Publications by authors named "Patrick Cheung"

120 Publications

An international Delphi consensus for pelvic Stereotactic Ablative Radiotherapy re-irradiation.

Radiother Oncol 2021 Sep 21. Epub 2021 Sep 21.

Leeds Teaching Hospitals NHS Trust, Beckett Street, Leeds, LS9 7TF, UK; University of Leeds, Leeds, LS2 9JT, UK. Electronic address:

Introduction: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat metastatic oligorecurrence and locoregional recurrences but limited evidence/guidance exists in the setting of pelvic re-irradiation. An international Delphi study was performed to develop statements to guide practice regarding patient selection, pre-treatment investigations, treatment planning, delivery and cumulative organs at risk (OARs) constraints.

Materials And Methods: Forty-one radiation oncologists were invited to participate in three online surveys. In Round 1, information and opinion was sought regarding participants' practice. Guidance statements were developed using this information and in Round 2 participants were asked to indicate their level of agreement with each statement. Consensus was defined as ≥75% agreement. In Round 3, any statements without consensus were re-presented unmodified, alongside a summary of comments from Round 2.

Results: Twenty-three radiation oncologists participated in Round 1 and, of these, 21 (91%) and 22 (96%) completed Rounds 2 and 3 respectively. Twenty-nine of 44 statements (66%) achieved consensus in Round 2. The remaining 15 statements (34%) did not achieve further consensus in Round 3. Consensus was achieved for 10 of 17 statements (59%) regarding patient selection/pre-treatment investigations; 12 of 13 statements (92%) concerning treatment planning and delivery; and 7 of 14 statements (50%) relating to OARs. Lack of agreement remained regarding the minimum time interval between irradiation courses, the number/size of pelvic lesions that can be treated and the most appropriate cumulative OAR constraints.

Conclusions: This study has established consensus, where possible, in areas of patient selection, pre-treatment investigations, treatment planning and delivery for pelvic SABR re-irradiation for metastatic oligorecurrence and locoregional recurrences. Further research into this technique is required, especially regarding aspects of practice where consensus was not achieved.
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http://dx.doi.org/10.1016/j.radonc.2021.09.010DOI Listing
September 2021

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

Stereotactic Radiotherapy for Oligoprogression in Metastatic Renal Cell Cancer Patients Receiving Tyrosine Kinase Inhibitor Therapy: A Phase 2 Prospective Multicenter Study.

Eur Urol 2021 Aug 13. Epub 2021 Aug 13.

Division of Medical Oncology, Department of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada. Electronic address:

Background: Despite the paucity of prospective evidence, stereotactic radiotherapy (SRT) is increasingly being considered in the setting of oligoprogression to delay the need to change systemic therapy.

Objective: To determine the local control (LC), progression-free survival (PFS), cumulative incidence of changing systemic therapy, and overall survival (OS) after SRT to oligoprogressive metastatic renal cell carcinoma (mRCC) lesions in patients who are on tyrosine kinase inhibitor (TKI) therapy.

Design, Setting, And Participants: A prospective multicenter study was performed to evaluate the use of SRT in oligoprogressive mRCC patients. Patients with mRCC who had previous stability or response after ≥3 mo of TKI therapy were eligible if they developed progression of five of fewer metastases. Thirty-seven patients with 57 oligoprogressive tumors were enrolled.

Intervention: Oligoprogressive tumors were treated with SRT, and the same TKI therapy was continued afterward.

Outcome Measurements And Statistical Analysis: Competing risk analyses and the Kaplan-Meir methodology were used to report the outcomes of interest.

Results And Limitations: The median duration of TKI therapy prior to study entry was 18.6 mo; 1-yr LC of the irradiated tumors was 93% (95% confidence interval [CI] 71-98%). The median PFS after SRT was 9.3 mo (95% CI 7.5-15.7 mo). The cumulative incidence of changing systemic therapy was 47% (95% CI 32-68%) at 1 yr, with a median time to change in systemic therapy of 12.6 mo (95% CI 9.6-17.4 mo). One-year OS was 92% (95% CI 82-100%). There were no grade 3-5 SRT-related toxicities.

Conclusions: LC of irradiated oligoprogressive mRCC tumors was high, and the need to change systemic therapy was delayed for a median of >1 yr.

Patient Summary: The use of stereotactic radiotherapy in metastatic kidney cancer patients, who develop growth of a few tumors while on oral targeted therapy, can significantly delay the need to change to the next line of drug therapy.
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http://dx.doi.org/10.1016/j.eururo.2021.07.026DOI Listing
August 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

Organ at Risk Dose Constraints in SABR: A Systematic Review of Active Clinical Trials.

Pract Radiat Oncol 2021 Jul-Aug;11(4):e355-e365

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

Purpose: Organ at risk (OAR) dose constraints are a critical aspect of SABR treatment planning. There is limited evidence supporting preferred dose constraints for many OARs. We sought to evaluate OAR dose constraints used in ongoing clinical trials of SABR for oligometastatic disease.

Methods And Materials: Clinicaltrials.gov was searched from inception to February 2020 to capture actively accruing clinical trials using SABR in oligometastatic disease. Dose constraints were obtained by contacting principal investigators and abstracted by 2 authors. Variability of constraints was assessed by comparing the width of the interquartile range and difference between the maximum and minimum dose to a volume.

Results: Fifty-three of 85 eligible clinical trials contributed OAR constraints used in analysis. Dose constraints for 1 to 8 fractions of SABR were collected for 33 OARs. Variability was found in the absolute allowable OAR doses, use of planning OAR volumes, and whether constraints were optional versus mandatory. For many OARs, modal dose constraints often matched a pre-existing publication, but no single pre-existing publication matched the modes of all OAR dose constraints. Organs displaying the most variability were the rectum, penile bulb, and chest wall and ribs. The esophagus, stomach, duodenum, and small bowel also indicated high variability for at least 1 constraint. OARs previously evaluated by HyTEC appeared to have less variability among study protocols.

Conclusions: We found substantial variability in OAR dose constraints used in current clinical trials evaluating SABR in oligometastatic disease. We are unable to comment on toxicity rates or acceptability of dose constraints used. Future research and recommendations for standardized OAR dose constraints, as well as consistency in implementing planning OAR volume margins, should be priorities for the field of radiation oncology.
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http://dx.doi.org/10.1016/j.prro.2021.03.005DOI Listing
September 2021

Outcomes of extra-cranial stereotactic body radiotherapy for metastatic breast cancer: Treatment indication matters.

Radiother Oncol 2021 08 10;161:159-165. Epub 2021 Jun 10.

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

Background And Purpose: To summarize the clinical outcomes of stereotactic body radiotherapy (SBRT) for metastatic breast cancer (mBC) from a large institution.

Materials And Methods: Patients with mBC who received extra-cranial SBRT to metastatic lesions from 2011 to 2017 were identified. Treatment indications were: oligometastases, oligoprogression, and local control of dominant tumor (CDT). Endpoints included overall survival (OS), progression-free survival (PFS), local control (LC) and cumulative incidence of starting/changing chemo or hormonal therapy (SCT). Univariate and multivariate analyses were used to identify predictive factors.

Results: We analyzed 120 patients (193 treated metastatic lesions) with a median follow up of 15.25 months. 1-and 2-year LC rates were 89% and 86.6%, respectively. 1-and 2-year OS rates were 83.5% and 70%, respectively, with treatment indication and molecular subtype being the predictive factors on MVA. 1-year OS was 91.0%, 78.5% and 63.9% for oligometastases, oligoprogression and CDT, respectively (p = 0.003). The worst OS was seen in basal subtype with 1-and 2-year OS rates of 59.2% and 39.5% (p = 0.01). Treatment indication was found to be predictive for PFS and lower rates of SCT on MVA. 1-and 2-year PFS rates were 45% and 32%, respectively. The 1-year PFS for oligometastases, oligoprogression, and CDT was 66%, 19.6%, and 14.3%, respectively (p < 0.001). The cumulative incidence of SCT at 1-year was 12% for oligometastases, 39.7% for oligoprogression and 53.3% for CDT (p < 0.001).

Conclusion: Patients treated for oligometastases have better OS and PFS than those treated for oligoprogression or CDT. SBRT may delay SCT in mBC patients, particularly those with oligometastases. SBRT provided an excellent LC in mBC patients.
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http://dx.doi.org/10.1016/j.radonc.2021.06.012DOI Listing
August 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

Biomarker testing and mutation prevalence in metastatic colorectal cancer patients in five European countries using a large oncology database.

Future Oncol 2021 Apr 19;17(12):1483-1494. Epub 2021 Jan 19.

Department of Pathology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.

The literature on biomarker testing for metastatic colorectal cancer (mCRC) in Europe is scarce. This study aimed to estimate the percentage of mCRC patients from five European countries tested for biomarkers over time. An oncology database was retrospectively analyzed; evaluated biomarkers were ,  and microsatellite instability (MSI). The patients were drug treated during 2018 and tested for relevant biomarkers in 2013-2018. testing was conducted in >90% of mCRC patients from 2014 onwards. testing increased from 31% of mCRC patients in 2013 to 67% in 2018. MSI testing increased from 10 to 41%. There was no notable trend over time for and mutation or MSI-high prevalence. Biomarker testing among patients diagnosed with mCRC was increased over time. This study demonstrates the quick uptake of biomarker testing in clinical practice. These findings are significant as biomarker-based drugs are becoming more common.
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http://dx.doi.org/10.2217/fon-2020-0975DOI Listing
April 2021

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 03 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
March 2021

Stereotactic Body Radiation Therapy for Mediastinal and Hilar Lymph Node Metastases.

Int J Radiat Oncol Biol Phys 2021 03 25;109(3):764-774. Epub 2020 Oct 25.

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

Purpose: Stereotactic body radiation therapy (SBRT) to metastatic mediastinal and hilar lymphadenopathy (MHL) is challenging owing to the proximity of centrally located organs-at-risk. As limited data exist on the safety and efficacy of SBRT for MHL, a retrospective review of clinical outcomes was conducted from a large academic center.

Methods And Materials: Eligible patients received SBRT to MHL between 2014 to 2019 for the following indications: oligometastases, oligoprogression, or local control of a dominant area of progression. The primary endpoint was grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). The cumulative incidence function evaluated local failure (LF) and starting or changing systemic therapy (SCST). Kaplan-Meier methodology estimated progression-free survival (PFS) and overall survival (OS).

Results: Fifty-two patients (84 metastases) were included. Median follow-up was 20 months. Primary cancer sites included kidney (53.8%), lung (13.4%), breast (7.7%), and other (25.1%). Indications for SBRT were oligoprogression (n = 35; 67.3%), oligometastases (n = 10; 19.2%), or local failure of a dominant area of progression (n = 7; 13.5%). The majority (n = 31; 59.6%) received SBRT to a single lymph node metastasis. Median SBRT dose was 35 Gy (range, 30-50 Gy) with a median biologically effective dose of 59.5 Gy (range, 48-100 Gy). All treatments were in 5 fractions. Seven grade ≥3 toxicities were experienced by 6 patients (11.5%) and were mostly transient (5/7; 71%). There was a single (1.9%) grade 5 toxicity (radiation pneumonitis). The cumulative incidence of LF was 9.0% at 2 years. The cumulative incidence of SCST was 33.2% and 57.1% at 1 and 2 years, respectively. Median PFS was 4.0 months (95% confidence interval, 2.8-7.3) and median OS was 31.7 months (95% confidence interval, 23.8-87.5).

Conclusions: In one of the largest single institutional series of SBRT for MHL, moderate rates of grade ≥3 toxicity were observed, although the majority were transient. This treatment resulted in low LF rates and potentially delayed SCST for many patients.
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http://dx.doi.org/10.1016/j.ijrobp.2020.10.004DOI Listing
March 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

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 2021 01 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
January 2021

A review of ongoing trials of stereotactic ablative radiotherapy for oligometastatic disease in the context of new consensus definitions.

Ann Palliat Med 2021 May 7;10(5):6045-6051. Epub 2020 Aug 7.

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

The characterization and treatment of oligometastatic disease (OMD) are rapidly growing areas of research. Consensus statements have recently been developed by European Society for Radiotherapy and Oncology (ESTRO)/American Society for Radiation Oncology (ASTRO) and ESTRO/European Organization for Research and Treatment of Cancer (EORTC) in an effort to harmonize terminology describing OMD. The purpose of this study was to assess patient populations eligible for ongoing clinical trials evaluating stereotactic ablative radiotherapy (SABR) in OMD in the context of key definitions from both statements. Using the clinicaltrials.gov database, a search of ongoing OMD clinical trials evaluating the use of SABR was performed from inception to January 2020, using the keywords "oligometastasis", "stereotactic radiotherapy", and related terms. Results were independently reviewed by two investigators, with discrepancies settled by a third. Information from these trials including study design, population criteria, and primary endpoints were extracted. OMD was defined in general as a limited number of metastases that could be safely treated with metastasis-directed therapy. States of OMD were broadly categorized into de novo, repeat, and induced, with synchronous and metachronous being subsets of de novo. The initial search strategy identified 293 trials, of which 85 met our eligibility criteria. Phase II trials were by far the most common (n=46, 52%). Most trials had a single treatment arm (n=43, 51%), and 31 (36%) were randomized. The majority of trials (n=65, 76%) had populations that included all three subsets of OMD. Notably, 70 trials (82%) also included oligoprogressive disease, which is debatably a distinct entity from OMD. Progression-free survival was the most common primary endpoint (n=31, 36%), followed by local control (n=17, 20%), toxicity (n=14, 16%) and overall survival (n=7, 8%). Although the use of SABR for OMD is an active area of prospective clinical trial research, ongoing studies include mixed populations as defined by new consensus statements. Therefore, the applicability of results from these trials should be considered within relevant OMD scenarios.
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http://dx.doi.org/10.21037/apm-20-847DOI Listing
May 2021

[Formula: see text]: deep learning-based radiomics for the time-to-event outcome prediction in lung cancer.

Sci Rep 2020 07 23;10(1):12366. Epub 2020 Jul 23.

Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.

Hand-crafted radiomics has been used for developing models in order to predict time-to-event clinical outcomes in patients with lung cancer. Hand-crafted features, however, are pre-defined and extracted without taking the desired target into account. Furthermore, accurate segmentation of the tumor is required for development of a reliable predictive model, which may be objective and a time-consuming task. To address these drawbacks, we propose a deep learning-based radiomics model for the time-to-event outcome prediction, referred to as DRTOP that takes raw images as inputs, and calculates the image-based risk of death or recurrence, for each patient. Our experiments on an in-house dataset of 132 lung cancer patients show that the obtained image-based risks are significant predictors of the time-to-event outcomes. Computed Tomography (CT)-based features are predictors of the overall survival (OS), with the hazard ratio (HR) of 1.35, distant control (DC), with HR of 1.06, and local control (LC), with HR of 2.66. The Positron Emission Tomography (PET)-based features are predictors of OS and recurrence free survival (RFS), with hazard ratios of 1.67 and 1.18, respectively. The concordance indices of [Formula: see text], [Formula: see text], and [Formula: see text] for predicting the OS, DC, and RFS show that the deep learning-based radiomics model is as accurate or better in predicting predefined clinical outcomes compared to hand-crafted radiomics, with concordance indices of [Formula: see text], [Formula: see text], and [Formula: see text], for predicting the OS, DC, and RFS, respectively. Deep learning-based radiomics has the potential to offer complimentary predictive information in the personalized management of lung cancer patients.
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http://dx.doi.org/10.1038/s41598-020-69106-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378058PMC
July 2020

Stereotactic ablative radiotherapy for malignant mediastinal and hilar lymphadenopathy: a systematic review.

J Thorac Dis 2020 May;12(5):2280-2287

Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.

Background: Stereotactic ablative radiotherapy (SABR) safety and efficacy for mediastinal and hilar lymphadenopathy (MHL) is not yet established, given its potential for toxicity due to the proximity to esophagus and proximal bronchial tree (PBT). This review summarized current reported outcomes of MHL SABR.

Methods: This systematic review, based on the PRISMA guidelines, was performed using MEDLINE® (PubMed®), EMBASE and Cochrane Library databases from inception until December 2018. Studies reporting outcomes from SABR specifically for MHL from all primary malignancies were included. Non- English studies, guidelines, reviews, non-peer reviewed correspondences were excluded. Only the most recent publication and/or largest cohort from a single institution would be included for analysis.

Results: From the 222 studies identified, 4 retrospective studies totaling 196 patients were included in the analysis. One study included a small number of patients receiving non-ablative doses of stereotactic radiotherapy (RT). Non-small cell lung cancer (NSCLC) was the most common primary (65%), followed by breast (8%). Median follow-up ranged between 12 and 32 months. Reported dose and fractionation ranged from 21 to 60 Gy in 3-11 fractions, with median BED10 ranged from 46-106 Gy10. Three studies reported local control (LC) rates: study 1, 97% (1-year) and 77% (5-year); study 4, 88% (2-year); and study 2, 69% (6-month) and 66% (16-month). Pooled grade 3-5 toxicity rate according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 was 6% (n=11). Pooled SABR-related mortality (grade 5 toxicity) rate was 2% (n=4). Three SABR-related deaths from esophageal fistulae (2 to trachea, 1 to mediastinum) were reported, with all 3 having prior RT to the subcarinal nodes.

Conclusions: Our review suggested SABR for MHL to be feasible and effective, though there is a potential for serious toxicity especially in the re-irradiation scenario. Multi-institutional and/or prospective studies will help determine the therapeutic benefit of SABR in this high-risk treatment scenario.
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http://dx.doi.org/10.21037/jtd.2020.03.112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330368PMC
May 2020

Gantry-Mounted Linear Accelerator-Based Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer.

Adv Radiat Oncol 2020 May-Jun;5(3):404-411. Epub 2019 Oct 14.

Department of Radiation Oncology, University of California, Los Angeles, California.

Purpose: To establish the safety and efficacy of gantry-mounted linear accelerator-based stereotactic body radiation therapy (SBRT) for low- and intermediate-risk prostate cancer.

Methods: We pooled 921 patients enrolled on 7 single-institution prospective phase II trials of gantry-based SBRT from 2006 to 2017. The cumulative incidences of biochemical recurrence (defined by the Phoenix definition) and physician-scored genitourinary (GU) and gastrointestinal (GI) toxicities (defined per the original trials using Common Terminology Criteria for Adverse Events) were estimated using a competing risk framework. Multivariable logistic regression was used to evaluate the relationship between late toxicity and prespecified covariates: biologically effective dose, every other day versus weekly fractionation, intrafractional motion monitoring, and acute toxicity.

Results: Median follow-up was 3.1 years (range, 0.5-10.8 years). In addition, 505 (54.8%) patients had low-risk disease, 236 (25.6%) had favorable intermediate-risk disease, and 180 (19.5%) had unfavorable intermediate-risk disease. Intrafractional motion monitoring was performed in 78.0% of patients. The 3-year cumulative incidence of biochemical recurrence was 0.8% (95% confidence interval [CI], 0-1.7%), 2.2% (95% CI, 0-4.3%), and 5.1% (95% CI, 1.0-9.2%) for low-, favorable intermediate-, and unfavorable intermediate-risk disease. Acute grade ≥2 GU and GI toxicity occurred in 14.5% and 4.6% of patients, respectively. Three-year cumulative incidence estimates of late grade 2 GU and GI toxicity were 4.1% (95% CI, 2.6-5.5%) and 1.3% (95% CI, 0.5-2.1%), respectively, with late grade ≥3 GU and GI toxicity estimates of 0.7% (95% CI, 0.1-1.3%) and 0.4% (95% CI, 0-0.8%), respectively. The only identified significant predictors of late grade ≥2 toxicity were acute grade ≥2 toxicity ( < .001) and weekly fractionation ( < .01), although only 12.4% of patients were treated weekly.

Conclusions: Gantry-based SBRT for prostate cancer is associated with a favorable safety and efficacy profile, despite variable intrafractional motion management techniques. These findings suggest that multiple treatment platforms can be used to safely deliver prostate SBRT.
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http://dx.doi.org/10.1016/j.adro.2019.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276661PMC
October 2019

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

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 05 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

Stereotactic Body Radiation Therapy for Extracranial Oligometastatic Non-small-cell Lung Cancer: A Systematic Review.

Clin Lung Cancer 2020 03 30;21(2):95-105.e1. Epub 2019 Dec 30.

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

Stereotactic body radiation therapy (SBRT) has emerged as a treatment modality for selected patients with oligometastatic non-small-cell lung cancer (NSCLC). The objectives of this systematic review were to explore the benefits and risks of SBRT for extracranial oligometastatic NSCLC. The MEDLINE, Embase, PubMed, and CENTRAL databases were searched for relevant articles from January 1, 2000 to July 23, 2019. Fully published phase III or phase II trials of any sample size were included. Retrospective series published in manuscript form with at least 50 patients were also included. Four prospective phase II randomized trials (total, 188 participants), 4 prospective non-randomized studies (total, 140 participants), and eleven retrospective studies (total, 1288 participants) were included in this systematic review. A variety of dose fractionation schemes were used. The median overall survival (OS) ranged from 13.5 to 55 months. Progression-free survival (PFS) ranged from 4.4 to 14.7 months. Quality of life outcomes were reported in 2 studies. None of the studies reported symptom control outcomes. There are no fully completed phase III randomized trials that clarify the risks and benefits of SBRT for oligometastatic NSCLC. Higher PFS and OS with SBRT were reported in 4 phase II randomized studies. The results from mature phase III randomized data regarding whether SBRT for oligometastatic NSCLC benefits patients in terms of OS, PFS, quality of life, and symptom control are needed.
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http://dx.doi.org/10.1016/j.cllc.2019.11.007DOI Listing
March 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

Outcomes of extra-cranial stereotactic body radiotherapy for metastatic colorectal cancer: Dose and site of metastases matter.

Radiother Oncol 2020 01 19;142:236-245. Epub 2019 Sep 19.

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

Background And Purpose: To review the clinical outcomes following the use of stereotactic body radiotherapy (SBRT) in patients with metastatic colorectal cancer (mCRC) from a large academic institution.

Materials And Methods: Patients with mCRC treated with extracranial SBRT between 2008 and 2016 were identified from an institutional database. Treatment indications were oligometastases, oligoprogression, and local control of dominant tumors. Endpoints included local progression (LP), overall survival (OS), progression-free survival (PFS), and cumulative incidence of starting or changing systemic therapy (SCST). Univariate and multivariable analyses (MVA) were performed to identify predictive factors.

Results: One hundred and sixty-five patients (262 lesions treated) were included. The 2-year cumulative incidence of LP was 23.8%. Lower SBRT doses and tumor location in the liver were significant predictors of LP on MVA. Median OS was 49.3 months, 19.3 months, and 9.0 months for oligometastases, oligoprogression, and local control of dominant tumors, respectively. Primary tumor not in situ, smaller tumors, fewer lines of previous systemic therapy, lower CEA, and oligometastases treatment indications were significant predictors of higher OS on MVA. For the entire cohort, median PFS was 9.9 months, while oligometastatic patients had a median PFS of 12.4 months. 2-year cumulative incidence of SCST was 41.7%.

Conclusions: Survival outcomes are favorable after SBRT for mCRC patients. A significant proportion of patients did not have a change in systemic therapy after SBRT. Higher doses are required to obtain the best local control. Efforts should be made to better optimize SBRT delivery for liver metastases given their higher local failure rate.
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http://dx.doi.org/10.1016/j.radonc.2019.08.018DOI Listing
January 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

Two StereoTactic ablative radiotherapy treatments for localized prostate cancer (2STAR): Results from a prospective clinical trial.

Radiother Oncol 2019 06 19;135:86-90. Epub 2019 Mar 19.

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

Purpose: Ultrahypofractionation is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index. Here we report the outcomes of a phase II prostate SABR trial using two fractions.

Methods: Patients had low or intermediate risk prostate cancer. Three gold fiducials were implanted for image guidance. The clinical target volume (CTV) included the prostate only, and the planning target volume (PTV) was a 3 mm expansion enabled through the use of a rectal immobilization device. The dose prescribed was 26 Gy in 2 weekly fractions (EQD2 110 Gy). The primary endpoint was quality of life using EPIC, and minimal clinically important change (MCIC) was defined as an EPIC QOL decrease >0.5 SD.

Results: 30 patients were accrued with a median follow-up of 49.3 months. 10% had low-risk, 33% had favourable intermediate-risk and 57% had unfavourable intermediate-risk PCa. Five patients received a short course of ADT. Median nPSA was 0.2 ng/ml. One patient had BF and is being observed. 56.6% of patients had a 4yPSARR. Six (20.7%) patients had a MCIC in the urinary domain, 6 (21.4%) had a MCIC in the bowel domain, and 3 (20%) had a MCIC in the sexual domain.

Conclusions: Two-fraction SABR in prostate cancer is safe and feasible, with a minimal change in QOL and a low rate of late grade 3-4 toxicity. The PSA kinetics and biochemical control rates are encouraging given that the majority had unfavourable intermediate-risk disease, although longer follow-up is required.
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http://dx.doi.org/10.1016/j.radonc.2019.03.002DOI Listing
June 2019

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

Trends in Management of Oligometastatic Hormone-Sensitive Prostate Cancer.

Curr Oncol Rep 2019 03 27;21(5):43. Epub 2019 Mar 27.

Sir Peter MacCallum Department of Oncology, University of Melbourne, 305 Grattan Street, Peter MacCallum Cancer Center, Melbourne, Victoria, 3000, Australia.

Purpose Of Review: Systemic therapy for patients with hormone-sensitive oligometastatic prostate cancer is non-curative and associated with toxicities. Meanwhile, this population presents unique clinical opportunities to improve outcomes, including the demonstrated benefits of radiotherapy to the primary tumor or oligometastatic sites.

Recent Findings: Recently published randomized studies have demonstrated benefits with the addition of radiotherapy to the primary disease or metastatic lesions in patients with synchronous or metachronous disease. The introduction of novel PET imaging has improved the sensitivity and specificity for detecting metastatic disease and provides an opportunity to better select patients who will benefit from local therapy. The data presented in this review supports revisiting practice guidelines for patients with hormone-sensitive metastatic prostate cancer, particularly in relation to the role of radiotherapy to the primary tumor and sites of oligometastatic disease. Future trials will aim to further establish the role of metastasis-directed therapies in metachronous, synchronous, and castrate-resistant disease.
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http://dx.doi.org/10.1007/s11912-019-0791-5DOI Listing
March 2019

Long-term Outcomes of Stereotactic Body Radiotherapy for Low-Risk and Intermediate-Risk Prostate Cancer.

JAMA Netw Open 2019 02 1;2(2):e188006. Epub 2019 Feb 1.

Department of Radiation Oncology, University of California, Los Angeles.

Importance: Stereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported.

Objective: To assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer.

Design, Setting, And Participants: This cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018.

Main Outcomes And Measures: The cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method.

Results: A total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n = 13) and of gastrointestinal toxic events was 0.09% (n = 2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%).

Conclusions And Relevance: In this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.
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http://dx.doi.org/10.1001/jamanetworkopen.2018.8006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484596PMC
February 2019

Intrinsic valley Hall transport in atomically thin MoS.

Nat Commun 2019 02 5;10(1):611. Epub 2019 Feb 5.

Department of Physics and the Center for Quantum Materials, the Hong Kong University of Science and Technology, Hong Kong, China.

Electrons hopping in two-dimensional honeycomb lattices possess a valley degree of freedom in addition to charge and spin. In the absence of inversion symmetry, these systems were predicted to exhibit opposite Hall effects for electrons from different valleys. Such valley Hall effects have been achieved only by extrinsic means, such as substrate coupling, dual gating, and light illuminating. Here we report the first observation of intrinsic valley Hall transport without any extrinsic symmetry breaking in the non-centrosymmetric monolayer and trilayer MoS, evidenced by considerable nonlocal resistance that scales cubically with local resistance. Such a hallmark survives even at room temperature with a valley diffusion length at micron scale. By contrast, no valley Hall signal is observed in the centrosymmetric bilayer MoS. Our work elucidates the topological origin of valley Hall effects and marks a significant step towards the purely electrical control of valley degree of freedom in topological valleytronics.
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http://dx.doi.org/10.1038/s41467-019-08629-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363770PMC
February 2019

Determining Interaction Enhanced Valley Susceptibility in Spin-Valley-Locked MoS.

Nano Lett 2019 03 7;19(3):1736-1742. Epub 2019 Feb 7.

Department of Physics and Center for Quantum Materials , The Hong Kong University of Science and Technology , Clear Water Bay , Hong Kong , China.

Two-dimensional transition metal dichalcogenides (TMDCs) are recently emerged electronic systems with various novel properties, such as spin-valley locking, circular dichroism, valley Hall effect, and superconductivity. The reduced dimensionality and large effective masses further produce unconventional many-body interaction effects. Here we reveal strong interaction effects in the conduction band of MoS by transport experiment. We study the massive Dirac electron Landau levels (LL) in high-quality MoS samples with field-effect mobilities of 24 000 cm/(V·s) at 1.2 K. We identify the valley-resolved LLs and low-lying polarized LLs using the Lifshitz-Kosevitch formula. By further tracing the LL crossings in the Landau fan diagram, we unambiguously determine the density-dependent valley susceptibility and the interaction enhanced g-factor from 12.7 to 23.6. Near integer ratios of Zeeman-to-cyclotron energies, we discover LL anticrossings due to the formation of quantum Hall Ising ferromagnets, the valley polarizations of which appear to be reversible by tuning the density or an in-plane magnetic field. Our results provide evidence for many-body interaction effects in the conduction band of MoS and establish a fertile ground for exploring strongly correlated phenomena of massive Dirac electrons.
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http://dx.doi.org/10.1021/acs.nanolett.8b04731DOI Listing
March 2019
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