Publications by authors named "John Amanie"

23 Publications

  • Page 1 of 1

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

Patient Reported Outcomes in NRG Oncology RTOG 0938, Evaluating Two Ultrahypofractionated Regimens for Prostate Cancer.

Int J Radiat Oncol Biol Phys 2018 10 18;102(2):287-295. Epub 2018 Jun 18.

Vanderbilt University Medical Center, Nashville, Tennessee.

Purpose: There is considerable interest in very short (ultrahypofractionated) radiation therapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience, and resource allocation benefits. Our objective is to demonstrate that detectable changes in health-related quality of life measured by the bowel and urinary domains of the Expanded Prostate Cancer Index Composite (EPIC-50) were not substantially worse than baseline scores.

Methods And Materials: NRG Oncology's RTOG 0938 is a nonblinded randomized phase 2 study of National Comprehensive Cancer Network low-risk prostate cancer in which each arm is compared with a historical control. Patients were randomized to 5 fractions (7.25 Gy in 2 weeks) or 12 fractions (4.3 Gy in 2.5 weeks). The co-primary endpoints were the proportion of patients with a change in EPIC-50 bowel score at 1 year (baseline to 1 year) >5 points and in EPIC-50 urinary score >2 points tested with a 1-sample binomial test.

Results: The study enrolled 127 patients to 5 fractions (121 analyzed) and 128 patients to 12 fractions (125 analyzed). Median follow-up for all patients at the time of analysis was 3.8 years. The 1-year frequency for >5 point change in bowel score were 29.8% (P < .001) and 28.4% (P < .001) for 5 and 12 fractions, respectively. The 1-year frequencies for >2 point change in urinary score were 45.7% (P < .001) and 42.2% (P < .001) for 5 and 12 fractions, respectively. For 5 fractions, 32.9% of patients had a drop in 1-year EPIC-50 sexual score of ≥11 points (P = .34); for 12 fractions, 30.9% of patients had a drop in 1-year EPIC-50 sexual score of ≥ 11 points (P = .20). Disease-free survival at 2 years is 99.2% (95% confidence interval: 97.5-100) in the 5-fraction arm and 97.5% (95% confidence interval: 94.6-100) in the 12-fraction arm. There was no late grade 4 or 5 treatment-related urinary or bowel toxicity.

Conclusions: This study confirms that, based on changes in bowel and urinary domains and toxicity (acute and late), the 5- and 12-fraction regimens are well tolerated. These ultrahypofractionated approaches need to be compared with current standard radiation therapy regimens.
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http://dx.doi.org/10.1016/j.ijrobp.2018.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248906PMC
October 2018

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

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

Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance.

World J Radiol 2016 Apr;8(4):410-8

Larissa J Vos, Keith Wachowicz, Atiyah Yahya, Oleksandr Boychak, John Amanie, Nadeem Pervez, Matthew B Parliament, Edith Pituskin, B Gino Fallone, Nawaid Usmani, Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 1Z2, Canada.

Aim: To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer.

Methods: Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated.

Results: During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity).

Conclusion: Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods.
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http://dx.doi.org/10.4329/wjr.v8.i4.410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840199PMC
April 2016

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

Carcinoma of unknown primary in the inguinal lymph node region of squamous cell origin: A case series.

Pract Radiat Oncol 2014 Nov-Dec;4(6):404-8. Epub 2014 Feb 18.

Allan Blair Cancer Centre, Regina, Saskatchewan, Canada.

Purpose: Cancer of unknown primary (CUP) of the inguinal region is a rare clinical entity that accounts for 1%-3 % of all CUPs. Of the inguinal lymph node region CUPs, about 10%-15% are of squamous cell origin. This study presents a case series of CUP of the inguinal region of squamous cell origin treated in our institution and review of the outcome.

Methods And Materials: We have identified 9 patients treated during the period of 1990-2010. All patients were treated radically with chemoradiation. Regimens used were 5-fluorouracil (5-FU)/cisplatin combination (n = 8) or 5-FU/mitomycin-C (n = 1) regimen. Tumor doses were 5400 cGy (n = 7), 5500 cGy (n = 1), and 5040 cGy (n = 1).

Results: The median duration of follow-up was 56 months (range, 10-76 months) for the whole group. There were no deaths or local or distant recurrences reported till the last recorded date of follow-up.

Conclusions: Our retrospective data showed significant long-term disease control for patients with localized inguinal region CUP of squamous cell origin who received concurrent chemoradiation.
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http://dx.doi.org/10.1016/j.prro.2013.12.007DOI Listing
July 2015

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

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

A Phase I Study of Tomotherapy in Patients With Primary Benign and Low-grade Brain Tumors: Late Toxicity and Quality of Life.

Am J Clin Oncol 2016 Apr;39(2):160-6

*Department of Radiation Oncology, Cross Cancer Institute, Edmonton, AB †Department of Radiation Oncology, London Health Sciences Centre, London, ON ‡Department of Radiation Oncology, Montreal General Hospital, McGill, QC, Canada.

Objectives: To evaluate longitudinal quality of life and late neurotoxicity (>12 mo) of tomotherapy in patients with primary benign and low-grade brain tumors.

Methods: Between January 2006 and October 2009, 49 patients with brain tumors were treated with tomotherapy at 2 radiotherapy centers in Canada. The median age of the patients was 51.0 years (range, 21 to 74 y); there were 21 men (42.86%) and 28 women (57.14%). All 49 patients had an initial Karnofsky performance score ≥70. One patient (2.04%) received 45 Gy in 25 fractions, 27 patients (55.10%) received 50.4 Gy in 28 fractions, 15 patients (30.6%) received 54 Gy in 30 fractions, and 5 patients (10.2%) received 60 Gy in 30 fractions. A total of 47 patients were analyzed for late toxicity and outcomes.

Results: Changes in the Karnofsky Performance Status of the patients did not reach statistical significance (P>0.05). The majority of the quality of life parameters that reached a statistically significant level (P<0.05) of change at 2 years were changes toward improvement (drowsiness, itchy skin, emotional functioning, fatigue, nausea, and appetite). Statistically significant (P<0.05) interval deterioration in physical, role, and social functioning was observed. Actuarial overall survival at 5 years was 91.6%; disease-free survival at 5 years was 86.6%.

Conclusions: IMRT helical tomotherapy is well tolerated, without statistically significant constitutional and late neurotoxicity up to the 2-year mark.
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http://dx.doi.org/10.1097/COC.0000000000000034DOI Listing
April 2016

The biodistribution and pharmacokinetic evaluation of choline-bound gold nanoparticles in a human prostate tumor xenograft model.

Clin Invest Med 2013 Jun 1;36(3):E133-42. Epub 2013 Jun 1.

Division of General Surgery, Department of Surgery, University of Alberta Hospital, Edmonton, Alberta, Canada.

Purpose: Gold nanoparticles (GNPs) have attracted significant attention in the treatment of cancer due to their potential as novel radiation enhancers, particularly when functionalized with various targeting ligands. The aim of this study was to assess the biodistribution and pharmacokinetic characteristics of a novel choline-bound GNP (choline-GNP) stabilized with polyethelenimine (PEI).

Methods: Choline bound to 27 nm diameter GNPs was characterized using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Toxicity of choline-GNPs was examined on DU-145 prostate cancer cells using an MTT assay. Using balb/c mice bearing flank DU-145 prostate tumors, choline-GNPs bio-distribution was measured using inductively coupled mass spectroscopy (ICP-MS). Blood, heart, lung, liver, spleen, brain, kidney and tumor gold content were examined at multiple time points over a 24-hour period after tail vein injection.

Results: An MTT assay using DU-145 prostate cancer cells yielded a 95% cell viability 72 hours after choline-GNP administration. The tumor GNP area under the concentration-time curve during the first 4 hours (AUC0-4) was 2.2 µg/ml h, representing 13% of the circulating blood GNP concentration over the same time period. The maximum intra-tumor GNP concentration observed was 1.4% of the injected dose per gram of tumor tissue (%ID/g) one hour post injection.

Conclusions: GNPs functionalized with choline demonstrates a viable future nanoparticle platform with increased intra-tumor uptake as compared to unconjugated GNPs. Decreased intra-hepatic accumulation appears to be the reason for the improved systemic bioavailability. The next logical translational investigation will incorporate external beam radiation with the observed maximum intra-tumor uptake.
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http://dx.doi.org/10.25011/cim.v36i3.19724DOI Listing
June 2013

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

An evaluation of the Clarity 3D ultrasound system for prostate localization.

J Appl Clin Med Phys 2012 Jul 5;13(4):3753. Epub 2012 Jul 5.

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

The purpose of this study is to evaluate the accuracy and precision of the Clarity 3D ultrasound system to track prostate gland positional variations due to setup error and organ motion. Seventeen patients (n = 17) undergoing radical external beam radiation therapy for localized prostate cancer were studied. Subsequent to initial reference ultrasound and planning CT scans, each patient underwent seven repeat weekly tracking CT and ultrasound (US) scans during the course of treatment. Variations in the location of the prostate between reference and tracking scans were measured. Differences reported by CT and ultrasound scans are compared. Ultrasound tracking was initially performed clinically by a group of trained general users. Retrospective prostate localization was then performed by a trained dedicated user upon the original raw data set and also a reduced data set derived from the original by an expert user from Resonant Medical. Correlation accuracy between ultrasound and CT shifts acquired and delineated by a pool of trained general users was deemed unacceptable for radiotherapy purposes. A mean discrepancy between CT and US localizations of greater than 10 mm, with a 5 mm or greater discrepancy rate of nearly 90%, was observed. Retrospective analysis by a dedicated user of both the original and Resonant Medical reduced data sets yielded mean CT-Us discrepancies of 8.7 mm and 7.4 mm, respectively. Unfortunately, the 5 mm or greater CT-US discord rate for these retrospective analyses failed to drop below 80%. The greatest disparity between CT and ultrasound was consistently observed in the superior-inferior direction, while greatest agreement was achieved in the lateral dimension. Despite an expert reanalysis of the original data, the Clarity ultrasound system failed to deliver an acceptable level of geometric accuracy required for modern radiotherapy purposes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716521PMC
http://dx.doi.org/10.1120/jacmp.v13i4.3753DOI Listing
July 2012

Skin-sparing helical tomotherapy vs 3D-conformal radiotherapy for adjuvant breast radiotherapy: in vivo skin dosimetry study.

Int J Radiat Oncol Biol Phys 2012 Aug 12;83(5):e583-90. Epub 2012 May 12.

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

Purpose: We investigated whether treatment-planning system (TPS)-calculated dose accurately reflects skin dose received for patients receiving adjuvant breast radiotherapy (RT) with standard three-dimensional conformal RT (3D-CRT) or skin-sparing helical tomotherapy (HT).

Methods And Materials: Fifty patients enrolled in a randomized controlled trial investigating acute skin toxicity from adjuvant breast RT with 3D-CRT compared to skin-sparing HT, where a 5-mm strip of ipsilateral breast skin was spared. Thermoluminescent dosimetry or optically stimulated luminescence measurements were made in multiple locations and were compared to TPS-calculated doses. Skin dosimetric parameters and acute skin toxicity were recorded in these patients.

Results: With HT there was a significant correlation between calculated and measured dose in the medial and lateral ipsilateral breast (r = 0.67, P<.001; r = 0.44, P=.03, respectively) and the medial and central contralateral breast (r = 0.73, P<.001; r = 0.88, P<.001, respectively). With 3D-CRT there was a significant correlation in the medial and lateral ipsilateral breast (r = 0.45, P=.03; r = 0.68, P<.001, respectively); the medial and central contralateral breast (r = 0.62, P=.001; r = 0.86, P<.001, respectively); and the mid neck (r = 0.42, P=.04, respectively). On average, HT-calculated dose overestimated the measured dose by 14%; 3D-CRT underestimated the dose by 0.4%. There was a borderline association between highest measured skin dose and moist desquamation (P=.05). Skin-sparing HT had greater skin homogeneity (homogeneity index of 1.39 vs 1.65, respectively; P=.005) than 3D-CRT plans. HT plans had a lower skin(V50) (1.4% vs 5.9%, respectively; P=.001) but higher skin(V40) and skin(V30) (71.7% vs 64.0%, P=.02; and 99.0% vs 93.8%, P=.001, respectively) than 3D-CRT plans.

Conclusion: The 3D-CRT TPS more accurately reflected skin dose than the HT TPS, which tended to overestimate dose received by 14% in patients receiving adjuvant breast RT.
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http://dx.doi.org/10.1016/j.ijrobp.2012.01.086DOI Listing
August 2012

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

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

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

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

Results of a phase I study to dose escalate using intensity modulated radiotherapy guided by combined PET/CT imaging with induction chemotherapy for patients with non-small cell lung cancer.

Radiother Oncol 2004 Dec;73(3):285-7

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

Intensity modulated radiation therapy (IMRT) guided by PET/CT imaging with respiratory gating was employed to dose escalate in patients with non-small cell lung cancer (NSCLC), using accelerated fractionation with induction chemotherapies. One patient developed a grade 5 pneumonitis and the study was halted at 84 Gy in 35 fractions.
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http://dx.doi.org/10.1016/j.radonc.2004.07.033DOI Listing
December 2004