prostate cancer patients treated with hypofractionated radiation treatment with androgen suppression therapy.

Methods: Sixty high-risk prostate cancer patients were enrolled. IMRT prescription was 68 Gy/25 fractions (2.7 Gy/fraction) to the prostate and proximal seminal vesicles (SV). The pelvic lymph nodes (PLN) and distal SV concurrently received 45 Gy/25 fractions (1.8 Gy/fraction). The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification before each treatment. RTOG Toxicity scores were recorded for a 5-year period.

Results: Sixty patients completed RT with median follow-up of 63 months (range, 7 to 80 mo).At 5 years follow-up timepoint: Grade (G)2 and G3 late genitourinary toxicity was experienced in 7 (17.0%) and 1 (2.44%), respectively; gastrointestinal G2 as highest toxicity recorded in only 1 (2.44%) patient. There was no G3 gastrointestinal toxicity recorded at this timepoint.With 63-month median follow-up (mean of 65.41±1.72 mo), the 5-year overall survival was 86.67%; 5 years freedom from biochemical failure was 91.67% and freedom from clinical failure was 96.67%.

Conclusions: Dose escalation and hypofractionated radiation treatment with IMRT treating the prostate and proximal SV concurrently with the pelvic lymph nodes and distal SV and long-term androgen suppression therapy is well tolerated with respect to acute and late toxicity with 5-year actuarial overall survival 86.67%, freedom from biochemical failure 91.38%, and freedom from clinical failure 96.67%. Longer follow-up will provide more information on 10-year survival outcomes.
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http://dx.doi.org/10.1097/COC.0000000000000133DOI Listing
April 2017

Single-nucleotide polymorphisms studied for associations with urinary toxicity from (125)I prostate brachytherapy implants.

Brachytherapy 2014 May-Jun;13(3):285-91. Epub 2014 Mar 18.

Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.

Purpose: To identify clinical, dosimetric, and genetic factors that are associated with late urinary toxicity after a (125)I prostate brachytherapy implant.

Methods And Materials: Genomic DNA from 296 men treated with (125)I prostate brachytherapy monotherapy was extracted from saliva samples for this study. A retrospective database was compiled including clinical, dosimetric, and toxicity data for this cohort of patients. Fourteen candidate single-nucleotide polymorphism (SNPs) from 13 genes (TP53, ERCC2, GSTP1, NOS, TGFβ1, MSH6, RAD51, ATM, LIG4, XRCC1, XRCC3, GSTA1, and SOD2) were tested in this cohort for correlations with toxicity.

Results: This study identified 217 men with at least 2 years of followup. Of these, 39 patients developed Grade ≥2 late urinary complications with a transurethral resection of prostate, urethral stricture, gross hematuria, or a sustained increase in their International Prostate Symptom Score. The only clinical or dosimetric factor that was associated with late urinary toxicity was age (p = 0.02). None of the 14 SNPs tested in this study were associated with late urinary toxicity in the univariate analysis.

Conclusions: This study identified age as the only variable being associated with late urinary toxicity. However, the small sample size and the candidate gene approach used in this study mean that further investigations are essential. Genome-wide association studies are emerging as the preferred approach for future radiogenomic studies to overcome the limitations from a candidate gene approach.
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http://dx.doi.org/10.1016/j.brachy.2014.02.002DOI Listing
September 2014

Evidence for photochemical and microbial debromination of polybrominated diphenyl ether flame retardants in San Francisco Bay sediment.

Chemosphere 2014 Jul 28;106:36-43. Epub 2014 Jan 28.

San Francisco Estuary Institute, 4911 Central Avenue, Richmond, CA 94804, United States.

Brominated diphenyl ethers (BDEs) are flame retardant compounds that have been classified as persistent organic pollutants under the Stockholm Convention and targeted for phase-out. Despite their classification as persistent, PBDEs undergo debromination in the environment, via both microbial and photochemical pathways. We examined concentrations of 24 PBDE congeners in 233 sediment samples from San Francisco Bay using Positive Matrix Factorization (PMF). PMF analysis revealed five factors, two of which contained high proportions of congeners with two or three bromines, indicating that they are related to debromination processes. One of the factors included PBDE 15 (4,4'-dibromo diphenyl ether, comprising 20% of the factor); the other included PBDE 7 (2,4-dibromo diphenyl ether; 12%) and PBDE 17 (2,2',4-tribromo diphenyl ether; 16%). The debromination processes that produce these congeners are probably photochemical debromination and anaerobic microbial debromination, although other processes could also be responsible. Together, these two debromination factors represent about 8% of the mass and 13% of the moles of PBDEs in the data matrix, suggesting that PBDEs undergo measurable degradation in the environment.
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http://dx.doi.org/10.1016/j.chemosphere.2013.12.083DOI Listing
July 2014

Comparison of low and intermediate source strengths for (125)I prostate brachytherapy implants.

Brachytherapy 2013 Sep-Oct;12(5):442-8. Epub 2013 May 23.

Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

Purpose: To compare the implant quality and clinical outcomes for patients treated with low and intermediate strength (125)I seeds in prostate brachytherapy implants.

Methods And Materials: This retrospective review included 390 consecutive patients treated with prostate brachytherapy from 1999 to 2006. The first 142 patients were implanted with source strengths lower than 0.415U (0.327mCi), with the subsequent 248 patients implanted with source strengths higher than 0.493U (0.388mCi). Clinical, dosimetric, toxicity, and outcome data were compared between these two cohorts of patients.

Results: Despite having similar prostate volumes, fewer sources (median, 95 vs. 113; p<0.0001) and fewer needles (median, 23 vs. 29; p<0.0001) were implanted in the intermediate strength cohort. The postimplant dosimetry demonstrated better quality implants in patients treated with intermediate strength sources (median D90, 160.0Gy vs. 139.6Gy; p<0.0001), with greater dose inhomogeneity identified in the intermediate strength cohort of patients. A higher incidence of late rectal toxicity was identified in patients treated with intermediate strength sources despite lower rectal doses in this cohort. The biochemical relapse-free survival, prostate cancer survival, and overall survival were not significantly different between the two cohorts.

Conclusions: The transition from low to intermediate strength sources has led to fewer resources being used and improved postoperative dosimetry. Although there were more rectal complications identified in the intermediate strength cohort of patients in this analysis, there were no other significantly worse clinical or biochemical outcomes for patients implanted with intermediate strength sources.
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http://dx.doi.org/10.1016/j.brachy.2013.02.004DOI Listing
May 2014

Regional treatment margins for prostate brachytherapy.

Brachytherapy 2013 Nov-Dec;12(6):596-602. Epub 2013 May 7.

Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.

Purpose: This study quantified the treatment margin (TM) around the prostate that received 100% of the prescribed dose and analyzed postimplant dosimetry in different regions of the prostate for (125)I seed implants.

Methods And Materials: An average target volume (ATV) was created from postoperative MRI scan contours drawn independently by five radiation oncologists in 40 patients. The MRI was fused with the postoperative CT for dosimetry purposes. The TM, defined as the radial distance between the ATV and the 100% isodose line, was measured at 16 points at the base, midgland, and apex. The ATV was divided into four quadrants: anterior-superior, posterior-superior, anterior-inferior, and posterior-inferior quadrants. The values of the dose that covers 90% of the ATV (D90) and the percentage of the ATV receiving the prescribed dose (V100) received by the whole prostate and its four quadrants were documented.

Results: The range of the mean TM, in millimeter, was -8.88 to 3.68, 1.12 to 10.42, and 6.27 to 18.25 at the base, midgland, and apex, respectively. The mean D90 was 135.8, 162.8, 191.0, and 194.6 Gy for the anterior-superior, posterior-superior, anterior-inferior, and posterior-inferior quadrants, respectively.

Conclusions: Despite having a relatively uniform preoperative planning target volume, this study identified variable TMs postoperatively in different regions of the prostate. In particular, the anterior base is most underdosed, whereas the lateral regions of the midgland and apex have generous TMs. Postimplant dosimetric parameters were lowest in the anterior-inferior quadrant.
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http://dx.doi.org/10.1016/j.brachy.2013.04.003DOI Listing
May 2014

Radiation Oncology Workforce Recruitment Survey of 2000-2010 Graduates: Is There a Need for Better Physician Resource Planning?

Can Med Educ J 2012 31;3(1):e52-63. Epub 2012 Mar 31.

Dept. of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.

Purpose Of The Study: To survey employment and training characteristics of Canadian radiation oncology training program graduates and foreign medical graduates with Canadian radiation oncology post-graduate education or specialist certification.

Methods: A 38-question, web-based survey was distributed to radiation oncologists who completed specialty training between 2000-2010.

Results: Out of 256 radiation oncologists contacted, 148 completed the survey (58% response rate). Thirty-two respondents (22%) were foreign MD graduates. One-hundred and fifteen respondents (78%) undertook fellowship training after residency. Many Canadian MD graduates (77%) and foreign MD graduates (34%) had staff positions in Canada, while 11% of all respondents had staff positions outside Canada, and 21% did not have a commitment for staff employment. Of the 31 respondents without a staff position, 22 graduated from Canadian residency training in 2009 or 2010, and 21 had completed medical school training in Canada.

Conclusions: The majority of respondents were successful in securing staff positions in Canada. A sizeable proportion extended training with fellowships. New graduates may have more difficulty in finding Canadian staff positions in radiation oncology in the near future. Implications for specialty training programs and for an improved national strategy for physician resource planning are discussed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563643PMC
October 2015

Comparison of prostate volume, shape, and contouring variability determined from preimplant magnetic resonance and transrectal ultrasound images.

Brachytherapy 2012 Jul-Aug;11(4):284-91. Epub 2011 Dec 23.

Division of Medical Physics, Cross Cancer Institute, Edmonton, Alberta, Canada.

Purpose: To compare preimplant prostate contours and contouring variability between magnetic resonance (MR) and transrectal ultrasound images.

Methods And Materials: Twenty-three patients were imaged using ultrasound (US) and MR before permanent brachytherapy treatment. Images were anonymized, randomized, and duplicated, and the prostate was independently delineated by five radiation oncologists. Contours were compared in terms of volume, dimensions, posterior rectal indentation, and observer variability. The Jaccard index quantified spatial overlap between contours from duplicated images.

Results: The mean US/MR volume ratio was 0.99±0.08 (p=0.5). The width, height, and length ratios for the prostate were 0.98±0.06 (p=0.09), 0.99±0.08 (p=0.4), and 1.05±0.14 (p=0.1). Rectal indentation was larger on US by 0.18mL (p=0.01) and correlated with prostate volume (p<0.01). MR and US interobserver variability in volume were similar at 3.5±1.7 and 3.3±1.9mL (p=0.6). Intraobserver variability was smaller on US at 1.4±1.1mL compared with MR at 2.4±2.2mL (p=0.01). Local intraobserver variability was lower on US at the midgland slice (p<0.01) but lower on MR at the base (p<0.01) and apex (p<0.01) slices.

Conclusions: US is comparable to MR for preimplant prostate delineation, with no significant difference in volume and dimensions. Rectal indentation because of the transrectal ultrasound probe was measurable, although the effects were small. Intraobserver variability was lower on US for the prostate volume but was lower on MR locally at the base and apex. However, the difference was not observed for the interobserver variability, which was similar between MR and US.
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http://dx.doi.org/10.1016/j.brachy.2011.11.004DOI Listing
November 2012

Clinical trial of post-chemotherapy consolidation thoracic radiotherapy for extensive-stage small cell lung cancer.

Radiother Oncol 2012 Feb 17;102(2):234-8. Epub 2011 Sep 17.

Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.

Background And Purpose: To define the rate of development of symptomatic chest failures in extensive stage small cell lung cancer (ES-SCLC) after undergoing post-chemotherapy chest radiotherapy (RT).

Materials And Methods: Patients had ES-SCLC, attained an objective response to chemotherapy and signed study consent. Target accrual was 33 patients. Patients were offered prophylactic cranial irradiation (PCI) as per department policy. PCI (25 Gy/10 fractions) and chest RT (40 Gy/15 fractions) were given simultaneously 4-8 weeks after chemotherapy completion. Thoracic target volume was the post-chemotherapy residual chest disease plus margin. Patients were evaluated for RT toxicities, local control, disease-free and overall survival.

Results: Thirty-two patients were evaluable. Twenty-nine patients completed RT without delay. There were 4 complete responses and 28 partial responses to chemotherapy. All study patients received PCI. Maximal acute RT toxicity was grade 2 esophagitis (18 patients). There were no RT-related deaths. Median time to disease progression and overall survival were 4.2 and 8.3 months, respectively (median follow-up=21.8 months). Of 16 chest recurrences, 7 were in the irradiated region and 5 were symptomatic.

Conclusions: Post-chemotherapy consolidation chest RT for ES-SCLC patients on this trial was well tolerated and associated with symptomatic chest recurrences in only 5/32 treated patients.
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http://dx.doi.org/10.1016/j.radonc.2011.08.042DOI Listing
February 2012

2009 Canadian radiation oncology resident survey.

Int J Radiat Oncol Biol Phys 2012 Mar 2;82(4):1326-31. Epub 2011 Jun 2.

Department of Radiation Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.

Purpose: Statistics from the Canadian post-MD education registry show that numbers of Canadian radiation oncology (RO) trainees have risen from 62 in 1999 to approximately 150 per year between 2003 and 2009, contributing to the current perceived downturn in employment opportunities for radiation oncologists in Canada. When last surveyed in 2003, Canadian RO residents identified job availability as their main concern. Our objective was to survey current Canadian RO residents on their training and career plans.

Methods And Materials: Trainees from the 13 Canadian residency programs using the national matching service were sought. Potential respondents were identified through individual program directors or chief resident and were e-mailed a secure link to an online survey. Descriptive statistics were used to report responses.

Results: The eligible response rate was 53% (83/156). Similar to the 2003 survey, respondents generally expressed high satisfaction with their programs and specialty. The most frequently expressed perceived weakness in their training differed from 2003, with 46.5% of current respondents feeling unprepared to enter the job market. 72% plan on pursuing a postresidency fellowship. Most respondents intend to practice in Canada. Fewer than 20% of respondents believe that there is a strong demand for radiation oncologists in Canada.

Conclusions: Respondents to the current survey expressed significant satisfaction with their career choice and training program. However, differences exist compared with the 2003 survey, including the current perceived lack of demand for radiation oncologists in Canada.
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http://dx.doi.org/10.1016/j.ijrobp.2011.04.030DOI Listing
March 2012

Temporal lung tumor volume changes in small-cell lung cancer patients undergoing chemoradiotherapy.

Int J Radiat Oncol Biol Phys 2011 May 18;80(1):142-7. Epub 2010 Jun 18.

Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.

Purpose: Small-cell lung cancer is considered to be relatively chemosensitive and radiosensitive. Small-cell tumor volume changes during concurrent chemoradiotherapy have not been quantified. The purpose of this work is to quantify small-cell lung tumor volume variations in limited-stage patients undergoing chemoradiotherapy.

Methods And Materials: Eligible patients had pathologically confirmed limited-stage small-cell lung cancer, underwent concurrent chemoradiotherapy, and signed study-specific consent forms. Patients underwent serial chest computed tomography (CT) scans on a CT simulator with images acquired at the same phase of patients' respiratory cycle. Computed tomography scans were obtained at the time of planning CT scan and 3 times a week during radiotherapy (RT). Gross tumor volumes (GTVs) were contoured on each CT scan. Gross tumor volumes defined on each CT scan were analyzed for volume changes relative to pre-RT scans.

Results: We obtained 104 CT scans (median, 11.5 scans per patient). The median tumor dose was 50 Gy. The median pre-RT GTV was 98.9 cm(3) (range, 57.8-412.4 cm(3)). The median GTV at the final serial CT scan was 10.0 cm(3) (range, 4.2-81.6 cm(3)). The mean GTV relative to pre-RT volume at the end of each RT week was 53.0% for Week 1, 29.8% for Week 2, 22.9% for Week 3, 19.5% for Week 4, and 12.4% for Week 5.

Conclusions: Dramatic shrinkage of small-cell lung tumors occurred in patients undergoing chemoradiotherapy in this trial. Most of the observed GTV shrinkage occurred during the first week of RT.
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http://dx.doi.org/10.1016/j.ijrobp.2010.01.056DOI Listing
May 2011

Can images obtained with high field strength magnetic resonance imaging reduce contouring variability of the prostate?

Int J Radiat Oncol Biol Phys 2011 Jul 12;80(3):728-34. Epub 2010 Jul 12.

Department of Radiation Oncology, Cross Cancer Institute, Edmonton, AB, Canada.

Purpose: The objective of this study is to determine whether there is less contouring variability of the prostate using higher-strength magnetic resonance images (MRI) compared with standard MRI and computed tomography (CT).

Methods And Materials: Forty patients treated with prostate brachytherapy were accrued to a prospective study that included the acquisition of 1.5-T MR and CT images at specified time points. A subset of 10 patients had additional 3.0-T MR images acquired at the same time as their 1.5-T MR scans. Images from each of these patients were contoured by 5 radiation oncologists, with a random subset of patients repeated to quantify intraobserver contouring variability. To minimize bias in contouring the prostate, the image sets were placed in folders in a random order with all identifiers removed from the images.

Results: Although there was less interobserver contouring variability in the overall prostate volumes in 1.5-T MRI compared with 3.0-T MRI (p < 0.01), there was no significant differences in contouring variability in the different regions of the prostate between 1.5-T MRI and 3.0-T MRI. MRI demonstrated significantly less interobserver contouring variability in both 1.5-T and 3.0-T compared with CT in overall prostate volumes (p < 0.01, p = 0.01), with the greatest benefits being appreciated in the base of the prostate. Overall, there was less intraobserver contouring variability than interobserver contouring variability for all of the measurements analyzed.

Conclusions: Use of 3.0-T MRI does not demonstrate a significant improvement in contouring variability compared with 1.5-T MRI, although both magnetic strengths demonstrated less contouring variability compared with CT.
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http://dx.doi.org/10.1016/j.ijrobp.2010.03.019DOI Listing
July 2011

Phase I dose escalation trial of hypofractionated limited-field external beam thoracic radiotherapy for limited-stage small cell carcinoma of the lung.

Radiother Oncol 2010 Jul 11;96(1):78-83. Epub 2010 Jun 11.

Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alta., Canada.

Purpose: To define the maximal tolerated dose of hypofractionated thoracic radiotherapy given with concurrent chemotherapy for limited-stage small cell lung cancer.

Materials And Methods: Limited-stage small cell lung cancer patients were prescribed 54, 58, 62 or 65 Gy, all given in 25 daily fractions and commenced on or before the second chemotherapy cycle. Dose level accrual was performed sequentially. Conformal radiotherapy techniques were used and targeted gross disease plus margin. Four cycles of platinum-based chemotherapy were prescribed. Primary endpoint was the rate of acute RT toxicities according to NCI Common Toxicity Criteria scales. The dose which caused unacceptable acute radiotherapy toxicity rates according to pre-defined stopping rules defined the maximal tolerated radiotherapy dose.

Results: Six patients were accrued to each of the 54, 58 and 62 Gy dose levels. There were no radiotherapy-related deaths. No grade 3 toxicities occurred in the 54 and 58 Gy groups. There were 2 grade 3 RT toxicities in the 62 Gy group. There were 14 complete responses. Trial accrual has stopped at the 62 Gy group according to trial stopping rules.

Conclusions: The maximal tolerated hypofractionated thoracic radiotherapy dose in this trial was 58 Gy in 25 daily fractions.
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http://dx.doi.org/10.1016/j.radonc.2010.05.013DOI Listing
July 2010

Identification of a new microRNA expression profile as a potential cancer screening tool.

Clin Invest Med 2010 Apr 1;33(2):E124. Epub 2010 Apr 1.

Alberta Laboratory for Environmental Cancer Risk & Assessment, Alberta, Canada.

Purpose: Small non-coding microRNAs (miRNAs) are key components of cancer development and are considered as potential biomarkers for cancer diagnosis and treatment monitoring. This study investigated miRNA expression profiles of human cancer cells in order to develop a screening method for lung cancer.

Methods: A series of lung cancer related miRNAs (miR-21, miR-145, miR-155, miR-205, miR-210, miR-92, miR-17-5p, miR-143, miR-182, miR-372, let-7a) were selected as candidates for miRNA expression profiles of human lung cancer cell lines (A549, SK-mes-1). MicroRNA u6 was the endogenous control. Cancer cell lines for positive controls; breast MCF-7, prostate Du-145, and glioblastoma U118. The negative control was normal lung fibroblast cell line MRC-5. RT-PCR was performed on StepOnePlus (Applied Biosystem, USA). MiRNA expressions of malignant cells were compared with normal fibroblast cells as well as endogenous control (u6) using the thermal cycle at threshold. Assessment of miRNA expression profiles were then performed using agglomerative hierarchical cluster analysis software (SPSS13, USA).

Results: We demonstrated that miR-21, miR-182 and let7-5a were over-expressed, and miR-145 and miR-155 were under-expressed in all cancer cell lines. Combined with the cluster analysis we were able to clearly distinguish cell lines for normal fibroblasts, breast cancer, prostate cancer, glioblastoma, and lung cancer.

Conclusion: There is potential utility of screening for lung cancer with miRNA expression profiles. Future work will focus on the sensitivity of such miRNA expression profiles in screening sputum for lung cancer, which can be performed in real time.
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http://dx.doi.org/10.25011/cim.v33i2.12351DOI Listing
April 2010

Time course of prostatic edema post permanent seed implant determined by magnetic resonance imaging.

Brachytherapy 2010 Oct-Dec;9(4):354-61. Epub 2010 Jan 29.

Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta, Canada.

Purpose: To quantify the time course of postimplant prostatic edema magnitude and spatial isotropy using serial magnetic resonance imaging (MRI).

Methods And Materials: Forty patients with histologic diagnosis of prostate cancer received an iodine-125 seed implant (Day 0) and consented to 1.5-T MRI on Days -1, 0, 14, and 28. Seeds of strength 0.39mCi were placed in a modified peripheral loading pattern to deliver 145Gy to the target volume. MR images consisted of 3-4mm thick axial slices with no gap. The image sets were anonymized and randomized to minimize contouring bias, then contoured by a single radiation oncologist. Contours were reoriented about their center of mass to align the prostate long axis with the superior-inferior (S-I) direction; prostate volumes and dimensions in the left-right (L-R), anterior-posterior (A-P), and S-I directions through the center of mass were calculated.

Results: The average relative edema volume was 1.18±0.14 (1standard deviation) on Day 0 and 1.01±0.15 on Day 30. Between Days 0 and 30, the edema resolved linearly with time on average. Average relative edema dimensions on Day 0 in the L-R, A-P, and S-I directions were 1.01±0.07, 1.11±0.09, and 1.08±0.13, respectively.

Conclusions: As measured using MRI, the average edema magnitude for our study population was ∼20% on Day 0 and resolved linearly with time to ∼0% on Day 30. The edema exhibited spatial anisotropy, the prostate expanding on Day 0 by ∼10% in each of the A-P and S-I directions and by ∼0% in the L-R direction.
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http://dx.doi.org/10.1016/j.brachy.2009.09.008DOI Listing
February 2011

A case of indirect cauda equina syndrome from metastatic prostate cancer.

Can Urol Assoc J 2009 Aug;3(4):E31-E35

Departments of Radiation Oncology and.

We report the case of a patient with metastatic hormone refractory prostate cancer in whom "indirect" cauda equina syndrome developed concurrent with multilevel spinal cord compression (SCC). Three months after his first positive bone scan, a 65-year-old otherwise healthy man presented with severe back pain, bilateral lower extremity paresthesias, leg weakness and urinary retention. Magnetic resonance imaging (MRI) showed a dural-based mass causing SCC at the T9, T10 and T11 vertebrae, with a normal cauda equina. He received corticosteroids and palliative external beam radiotherapy, resulting in good pain control and gradual improvement in his neurological symptoms. He did well for 8 months, at which time his residual bilateral leg weakness abruptly worsened and he experienced numbness, paresthesias, urinary incontinence and constipation. Repeat MRI showed progression of epidural metastatic disease compressing the spinal cord or thecal sac at 7 thoracic vertebral levels. The cauda equina was also distorted and flattened without evidence of direct solid tumour impingement. We hypothesized that the etiology was increased intrathecal pressure due to disrupted cerebrospinal fluid flow resulting from multiple levels of upstream thecal sac compression. It is essential to image the entire spinal cord and cauda equina when patients with metastatic bone disease present with neurological symptoms to institute correct treatment and preserve function and mobility.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723889PMC
http://dx.doi.org/10.5489/cuaj.1137DOI Listing
August 2009

Cone beam CT imaging analysis of interfractional variations in bladder volume and position during radiotherapy for bladder cancer.

Int J Radiat Oncol Biol Phys 2010 Mar 18;76(4):1045-53. Epub 2009 Jun 18.

Department of Radiation Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada.

Purpose: To quantify daily bladder size and position variations during bladder cancer radiotherapy.

Methods And Materials: Ten bladder cancer patients underwent daily cone beam CT (CBCT) imaging of the bladder during radiotherapy. Bladder and planning target volumes (bladder/PTV) from CBCT and planning CT scans were compared with respect to bladder center-of-mass shifts in the x (lateral), y (anterior-posterior), and z (superior-inferior) coordinates, bladder/PTV size, bladder/PTV margin positions, overlapping areas, and mutually exclusive regions.

Results: A total of 262 CBCT images were obtained from 10 bladder cancer patients. Bladder center of mass shifted most in the y coordinate (mean, -0.32 cm). The anterior bladder wall shifted the most (mean, -0.58 cm). Mean ratios of CBCT-derived bladder and PTV volumes to planning CT-derived counterparts were 0.83 and 0.88. The mean CBCT-derived bladder volume (+/- standard deviation [SD]) outside the planning CT counterpart was 29.24 cm(3) (SD, 29.71 cm(3)). The mean planning CT-derived bladder volume outside the CBCT counterpart was 47.74 cm(3) (SD, 21.64 cm(3)). The mean CBCT PTV outside the planning CT-derived PTV was 47.35 cm(3) (SD, 36.51 cm(3)). The mean planning CT-derived PTV outside the CBCT-derived PTV was 93.16 cm(3) (SD, 50.21). The mean CBCT-derived bladder volume outside the planning PTV was 2.41 cm(3) (SD, 3.97 cm(3)). CBCT bladder/ PTV volumes significantly differed from planning CT counterparts (p = 0.047).

Conclusions: Significant variations in bladder and PTV volume and position occurred in patients in this trial.
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http://dx.doi.org/10.1016/j.ijrobp.2009.03.022DOI Listing
March 2010

Acute toxicity in high-risk prostate cancer patients treated with androgen suppression and hypofractionated intensity-modulated radiotherapy.

Int J Radiat Oncol Biol Phys 2010 Jan;76(1):57-64

Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.

Purpose: To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients.

Methods And Materials: Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of > or =T3a or an initial prostate-specific antigen [PSA] level of > or =20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales.

Results: All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity.

Conclusion: Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required.
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http://dx.doi.org/10.1016/j.ijrobp.2009.01.048DOI Listing
January 2010

Enhanced radiation sensitivity in prostate cancer by gold-nanoparticles.

Clin Invest Med 2008 ;31(3):E160-7

Alberta Laboratory for Environmental Cancer Risk & Assessment, Cross Cancer Institute, Edmonton, Alberta.

Purpose: Nanotechnology is an emerging field with significant translational potential in medicine. In this study, we applied gold nanoparticles (GNP) to enhance radiation sensitivity and growth inhibition in radiation-resistant human prostate cancer cells.

Methods: Gold nanoparticles (GNPs) were synthesized using HAuCl4 as the gold particle source and NaBH4 as the reductant. Either thio-glucose or sodium citrate was then added to the solution separately to bind the GNPs to form thio-glucose-capped gold nanoparticles (Glu-GNP) and neutral gold nanoparticles (TGS-GNPs). Human prostate carcinoma DU-145 cells were exposed to vehicle, irradiation, 15nM TGS-GNPs, or 15nM Glu-GNPs, or GNPs plus irradiation. The uptake assays of GNP were performed using hemocytometer to count cells and the mass spectrometry was applied to calculate gold mass. The cytotoxicity induced by GNPs, irradiation, or GNPs plus irradiation was measured using a standard colorimetric MTT assay.

Results: Exposure to Glu-GNPs resulted in a three times increase of nanoparticle uptake compared to that of TGS-GNPs in each target cell (p < 0.005). Cytoplasmic intracellular uptake of both TGS-GNPs and Glu-GNPs resulted in a growth inhibition by 30.57% and 45.97% respectively, comparing to 15.88% induced by irradiation alone, in prostate cancer cells after exposure to the irradiation. Glu-GNPs showed a greater enhancement, 1.5 to 2 fold increases within 72 hours, on irradiation cytotoxicity compared to TGS-GNPs. Tumour killing, however, did not appear to correlate linearly with nanoparticle uptake concentrations.

Conclusion: These results showed that functional glucose-bound gold nanoparticles enhanced radiation sensitivity and toxicity in prostate cancer cells. In vivo studies will be followed to verify our research findings.
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http://dx.doi.org/10.25011/cim.v31i3.3473DOI Listing
August 2008

Malignant spinal cord compression secondary to testicular seminoma at the time of initial presentation and at relapse while on surveillance.

Can Urol Assoc J 2007 Mar;1(1):59-63

Department of Oncology, and Division of Radiology, Cross Cancer Institute, Edmonton, Alta.

We report cases of 2 pure seminoma patients who developed metastatic spinal cord compressions. One patient was diagnosed at age 33 years with stage 1 seminoma and, after undergoing an orchidectomy, chose to be followed on a surveillance protocol. He was lost to follow-up and presented again 22 months later with back pain, leg weakness and sensory loss when his disease recurred as a spinal cord compression. He was treated with urgent surgical decompression and subsequent standard chemotherapy. More than 2 years posttreatment, he is disease-free with normal neurologic function in his lower extremities. The second patient presented at age 44 years with back pain and rapid loss of leg strength and sensation. Investigations revealed a malignant cord compression with lymphatic and vertebral body metastases. On physical examination, the patient was found to have a 6-cm left testicular mass. He was treated with emergency radiotherapy to the region of his cord compression followed by a left inguinal orchidectomy. Pathology confirmed a pure classic seminoma. Postoperatively, he received standard chemotherapy and eventually regained neurologic function in his legs. Although it is rare for malignant spinal cord compression to occur in seminoma patients-either as the initial presentation of disease or as a site of disease recurrence in stage 1 patients on surveillance-it is crucial to consider seminoma as a possible etiology in young men diagnosed with malignant spinal cord compression because timely contemporary treatments for seminoma will cure most of these patients and offer them excellent functional recovery.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2422929PMC
http://dx.doi.org/10.5489/cuaj.41DOI Listing
March 2007