Publications by authors named "Andrea Deabreu"

31 Publications

Elective nodal ultra hypofractionated radiation for prostate cancer: Safety and efficacy from four prospective clinical trials.

Radiother Oncol 2021 Sep 4;163:159-164. Epub 2021 Sep 4.

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

Background And Purpose: The role of elective nodal irradiation (ENI) in localized prostate cancer (PCa) is controversial. With increasing use of SBRT to the prostate, data is needed regarding the safety and efficacy of ENI using ultra-hypofractionated radiation (UHRT).

Materials And Methods: Between 2013-2020, 4 prospective clinical trials of intermediate or high-risk PCa receiving dose-escalated RT to the prostate (via HDR brachytherapy or SBRT boost) and ENI using UHRT (25 Gy in 5 weekly fractions) were conducted. Primary endpoints included acute genitourinary and gastrointestinal toxicities (CTCAE v3.0/4.0), and secondary endpoints included late genitourinary and gastrointestinal toxicities, patient-reported quality of life (EPIC) and biochemical failure (Phoenix definition).

Results: One-hundred sixty-five patients were enrolled, of whom 98 (59%) had high-risk disease. ADT was used in 141 (85%). Median follow-up was 38 months (IQR 10-63). The worst acute genitourinary and gastrointestinal toxicities respectively were 48% and 7.5% for grade 2, and 2.7% and 0% for grade 3. Cumulative incidence of late grade 2+ genitourinary and gastrointestinal toxicities at 36 months were 58% and 11.3% and for late grade 3+ toxicities were 1% and 0%, respectively. No grade 4+ acute or late toxicities were observed. Bowel and sexual toxicity significantly worsened up to 1-year compared to baseline. Over time, urinary (p < 0.0001), bowel (p = 0.0018) and sexual (p < 0.0001) scores significantly improved. The 3-year biochemical recurrence-free survival was 98%.

Conclusion: ENI using UHRT is associated with low incidence of grade 3+ toxicity, while grade 1-2 acute genitourinary and gastrointestinal toxicity is common. Randomized phase 3 trials are needed.
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http://dx.doi.org/10.1016/j.radonc.2021.08.017DOI Listing
September 2021

Elective pelvic nodal irradiation with a simultaneous hypofractionated integrated prostate boost for localized high risk prostate cancer: Long term results from a prospective clinical trial.

Radiother Oncol 2021 Jul 26;163:21-31. Epub 2021 Jul 26.

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

Background: To report on long-term results of elective pelvic nodal irradiation (EPNI) and a simultaneous hypofractionated prostate boost for high-risk prostate cancer.

Materials And Methods: This was a prospective single-arm study. Patients with high-risk disease (cT3, PSA >20 ng/mL, or Gleason score 8-10) were eligible. Patients received 45 Gy in 25 fractions to the prostate and pelvic lymph nodes with a simultaneous intensity-modulated radiotherapy boost of 22.5 Gy to the prostate (total dose 67.5 Gy in 25 fractions), with androgen deprivation therapy (ADT) for 2-3 years. The primary endpoint was biochemical failure. Secondary endpoints included distant metastases and overall survival. Multivariable analysis was performed to look for predictive factors. Late toxicity was assessed using CTCAE v3.0.

Results: 230 patients enrolled. Median follow-up was 11.2 years (IQR 8.1-12.9). At 10 years, cumulative incidence of biochemical failure was 33.4%, distant metastasis was 16.5%, and overall survival was 76.3%. On multivariable analysis, PSA nadir ≥0.05 ng/mL was associated with biochemical failure (HR 6.8, 95% CI 4-11.8, p < 0.001) and distant metastases (HR 7.5, 95% CI 3.9-14.5, p < 0.0001). PSA nadir ≥0.1 ng/mL (HR 5.2, 95% 2.2-12, p = 0.0001) and ADT use ≤12 months (versus >24 months) (HR 2.3, 95% CI 1.3-3.9, p = 0.004) were associated with worse survival. The 5-year cumulative incidence of any late grade ≥3 gastrointestinal and genitourinary toxicity was 2.3% and 7.5%, respectively.

Conclusion: EPNI and a simultaneous hypofractionated prostate boost combined with long-term ADT for high-risk prostate cancer resulted in acceptable 10-year biochemical control and survival with low grade ≥3 toxicity.
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http://dx.doi.org/10.1016/j.radonc.2021.07.018DOI Listing
July 2021

Stereotactic pelvic radiotherapy with HDR boost for dose escalation in intermediate and high-risk prostate cancer (SPARE): Efficacy, toxicity and quality of life.

Radiother Oncol 2021 08 3;161:40-46. Epub 2021 Jun 3.

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

Background: The ASCO/CCO guidelines recommend brachytherapy (BT) boost for eligible intermediate- (IR) or high-risk (HR) prostate cancer (PCa) patients. We present efficacy, toxicity and quality-of-life (QoL) outcomes in patients treated on a prospective protocol of MRI dose-painted high-dose-rate BT boost (HDR-BT) followed by 5-fraction pelvic radiotherapy (RT) and 6-18 months of androgen deprivation therapy (ADT).

Methods: In this phase I/II study, IR or HR PCa patients received HDR-BT 15 Gy × 1 to prostate and up to 22.5 Gy to MRI nodule, followed by 25 Gy in 5, weekly fractions to pelvis. Toxicity was assessed using CTCAEv3.0, and QoL was captured using EPIC questionnaire. Biochemical failure (BF; nadir + 2.0), and proportion of patients with PSA < 0.4 ng/ml at 4-years (4yPSARR) were evaluated. A minimally clinically important change (MCIC) was recorded if QoL score decreased >0.5 standard deviation of baseline scores.

Results: Thirty-one patients (NCCN 3.2% favorable IR, 48.4% unfavorable IR and 48.4% HR) completed treatment with a median follow-up of 61 months. Median D90 to MR nodule was 19.0 Gy and median prostate V100% was 96.5%. The actuarial 5-year BF rate was 18.2%, and the 4yPSARR was 71%. One patient died of PCa. Acute grade 2 and 3 toxicities: GU: 50%, 7%, and GI: 3%, none, respectively. Late grade 2 and 3 toxicities were: GU: 23%, 3%, and GI: 7%, none, respectively. Proportion of patients with MCIC was 7.7% for urinary domain and 32.0% for bowel domain.

Conclusions: This novel treatment protocol incorporating MRI dose-painted HDR-BT boost and 5-fraction pelvic RT with ADT is well tolerated.
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http://dx.doi.org/10.1016/j.radonc.2021.05.024DOI Listing
August 2021

Accelerating prostate stereotactic ablative body radiotherapy: Efficacy and toxicity of a randomized phase II study of 11 versus 29 days overall treatment time (PATRIOT).

Radiother Oncol 2020 08 27;149:8-13. Epub 2020 Apr 27.

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

Background: Prostate stereotactic ablative radiotherapy (SABR) regimens differ in time, dose, and fractionation. We report an update of a multicentre, Canadian randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL), efficacy, and toxicity.

Methods: Men with intermediate risk prostate cancer were randomized to 40 Gy in 5 fractions delivered every other day (EOD) versus once per week (QW). Primary outcome was proportion of patients experiencing a minimally clinically important change (MCIC) in acute bowel QOL using EPIC. Secondary outcomes were toxicity, biochemical failure (BF), other QOL domains, and the rate of salvage therapy.

Findings: 152 men from 3 centers were randomized; the median follow-up was 62 months. Results are described for EOD versus QW. Acute bowel and urinary QOL was reported previously. Late changes in QOL were not significantly different between the two arms. There were 1 (1.3%) vs 3 (2.7%) late grade 3 + GI toxicities (p = 0.36) and 5 (6.7%) vs 2 (2.7%) late grade 3 GU toxicities (p = 0.44). Two and 5 patients had BF (5-year failure rate 3.0 vs 7.2%, p = 0.22); 0 and 4 patients received salvage therapy (p = 0.04). 5-Year OS and CSS was 95.8% and 98.6% with no difference between arms (p = 0.49, p = 0.15). 3 patients in the QW arm developed metastases.

Interpretation: Although we previously reported that weekly prostate SABR had better bowel and urinary QOL compared to EOD, the updated results show no difference in late toxicity, QOL, BF, or PSA kinetics. Patients should be counseled that QW SABR reduces short-term toxicity compared to QW SABR.
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http://dx.doi.org/10.1016/j.radonc.2020.04.039DOI Listing
August 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

Dosimetric predictors of toxicity and quality of life following prostate stereotactic ablative radiotherapy.

Radiother Oncol 2020 03 3;144:135-140. Epub 2019 Dec 3.

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

Purpose: SABR offers an effective treatment option for clinically localized prostate cancer. Here we report the dosimetric predictors of late toxicity and quality of life (QOL) in a pooled cohort of patients from four phase II trials.

Methods: The combined cohort included all three prostate cancer risk groups. The prescription dose was 35-40 Gy in 5 fractions. Toxicity (CTCAE) and QOL (EPIC) were collected. Multiple dosimetric parameters for the bladder, rectum and penile bulb were collected. Univariate (UVA) followed by multivariate (MVA) logistic regression analysis was conducted to search for significant dosimetric predictors of late GI/GU toxicity, or minimal clinically important change in the relevant QOL domain.

Results: 258 patients were included with median follow up of 6.1 years. For QOL, bladder Dmax, V38, D1cc, D2cc, D5cc and rectal V35 were predictors of urinary and bowel MCIC on UVA. On MVA, only bladder V38 remained significant. For late toxicity, various parameters were significant on UVA but only rectal Dmax, V38 and bladder D2cc were significant predictors on MVA.

Conclusions: This report confirms that the high-dose regions in the bladder and rectum are more significant predictors of late toxicity and QOL after prostate SABR compared to low-dose regions. Caution must be taken to avoid high doses and hotspots in those organs.
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http://dx.doi.org/10.1016/j.radonc.2019.11.017DOI Listing
March 2020

Two versus five stereotactic ablative radiotherapy treatments for localized prostate cancer: A quality of life analysis of two prospective clinical trials.

Radiother Oncol 2019 11 29;140:105-109. Epub 2019 Jun 29.

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

Purpose: Stereotactic ablative radiotherapy (SABR) is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index and lead to a better quality of life (QOL). Here we report the outcomes of a QOL comparison between two phase II clinical trials: two vs. five fraction prostate SABR.

Methods: Patients had low or intermediate risk PCa. The doses prescribed were 26 Gy/2 and 40 Gy/5. Expanded prostate cancer index composite was collected. Urinary, bowel and sexual domains were analyzed. Minimal clinically important change (MCIC) was defined as >0.5 standard deviation.

Results: 30 and 152 patients were treated with 2-fraction and 5-fraction SABR. Median follow-up was 55 and 62 months. Five-year biochemical failure rate was 3.3% and 4.6%. The 2-fraction cohort had a significantly better mean QOL over time in the bowel domain (p = 0.0004), without a significant difference in the urinary or sexual domains. The 2-fraction cohort had a significantly lower rate of bowel MCIC (17.8% vs 42.3%, p = 0.01), but there was no difference in urinary (24.1% vs 35.7%) or sexual (15.3% vs 29.2%) MCIC. For MCIC x2 (moderate QOL change), the 2-fraction trial had significantly lower MCIC rates in both the bowel (7.1% vs 24%, p = 0.04) and sexual (0 vs 17.6%, p = 0.01) domains.

Conclusions: 2-Fraction SABR is feasible to deliver and well tolerated, with significant signals of improved bowel and sexual QOL. A randomized trial of two vs. five fractions for prostate SABR is needed to confirm the promising findings of this study.
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http://dx.doi.org/10.1016/j.radonc.2019.06.018DOI Listing
November 2019

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

SABR in High-Risk Prostate Cancer: Outcomes From 2 Prospective Clinical Trials With and Without Elective Nodal Irradiation.

Int J Radiat Oncol Biol Phys 2019 05 14;104(1):36-41. Epub 2018 Nov 14.

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

Purpose: There is limited data on stereotactic ablative radiation therapy (SABR) in high-risk prostate cancer (PCa), especially regarding the role of elective nodal irradiation (ENI). This study compares 2 prospective phase 2 trials using SABR in high-risk PCa, with and without ENI.

Methods And Materials: Patients had high-risk PCa. Those in trial 1 received 40 Gy in 5 fractions to the prostate and 30 Gy in 5 fractions to the seminal vesicles. Patients in trial 2 received 40 Gy in 5 fractions to the prostate and 25 Gy in 5 fractions to the pelvis and seminal vesicles. National Cancer Institute Common Terminology Criteria for Adverse Events toxicities were collected. Biochemical failure (BF) was defined as nadir + 2, and the 4-year prostate-specific antigen (PSA) response rate (4yPSARR) was <0.4 ng/mL.

Results: Sixty patients were included (trial 1, n = 30; trial 2, n = 30). Median follow-up was 5.6 years and 4.0 years. The median nadir PSA was 0.02 ng/mL for both trials. Six patients had BF, all from trial 1. The BF rate was 14.6% at 5 years in trial 1 and 0% in trial 2. Sixty-three percent of patients in trial 1 and 93% in trial 2 had a 4yPSARR. Two patients died in trial 1, 1 from metastatic disease. One patient in trial 2 died of other causes. No other patients developed metastatic disease, and 1 patient in trial 1 had castrate resistant PCa. Overall survival at 5 years was 93.2% and 96.7% (P = .86). There was significantly worse late gastrointestinal and sexual toxicity in trial 1, but there was no difference in late genitourinary toxicity.

Conclusions: SABR in high-risk PCa yields biochemical control rates that may be comparable to that of other radiation therapy modalities. ENI using SABR is feasible and may lead to a significant improvement in biochemical control and in 4yPSARR, without an increase in late gastrointestinal or genitourinary toxicity. Longer follow-up would provide a better assessment of biochemical control. Well-conducted phase 3 trials are needed to fully establish the role of SABR and ENI in high-risk PCa.
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http://dx.doi.org/10.1016/j.ijrobp.2018.11.011DOI Listing
May 2019

Phase 1-2 Study of Stereotactic Ablative Radiotherapy Including Regional Lymph Node Irradiation in Patients With High-Risk Prostate Cancer (SATURN): Early Toxicity and Quality of Life.

Int J Radiat Oncol Biol Phys 2018 12 31;102(5):1438-1447. Epub 2018 Jul 31.

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

Purpose: Five-fraction stereotactic ablative radiation therapy appears to be gaining popularity in treatment of prostate cancer, but it has not been extensively tested in the context of pelvic radiation. The objective of this prospective prostate and pelvic SABR study is to report the acute toxicity, late toxicity, and quality of life (QoL) after study completion.

Methods And Materials: A phase 1/2 study was conducted for patients with high-risk prostate cancer. Radiation therapy was planned to deliver 25 Gy to pelvis and seminal vesicles (SV) and a simultaneous integrated boost (SIB) of up to 40 Gy to the prostate in 5 fractions, weekly, over 29 days. Androgen deprivation therapy was used for 12 to 18 months. Common Terminology Criteria for Adverse Events version 3.0 was used to assess worst acute and late toxicities. QoL data was captured using the Expanded Prostate Cancer Index Composite questionnaire (EPIC).

Results: Thirty patients completed the planned treatment with a median follow-up of 25.7 months (range, 18.5-30.7 months). The following "worst" acute and late toxicities were observed: grade 2 genitourinary toxicity, 46.7% and 52%, respectively; grade 2 gastrointestinal toxicity, 3.3% and 32%, respectively. No grade 3 or higher toxicities were noted. Mean (95% confidence interval) EPIC urinary QoL scores were 86.6 (81.9-91.3), 87.1 (81.4-92.6), and 87.9 (80.1-95.7) at baseline, 3 months and 24 months; bowel scores were 94.1 (91.3-97.0), 93.2 (89.1-97.2), and 92.4 (87.7- 97.1), respectively.

Conclusions: This gantry-based novel fractionation schedule incorporating pelvic radiation for high-risk prostate cancer in combination with androgen deprivation therapy is feasible and well tolerated.
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http://dx.doi.org/10.1016/j.ijrobp.2018.07.2005DOI Listing
December 2018

Dose escalation for prostate stereotactic ablative radiotherapy (SABR): Late outcomes from two prospective clinical trials.

Radiother Oncol 2018 May 24;127(2):213-218. Epub 2018 Mar 24.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Measurement & Evaluation, University of Toronto, Toronto, ON, Canada. Electronic address:

Purpose: Optimal prostate SABR dose-fractionation is unknown. This study compares long-term outcomes from two prospective trials.

Methods: Study1 patients had low-risk PCa and received 35 Gy/5. Study2 patients had low/intermediate-risk PCa and received 40 Gy/5. Biochemical failure (BF) was defined as nadir + 2.

Results: 114 patients were included (study1, n = 84; study2, n = 30). Median follow-up was 9.6 years and 6.9 years. Median nPSA was 0.4 and 0.1 ng/ml. Nine patients had BF (8 in study1, 1 in study2); two were managed with ADT and four had local salvage. The BF rate was 2.5% and 12.8% at 5 and 10 years for study1 and 3.3% at 5 years for study 2. BF probability was 0% if PSA <0.4 at 4 years, and 20.5% at 10 years if PSA ≥0.4 (p = 0.02). Nine patients died, none of PCa. No patient has metastases or castrate-resistance. At 10 years, OS and CSS were 90.4% (p = 0.25) and 100%.

Conclusions: Dose-escalated prostate SABR was associated with lower nPSAs but no difference in BF, OS, CSS or MFS. PSA <0.4 at 4 years was a predictor of biochemical control. Half of patients with BF were successfully salvaged. Given that this is a favorable-risk cohort, longer follow-up will be needed to see if the lower nPSA translates into lower BF rates.
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http://dx.doi.org/10.1016/j.radonc.2018.03.005DOI Listing
May 2018

Once-weekly versus every-other-day stereotactic body radiotherapy in patients with prostate cancer (PATRIOT): A phase 2 randomized trial.

Radiother Oncol 2018 May 15;127(2):206-212. Epub 2018 Mar 15.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.

Background And Purpose: Prostate stereotactic body radiotherapy (SBRT) regimens differ in time, dose, and fractionation. We completed a multicentre, randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL).

Material And Methods: Men with low and intermediate-risk prostate cancer were randomly assigned to 40 Gy in 5 fractions delivered once per week (QW) vs. every other day (EOD). QOL was assessed using the Expanded Prostate Cancer Index Composite. The primary endpoint was the proportion with a minimum clinically important change (MCIC) in bowel QOL during the acute (≤12 week) period, and analysis was by intention-to-treat. ClinicalTrials.gov NCT01423474.

Results: 152 men from 3 centres were randomized with median follow-up of 47 months. Patients treated QW had superior acute bowel QOL with 47/69 (68%) reporting a MCIC compared to 63/70 (90%) treated EOD (p = 0.002). Fewer patients treated QW reported moderate-severe problems with bowel QOL during the acute period compared with EOD (14/70 [20%] vs. 40/70 [57%], p < 0.001). Acute urinary QOL was also better in the QW arm, with 52/67 (78%) vs 65/69 (94%) experiencing a MCIC (p = 0.006). There were no significant differences in late urinary or bowel QOL at 2 years or last follow-up.

Conclusion: Prostate SBRT delivered QW improved acute bowel and urinary QOL compared to EOD. Patients should be counselled regarding the potential for reduced short-term toxicity and improved QOL with QW prostate SBRT.
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http://dx.doi.org/10.1016/j.radonc.2018.02.029DOI Listing
May 2018

Stereotactic ablative radiotherapy in the treatment of low and intermediate risk prostate cancer: Is there an optimal dose?

Radiother Oncol 2017 06 19;123(3):478-482. Epub 2017 Apr 19.

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

Purpose: To investigate if stereotactic ablative radiotherapy (SABR) dose is associated with PSA at 3years (PSA) in the treatment of localized prostate cancer and to explore predictors of late genitourinary (GU) toxicity.

Materials And Methods: Three prospective trials of SABR were undertaken at our institution: 1) 35Gy/5 fractions/29days; 2) 40Gy/5 fractions/29days; 3) 40Gy/5 fractions/11 or 29days. PSA was analyzed as a continuous variable. Toxicity was defined as the worst new toxicity and assessed using the radiation therapy oncology group (RTOG) late morbidity scheme. Univariate and multivariable regression analyses were conducted to assess the association between dose and PSA, and to explore predictors of late grade 2+ GU toxicity.

Results: Median PSA3y was 0.64 (intraquartile range (IQR): 0.41-1.12) and 0.27 (IQR: 0.12-0.55) ng/mL for patients treated with 35 and 40Gy respectively. A dose of 40Gy was an independent predictor of lower PSA on multivariable analysis (p<0.001). Dose of 40Gy (odds ratio (OR): 16.69, 95%CI: 5.78, 48.20, p<0.001) and higher International Prostate Symptom Score (OR: 1.01, 95%CI: 1.04, 1.16, p=0.001) predicted for late grade 2+ GU toxicity on multivariable logistic regression.

Conclusions: This analysis suggests that higher SABR dose is associated with lower PSA. Strategies to allow safe SABR dose escalation should be further investigated.
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http://dx.doi.org/10.1016/j.radonc.2017.03.006DOI Listing
June 2017

Dose-Escalated Stereotactic Body Radiation Therapy for Prostate Cancer: Quality-of-Life Comparison of Two Prospective Trials.

Front Oncol 2016 29;6:185. Epub 2016 Aug 29.

University of Toronto, Toronto, ON, Canada; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Introduction: The optimal prostate stereotactic body radiation therapy (SBRT) dose-fractionation scheme is controversial. This study compares long-term quality of life (QOL) from two prospective trials of prostate SBRT to investigate the effect of increasing dose (NCT01578902 and NCT01146340).

Material And Methods: Patients with localized prostate cancer received SBRT 35 or 40 Gy delivered in five fractions, once per week. QOL was measured using the Expanded Prostate Cancer Index Composite at baseline and every 6 months. Fisher's exact test and generalized estimating equations were used to analyze proportions of patients with clinically significant change and longitudinal changes in QOL.

Results: One hundred fourteen patients were included, 84 treated with 35 Gy and 30 treated with 40 Gy. Median QOL follow-up was 56 months [interquartile range (IQR) 46-60] and 38 months (IQR 32-42), respectively. The proportion of patients reporting clinically significant declines in average urinary, bowel, and sexual scores were not significantly different between dose levels, and were 20.5 vs. 24.1% (p = 0.60), 26.8 vs. 41.4% (p = 0.16), and 42.9 vs. 38.5% (p = 0.82), respectively. Similarly, longitudinal analysis did not identify significant differences in QOL between treatment groups.

Conclusion: Dose-escalated prostate SBRT from 35 to 40 Gy in five fractions was not associated with significant decline in long-term QOL.
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http://dx.doi.org/10.3389/fonc.2016.00185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002986PMC
September 2016

Predictive Parameters of Symptomatic Hematochezia Following 5-Fraction Gantry-Based SABR in Prostate Cancer.

Int J Radiat Oncol Biol Phys 2016 Apr 23;94(5):1043-51. Epub 2015 Dec 23.

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

Purpose: This study identified predictors of high-grade late hematochezia (HH) following 5-fraction gantry-based stereotactic ablative radiation therapy (SABR).

Methods And Materials: Hematochezia data for 258 patients who received 35 to 40 Gy SABR in 5-fractions as part of sequential phase 2 prospective trials was retrieved. Grade 2 or higher late rectal bleeding was labeled HH. Hematochezia needing steroid suppositories, 4% formalin, or 1 to 2 sessions of argon plasma coagulation (APC) was labeled grade 2. More than 2 sessions of APC, blood transfusion, or a course of hyperbaric oxygen was grade 3 and development of visceral fistula, grade 4. Various dosimetric and clinical factors were analyzed using univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis and recursive partitioning analysis were used to determine clinically valid cut-off points and identify risk groups, respectively.

Results: HH was observed in 19.4%, grade ≥3 toxicity in 3.1%. Median follow-up was 29.7 months (interquartile range [IQR]: 20.6-61.7) Median time to develop HH was 11.7 months (IQR: 9.0-15.2) from the start of radiation. At 2 years, cumulative HH was 4.9%, 27.2%, and 42.1% in patients who received 35 Gy to prostate (4-mm planning target volume [PTV] margin), 40 Gy to prostate (5-mm PTV margin), and 40 Gy to prostate/seminal vesicles (5-mm PTV margin), respectively (P<.0001). In the ROC analysis, volume of rectum receiving radiation dose of 38 Gy (V38) was a strong predictor of HH with an area under the curve of 0.65. In multivariate analysis, rectal V38 (≥2.0 cm(3); odds ratio [OR]: 4.7); use of anticoagulants in the follow-up period (OR: 6.5) and presence of hemorrhoids (OR: 2.7) were the strongest predictors. Recursive partitioning analysis showed rectal V38 < 2.0 cm(3), and use of anticoagulants or rectal V38 ≥ 2.0 cm(3) plus 1 other risk factor resulted in an HH risk of >30%.

Conclusions: Rectal V38 and 2 clinical factors were strong predictors of HH following 5-fraction SABR. Planning constraints should keep rectal V38 below 2.0 cm(3).
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http://dx.doi.org/10.1016/j.ijrobp.2015.12.010DOI Listing
April 2016

Dose-escalation of five-fraction SABR in prostate cancer: Toxicity comparison of two prospective trials.

Radiother Oncol 2016 Jan 12;118(1):112-7. Epub 2016 Jan 12.

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

Purpose: To compare biochemical outcome and toxicities of two prospective 5-fraction stereotactic ablative radiotherapy (SABR) studies in prostate cancer.

Materials And Methods: 84 patients in pHART3 received 35 Gy, 30 patients in pHART6 received 40 Gy in 5-fractions to the prostate alone, once weekly. 4mm and 5mm PTV margins were used, respectively. Biochemical outcome, acute, late and cumulative genitourinary (GU)/gastrointestinal (GI) toxicities were compared.

Results: Median follow-up was 74 and 36 months, respectively. Median prostate specific antigen nadir was 0.4 ng/ml and 0.3 ng/ml. 2-, 4- and 6-year biochemical relapse-free survival (bRFS-2+nadir) was 100%, 98.7% and 95.9% in pHART3; 100%, 100% and not reached in pHART6 (p=0.91). There was one acute grade 3 GU (retention) and late grade 4 GI (fistula) toxicity in pHART3, none in pHART6. One patient in each study had persisting grade 2+ toxicity at the last follow-up. pHART6 patients had a greater grade 2+ cumulative GU (5% versus 24.2%) and GI (7.6% versus 26.2%) toxicities.

Conclusions: Patients receiving dose-escalated SABR had slightly lower PSA nadir and similar bRFS, longer follow-up is needed to better estimate biochemical outcomes. There was a greater risk of grade 2 toxicity in pHART6 but not grade 3+ toxicities. Persisting toxicity at the last follow-up is similar.
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http://dx.doi.org/10.1016/j.radonc.2015.12.020DOI Listing
January 2016

High dose-rate brachytherapy boost for intermediate risk prostate cancer: Long-term outcomes of two different treatment schedules and early biochemical predictors of success.

Radiother Oncol 2015 Apr 11;115(1):84-9. Epub 2015 Mar 11.

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

Background And Purpose: To report long-term cancer control rates following high dose-rate (HDR) brachytherapy boost for intermediate risk prostate cancer and explore early biochemical predictors of success.

Material And Methods: Results of two sequential phase II trials are updated and compared: (1) Single 15 Gy HDR-boost followed by external beam radiotherapy (EBRT) 37.5 Gy/15fractions, (2) Two HDR fractions of 10 Gy followed by EBRT 45 Gy/25fractions. Patients were followed prospectively for clinical and biochemical outcomes. Nadir PSA (nPSA) and PSA at 3-years were analyzed as continuous variables, and ROC analysis was used to identify the optimal cutoff values. Kaplan-Meier bDFS curves were generated and the log-rank test used to compare different groups

Results: 183 patients were accrued; 123 to the single fraction trial and 60 to the standard fractionation trial, with a median follow-up of 74 months and 99 months, respectively. The 5-year biochemical relapse-free survival was 97.4% and 92.7%, respectively (p=0.995). Median nPSA was 0.08 ng/ml. Failure to achieve a nPSA <0.4 ng/ml was associated with a significantly higher rate of biochemical relapse (5-year bDFS: 100% vs. 72%; p<0.0001).

Conclusion: HDR boost with single fraction 15 Gy provides durable long-term biochemical disease-free survival. PSA nadir <0.4 ng/ml is associated with very low risk of biochemical failure.
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http://dx.doi.org/10.1016/j.radonc.2015.02.023DOI Listing
April 2015

A comparative study of quality of life in patients with localized prostate cancer treated at a single institution: stereotactic ablative radiotherapy or external beam+high dose rate brachytherapy boost.

Radiother Oncol 2014 Dec 14;113(3):404-9. Epub 2014 Nov 14.

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

Purpose: To compare the quality of life (QOL) in patients treated with stereotactic ablative radiation therapy (SABR) alone or high dose rate (HDR) brachytherapy+hypofractionated external beam radiotherapy (EBRT).

Methods And Materials: Patient self-reported QOL was prospectively measured among patients from two sequential phase 2 clinical trials: 1-SABR 35Gy/5fractions/5 weeks, 2-15Gy HDR 1 fraction, followed by EBRT 37.5Gy/15 fractions/3 weeks. The expanded prostate cancer index composite was assessed at baseline and q6 monthly up to 5 years. Urinary, bowel and sexual domains were analyzed. A minimally clinical important change (MCIC) was defined as 0.5*standard deviation of the baseline for each domain. Fisher exact test and general linear mixed model were used (p<0.05).

Results: 84 and 123 patients were treated on the SABR and HDR boost studies, with a median follow up of 51 and 61 months respectively. There was a significant difference in MCIC between treatments in the urinary function and bother (p<0.0001), the bowel function (p=0.0216) and the sexual function (p=0.0419) and bother (p=0.0290) domains in favor of the SABR group. Of patients who reported no problem with their sexual function at baseline, 7% and 23% respectively considered it to be a moderate to big problem on follow up (p=0.0077).

Conclusion: Patients treated with HDR-boost reported deterioration of QOL particularly in sexual domains in comparison with SABR.
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http://dx.doi.org/10.1016/j.radonc.2014.10.013DOI Listing
December 2014

The clinical significance of persistent cancer cells on prostate biopsy after high-dose-rate brachytherapy boost for intermediate-risk prostate cancer.

Brachytherapy 2015 May-Jun;14(3):309-14. Epub 2014 Nov 25.

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

Purpose: To evaluate the association between post-treatment biopsy results and the probability of biochemical disease-free survival (bDFS).

Methods And Materials: Two sequential prospective clinical trials were undertaken in men with intermediate-risk prostate cancer (T1-T2 with either Gleason score 7 and prostate-specific antigen [PSA] level lower than 20 ng/mL or Gleason score 6 and PSA level of 10-20 ng/mL). All patients had high-dose-rate brachytherapy (two fractions of 10Gy separated by 1 week or a single 15-Gy fraction) followed by external beam radiotherapy. Both study groups were followed prospectively with regular PSA readings and prostate biopsy at 2 years. Biopsies were reported as: positive=malignant cells with no or only partial radiation effect, negative=no malignant cells seen, and indeterminate=malignant cells with marked radiation effect. Biochemical failure was defined using the nadir+2 ng/mL definition and estimated using the Kaplan-Meier curves. Fisher exact test was performed to investigate any relationships between high-dose-rate treatment and biopsy results.

Results: A total of 181 patients were included in this analysis. The median followup for all patients was 6.2 years (range, 0.3-10.5). Post-treatment biopsy was performed in 111 patients of which 82 (74%) were negative, 17 (15%) indeterminate, and 12 (11%) malignant. The 5-year bDFS was 97.5%, 93.8%, and 83.3% for those with benign, indeterminate, and malignant biopsies, respectively (p=0.4398). Median PSA nadir was 0.08 ng/mL (range, 0.01-3.63), with no difference in PSA change over time by treatment (p=0.9953) or biopsy result (p=0.4398) CONCLUSIONS: Routine biopsy at 2 years was not able to reliably predict which patients would ultimately fail as even those with a positive biopsy had a long-term bDFS higher than 80%.
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http://dx.doi.org/10.1016/j.brachy.2014.10.003DOI Listing
December 2015

Prostatic displacement during extreme hypofractionated radiotherapy using volumetric modulated arc therapy (VMAT).

Radiat Oncol 2014 Nov 28;9:262. Epub 2014 Nov 28.

Department of Radiation Oncology, University of Toronto, Toronto, Canada.

Background: To determine prostate displacement during extreme hypofractionated volume modulated arc radiotherapy (VMAT) using pre- and post-treatment orthogonal images with three implanted gold seed fiducial markers.

Methods: A total of 150 image pairs were obtained from 30 patients who underwent extreme hypofractionated radiotherapy to a dose of 40 Gy in five fractions on standard linear accelerators. Position verification was obtained with orthogonal x-rays before and after treatment and were used to determine intra-fraction prostate displacement.

Results: The mean prostate displacements were 0.03 ± 1.23 mm (1SD), 0.18 ± 1.55 mm, and 0.37 ± 1.95 mm in the left-right, superior-inferior, and anterior-posterior directions, respectively. The mean 3D displacement was 2.32 ± 1.55 mm. Only 6 (4%) fractions had a 3D displacement of >5 mm. The average time of treatment delivery for a given fraction was 195 ± 59 seconds.

Conclusions: The mean intra-fraction prostate displacement during a course of extreme hypofractionated radiotherapy delivered via VMAT, continues to be small. Clinical margins typically used in a similar fixed-angle IMRT treatment are adequate. The use of VMAT in further extreme hypofractionation may limit prostatic motion uncertainties that would be otherwise be associated with longer treatment times.
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http://dx.doi.org/10.1186/s13014-014-0262-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251941PMC
November 2014

Improving clinical trial accrual through a novel feedback approach: Lessons learned from a single disease site group.

Pract Radiat Oncol 2015 Mar-Apr;5(2):70-3. Epub 2014 Jul 3.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Health Policy, Measurement and Evaluation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Purpose: Physician participation is critical for the success of clinical trials. Many efforts have been made to aid physicians with accrual. The aim of our study was to determine what impact a new feedback initiative had on clinical trial accrual and recruitment within a large disease site group.

Methods And Materials: A novel feedback initiative was implemented within a large multidisciplinary disease site group. Feedback on trial recruitment by physician and by study for the month and year to date was formally presented at the end of each trial month at weekly tumor board meetings. In addition, the feedback was sent via email. Trial recruitment was assessed both preintervention and postintervention.

Results: A 9-month reporting period both preintervention and postintervention are reported. Total accruals within each observation window were 79 versus 209 patients, respectively. Preintervention, the mean number of patients accrued per month was 8.44 (range, 2-16). Postintervention, the mean number of patients accrued was 23.2 (range, 14-48). Preintervention, physicians only accrued to trials within their specialty. Postintervention, this improved by 4% monthly.

Conclusions: Physicians play a key role in the success of clinical trials. By adopting a simple monthly feedback communication initiative, we were able to improve clinical trial accruals. Long-term assessment is required to understand longitudinal impact on accrual rates.
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http://dx.doi.org/10.1016/j.prro.2014.05.009DOI Listing
December 2015

Dosimetric and patient correlates of quality of life after prostate stereotactic ablative radiotherapy.

Radiother Oncol 2014 Jul 5;112(1):83-8. Epub 2014 Jul 5.

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

Background And Purpose: Initial results of Stereotactic Ablative Body Radiotherapy (SABR) in the treatment of localized prostate cancer appear promising however long-term quality of life (QOL) outcomes and dosimetric correlates are necessary.

Material And Methods: A phase I/II study was performed where low risk prostate cancer patients received SABR 35 Gy in 5 fractions, once weekly. Patient self-reported QOL was measured using the Expanded Prostate Cancer Index Composite (EPIC) at baseline and q6 month up to 5 years. Urinary, bowel and sexual domains were analyzed. A minimally clinical important change (MCIC) was defined as 0.5∗standard deviation of the baseline. Univariate and multivariate logistic regression were used to identify dosimetric predictors of MCIC.

Results: 84 patients were included. The median follow-up was 50.8 months (interquartile range [IQR], 44.7-56.3). 17.9%, 26.2% and 37.5% of patients reported worse QOL on follow up in the urinary, bowel and sexual domains respectively. On univariate analysis Rectal V31.8>10%, D1cc>35 Gy were associated with bowel MCIC, penile bulb (PB) V35>4%, V20>40% with sexual MCIC. Of these factors only rectal D1cc and PB V35 were predictors of worse QOL on multivariate analysis.

Conclusions: Long-term single-institution QOL outcomes are encouraging. Rigorous dosimetric constraints are needed to keep bothersome side effects low.
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http://dx.doi.org/10.1016/j.radonc.2014.06.009DOI Listing
July 2014

Prostate stereotactic ablative body radiotherapy using a standard linear accelerator: toxicity, biochemical, and pathological outcomes.

Radiother Oncol 2013 May 3;107(2):153-8. Epub 2013 May 3.

Department of Radiation Oncology, University of Toronto, Canada.

Background And Purpose: Biological dose escalation through stereotactic ablative radiotherapy (SABR) holds promise of improved patient convenience, system capacity and tumor control with decreased cost and side effects. The objectives are to report the toxicities, biochemical and pathologic outcomes of this prospective study.

Materials And Methods: A phase I/II study was performed where low risk localized prostate cancer received SABR 35 Gy in 5 fractions, once weekly on standard linear accelerators. Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group late morbidity scores were used to assess acute and late toxicities, respectively. Biochemical control (BC) was defined by the Phoenix definition.

Results: As of May 2012, 84 patients have completed treatment with a median follow-up of 55 months (range 13-68 months). Median age was 67 years and median PSA was 5.3 ng/ml. The following toxicities were observed: acute grade 3+: 0% gastrointestinal (GI), 1% genitourinary (GU), 0% fatigue; late grade 3+: 1% GI, 1% GU. Ninety-six percent were biopsy negative post-treatment. The 5-year BC was 98%.

Conclusions: This novel technique employing standard linear accelerators to deliver an extreme hypofractionated schedule of radiotherapy is feasible, well tolerated and shows excellent pathologic and biochemical control.
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http://dx.doi.org/10.1016/j.radonc.2013.03.022DOI Listing
May 2013

The effect of radiation technique and bladder filling on the acute toxicity of pelvic radiotherapy for localized high risk prostate cancer.

Radiother Oncol 2012 Nov 22;105(2):193-7. Epub 2012 Nov 22.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.

Purpose: The goal of this project was to see if using IMRT to deliver elective pelvic nodal irradiation (EPNI) for prostate cancer reduced acute treatment toxicity.

Methods: Two hundred and thirty patients were enrolled into prospective trials delivering EPNI with a concomitant hypofractionated IMRT boost to the prostate. During accrual, the method of EPNI delivery changed as new literature emerged. Three methods were used (1) 4FB, (2) IMRT with 2cm CTV margins around the pelvic vessels as suggested by Shih et al. (2005) [7] (IMRT-Shih), and (3) IMRT with nodal volumes suggested by the RTOG (IMRT-RTOG). Initially patients were treated with an empty bladder, with the remainder treated with bladder full.

Results: Patients in the 4FB group had higher rates of grade 2 acute GI toxicities compared to the IMRT-Shih and IMRT-RTOG groups (31.9% vs 20.8% vs 7.2%, p=0.0009). Patients in the 4FB group had higher rates of grade 3 urinary frequency compared to the two IMRT groups (8.5% vs 0% vs 0%, p=0.027). However, multivariate analysis suggested the factor that most influenced toxicity was bladder filling followed by IMRT.

Conclusions: Bladder filling appeared to be the dominant factor which predicted for acute toxicity, followed by the use of IMRT.
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http://dx.doi.org/10.1016/j.radonc.2012.09.020DOI Listing
November 2012

Quality of life after hypofractionated concomitant intensity-modulated radiotherapy boost for high-risk prostate cancer.

Int J Radiat Oncol Biol Phys 2012 Jun 11;83(2):617-23. Epub 2011 Nov 11.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Purpose: To evaluate the change in health-related quality of life (QOL) of patients with high-risk prostate cancer treated using hypofractionated radiotherapy combined with long-term androgen deprivation therapy.

Methods And Materials: A prospective Phase I-II study enrolled patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level ≥20 ng/mL, or Gleason score 8-10. Radiotherapy consisted of 45 Gy (1.8 Gy per fraction) to the pelvic lymph nodes with a concomitant 22.5 Gy intensity-modulated radiotherapy boost to the prostate, for a total of 67.5 Gy (2.7 Gy per fraction) in 25 fractions over 5 weeks. Daily image guidance was performed using three gold seed fiducials. Quality of life was measured using the Expanded Prostate Cancer Index Composite (EPIC), a validated tool that assesses four primary domains (urinary, bowel, sexual, and hormonal).

Results: From 2004 to 2007, 97 patients were treated. Median follow-up was 39 months. Compared with baseline, at 24 months there was no statistically significant change in the mean urinary domain score (p = 0.99), whereas there were decreases in the bowel (p < 0.01), sexual (p < 0.01), and hormonal (p < 0.01) domains. The proportion of patients reporting a clinically significant difference in EPIC urinary, bowel, sexual, and hormonal scores at 24 months was 27%, 31%, 55%, and 60%, respectively. However, moderate and severe distress related to these symptoms was minimal, with increases of only 3% and 5% in the urinary and bowel domains, respectively.

Conclusions: Hypofractionated radiotherapy combined with long-term androgen deprivation therapy was well tolerated. Although there were modest rates of clinically significant patient-reported urinary and bowel toxicity, most of this caused only mild distress, and moderate and severe effects on QOL were limited. Additional follow-up is ongoing to characterize long-term QOL.
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http://dx.doi.org/10.1016/j.ijrobp.2011.07.005DOI Listing
June 2012

Is single fraction 15 Gy the preferred high dose-rate brachytherapy boost dose for prostate cancer?

Radiother Oncol 2011 Sep 14;100(3):463-7. Epub 2011 Sep 14.

Sunnybrook Odette Cancer Centre, Toronto, Canada.

Background And Purpose: High dose-rate (HDR) brachytherapy is most commonly administered as a boost in two or more fractions combined with external beam radiotherapy (EBRT). Our purpose is to compare outcomes with a single fraction HDR boost to that with a standard fractionated boost in intermediate risk prostate cancer.

Materials And Methods: Results of two sequential phase II clinical trials are compared. The Single Fraction protocol consists of 15 Gy HDR in one fraction followed by 37.5 Gy EBRT in 15 fractions over 3 weeks; the Standard Fractionation protocol consisted of two HDR fractions each of 10 Gy, 1 week apart, followed by 45 Gy EBRT in 25 fractions. Patients had intermediate risk disease, and were well balanced for prognostic factors. Patients were followed prospectively for efficacy, toxicity and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition, and by biopsy at 2 years.

Results: The Single Fraction protocol accrued 123 patients and the Standard Fractionation protocol, 60. With a median follow-up of 45 and 72 months, respectively, the biochemical disease-free survival was 95.1% and 97.9% in the Single and Standard Fractionation trials (p=0.3528). Two-year prostate biopsy was positive in only 4% and 8%, respectively. There was no difference in late urinary or rectal toxicity rates, or in health-related quality of life between the two protocols.

Conclusions: The Single Fraction HDR protocol results in high disease control rate and low toxicity similar to our previous protocol using two HDR insertions, with significant savings in resources. While mature results with longer follow-up are awaited, a single 15 Gy may be considered as a standard fractionation regimen in combination with EBRT for men with intermediate risk disease.
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http://dx.doi.org/10.1016/j.radonc.2011.08.022DOI Listing
September 2011

Hypofractionated concomitant intensity-modulated radiotherapy boost for high-risk prostate cancer: late toxicity.

Int J Radiat Oncol Biol Phys 2012 Feb 14;82(2):898-905. Epub 2011 Jan 14.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Purpose: To report the acute and late toxicities of patients with high-risk localized prostate cancer treated using a concomitant hypofractionated, intensity-modulated radiotherapy boost combined with long-term androgen deprivation therapy.

Methods And Materials: A prospective Phase I-II study of patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level ≥ 20 ng/mL, or Gleason score 8-10. A dose of 45 Gy (1.8 Gy/fraction) was delivered to the pelvic lymph nodes with a concomitant 22.5 Gy prostate intensity-modulated radiotherapy boost, to a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions within 5 weeks. Image guidance was performed using three gold seed fiducials. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, and Radiation Therapy Oncology Group late morbidity scores were used to assess the acute and late toxicities, respectively. Biochemical failure was determined using the Phoenix definition.

Results: A total of 97 patients were treated and followed up for a median of 39 months, with 88% having a minimum of 24 months of follow-up. The maximal toxicity scores were recorded. The grade of acute gastrointestinal toxicity was Grade 0 in 4%, 1 in 59%, and 2 in 37%. The grade of acute urinary toxicity was Grade 0 in 8%, 1 in 50%, 2 in 39%, and 3 in 4%. The grade of late gastrointestinal toxicity was Grade 0 in 54%, 1 in 40%, and 2 in 7%. No Grade 3 or greater late gastrointestinal toxicities developed. The grade of late urinary toxicity was Grade 0 in 82%, 1 in 9%, 2 in 5%, 3 in 3%, and 4 in 1% (1 patient). All severe toxicities (Grade 3 or greater) had resolved at the last follow-up visit. The 4-year biochemical disease-free survival rate was 90.5%.

Conclusions: A hypofractionated intensity-modulated radiotherapy boost delivering 67.5 Gy in 25 fractions within 5 weeks combined with pelvic nodal radiotherapy and long-term androgen deprivation therapy was well tolerated, with low rates of severe toxicity. The biochemical control rate at early follow-up has been promising. Additional follow-up is needed to determine the long-term biochemical control and prostate biopsy results.
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http://dx.doi.org/10.1016/j.ijrobp.2010.11.003DOI Listing
February 2012

Health-related quality of life after single-fraction high-dose-rate brachytherapy and hypofractionated external beam radiotherapy for prostate cancer.

Int J Radiat Oncol Biol Phys 2011 Aug 12;80(5):1299-305. Epub 2010 Aug 12.

Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.

Purpose: To investigate the change in health-related quality of life for men after high-dose-rate brachytherapy and external beam radiotherapy for prostate cancer and the factors associated with this change.

Methods And Materials: Eligible patients had clinically localized intermediate-risk prostate cancer. The patients received high-dose-rate brachytherapy as a single 15-Gy implant, followed by external beam radiotherapy to 37.5 Gy in 15 fractions. The patients were monitored prospectively for toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and health-related quality of life (Expanded Prostate Cancer Index Composite [EPIC]). The proportion of patients developing a clinically significant difference in the EPIC domain score (minimally important difference of >0.5 standard deviation) was determined and correlated with the baseline clinical and dosimetric factors. The study accrued 125 patients, with a median follow-up of 24 months.

Results: By 24 months, 23% had Grade 2 urinary toxicity and only 5% had Grade 2 bowel toxicity, with no Grade 3 toxicity. The proportion of patients reporting a significant decrease in EPIC urinary, bowel, sexual, and hormonal domain scores was 53%, 51%, 45%, and 40% at 12 months and 57%, 65%, 51%, and 30% at 24 months, respectively. The proportion with a >1 standard deviation decrease in the EPIC urinary, bowel, sexual, and hormonal domain scores was 38%, 36%, 24%, and 20% at 12 months and 46%, 48%, 19%, and 8% at 24 months, respectively. On multivariate analysis, the dose to 10% of the urethra was associated with a decreasing EPIC urinary domain score (p = .0089) and, less strongly (p = .0312) with a decreasing hormonal domain score. No association was found between the prostate volume, bladder dose, or high-dose volume and urinary health-related quality of life. A high baseline International Index of Erectile Function score was associated (p = .0019) with a decreasing sexual domain score. The optimal maximal dose to 10% of the urethra cutpoint for urinary health-related quality of life was 120% of the prescription dose.

Conclusion: EPIC was a more sensitive tool for detecting the effects on function and bother than were the generic toxicity scales. The urethral dose had the strongest association with a deteriorating urinary quality of life.
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http://dx.doi.org/10.1016/j.ijrobp.2010.04.046DOI Listing
August 2011

Single-fraction high-dose-rate brachytherapy and hypofractionated external beam radiotherapy for men with intermediate-risk prostate cancer: analysis of short- and medium-term toxicity and quality of life.

Int J Radiat Oncol Biol Phys 2010 Jul 14;77(3):811-7. Epub 2009 Oct 14.

Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, Canada.

Purpose: To determine the short- and medium-term effects of a single high-dose-rate brachytherapy fraction of 15 Gy and hypofractionated external beam radiation therapy for prostate cancer.

Methods And Materials: Eligible patients had localized prostate cancer with a Gleason score of 7 and a prostate-specific antigen (PSA) concentration of <20 ng/ml or a Gleason score of 6 with a PSA concentration of 10 to 20 ng/ml. Patients received high-dose-rate brachytherapy as a single 15-Gy dose, followed by external beam radiation therapy at 37.5 Gy in 15 fractions, and were followed prospectively for toxicity (using Common Terminology Criteria for Adverse Events version 3.0), urinary symptoms (using the International Prostate Symptom Score [IPSS]), erectile function (with the International Index of Erectile Function [IIEF]), and health-related quality of life (with the Expanded Prostate Cancer Index Composite [EPIC]). Clinical examinations and PSA measurements were performed at every visit, and prostate biopsies were repeated at 2 years. The trial accrued 125 patients, with a median follow-up of 1.14 years.

Results: Acute grade 2 and 3 genitourinary toxicity occurred in 62% and 1.6% of patients, respectively, and acute grade 2 gastrointestinal toxicity occurred in 6.5% of patients. No grade 3 late toxicity has occurred: 47% of patients had grade 2 genitourinary and 10% of patients had grade 2 gastrointestinal toxicity. Median IPSSs rose from 5 at baseline to 12 at 1 month and returned to 7 at 3 months. Of the total number of patients who were initially potent (IIEF, >21), 8% of patients developed mild to moderate dysfunction, and 27% of patients developed severe erectile dysfunction. Baseline EPIC bowel, urinary, and sexual bother scores decreased by 9, 7, and 19 points, respectively, at 1 year. No patient has experienced biochemical failure, and 16 of the first 17 biopsy results showed no malignancy.

Conclusions: Treatment is well tolerated in the short and medium term, with low toxicity and encouraging early indicators of disease control.
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http://dx.doi.org/10.1016/j.ijrobp.2009.05.054DOI Listing
July 2010
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