Publications by authors named "Gerard Morton"

106 Publications

Utilization of Salvage and Systemic Therapies for Recurrent Prostate Cancer as a Result of F-DCFPyL PET/CT Restaging.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100553. Epub 2020 Sep 9.

Department of Oncology, Division of Radiation Oncology, London Health Sciences Centre and Western University, London, Canada.

Purpose: Our purpose was to investigate the effect of the addition of prostate-specific membrane antigen (PSMA)-targeted positron emission tomography/computed tomography (PET/CT) in patients with recurrent prostate cancer post-primary radiation therapy.

Methods And Materials: A prospective, multi-institutional clinical trial evaluated 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (F-DCFPyL) PET/CT restaging in 79 men with recurrent prostate cancer post-primary radiation therapy. We report actual patient management and compare this with proposed management both before and after PSMA-targeted PET/CT.

Results: Most patients (59%) had a major change in actual management compared with pre-PET/CT proposed management. The rate of major change was underestimated by immediately post-PET/CT surveys (32%). Eighteen patients with PSMA avidity in the prostate gland suspicious for malignancy had a prostate biopsy. Sensitivity, specificity, and positive predictive values of PSMA uptake in the prostate were 86%, 67%, and 92%, respectively. Thirty percent of patients had directed salvage therapy and 41% underwent systemic therapy. Eleven out of 79 patients (14%) had high-dose-rate brachytherapy alone for local recurrence, and 91% were free of recurrence at a median follow-up of 20 months.

Conclusions: Most patients had a major change in actual management compared with pre-PSMA-targeted PET/CT planned management, and this was underestimated by post-PET/CT questionnaires.
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http://dx.doi.org/10.1016/j.adro.2020.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820022PMC
September 2020

Prostate high dose-rate brachytherapy as monotherapy for prostate cancer: Late toxicity and patient reported outcomes from a randomized phase II clinical trial.

Radiother Oncol 2021 Jan 4;156:160-165. Epub 2021 Jan 4.

Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Canada. Electronic address:

Background And Purpose: Long-term toxicity of high dose-rate brachytherapy as monotherapy for prostate cancer is not well defined. We report late toxicity and health related quality of life (HRQOL) changes from a randomized phase II clinical trial of two different fractionation schemes.

Materials And Methods: Eligible patients had NCCN low or intermediate risk prostate cancer. 170 patients were randomized to receive either a single 19 Gy or two-fractions of 13.5 Gy one week apart. Toxicity was measured using Common Terminology for Adverse Events (CTCAE) v4.0, and HRQOL was measured using the Expanded Prostate Index Composite (EPIC).

Results: Median follow-up was 63 months. The 5-year cumulative incidence of Grade 2 or higher genitourinary (GU) and gastrointestinal (GI) toxicity was 62% and 12% in the single-fraction arm, and 47% and 9% in the two-fraction arm, respectively. Grade 3 GU toxicity was only seen in the single fraction arm with a cumulative incidence of 2%. The 5-year prevalence of Grade 2 GU toxicity was 29% and 21%, in the single- and two-fraction arms, respectively, with Grade 2 GI toxicity of 1% and 2%. Beyond the first year, no significant differences in mean urinary HRQOL were seen compared to baseline in the two-fraction arm, in contrast to the single-fraction arm where a decline in urinary HRQOL was seen at 4 and 5 years. Sexual HRQOL was significantly reduced in both treatment arms at all timepoints, with no changes in the bowel domain.

Conclusions: HDR monotherapy is well tolerated with minimal impact on HRQOL.
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http://dx.doi.org/10.1016/j.radonc.2020.12.021DOI Listing
January 2021

Current topics in radiotherapy for genitourinary cancers: Consensus statements of the Genitourinary Radiation Oncologists of Canada.

Can Urol Assoc J 2020 Nov;14(11):E588-E593

Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, ON, Canada.

Introduction: The biennial meeting of the Genitourinary Radiation Oncologists of Canada (GUROC) took place November 22-23, 2019. A consensus-building session was held during the meeting addressing topics of emerging interest or controversy in the management of genitourinary malignancies.

Methods: Draft statements were debated among all meeting attendees in an open forum with anonymous live voting. Statements for which there was at least 75% agreement among attendees were adopted as GUROC consensus.

Results: Four evidence-based consensus statements were developed. First, the use of prostate radiotherapy is recommended in the setting of de novo low-volume metastatic hormone-sensitive prostate cancer to improve overall survival. Second, the support of ongoing randomized trials evaluating metastasis-directed ablative local therapy in oligometastatic prostate cancer is recommended; where such trials are available, off-trial use of oligometastasis-directed ablative radiotherapy at this time is strongly discouraged. Third, routine use of prostate-rectal hydrogel spacer devices in patients with localized prostate cancer planned to receive external beam radiotherapy is not recommended; instead, selective use in patients at highest risk of rectal toxicity may be considered. Finally, multidisciplinary consultation is recommended for all patients with newly diagnosed localized muscle-invasive bladder cancer.

Conclusions: The GUROC consensus statements provide practical guidance to clinicians in areas of current controversy in the management of prostate and bladder cancer, and it is hoped that their implementation will contribute to improved outcomes in real-world practice and greater support of clinical trials.
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http://dx.doi.org/10.5489/cuaj.6649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673835PMC
November 2020

Estimating acute urinary retention risk post prostate high dose-rate (HDR) brachytherapy: A clinical-based recursive partitioning analysis.

Radiother Oncol 2020 Sep 20;154:118-122. Epub 2020 Sep 20.

Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: To determine factors associated with need for post-procedural catheterization in prostate cancer patients treated with 15 Gy high dose-rate brachytherapy boost (HDR-BT).

Material And Methods: Patients treated with 15 Gy HDR-BT followed by EBRT were retrospectively evaluated for development of urinary retention and hematuria requiring catheterization in the first 30 days post procedure. Clinical characteristics and treatment details were obtained and used as independent variables under study. Univariable and multivariable logistic regression analysis were used to determine predictors of post brachytherapy complications and a classification tree for risk of urinary retention was created using recursive partitioning analysis (RPA).

Results: A total of 425 patients treated with 15 Gy HDR-BT were included in this analysis. 27 patients (6.3%) required catheter placement due to acute urinary retention and thirteen other patients (3%) developed hematuria requiring urinary catheter insertion ± continuous bladder irrigation. Number of needles, prostate volume and prior use of ADT, alpha-blockers or 5α-reductase inhibitors were statistically associated with urinary retention in the univariable logistic regression analysis. In multivariable analysis, prostate volume, previous use of alpha-blocker, and use of ADT remained significant. In the RPA, populations were identified in which the rate of urinary retention ranged from 2% to 50% depending on presence of one or more of these risk factors.

Conclusion: The overall rate of acute urinary complications post HDR brachytherapy is low, but the individual risk of urinary retention can increase depending on the number of risk factors present. A more patient-directed retention risk estimation can be performed by using the classification risk tree presented here.
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http://dx.doi.org/10.1016/j.radonc.2020.09.023DOI Listing
September 2020

Single-fraction HDR brachytherapy as monotherapy in low and intermediate risk prostate cancer: Outcomes from two clinical trials with and without an MRI-guided boost.

Radiother Oncol 2020 Sep 10;154:29-35. Epub 2020 Sep 10.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Canada. Electronic address:

Purpose: Single-fraction HDR monotherapy for the treatment of localized prostate cancer is appealing, but published outcomes are discouraging. An approach to improve local control is MRI-guided focal dose-escalation to the dominant intraprostatic lesion (DIL). Here we report a comparison of outcomes from two phase II clinical trials with and without a focal boost.

Methods: Patients had low or intermediate-risk disease. Patients in Trial1 received a single 19 Gy HDR implant to the whole prostate. Trial2 incorporated an additional MRI-guided focal DIL boost to at least 23 Gy. ADT was not allowed. Toxicities (CTCAEv4.0) and quality of life (EPIC) were collected. Biochemical failure (BF) was defined as nadir +2. Univariate and multivariate logistic regression analysis was conducted to search for predictors of BF.

Results: Trial1 had 87 patients with a median follow-up of 62 months, while Trial2 had 60 patients with a median follow-up of 50 months. The five-year cumulative BF rate was 32.6% and 31.3%, respectively (p = 0.9). 77.5% of failures were biopsy-confirmed local failures, all of which underwent local salvage therapy. The addition of a DIL boost was not associated with worse toxicity or QOL. Baseline PSA and Gleason score correlated with BF, but none of the dosimetric parameters was a significant predictor of BF.

Conclusions: MRI-guided focal boost was safe and well tolerated, but did not improve local control after 19 Gy single-fraction HDR monotherapy, and the control rates were unacceptable. Single-fraction HDR monotherapy for prostate cancer should not be offered outside of clinical trials.
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http://dx.doi.org/10.1016/j.radonc.2020.09.007DOI Listing
September 2020

Is prostate brachytherapy a dying art? Trends and variation in the definitive management of prostate cancer in Ontario, Canada.

Radiother Oncol 2020 Nov 24;152:42-48. Epub 2020 Jul 24.

Division of Radiation Oncology, Department of Oncology, London Health Sciences Centre, London, Canada.

Background And Purpose: Declining prostate brachytherapy utilization has been reported in several studies, despite strong evidence for efficacy and safety compared to alternatives. We sought to evaluate contemporary trends in brachytherapy, external beam radiotherapy (EBRT) and prostatectomy utilization in a publicly funded healthcare system.

Materials And Methods: Men with localized prostate cancer diagnosed and treated between 2006 and 2017 in Ontario, Canada were identified using administrative data. Men received EBRT, brachytherapy (monotherapy or boost) or prostatectomy as initial definitive management. Multivariable logistic regression evaluated patient-, tumour-, and provider-factors on treatment utilization.

Results: 61,288 men were included. On multivariable regression, the odds of receiving brachytherapy boost increased 24% per year (odds ratio [OR]:1.24, 95% CI 1.22-1.26, p < 0.01), brachytherapy monotherapy increased 3% per year (OR:1.03, 95% CI:1.02-1.04, p < 0.01), and prostatectomy declined by 6% per year (OR:0.94, 95% CI 0.93-0.95, p < 0.01). Treatment year was not significant on multivariable modelling of EBRT. In a separate multivariable model limited to those who received radiotherapy, if the first radiation oncologist seen performed brachytherapy, the OR of receiving brachytherapy monotherapy over EBRT was 5.66 (95% CI: 5.11-6.26, p < 0.01) and 2.88 (95% CI: 2.60-3.19, p < 0.01) for brachytherapy boost over EBRT alone. Substantial geographic, provider and patient variation in treatment receipt was observed.

Conclusion: We found increasing brachytherapy utilization, largely driven by increasing utilization of brachytherapy boost. To our knowledge, this is the first report of increasing brachytherapy use in the era of dose escalated EBRT.
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http://dx.doi.org/10.1016/j.radonc.2020.07.036DOI Listing
November 2020

Dosimetric evaluation of MRI-to-ultrasound automated image registration algorithms for prostate brachytherapy.

Brachytherapy 2020 Sep - Oct;19(5):599-606. Epub 2020 Jul 22.

Department of Medical Physics, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address:

Purpose: Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy treatment planning remains a significant challenge. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study assesses the dosimetric impact attributed to differences in DIL contours generated using commonly available MRI to TRUS automated registration: rigid, semi-rigid, and deformable image registration, respectively.

Methods And Materials: Ten patients, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists with expertise in TRUS-based high-dose-rate brachytherapy were asked cognitively to transfer the DIL from the mpMRI images of each patient to the TRUS image. The contours were analyzed for concordance using simultaneous truth and performance level estimation (STAPLE) algorithm. The impact of DIL contour differences due to registration variability was evaluated by comparing the STAPLE-DIL dosimetry from the reference (STAPLE) plan with that from the evaluation plans (manual and automated registration) for each patient. The dosimetric impact of the automatic registration approach was also validated using a margin expansion that normalizes the volume of the autoregistered DILs to the volumes of the STAPLE-DILs. Dose metrics including D, D, V, and V to the prostate and DIL were reported. For urethra and rectum, D and V were reported.

Results: Significant differences in DIL coverage between reference and evaluation plans were found regardless of the algorithm methodology. No statistical difference was reported in STAPLE-DIL dosimetry when manual registration was used. A margin of 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm was required to be added for rigid, semi-rigid, and deformable registration, respectively, to mitigate the difference in STAPLE-DIL coverage between the evaluation and reference plans.

Conclusion: The dosimetric impact of integrating an MRI-delineated DIL into a TRUS-based brachytherapy workflow has been validated in this study. The results show that rigid, semi-rigid, and deformable registration algorithms lead to a significant undercoverage of the DIL D and D. A margin of at least 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm is required to be added to the rigid, semi-rigid, and deformable DIL registration to be suitable for DIL-boosting during prostate brachytherapy.
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http://dx.doi.org/10.1016/j.brachy.2020.06.014DOI Listing
July 2020

Radiation Oncology Fellowship: a Value-Based Assessment Among Graduates of a Mature Program.

J Cancer Educ 2020 Jul 18. Epub 2020 Jul 18.

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, M5G 2M9, Canada.

The University of Toronto - Department of Radiation Oncology (UTDRO) has had a well-established Fellowship Program for over 20 years. An assessment of its graduates was conducted to evaluate training experience and perceived impact on professional development. Graduates of the UTDRO Fellowship Program between 1991 and 2015 were the focus of our review. Current employment status was collected using online tools. A study-specific web-based questionnaire was distributed to 263/293 graduates for whom active e-mails were identified; questions focused on training experience, and impact on career progression and academic productivity. As a surrogate measure for the impact of UTDRO Fellowship training, a comparison of current employment and scholarly activities of individuals who obtained their Fellow of the Royal College of Physicians of Canada (FRCPC) designation in Radiation Oncology between 2000 and 2012, with (n = 57) or without (n = 230) UTDRO Fellowship training, was conducted. Almost all UTDRO Fellowship graduates were employed as staff radiation oncologists (291/293), and most of those employed were associated with additional academic (130/293), research (53/293), or leadership (68/293) appointments. Thirty-eight percent (101/263) of alumni responded to the online survey. The top two reasons for completing the Fellowship were to gain specific clinical expertise and exposure to research opportunities. Respondents were very satisfied with their training experience, and the vast majority (99%) would recommend the program to others. Most (96%) felt that completing the Fellowship was beneficial to their career development. University of Toronto, Department of Radiation Oncology Fellowship alumni were more likely to hold university, research, and leadership appointments, and author significantly more publications than those with FRCPC designation without fellowship training from UTDRO. The UTDRO Fellowship Program has been successful since its inception, with the majority of graduates reporting positive training experiences, benefits to scholarly output, and professional development for their post-fellowship careers. Key features that would optimize the fellowship experience and its long-term impact on trainees were also identified.
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http://dx.doi.org/10.1007/s13187-020-01767-5DOI Listing
July 2020

Does ADT benefit unfavourable intermediate risk prostate cancer patients treated with brachytherapy boost and external beam radiotherapy? A propensity-score matched analysis.

Radiother Oncol 2020 Sep 30;150:195-200. Epub 2020 Jun 30.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada. Electronic address:

Purpose: To investigate the role of androgen deprivation therapy (ADT) in unfavorable intermediate risk (UIR) prostate cancer patients treated with high-dose rate (HDR) brachytherapy (BT) boost.

Material And Methods: Data from 326 consecutive NCCN UIR prostate cancer patients treated in a single institution from 2009 to 2016 with 15 Gy HDR-BT boost plus 37.5 Gy external beam radiotherapy (EBRT) in 15 fractions to prostate and proximal seminal vesicles were retrospectively collected. Baseline information was collected and patients receiving vs. not receiving ADT were matched using a propensity-score model. Primary endpoint was biochemical-failure-free survival (BFFS). Kaplan-Meier estimates and stratified log-rank tests (adjusting for matched design) were used to compare BFFS, castration-resistance (CRFS) and metastasis free survival (MFS) outcomes between both groups.

Results: A total of 326 patients were included in the analysis of which 52 ADT patients were matched to 104 non-ADT patients in a 1:2 ratio. Median follow-up was 3.4 years and 5.5 years for ADT and non-ADT respectively. No significant baseline differences were observed. ADT was used for a median total time of 6 months (interquartile range [IQR]: 4-6) and delivered a median time of 2.7 months (IQR: 1.7-4.3) prior to HDR-BT. BFFS was significantly improved in the ADT group (stratified log-rank: p = 0.043) with 3-year and 6-year BFFS of 98% and 90% for the ADT group and 92% and 82% for the non-ADT group, respectively. No significant differences were detected for CRFS or MFS.

Conclusion: Short-term ADT increased BFFS in UIR prostate cancer patients treated with HDR-BT boost plus EBRT.
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http://dx.doi.org/10.1016/j.radonc.2020.06.039DOI Listing
September 2020

Brachytherapy education and certification-A Canadian approach.

Brachytherapy 2020 Nov - Dec;19(6):857-860. Epub 2020 Jun 24.

BC Cancer Kelowna, University of British Columbia, Kelowna, BC, Canada.

The Royal College of Physicians and Surgeons of Canada has established a diploma certification program in brachytherapy, with the goal of standardizing brachytherapy training and standards. The diploma may be obtained either by way of a training route or a Practice Eligibility Route. Training is undergone through a Royal College-accredited brachytherapy program, analogous to a residency program with clearly defined curriculum, objectives, and expectations. The trainee submits a portfolio demonstrating achievement of the various competencies required and typically takes 12 months to complete. The trainee is then equipped to function as a competent specialist in brachytherapy, capable of an enhanced practice in this area. To date, the University of Toronto has the only Royal College-accredited training program in brachytherapy, but other Universities are in the process of applying for accreditation. Those already in practice may apply for accreditation through a Practice Eligibility Route, by submitting evidence of competency in brachytherapy. Either route can lead to the awarding of a diploma in brachytherapy, recognized by the designation DRCPSC. The overall goal of this program is to enhance quality of care and improve patient safety by setting pan-Canadian standards for training and practice in this area.
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http://dx.doi.org/10.1016/j.brachy.2020.05.004DOI Listing
June 2020

Conventional vs machine learning-based treatment planning in prostate brachytherapy: Results of a Phase I randomized controlled trial.

Brachytherapy 2020 Jul - Aug;19(4):470-476. Epub 2020 Apr 19.

Department of Medical Physics, Sunnybrook Odette Cancer Centre, Toronto, ON, Canada. Electronic address:

Purpose: The purpose of this study was to evaluate the noninferiority of Day 30 dosimetry between a machine learning-based treatment planning system for prostate low-dose-rate (LDR) brachytherapy and the conventional, manual planning technique. As a secondary objective, the impact of planning technique on clinical workflow efficiency was also evaluated.

Materials And Methods: 41 consecutive patients who underwent I-125 LDR monotherapy for low- and intermediate-risk prostate cancer were accrued into this single-institution study between 2017 and 2018. Patients were 1:1 randomized to receive treatment planning using a machine learning-based prostate implant planning algorithm (PIPA system) or conventional, manual technique. Treatment plan modifications by the radiation oncologist were evaluated by computing the Dice coefficient of the prostate V isodose volume between either the PIPA-or conventional-and final approved plans. Additional evaluations between groups evaluated the total planning time and dosimetric outcomes at preimplant and Day 30.

Results: 21 and 20 patients were treated using the PIPA and conventional techniques, respectively. No significant differences were observed in preimplant or Day 30 prostate D, V, rectum V, or rectum D between PIPA and conventional techniques. Although the PIPA group had a larger proportion of patients with plans requiring no modifications (Dice = 1.00), there was no significant difference between the magnitude of modifications between each arm. There was a large significant advantage in mean planning time for the PIPA arm (2.38 ± 0.96 min) compared with the conventional (43.13 ± 58.70 min) technique (p > 0.05).

Conclusions: A machine learning-based planning workflow for prostate LDR brachytherapy has the potential to offer significant time savings and operational efficiencies, while producing noninferior postoperative dosimetry to that of expert, conventional treatment planners.
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http://dx.doi.org/10.1016/j.brachy.2020.03.004DOI Listing
April 2020

Prostate high dose-rate brachytherapy as monotherapy for low and intermediate risk prostate cancer: Efficacy results from a randomized phase II clinical trial of one fraction of 19 Gy or two fractions of 13.5 Gy.

Radiother Oncol 2020 May 5;146:90-96. Epub 2020 Mar 5.

Sunnybrook Odette Cancer Centre, University of Toronto, Canada.

Background And Purpose: High dose-rate (HDR) brachytherapy as monotherapy is a treatment option for localized prostate cancer, but optimal dose and fractionation is unknown. We report efficacy results of a randomized phase II trial of HDR monotherapy delivered as either one or two fractions.

Materials And Methods: Eligible patients had low or intermediate risk prostate cancer, prostate volume <60 cc, and no androgen deprivation use. 170 patients were randomized to receive HDR as either a single fraction of 19 Gy or as two fractions of 13.5 Gy one week apart. Median age was 65 years, median PSA was 6.33 ng/ml, and Grade Group 1, 2 and 3 was present in 28%, 60%, and 12%, respectively. There was no difference in baseline factors between arms and 19%, 51% and 30% had low risk, favourable intermediate and unfavourable intermediate risk disease, respectively. The Phoenix definition was used to define biochemical failure, all local failures were confirmed by biopsy and toxicity was assessed using CTCAE v.4.

Results: Median follow-up was 60 months. PSA decreased more quickly in the 2-fraction arm (p = 0.009). Median PSA at 5-years was 0.65 ng/ml in the single fraction and 0.16 ng/ml in the 2-fraction arm. The 5-year biochemical disease-free survival and cumulative incidence of local failure was 73.5% and 29% in the single fraction arm and 95% (p = 0.001) and 3% (p < 0.001) in the 2-fraction arm, respectively. Recurrence was not associated with initial stage, grade group, or risk group. Grade 2 late rectal toxicity occurred in 1% while the incidence of grade 2 and 3 urinary toxicity was 45% and 1%, respectively, with no difference between arms.

Conclusions: HDR monotherapy delivered as two fraction of 13.5 Gy is well tolerated with a high cancer control rate at 5 years. Single fraction monotherapy is inferior and should not be used.
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http://dx.doi.org/10.1016/j.radonc.2020.02.009DOI Listing
May 2020

Evaluating the Tolerability of a Simultaneous Focal Boost to the Gross Tumor in Prostate SABR: A Toxicity and Quality-of-Life Comparison of Two Prospective Trials.

Int J Radiat Oncol Biol Phys 2020 05 25;107(1):136-142. Epub 2020 Jan 25.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: Dose-escalated stereotactic ablative radiotherapy (SABR) to the whole prostate may be associated with better outcomes but has a risk of increased toxicity. An alternative approach is to focally boost the dominant intraprostatic lesion (DIL) seen on magnetic resonance imaging. We report the toxicity and quality-of-life (QOL) outcomes of 2 phase 2 trials of prostate and pelvic SABR, with or without a simultaneous DIL boost.

Methods And Materials: The first trial treated patients with high-risk prostate cancer to a dose of 40 Gy to the prostate and 25 Gy to the pelvis in 5 fractions. The second trial treated patients with intermediate-risk and high-risk prostate cancer to a dose of 35 Gy to the prostate, 25 Gy to the pelvis, and a DIL boost up to 50 Gy in 5 fractions. Acute toxicities, late toxicities, and QOL were assessed.

Results: Thirty patients were enrolled in each trial. In the focal boost cohort, the median DIL D90% was 48.3 Gy. There was no significant difference in acute grade ≥2 gastrointestinal or genitourinary toxicity between the 2 trials or in cumulative worst late gastrointestinal or genitourinary toxicity up to 24 months. There was no significant difference in QOL domain scores or minimally clinical important change between the 2 trials.

Conclusions: Prostate and pelvic SABR with a simultaneous DIL boost was feasible. Acute grade ≥2 toxicity, late toxicity, and QOL seemed to be comparable to a cohort that did not receive a focal boost. Further follow-up will be required to assess long-term outcomes, and randomized data are required to confirm these findings.
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http://dx.doi.org/10.1016/j.ijrobp.2019.12.044DOI Listing
May 2020

A Prospective Study of 18F-DCFPyL PSMA PET/CT Restaging in Recurrent Prostate Cancer following Primary External Beam Radiotherapy or Brachytherapy.

Int J Radiat Oncol Biol Phys 2020 03 12;106(3):546-555. Epub 2019 Nov 12.

Division of Radiation Oncology, Department of Oncology, London Health Sciences Centre and Western University, London, Canada. Electronic address:

Purpose: Radio-recurrent prostate cancer is typically detected by a rising prostate-specific antigen and may reflect local or distant disease. Positron emission tomography (PET) radiotracers targeting prostate-specific membrane antigen, such as 18F-DCFPyL have shown promise in restaging men with recurrent disease postprostatectomy but are less well characterized in the setting of radio-recurrent disease.

Methods And Materials: A prospective, multi-institutional study was conducted to evaluate the effect of 18F-DCFPyL PET/computed tomography (CT) when added to diagnostic imaging (DI; CT abdomen and pelvis, bone scan, multiparametric magnetic resonance imaging pelvis) for men with radio-recurrent prostate cancer. All men were imaged with DI and subsequently underwent 18F-DCFPyL PET/CT with local and central reads. Tie break reads were performed as required. Management questionnaires were completed after DI and again after 18F-DCFPyL PET/CT. Discordance in patterns of disease detected with 18F-DCFPyL PET/CT versus DI and changes in management were characterized.

Results: Seventy-nine men completed the study. Most men had T1 disease (62%) and Gleason score <7 (95%). Median prostate-specific antigen at diagnosis was 7.4 ng/mL and at relapse was 4.8 ng/mL. DI detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 9 out of 79 (11%), distant disease in 12 out of 79 (15%), and no disease in 26 out of 79 (33%). 18F-DCFPyL PET/CT detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 21 out of 79 (27%), distant disease in 24 out of 79 (30%), and no disease in 10 out of 79 (13%). DI identified 8 out of 79 (10%) patients to have oligometastatic disease, compared with 21 out of 79 (27%) with 18F-DCFPyL PET/CT. 18F-DCFPyL PET/CT changed proposed management in 34 out of 79 (43%) patients.

Conclusions: 18F-DCFPyL PET/CT identified extraprostatic disease in twice as many men with radio-recurrent prostate cancer compared with DI and detected a site of recurrence in 87% of men compared with 67% with DI. Furthermore, 18F-DCFPyL PET/CT identified potentially actionable disease (prostate only recurrence or oligometastatic disease) in 75% of men and changed proposed management in 43% of men.
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http://dx.doi.org/10.1016/j.ijrobp.2019.11.001DOI Listing
March 2020

A Phase 2 Randomized Pilot Study Comparing High-Dose-Rate Brachytherapy and Low-Dose-Rate Brachytherapy as Monotherapy in Localized Prostate Cancer.

Adv Radiat Oncol 2019 Oct-Dec;4(4):631-640. Epub 2019 Apr 18.

Department of Radiation Oncology and Research Centre CHU de Québec-Université Laval, Québec City, QC, Canada.

Purpose: To compare health-related quality of life (HRQOL) of high-dose-rate brachytherapy (HDRB) versus low dose-rate brachytherapy (LDRB) for localized prostate cancer in a multi-institutional phase 2 randomized trial.

Methods And Materials: Men with favorable-risk prostate cancer were randomized between monotherapy brachytherapy with either Iodine-125 LDRB to 144 Gy or single-fraction Iridium-192 HDRB to 19 Gy. HRQOL and urinary toxicity were recorded at baseline and at 1, 3, 6, and 12 months using the Expanded Prostate Cancer Index Composite (EPIC)-26 scoring and the International Prostate Symptom Score (IPSS). Independent samples test and mixed effects modeling were performed for continuous variables. Time to IPSS resolution, defined as return to its baseline score ±5 points, was calculated using Kaplan-Meier estimator curves with the log-rank test. A multiple-comparison adjusted value of ≤.05 was considered significant.

Results: LDRB and HDRB were performed in 15 and 16 patients, respectively, for a total of 31 patients. At 3 months, patients treated with LDRB had a higher IPSS score (mean, 15.5 vs 6.0, respectively;  .003) and lower EPIC urinary irritative score (mean, 69.2 vs 85.3, respectively;  .037) compared with those who received HDRB. On repeated measures at 1, 3, 6, and 12 months, the IPSS ( .003) and EPIC urinary irritative scores ( = .019) were significantly better in the HDR arm, translating into a lower urinary toxicity profile. There were no significant differences in the EPIC urinary incontinence, sexual, or bowel habit scores between the 2 groups at any measured time point. Time to IPSS resolution was significantly shorter in the HDRB group (mean, 2.0 months) compared with the LDRB group (mean, 6.0 months;  .028).

Conclusions: HDRB monotherapy is a promising modality associated with a lower urinary toxicity profile and higher HRQOL in the first 12 months compared with LDRB.
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http://dx.doi.org/10.1016/j.adro.2019.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817536PMC
April 2019

Postimplant Dosimetry of Permanent Prostate Brachytherapy: Comparison of MRI-Only and CT-MRI Fusion-Based Workflows.

Int J Radiat Oncol Biol Phys 2020 01 15;106(1):206-215. Epub 2019 Oct 15.

Department of Physics, Ryerson University, Toronto, Canada; Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada.

Purpose: The current magnetic resonance imaging-computed tomography (MRI-CT) fusion-based workflow for postimplant dosimetry of low-dose-rate (LDR) prostate brachytherapy takes advantage of the superior soft tissue contrast of MRI, but still relies on CT for seed visualization and detection. Recently an MR-only workflow has been proposed that employs standard MR sequences and visualizes conventional implanted seed with positive contrast solely through MR postprocessing. In this work, the novel MR-only based workflow is compared with the clinical CT-MRI fusion approach.

Methods And Materials: Twenty-four prostate patients with a total of 1775 implanted LDR seeds were scanned using a 3-dimensional multiecho gradient echo sequence on a 3 Tesla MR scanner within 30 days after implantation. Quantitative susceptibility mapping was used for seed visualization. Seeds were automatically segmented and localized on the quantitative susceptibility mapping using convolutional neural network and k-means clustering, respectively. To assess the MR-only seed localization error, CT and MR-derived seed positions were coregistered, and ultimately, the resulting dose-volume histograms were compared.

Results: The MR-based seed visualization, segmentation, and localization generated comparable results to the CT-MR registration approach. The accuracy of the MRI-only based seed identification was 99.1%. After a rigid registration between the MR and CT-derived seed centroids, the average localization error was 0.8 ± 0.8 mm. The average prostate D, V, V, and V for MRI-only and CT-MR fusion based dosimetry were 114.3 ± 12.5% versus 113.9 ± 11.9%, 95.1 ± 3.7% versus 95.3 ± 3.8%, 54.5 ± 14.5% versus 55.0 ± 13.2% and 22.9 ± 6.8% versus 23.2 ± 6.7%, respectively. No significant differences were observed in 3-dimensional seed positions and dosimetric parameters between MR-only and CT-MR fusion-based workflows (P > 0.2).

Conclusions: The MRI-only LDR postimplant dosimetry is feasible and has very good potential to eliminate the need for CT-based seed identification.
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http://dx.doi.org/10.1016/j.ijrobp.2019.10.009DOI Listing
January 2020

MRI assisted focal boost integrated with HDR monotherapy study in low and intermediate risk prostate cancer (MARS): Results from a phase II clinical trial.

Radiother Oncol 2019 12 26;141:144-148. Epub 2019 Sep 26.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Canada. Electronic address:

Purpose: There is growing concern that single-fraction HDR monotherapy to a dose of 19 Gy is suboptimal for the treatment of localized prostate cancer. We report the results of a phase II prospective trial of single-fraction 19 Gy HDR monotherapy with MRI-guided simultaneous focal boost.

Methods: Eligible patients had low or intermediate risk prostate cancer and an identified lesion on MRI. TRUS based single-fraction HDR monotherapy with MRI fusion was delivered. The dose prescribed was 19 Gy to the prostate and ≥23 Gy to the dominant intraprostatic lesion (DIL). ADT was not used. The purpose is to report early efficacy results.

Results: 60 patients were enrolled, with a median follow-up of 39 months. With MRI T-stage incorporated into the risk-group criteria, 8% had low-risk, 35% had favorable intermediate-risk and 57% had unfavorable intermediate-risk disease. The median dose to 90% of the DIL (D90) was 27.2 Gy, and the median prostate V100% was 96.9%. No acute or late grade ≥3 bowel or urinary toxicity was observed. The cumulative BF probability was 15.2% at 36 months and 31.6% at 48 months. All patients that were fully investigated had local failure only, and 88% of the local failures were at the site of original DIL. The median PSA nadir was 0.79 ng/ml, with a median time to nadir of 32 months.

Conclusions: Focal boost to the MRI-specified gross tumor was well tolerated, but did not adequately improve local control. Single-fraction HDR monotherapy to 19 Gy for prostate cancer provides suboptimal local control, and should not be offered outside of clinical trials.
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http://dx.doi.org/10.1016/j.radonc.2019.09.011DOI Listing
December 2019

Feasibility of an MRI-only workflow for postimplant dosimetry of low-dose-rate prostate brachytherapy: Transition from phantoms to patients.

Brachytherapy 2019 Nov - Dec;18(6):863-874. Epub 2019 Jul 20.

Department of Physics, Ryerson University, Toronto, Canada; Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada.

Purpose: The lack of positive contrast from brachytherapy seeds in conventional MR images remains a major challenge toward an MRI-only workflow for postimplant dosimetry of low-dose-rate brachytherapy. In this work, the feasibility of our recently proposed MRI-only workflow in clinically relevant scenarios is investigated and the necessary modifications in image acquisition and processing pipeline are proposed for transition to the clinic.

Methods And Materials: Four prostate phantoms with a total of 321 I-125 implanted dummy seeds and three patients with a total of 168 implanted seeds were scanned using a gradient echo sequence on 1.5 T and 3T MR scanners. Quantitative susceptibility mapping (QSM) was performed for seed visualization. Before QSM, the seed-induced distortion correction was performed followed by edge enhancement. Seed localization was performed using spatial clustering algorithms and was compared with CT. In addition, feasibility of the proposed method on detection of prostatic calcifications was studied.

Results: The proposed susceptibility-based algorithm generated consistent positive contrast for the seeds in phantoms and patients. All the 321 seeds in the four phantoms were correctly identified; the MR-derived seeds centroids agreed well with CT-derived positions (average error = 0.5 ± 0.3 mm). The proposed algorithm for seed visualization was found to be orientation invariant. In patient cases, all seeds were visualized and correctly localized (average error = 1.2 ± 0.9 mm); no significant differences between dose volume histogram parameters were found. Prostatic calcifications were depicted with negative contrast on QSM and spatially agreed with CT.

Conclusions: The proposed MRI-based approach has great potential to replace the current CT-based practices. Additional patient studies are necessary to further optimize and validate the workflow.
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http://dx.doi.org/10.1016/j.brachy.2019.06.004DOI Listing
April 2020

Single Fraction High-Dose-Rate Brachytherapy: Too Good to Be True?

Int J Radiat Oncol Biol Phys 2019 08;104(5):1054-1056

Mount Vernon Hospital, Northwood, Middlesex, United Kingdom.

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http://dx.doi.org/10.1016/j.ijrobp.2019.04.036DOI Listing
August 2019

Potential applications of the quantitative susceptibility mapping (QSM) in MR-guided radiation therapy.

Phys Med Biol 2019 07 16;64(14):145013. Epub 2019 Jul 16.

Department of Physics, Ryerson University, Toronto, Canada. Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Canada. Author to whom any correspondence should be addressed.

Magnetic resonance-guided radiation therapy (MR-GRT) offers great potential to improve radiation treatment outcomes by providing more accurate and patient-tailored therapy. Despite superior soft tissue contrast in MRI, one of the challenges towards MRI-only workflows is that the process often requires some sort of 'MR-invisible' metal-based devices. In this study, the feasibility of quantitative susceptibility mapping (QSM) for visualization of some MR-invisible radiation therapy devices was studied. Our recently proposed QSM-based algorithm for brachytherapy seed visualization was modified and the feasibility of the optimized algorithm for visualization of different devices including: brachytherapy seeds, plastic interstitial needles, CT-markers and obturators, and different types of fiducial markers in agar, prostate and meat phantoms were studied. All phantoms were scanned using 3T MR scanner with a 3D multi-echo gradient recalled echo (ME-GRE) pulse sequence. The QSM results in all phantoms were compared to CT images for spatial accuracy of the QSM. The applied post-processing algorithm was found to be insensitive to the seeds' type; also, presence of nearby calcifications had no effect on seed visualization. QSM successfully generated positive contrast for both types of investigated fiducial markers with high spatial accuracy compared to CT. Interstitial needles containing both aluminum-based CT-maker and titanium-based obturators were accurately depicted on the QSM. The proposed QSM-based technique relies on the standard MR pulse sequences and visualize the conventional MR-invisible metallic devices with CT-like positive contrast solely through post-processing. Upon in vivo validation of the technique, QSM may have the potential to replace CT for an MR-only guided radiation therapy.
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http://dx.doi.org/10.1088/1361-6560/ab2623DOI Listing
July 2019

Changes in ADC and T2-weighted MRI-derived radiomic features in patients treated with focal salvage HDR prostate brachytherapy for local recurrence after previous external-beam radiotherapy.

Brachytherapy 2019 Sep - Oct;18(5):567-573. Epub 2019 May 22.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: To explore the changes in T2-weighted (T2w) and apparent diffusion coefficient (ADC) magnetic resonance imaging -derived radiomic features of the gross tumor volume (GTV) from focal salvage high-dose-rate prostate brachytherapy (HDRB) and to correlate with clinical parameters.

Materials And Methods: Eligible patients included those with biopsy-confirmed local recurrence that correlated with MRI (T2w, ADC). Patients received 27 Gy in 2 fractions separated by 1 week to a quadrant consisting of the GTV. The MRI was repeated 1 year after HDRB. GTVs, planning target volumes, and normal prostate tissue control volumes were identified on the pre- and post-HDRB MRIs. Radiomic features from each GTV were extracted, and principle component analysis identified features with the highest variance.

Results: Pre- and post-HDRB MRIs were obtained from 14 trial patients. Principle component analysis showed that 18 and 17 features contributed to 93% and 86% of the variance observed in the T2w and ADC data, respectively. Sixteen T2w features and 1 ADC GTV feature were different from the control volumes in the pre-HDRB images (p < 0.05). Ten T2w and 7 ADC GTV post-HDRB features were different from those of pre-HDRB (p < 0.05).

Conclusions: Exploratory analysis reveals several radiomic features in the T2w and ADC image GTVs that distinguish the GTV from healthy prostate tissue and change significantly after salvage HDRB.
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http://dx.doi.org/10.1016/j.brachy.2019.04.006DOI Listing
February 2020

5-Year Outcomes of a Prospective Phase 1/2 Study of Accelerated Hypofractionated Radiation Therapy to the Prostate Bed.

Pract Radiat Oncol 2019 Sep - Oct;9(5):354-361. Epub 2019 May 16.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto; Institute for Health Policy, Measurement and Evaluation, University of Toronto. Electronic address:

Purpose: To report the 5-year outcomes from a single institution, prospective, phase 1/2 study on hypofractionated, accelerated radiation therapy to the prostate bed after radical prostatectomy.

Methods And Materials: Patients enrolled in this study were all eligible for postoperative radiation therapy and received a prescribed dose of 51 Gy in 17 fractions to the prostate bed. On follow-up, gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0; prostate-specific antigen (PSA) was evaluated and quality of life was assessed using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire.

Results: A total of 30 patients were enrolled between 2008 and 2011. Median age was 65 (52-75) years. Median pretreatment PSA was 0.12 ng/mL (0.01-1.42). Twenty-six (93%) patients had Gleason ≤7 disease, 13 (43%) had pT3 disease, and 20 (67%) had positive margins. Twenty-six patients (87%) underwent radiation therapy as salvage treatment. After a median follow-up of 6.4 (2.1-8.1) years, no patient experienced Common Terminology Criteria for Adverse Events grade 3/4 toxicity. Eleven patients (37%) had grade 2 genitourinary and 2 (7%) had grade 2 gastrointestinal toxicity. At baseline and 5 years after radiation therapy, mean EPIC urinary domain score was 80% (standard deviation, 18%) and 82% (17%). Mean EPIC bowel domain score was 93% (13%) and 93% (15%). One patient (4%) had a minimally clinically important change in urinary domain score and 1 patient (4%) had a minimally clinically important change in bowel domain score. Nelson-Aalen estimated cumulative incidence of biochemical failure was 31% (nadir +0.2) and 18% (nadir +2.0) at 5 years. Four-year PSA ≥0.4 was predictive of subsequent androgen deprivation therapy use (Nelson-Aalen cumulative incidence: 1.45; P < .0001). Five patients (17%) received hormonal therapy for biochemical failure. Nelson-Aalen estimated cumulative incidence of hormone therapy use was 14% at 5 years. All patients who received hormone therapy had PSA >0.4 at 4 years.

Conclusions: In this phase 1/2 study, hypofractionated postoperative radiation therapy seems to have good clinical efficacy without significant late toxicity. Phase 3 studies are warranted.
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http://dx.doi.org/10.1016/j.prro.2019.04.010DOI Listing
January 2020

Stereotactic Body Radiation Therapy Boost for Intermediate-Risk Prostate Cancer: A Phase 1 Dose-Escalation Study.

Int J Radiat Oncol Biol Phys 2019 08 16;104(5):1066-1073. Epub 2019 Apr 16.

Sunnybrook Health Sciences Centre-Odette Cancer Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada. Electronic address:

Purpose: High-dose-rate brachytherapy boost plus external beam radiation therapy is an established option for intermediate-risk prostate cancer (PCa). Stereotactic body radiation therapy (SBRT) boost can potentially mimic high-dose-rate boost and could be a viable alternative. Here we report the long-term outcomes of a phase 1 dose-escalation trial of single-fraction SBRT boost.

Methods And Materials: Patients had intermediate-risk PCa and were accrued to 3 different SBRT single-fraction dose-level cohorts (10 Gy, 12.5 Gy, and 15 Gy). All received supplemental radiation therapy afterwards (37.5 Gy in 15 fractions). Three gold fiducials were implanted for image guidance. Patients were simulated and treated with a foley catheter and intrarectal balloon. A T2 magnetic resonance imaging scan was used for contouring, and a cine magnetic resonance imaging scan was used to calculate patient-specific internal target volume margins. Toxicity and quality-of-life data were collected using Common Terminology Criteria for Adverse Events v3.0 and the Expanded Prostate Cancer Index Composite.

Results: 30 patients were accrued, 10 in each cohort. Median follow-up was 72 months. 60% had unfavorable intermediate-risk PCa. Two patients in the 15 Gy cohort developed late grade ≥3 gastrointestinal and genitourinary toxicity, with 1 patient suffering from a grade-4 rectal fistula after a rectal ulcer was biopsied repeatedly. Two patients had biochemical failure. Median PSA nadir was 0.4 ng/mL with 10 Gy, 0.09 ng/mL with 12.5 Gy and 0.07 ng/mL with 15 Gy. Median PSA at 4 years as well as proportion achieving a nadir <0.2 ng/mL improved significantly with higher doses. There was no significant change in quality of life from baseline in any of the domains, and the minimal clinically important change was not statistically different between the 3 cohorts.

Conclusions: Other than a grade 4 toxicity, which may in part be due to repeated biopsies of a rectal ulcer, single-fraction SBRT boost was feasible and well tolerated. Larger studies are warranted to better document the outcomes of such an approach.
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http://dx.doi.org/10.1016/j.ijrobp.2019.04.006DOI Listing
August 2019

Optimized penile surface mold brachytherapy using latest stereolithography techniques: A single-institution experience.

Brachytherapy 2019 May - Jun;18(3):348-352. Epub 2019 Feb 2.

University of Toronto, Toronto, Ontario, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address:

Purpose: To describe a technique of penile surface mold high-dose-rate (HDR) brachytherapy and early outcomes.

Methods And Materials: Five patients diagnosed with a T1aN0 squamous cell carcinoma of the penis were treated using a penile surface mold HDR brachytherapy technique. A negative impression of the penis was obtained using dental alginate. CT images were acquired of the penile impression; subsequently, a virtual model of the patient's penis was generated. The positive model was imported into a computer-assisted design program where catheter paths were planned such that an optimized offset of 5 mm from the penile surface was achieved. The virtual model was converted into a custom applicator. A total dose of 40 Gy was delivered in 10 fractions. Patients were followed at 1, 3, 6, and 12 months after treatment and then every 6 months thereafter. Toxicities were reported using Common Terminology Criteria for Adverse Events v4.0.

Results: All patients tolerated treatment well. Acute Grade 2 skin reactions were observed within the first month after treatment. Median followup was 35 months. Late Grade 1 skin toxicities were observed. One patient experienced a urethral stricture requiring dilatation. Two patients developed local recurrence.

Conclusion: This technique allows the delivery of penile HDR brachytherapy as an outpatient procedure with minimal discomfort to the patient during each application and is a repeatable and accurate setup. This technique warrants validation in larger series with longer followup.
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http://dx.doi.org/10.1016/j.brachy.2019.01.002DOI Listing
December 2019

A Prospective Phase 2 Trial of Transperineal Ultrasound-Guided Brachytherapy for Locally Recurrent Prostate Cancer After External Beam Radiation Therapy (NRG Oncology/RTOG-0526).

Int J Radiat Oncol Biol Phys 2019 02 9;103(2):335-343. Epub 2018 Oct 9.

Cedars-Sinai Medical Center, Los Angeles, California.

Purpose: Only retrospective data are available for low-dose-rate (LDR) salvage prostate brachytherapy for local recurrence after external beam radiation therapy (EBRT). The primary objective of this prospective phase 2 trial (NCT00450411) was to evaluate late gastrointestinal and genitourinary adverse events (AEs) after salvage LDR brachytherapy.

Methods And Materials: Eligible patients had low- or intermediate-risk prostate cancer before EBRT and biopsy-proven recurrence >30 months after EBRT, with prostate-specific antigen levels <10 ng/mL and no regional/distant disease. The primary endpoint was grade 3 or higher late treatment-related gastrointestinal or genitourinary AEs occurring 9 to 24 months after brachytherapy. These AEs were projected to be ≤10%, with ≥20% considered unacceptable. All events were graded with National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Multivariate analyses investigated associations of pretreatment or treatment variables with AEs.

Results: One hundred patients from 20 centers were registered from May 2007 to January 2014. The 92 analyzable patients had a median follow-up of 54 months (range, 4-97) and a median age of 70 years (interquartile range [IQR], 65-74). The initial Gleason score was 7 in 48% of patients. The median dose of EBRT was 74 Gy (IQR, 70-76) at a median interval of 85 months previously (IQR, 60-119). Only 16% had androgen deprivation at study entry. Twelve patients (14%) had late grade 3 gastrointestinal/genitourinary AEs, with no treatment-related grade 4 or 5 AEs. No pretreatment variable predicted late AEs, including prior EBRT dose and elapsed interval. Higher V100 (percentage of prostate enclosed by prescription isodose) predicted both occurrence of late AEs (odds ratio, 1.24; 95% confidence interval, 1.02-1.52; P = .03) and earlier time to first occurrence (hazard ratio, 1.18; 95% CI, 1.03-1.34; P = .02).

Conclusions: This prospective multicenter trial reports outcomes of salvage LDR brachytherapy for post-EBRT recurrence. The rate of late grade 3 AEs did not exceed the unacceptable threshold. The only factor predictive of late AEs was implant dosimetry reflected by V100. Efficacy outcomes will be reported at a minimum of 5-year follow-up.
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http://dx.doi.org/10.1016/j.ijrobp.2018.09.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368223PMC
February 2019

Clinical evaluation of an MRI-to-ultrasound deformable image registration algorithm for prostate brachytherapy.

Brachytherapy 2019 Jan - Feb;18(1):95-102. Epub 2018 Oct 2.

Department of Medical Physics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy (HDR-BT) treatment planning is challenging. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study evaluates the efficacy of an in-house software for MRI-to-TRUS DIL registration (MR2US) and compares its results to rigid and B-Spline deformable registration.

Methods And Materials: Ten patients with intermediate-risk prostate cancer, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists (ROs) with expertise in TRUS-based HDR-BT were asked to cognitively contour the DIL onto the TRUS image using mpMRI as reference. The contours were analyzed for concordance using simultaneous truth and performance level estimation algorithm. Similarity indices, DIL volumes, and distance between centroid positions were measured to compare the consensus contours against the contours from ROs and the automated algorithms; registration time between all contouring methods was recorded.

Results: MR2US registration had the highest dice coefficients among all patients with a mean of 0.80 ± 0.13 in comparison to rigid (0.65 ± 0.20) and B-Spline (0.51 ± 0.30). The distance between centroid positions between simultaneous truth and performance level estimation contour and MR2US, rigid, and B-Spline contours were 5 ± 2, 7 ± 5, and 18 ± 11 mm, respectively. The average registration time was significantly shorter for MR2US (11 ± 2 s) and rigid algorithm (7 ± 1 s) compared to ROs (227 ± 27 s) and B-Spline (199 ± 38 s).

Conclusions: The efficacy of integrating an MRI-delineated DIL into a TRUS-based BT workflow has been validated in this study. The MR2US software is fast and accurate enough to be used for DIL identification in prostate HDR-BT.
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http://dx.doi.org/10.1016/j.brachy.2018.08.006DOI Listing
April 2019

Focal Salvage High Dose-Rate Brachytherapy for Locally Recurrent Prostate Cancer After Primary Radiation Therapy Failure: Results From a Prospective Clinical Trial.

Int J Radiat Oncol Biol Phys 2018 11 2;102(3):561-567. Epub 2018 Jul 2.

Department of Radiation Oncology, Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: Although increasing data support whole-gland salvage therapy for recurrent prostate cancer, toxicity remains a significant concern. We hypothesized that focal therapy, treating only a portion of the prostate containing recurrent disease, might be equally effective and associated with less toxicity. The objectives of this prospective study were to explore the toxicities, quality of life, and efficacy of focal salvage high-dose-rate (HDR) brachytherapy in patients with multiparametric magnetic resonance imaging (MRI)-visible, biopsy-confirmed local recurrence after previous definitive external beam radiation therapy.

Materials And Methods: Fifteen patients with locally recurrent prostate cancer after external beam radiation therapy were enrolled in this prospective study. Patients were treated with ultrasound-based HDR brachytherapy with a prescription dose of 27 Gy divided in 2 implants, separated by 1 week, to the clinical target volume, which was defined as the quadrant of the prostate where the MRI-visible recurrent lesion was located. Toxicity, quality of life, and biochemical outcomes were analyzed. Postsalvage MRI was performed to assess radiation therapy response.

Results: Median follow-up was 36 months. The median size of the recurrence on MRI was 9 mm (range, 7-20 mm), and clinical target volume at the time of HDR was 6.1 mL (range, 2.2-16.1 mL). Only one grade 3 genitourinary toxicity event was observed. No urinary retention was observed. Three-year prostate-specific antigen failure-free rate was 61%. There was no significant change in Expanded Prostate Cancer Index Composite urinary or bowel domains over time. Of the 14 patients who had a post-HDR MRI, 12 had a treatment response.

Conclusions: Our results suggest that focal salvage HDR brachytherapy is well tolerated and promising. External validation is needed.
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http://dx.doi.org/10.1016/j.ijrobp.2018.06.039DOI Listing
November 2018

MRI-based automated detection of implanted low dose rate (LDR) brachytherapy seeds using quantitative susceptibility mapping (QSM) and unsupervised machine learning (ML).

Radiother Oncol 2018 12 19;129(3):540-547. Epub 2018 Sep 19.

Department of Physics, Ryerson University, Toronto, Canada; Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Canada.

Background And Purpose: Permanent seed brachytherapy is an established treatment option for localized prostate cancer. Currently, post-implant dosimetry is performed on CT images despite challenging target delineation due to limited soft tissue contrast. This work aims to develop an MRI-only workflow for post-implant dosimetry of prostate brachytherapy seeds.

Material And Methods: A prostate mimicking phantom containing twenty stranded I-125 dummy seeds and calcifications was constructed. A three-dimensional gradient-echo MR sequence was employed on 3T and 1.5T MR scanners. An optimized quantitative susceptibility mapping (QSM) technique was applied to generate positive contrast for the seeds and calcifications. Seed numbers, centroids, and orientations were determined using unsupervised machine learning algorithms (K-means and K-medoids clustering). The geometrical seed positions and the resulting dose distribution were compared to the clinical CT-based approach.

Results: The optimized QSM-based method generated high quality positive contrast for the seeds that were significantly different from that for calcifications and could be easily differentiated by thresholding. The estimated seed centroids from both 3T and 1.5T MR data were in perfect agreement with the standard CT-based seed detection algorithm (maximum difference of 0.7 mm). The estimated seed orientations were highly correlated with the actual orientations (R > 0.98).

Conclusions: The proposed MRI-based workflow enabling an accurate and robust means to localize the seeds (position and orientation) upon validation on complex seed configurations, has the potential to replace the current widely practiced CT-based workflow.
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http://dx.doi.org/10.1016/j.radonc.2018.09.003DOI Listing
December 2018

The American Brachytherapy Society and the American Radium Society Appropriate Use Criteria Genitourinary Committee Endorse the American Society of Clinical Oncology/Cancer Care Ontario Guidelines.

J Clin Oncol 2018 Sep 13:JCO1800626. Epub 2018 Sep 13.

Albert J. Chang, University of California, Los Angeles, Los Angeles, CA; Sean McBride, Memorial Sloan Kettering Cancer Center, New York, NY; Mira Keyes, British Columbia Cancer Agency and University of British Columbia, Vancouver, British Colombia, Canada; Hans T. Chung, University of Toronto and Odette Cancer Centre, Toronto, Ontario, Canada; Brian J. Davis, Mayo Clinic, Rochester, MN; Brett W. Cox, Northwell Health and Hofstra Northwell School of Medicine, New York, NY; Juanita Crook, British Columbia Cancer Agency, Cancer Center for the Southern Interior, Kelowna, British Columbia, Canada; David J. Demanes, University of California, Los Angeles, Los Angeles, CA; I. Chow Hsu, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Mitchell Kamrava, Cedars Sinai Medical Center, Los Angeles, CA; Daniel J. Krauss, Beaumont Health System, Royal Oak, MI; Gerard Morton, University of Toronto and Odette Cancer Centre, Toronto, Ontario, Canada; Peter F. Orio III, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Mack Roach III, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Puja S. Venkat, University of California, Los Angeles, Los Angeles, CA; Eric Vigneault, Centre de Recherche sur le Cancer, CHU de Québec, Université Laval, Québec, Canada; and Michael J. Zelefsky, Memorial Sloan Kettering Cancer Center, New York, NY.

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http://dx.doi.org/10.1200/JCO.18.00626DOI Listing
September 2018

High dose-rate brachytherapy in the treatment of prostate cancer.

Transl Androl Urol 2018 Jun;7(3):357-370

Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Canada.

High dose-rate (HDR) brachytherapy involves delivery of a high dose of radiation to the cancer with great sparing of surrounding organs at risk. Prostate cancer is thought to be particularly sensitive to radiation delivered at high dose-rate or at high dose per fraction. The rapid delivery and high conformality of dose results in lower toxicity than that seen with low dose-rate (LDR) implants. HDR combined with external beam radiotherapy results in higher cancer control rate than external beam only, and should be offered to eligible high and intermediate risk patients. While a variety of dose and fractionations have been used, a single 15 Gy HDR combined with 40-50 Gy external beam radiotherapy results in a disease-free survival of over 90% for intermediate risk and 80% for high risk. HDR monotherapy in two or more fractions (e.g., 27 Gy in 2 fractions or 34.5 Gy in 3) is emerging as a viable alternative to LDR brachytherapy for low and low-intermediate risk patients, and has less toxicity. The role of single fraction monotherapy to a dose of 19-20 Gy is evolving, with some conflicting data to date. HDR should also be considered as a salvage approach for recurrent disease following previous external beam radiotherapy. A particular advantage of HDR in this setting is the ease of delivering focal treatments, which combined with modern imaging allows focal dose escalation with minimal toxicity. Trans-rectal ultrasound (TRUS) based planning is replacing CT-based planning as the technique of choice as it minimizes or eliminates the need to move the patient between insertion, planning and treatment delivery, thus ensuring high accuracy and reproducibility of treatment.
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http://dx.doi.org/10.21037/tau.2017.12.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043748PMC
June 2018