Publications by authors named "Tom Pickles"

148 Publications

Outcome of limited stage nodular lymphocyte predominant Hodgkin lymphoma and the impact of a PET-adapted approach.

Blood Adv 2021 Aug 26. Epub 2021 Aug 26.

BC Cancer, Centre for Lymphoid Cancer, Vancouver, British Columbia, Canada.

Radiotherapy (RT) is typically incorporated into the treatment of limited stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), though it remains unknown if chemotherapy alone may be suitable in select cases. We evaluated outcomes of limited stage NLPHL at BC Cancer based on era-specific guidelines: 'Routine RT era': 1995-2005 (n=36), combined modality with 2 cycles of ABVD chemotherapy followed by RT, or RT alone; and 'PET era': ≥ 2005 (n=63), ABVD alone (4 cycles) if PET2 is negative, or treatment is changed to RT if PET2 is positive. Median age was 38 years (range 16-82), 73% were male, and 43% had stage II. With a median follow-up of 10.5 years for all patients, 5-year progression free survival (PFS) and overall survival (OS) were 93% and 97%, respectively, with no difference by treatment era (PFS p=0.13; OS p=0.35). For the 49 patients that had a PET2 scan: 86% were PET-negative and 14% were PET-positive by Deauville criteria with a 5-year PFS of 92% and 80% (p=0.70), respectively. This represents the largest experience of a PET-adapted approach in NLPHL and supports that ABVD alone may be a viable option in select patients with a PET2-negative scan, with consideration of acute and long-term toxicities.
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http://dx.doi.org/10.1182/bloodadvances.2021004375DOI Listing
August 2021

Efficacy of Palliative Radiation Therapy (RT) for Chemotherapy Relapsed or Refractory Diffuse Large B-Cell Lymphoma: A Population-Based Retrospective Review.

Pract Radiat Oncol 2021 Mar-Apr;11(2):e203-e209. Epub 2020 Nov 13.

BC Cancer - Vancouver, University of British Columbia. Electronic address:

Purpose: The study objective was to investigate the effectiveness of palliative radiation therapy (RT) for patients with diffuse large B-cell lymphoma (DLBCL) and to identify factors, such as chemotherapy relapsed/refractory (R/R) disease, that may influence RT outcomes.

Methods And Materials: Patients with DLBCL who received palliative RT from 2001 to 2015 in British Columbia were reviewed for patient characteristics, treatment details, and outcomes. Univariable and multivariable analyses for response and local progression were performed.

Results: Three-hundred and seventy courses of palliative RT in 217 patients were identified. Median equivalent dose in 2 Gy fractions was 19 Gy (range, 2-42 Gy). Clinical and/or radiologic response occurred in 230 (83%) of the 276 courses with response data available. Local control following palliative RT at 6 months was 66.7%. On univariable analysis, R/R disease was not associated with lower clinical response rates but had higher risk of progression (hazard ratio [HR], 0.5; P = .040). On multivariable analyses, patients with R/R disease who did not require concurrent steroids had greater response compared with those who received upfront palliative RT (odds ratio, 3.5; P = .011). Response to first-line chemotherapy and smaller lesion size were associated with improved local progression rates (HR, 0.2; P < .001 and HR, 0.5; P = .020, respectively). RT dose fractionation factors were not significant on any analyses.

Conclusions: Palliative RT for DLBCL is effective for symptom improvement, including in the chemotherapy R/R setting. Not requiring concurrent steroids, response to first-line chemotherapy, and smaller lesion size predicted better RT outcomes. There was no association between dose fractionation and response rates or local control to suggest that higher RT doses are more effective for palliation.
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http://dx.doi.org/10.1016/j.prro.2020.11.003DOI Listing
August 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

Long-term results of PET-guided radiation in patients with advanced-stage diffuse large B-cell lymphoma treated with R-CHOP.

Blood 2021 02;137(7):929-938

Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.

Consolidative radiation therapy (RT) for advanced-stage diffuse large B-cell lymphoma (DLBCL) remains controversial, with routine practice continuing to include RT in patients with initial bulky disease or residual masses. Positron emission tomography (PET)-computed tomography is a sensitive modality for detecting the presence of residual disease at the end of treatment (EOT). A PET-guided approach to selectively administering RT has been the policy in British Columbia since 2005. Patients with advanced-stage DLBCL diagnosed from 1 January 2005 to 1 March 2017 and treated with at least 6 cycles of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone plus rituximab), who underwent EOT PET, were included in this analysis. Those with complete metabolic response (PET-negative [PET-NEG]) were observed; those with PET-positive (PET-POS) scans were offered consolidative RT, when feasible. Of the patient records reviewed, 723 were identified, with median follow-up of 4.3 years: 517 (72%) were PET-NEG; 206 (28%) were PET-POS. Time to progression (TTP) and overall survival (OS) at 3 years were 83% vs 56% and 87% vs 64%, in patients with PET-NEG and PET-POS scans, respectively. PET-POS patients with nonprogressing disease treated with consolidative RT (109 and 206; 53%) had outcomes approaching those of PET-NEG patients, with 3-year estimates of 76% and 80% for TTP and OS. PET-NEG patients who had bulky disease (≥10 cm) at diagnosis had outcomes indistinguishable from those without bulk, despite the omission of RT. These data suggest that patients with advanced-stage DLBCL who are PET-NEG at EOT and receive no RT have excellent outcomes. 18F-fluorodeoxyglucose-PET can reliably guide selective administration of consolidative RT, even in patients with initially bulky disease.
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http://dx.doi.org/10.1182/blood.2020005846DOI Listing
February 2021

Prostate brachytherapy intraoperative dosimetry using a combination of radiographic seed localization with a C-arm and deformed ultrasound prostate contours.

Brachytherapy 2020 Sep - Oct;19(5):589-598. Epub 2020 Jul 15.

Department of Medical Physics, Vancouver Center, BC Cancer, Vancouver, British Columbia, Canada.

Purpose: The purpose of the study was to assess the feasibility of performing intraoperative dosimetry for permanent prostate brachytherapy by combining transrectal ultrasound (TRUS) and fluoroscopy/cone beam CT [CBCT] images and accounting for the effect of prostate deformation.

Methods And Materials: 13 patients underwent TRUS and multiview two-dimensional fluoroscopic imaging partway through the implant, as well as repeat fluoroscopic imaging with the TRUS probe inserted and retracted, and finally three-dimensional CBCT imaging at the end of the implant. The locations of all the implanted seeds were obtained from the fluoroscopy/CBCT images and were registered to prostate contours delineated on the TRUS images based on a common subset of seeds identified on both image sets. Prostate contours were also deformed, using a finite-element model, to take into account the effect of the TRUS probe pressure. Prostate dosimetry parameters were obtained for fluoroscopic and CBCT-dosimetry approaches and compared with the standard-of-care Day-0 postimplant CT dosimetry.

Results: High linear correlation (R > 0.8) was observed in the measured values of prostate D, V, and V, between the two intraoperative dosimetry approaches. The prostate D and V obtained from intraoperative dosimetry methods were in agreement with the postimplant CT dosimetry. Only the prostate V was on average 4.1% (p-value <0.05) higher in the CBCT-dosimetry approach and 6.7% (p-value <0.05) higher in postimplant CT dosimetry compared with the fluoroscopic dosimetry approach. Deformation of the prostate by the ultrasound probe appeared to have a minimal effect on prostate dosimetry.

Conclusions: The results of this study have shown that both of the proposed dosimetric evaluation approaches have potential for real-time intraoperative dosimetry.
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http://dx.doi.org/10.1016/j.brachy.2020.06.003DOI Listing
May 2021

Outcome of primary mediastinal large B-cell lymphoma using R-CHOP: impact of a PET-adapted approach.

Blood 2020 12;136(24):2803-2811

Centre for Lymphoid Cancer and Department of Medical Oncology and.

Cure rates for primary mediastinal large B-cell lymphoma (PMBCL) have improved with the integration of rituximab. However, the type of primary therapy and role of radiotherapy (RT) remains ill-defined. Herein, we evaluated the outcome of PMBCL primarily treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and the impact of an end-of-treatment (EOT) 18F-fluorodeoxyglucose positron emission tomography (PET) scan to guide consolidative RT. Patients ≥18 years of age with PMBCL treated with curative intent rituximab-chemotherapy were identified. Prior to 2005, patients were recommended to receive R-CHOP + RT (RT era). Beginning in 2005, EOT PET was used to guide RT and only those with a PET-positive scan received RT (PET era). In total, 159 patients were identified, 94% were treated with R-CHOP and 44% received RT (78% in RT era, 28% in PET era). The 5-year time to progression (TTP) and overall survival (OS) for the entire cohort were 80% and 89%, respectively, similar across treatment eras. Overall, 10% had refractory disease. In total, 113 patients had an EOT PET scan: 63% negative and 37% positive with a 5-year TTP of 90% vs 71% and 5-year OS of 97% vs 88%, respectively. For those with Deauville (D)-scored PET scans (n = 103), the 5-year TTP for PET-negative cases by Deauville criteria (D1-D3, DX) was 91%, with inferior outcomes for D5 vs D4 (5-year TTP 33% vs 87%, P = .0002). Outcomes for PMBCL treated with RCHOP are favorable and use of a PET-adapted approach reduces RT in the majority of patients. A small proportion have refractory disease and may benefit from an alternate treatment.
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http://dx.doi.org/10.1182/blood.2019004296DOI Listing
December 2020

Testosterone Breakthrough Rates during Androgen Deprivation Therapy for Castration Sensitive Prostate Cancer.

J Urol 2020 Sep 25;204(3):416-426. Epub 2020 Feb 25.

Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Purpose: Androgen deprivation therapy is an established therapy for castration sensitive prostate cancer and recent studies have observed that patients whose testosterone levels are suppressed below 0.7 nmol/l have improved outcomes. Testosterone breakthrough, or a rise in testosterone above a target threshold after the first month of androgen deprivation therapy, is generally associated with treatment deficiency. The purpose of this review is to summarize breakthrough rate data and explore the relationship to clinical outcomes in patients with castration sensitive prostate cancer receiving androgen deprivation therapy.

Materials And Methods: Our systematic search identified 45 studies with a total of 52 cohorts representing 6,047 total patients reporting testosterone breakthrough rates or derivative measures above the thresholds of 1.7 nmol/l (51 cohorts, 6,015 patients) or 0.7 nmol/l (15 cohorts, 2,495 patients).

Results: Significantly higher weighted mean breakthrough rates were seen for the 0.7 nmol/l threshold compared to 1.7 nmol/l (41.3% vs 6.9%, p <0.0001). A significant association between breakthrough rates and worse clinical outcomes overall was not found, although when larger trials (sample size greater than 100) and higher event rates (greater than 50%) were considered for the lowest threshold, significant associations between breakthrough rates and clinical outcomes were observed. Clinical factors such as administration and monitoring frequency, type of testosterone assay and type of androgen deprivation therapy did not significantly affect breakthrough rates, although nonvalidated assays were associated with a large degree of variability.

Conclusions: Results from our analysis indicate that testosterone breakthroughs likely result in worse clinical outcomes and should be avoided. Moreover, there is a need to standardize assessment of testosterone levels both clinically and in the research context to better inform treatment decisions and improve the reliability and comparability of results across studies.
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http://dx.doi.org/10.1097/JU.0000000000000809DOI Listing
September 2020

Consistent Biopsy Quality and Gleason Grading Within the Global Active Surveillance Global Action Plan 3 Initiative: A Prerequisite for Future Studies.

Eur Urol Oncol 2019 05 13;2(3):333-336. Epub 2018 Sep 13.

Kan-tonsspital Baden, Baden, Switzerland.

Within the Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative, 25 centers across the globe collaborate to standardize active surveillance (AS) protocols for men with low-risk prostate cancer (PCa). A centralized PCa AS database, comprising data of more than 15000 patients worldwide, was created. Comparability of the histopathology between the different cohorts was assessed by a centralized pathology review of 445 biopsies from 15 GAP3 centers. Grade group 1 (Gleason score 6) in 85% and grade group ≥2 (Gleason score ≥7) in 15% showed 89% concordance at review with moderate agreement (κ=0.56). Average biopsy core length was similar among the analyzed cohorts. Recently established highly adverse pathologies, including cribriform and/or intraductal carcinoma, were observed in 3.6% of the reviewed biopsies. In conclusion, the centralized pathology review of 445 biopsies revealed comparable histopathology among the 15 GAP3 centers with a low frequency of high-risk features. This enables further data analyses-without correction-toward uniform global AS guidelines for men with low-risk PCa. PATIENT SUMMARY: Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative combines data from 15000 men with low-risk prostate cancer (PCa) across the globe to standardize active surveillance protocols. Histopathology review confirmed that the histopathology was consistent with low-risk PCa in most men and comparable between different centers.
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http://dx.doi.org/10.1016/j.euo.2018.08.017DOI Listing
May 2019

A Population-Based Study of Palliative Radiation Therapy for Bone Metastases in Patients Dying of Prostate Cancer.

Pract Radiat Oncol 2019 May 11;9(3):e274-e282. Epub 2019 Jan 11.

University of British Columbia, BC Cancer - Vancouver, Vancouver, Canada. Electronic address:

Purpose: Increasing the survival of patients with metastatic prostate cancer (PCa) may affect the demand for palliative radiation to bone (PRTB). Our aim was to characterize the use of PRTB in patients who died of PCa in British Columbia between 2003 and 2015.

Methods And Materials: All patients with a diagnosis of PCa who died during the study period (n = 23,260) were identified from a population-based provincial registry. Patient and treatment characteristics were analyzed. PRTB utilization rate was calculated by year and location. Survival was calculated from the first and the last course of PRTB.

Results: A total of 5701 patients died of PCa, with a median survival from diagnosis of 5.2 years. The overall PRTB utilization rate was 38.6%, with an increasing trend over time. Multiple courses of PRTB were frequent, with 51% of patients receiving ≥2 courses of PRTB. Of the patients who died of PCa (15.2% of the PRTB cohort), 5.4% received PRTB within the last 4 weeks of life, 60% of whom received multiple fractions. Rural areas had a lower referral rate and lower use of PRTB. Patients with longer survival tended to receive multiple courses of treatment. The median survival after the first course of PRTB increased from 8.2 months in 2003 to 2004 to 9.4 months in 2013 to 2014 (P = .04).

Conclusions: PRTB is only used in a minority of patients dying of PCa. The majority who die of PCa after PRTB do so within a year of their first course. The use of multifractionation was common in the last 4 weeks of life. Survival after first PRTB increased minimally over time, and additional research is required to identify its association with recent changes in practice. The referral rate and PRTB utilization rate differ between rural and nonrural locations, underlying the importance of accessibility and referral for utilization of PRTB. Investigating other barriers and ensuring equitable access to radiation are needed.
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http://dx.doi.org/10.1016/j.prro.2019.01.002DOI Listing
May 2019

Using a surgical prostate-specific antigen threshold of >0.2 ng/mL to define biochemical failure for intermediate- and high-risk prostate cancer patients treated with definitive radiation therapy in the ASCENDE-RT randomized control trial.

Brachytherapy 2018 Nov - Dec;17(6):837-844. Epub 2018 Sep 21.

Clinical Professor, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; Radiation Oncologist, Vancouver Cancer Centre, Vancouver, British Columbia, Canada.

Purpose: To compare biochemical failure using a prostate-specific antigen (PSA) threshold of >0.2 ng/mL to that using Phoenix threshold (nadir+2 ng/mL).

Methods And Materials: Androgen suppression combined with elective nodal and dose-escalated radiation therapy (the ASCENDE-RT trial) is a randomized control trial in which 276 high-risk and 122 intermediate-risk patients were randomized to (1) a standard arm with 12 months of androgen deprivation therapy, pelvic external beam radiation therapy (EBRT) to 46 Gy, and an EBRT boost (dose-escalated EBRT [DE-EBRT]) to 78 Gy, or (2) an experimental arm which substituted a low-dose-rate prostate brachytherapy boost (LDR-PB). The primary endpoint was biochemical progression-free survival (b-PFS) using the Phoenix threshold. In this reanalysis of ASCENDE-RT, the b-PFS using phoenix is compared to the surgical PSA threshold of >0.2 ng/mL.

Results: Compared to nadir+2 ng/mL, the >0.2 ng/mL PSA threshold doubled the number of relapse events from 69 to 139. However, the increase was confined to the DE-EBRT subjects. The 7-year Kaplan-Meier b-PFS after DE-EBRT declined from 76% using nadir+2 ng/mL to 38% using the >0.2 ng/mL threshold (p < 0.001). Among the LDR-PB subset, there was no significant difference in b-PFS; the 7-year Kaplan-Meier b-PFS was 85% (>0.2 ng/mL) versus 88% (nadir+2 ng/mL) (p = 0.319).

Conclusions: Replacing Phoenix with a surgical threshold greatly increased biochemical failure after DE-EBRT boost but had no effect after LDR-PB. As a result of this finding, PSA outcomes after surgery or brachytherapy can be directly compared by using the surgical definition of PSA failure. In this context, a brachytherapy boost appears to produce superior b-PFS compared to contemporary surgical series.
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http://dx.doi.org/10.1016/j.brachy.2018.08.008DOI Listing
April 2019

Testosterone suppression in the treatment of recurrent or metastatic prostate cancer - A Canadian consensus statement.

Can Urol Assoc J 2018 Feb 19;12(2):30-37. Epub 2017 Dec 19.

Centre Hospitalier de l'Université de Montréal, Montreal, QC; Canada.

Testosterone suppression, achieved through orchiectomy or medically induced androgen-deprivation therapy (ADT), is a standard treatment for men with recurrent and metastatic prostate cancer. Current assay methods demonstrate the capacity for testosterone suppression to <0.7 nmol/l, and clinical data support improved outcomes from ADT when lower levels are achieved. Practical clinical guidelines are warranted to facilitate adoption of 0.7 nmol/l as the new standard castrate testosterone level.A pan-Canadian group of experts, representing diverse clinical specialties, identified key clinical issues, searched and reviewed relevant literature, and developed consensus statements on testosterone suppression for the treatment of prostate cancer. The expert panel found that current evidence supports the clinical benefit of achieving low testosterone levels during ADT, and encourage adoption of ≤0.7 nmol/l as a new castrate level threshold. The panel recommends regular monitoring of testosterone (e.g., every 3-6 months) and prostate-specific antigen (PSA) levels as clinically appropriate (e.g., every 3-6 months) during ADT, with reassessment of therapeutic strategy if testosterone is not suppressed or if PSA rises regardless of adequate testosterone suppression. The panel also emphasizes the need for greater awareness and education regarding testosterone assay specifications, and strongly promotes the use of mass spectrometry-based assays to ensure accurate measurement of testosterone at castrate levels.
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http://dx.doi.org/10.5489/cuaj.5116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937399PMC
February 2018

Can active surveillance really reduce the harms of overdiagnosing prostate cancer? A reflection of real life clinical practice in the PRIAS study.

Transl Androl Urol 2018 Feb;7(1):98-105

Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background: Active surveillance (AS) for low-risk prostate cancer (PCa) appears to provide excellent long-term PCa-specific and overall survival. The choice for AS as initial treatment is mainly based on avoiding side effects from invasive treatment; but AS entails regular check-ups and the possibility of still having to switch or deciding to switch to invasive treatment. Here, we assessed the long-term follow-up data from AS in real life clinical practices.

Methods: Data from the first 500 men, enrolled in PRIAS before July 2008 by 30 centers across 8 countries, were analyzed to provide long-term follow-up results. Men were advised to be regularly examined with prostate-specific antigen (PSA) tests, digital rectal examinations, and prostate biopsies. Men were advised to switch to invasive treatment if they had disease reclassification [Gleason score (GS) ≥3+4 on biopsy, more than two positive biopsy cores, a stage higher than cT2] or a PSA-doubling time of 0-3 years. We assessed time on AS, outcomes and reasons for discontinuing AS, and rates of potential unnecessary biopsies and treatments.

Results: The median follow-up time was 6.5 years. During this period, 325 (65%) men discontinued after a median of 2.3 years and 121 (24%) men had no recent (>1 year) data-update after a median of 7.3 years. The remaining 54 (11%) men were confirmed to be still on AS. Most men discontinued based on protocol advice; 38% had other reasons. During follow-up, 838 biopsy sessions were performed of which 79% to 90% did not lead to reclassification, depending on the criteria. Of the 325 discontinued men, 112 subsequently underwent radical prostatectomy (RP), 126 underwent radiotherapy, 57 switched to watchful waiting (WW) or died, and 30 had another or unknown treatment. RP results were available of 99 men: 34% to 68%, depending on definition, had favorable outcomes; 50% of unfavorable the outcomes occurred in the first 2 years. Of the 30 (6%) men who died, 1 man died due to PCa.

Conclusions: These data, reflecting real life clinical practice, show that more than half of men switched to invasive treatment within 2.3 years, indicating limitations to the extent in which AS is able to reduce the adverse effects of overdiagnosis. Therefore, despite guidelines stating that PCa diagnosis must be uncoupled from treatment, it remains important to avoid overdiagnosing PCa as much as possible.
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http://dx.doi.org/10.21037/tau.2017.12.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861273PMC
February 2018

High-intermediate prostate cancer treated with low-dose-rate brachytherapy with or without androgen deprivation therapy.

Brachytherapy 2017 Nov - Dec;16(6):1101-1105. Epub 2017 Oct 12.

Radiation Program, BC Cancer Agency, and Department of Radiotherapy and Developmental Radiotherapeutics, University of British Columbia, Vancouver, Canada.

Purpose: To describe outcomes of men with unfavorable (high-tier) intermediate risk prostate cancer (H-IR) treated with low-dose-rate (LDR) brachytherapy, with or without 6 months of androgen deprivation therapy (ADT).

Methods And Materials: Patients with H-IR prostate cancer, treated before 2012 with LDR brachytherapy without external radiation are included. Baseline tumor characteristics are described. Outcomes between groups receiving ADT are measured by Phoenix (nadir +2 ng/mL), and threshold 0.4 ng/mL biochemical relapse definitions (bNEDs), as well as clinical end points. Standard descriptive and actuarial statistics are used.

Results: Two hundred sixty men were eligible, 139 (53%) did not receive ADT and 121 (47%) did. Median follow-up was 5 years. Men treated with ADT had higher T stage and percent positive cores but lower pathologic grade group. bNED rates with and without ADT at 5 years are 86% and 85% (p = 0.52) with the Phoenix definition, and 83% and 78% (p = 0.13) with the threshold definition. Local recurrence or metastasis were rare in both groups (<5%, p = not significant). Death from prostate cancer only occurred in 4 patients, 2 in each group. Overall survival was 85% in those treated with ADT and 93% without at 8 years, p = 0.15.

Conclusions: The addition of 6 months of ADT to LDR brachytherapy for H-IR prostate cancer does not improve 5 year prostate specific antigen control, and we no longer routinely recommended it.
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http://dx.doi.org/10.1016/j.brachy.2017.08.003DOI Listing
June 2018

Brachytherapy for Intermediate-Risk Prostate Cancer, Androgen Deprivation, and the Risk of Death.

Int J Radiat Oncol Biol Phys 2018 01 4;100(1):45-52. Epub 2017 Sep 4.

Radiation Program, BC Cancer Agency, Vancouver, British Columbia, Canada; Department of Radiotherapy and Developmental Radiotherapeutics, University of British Columbia, Vancouver, British Columbia, Canada.

Purpose: To determine whether the use of 6 months' adjuvant androgen deprivation therapy (ADT) combined with brachytherapy for intermediate-risk (IR) and low-risk (LR) prostate cancer is associated with an increased risk of cardiovascular death.

Methods And Materials: This is a retrospective analysis of prospectively collected data from men treated in the British Columbia Cancer Agency brachytherapy program from 1998 to 2012. Men were categorized by risk group and ADT use. Cardiac and other comorbidities were recorded and compared between groups. Biochemical control (Phoenix definition, nadir + 2 ng/mL) was ascertained. Overall, prostate, cardiac, and other-cause mortality were analyzed by the Kaplan-Meier method and Fine and Gray competing-risk analysis.

Results: The study included 3155 men (1142 with LR cancer and 2013 with IR cancer) who have been followed up for a median of 7.9 years. ADT was received by 47% of IR patients and 37% of LR patients for a median of 6 months. Men with IR cancer were older and had more cardiac and other comorbidities than LR cases (P<.01). Biochemical control improved from 86% to 89% at 10 years with the use of ADT (P=.006). Overall survival was inferior in patients receiving ADT (84% vs 86% at 10 years, P=.0274), and on competing-risk analysis, cardiovascular mortality in patients receiving ADT was higher in IR cases, 5.2% versus 3.6% at 10 years (P=.0493), but not in LR cases. Multivariate analysis confirmed increased cardiac mortality in IR patients receiving ADT (hazard ratio, 1.95 [95% confidence interval, 1.15-3.34]; P=.014).

Conclusions: ADT adds little meaningful benefit in terms of biochemical control for IR men treated with low-dose-rate brachytherapy but likely decreases overall survival because of increased cardiac mortality. IR patients were older and had more cardiac risk factors than LR prostate cases; this may be because of a screening effect, case selection, or common etiologic cause.
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http://dx.doi.org/10.1016/j.ijrobp.2017.08.042DOI Listing
January 2018

Long-Term Prostate Specific Antigen Stability and Predictive Factors of Failure after Permanent Seed Prostate Brachytherapy.

J Urol 2018 01 19;199(1):120-125. Epub 2017 Aug 19.

British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

Purpose: Defining biochemical failure as nadir + 2 may overestimate cure after radiotherapy. We assessed long-term prostate specific antigen stability after low dose rate prostate brachytherapy and predictors of biochemical failure when prostate specific antigen was slowly rising below the nadir + 2 ng/ml threshold.

Materials And Methods: A total of 2,339 patients with low or intermediate risk prostate cancer received iodine brachytherapy from 1998 to 2010 with a minimum 3-year followup. In addition, 49.7% of the patients received 6 months of androgen deprivation. Clinical, dosimetric and prostate specific antigen data were retrieved from a prospective database. Biochemical results were classified as stable or rising prostate specific antigen (0.2 ng/ml or greater and increased 0.1 ng/ml or greater during the preceding 2 years), or biochemical failure (defined as nadir + 2). Multivariate analysis was done to identify predictors of failure used to create logistic regression models.

Results: At a median followup of 89 months (range 37 to 199) prostate specific antigen was stable (nadir 0.03 ng/ml and at 60 months 0.04 ng/ml) in 2,004 patients (86%) and rising (nadir 0.16 ng/ml and at 60 months 0.29 ng/ml) in 145 (6%) while biochemical failure (nadir 0.51 ng/ml, p <0.001) was noted in 190 (8%). When there was no prior androgen deprivation therapy, the prostate specific antigen nadir and prostate specific antigen at 60 months were the strongest predictors of failure (OR 20.6 and 18.3, respectively, each p <0.0001). The logistic regression model had 85% sensitivity and 98% specificity, and predicted failure in 8 of 82 men (9.8%). A second model was created for the group with androgen deprivation therapy and rising prostate specific antigen using the predictive factors prostate specific antigen at 60 months (OR 53.9, p <0.0001) and T stage (OR 0.25, p = 0.0008). This model predicted biochemical failure in 30 of 56 men (54%) with 85% sensitivity and 93% specificity. The 2 predictive models yield an anticipated 90% cure rate in the entire cohort.

Conclusions: Brachytherapy is highly curative with stable prostate specific antigen at a surgical ablation level in 86% of patients. Rising prostate specific antigen is rare at a 6% incidence and often innocuous.
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http://dx.doi.org/10.1016/j.juro.2017.07.089DOI Listing
January 2018

The impact of comorbidities on the benefits of prolonged androgen ablation in patients with T3-4 prostate cancer treated with external beam radiation therapy.

Radiother Oncol 2017 08 4;124(2):291-295. Epub 2017 Jul 4.

Radiation Therapy Program, BC Cancer Agency and University of BC, Vancouver, Canada. Electronic address:

Purpose: To determine whether the survival benefit associated with prolonged androgen deprivation therapy (ADT) and radiotherapy (EBRT) varies with baseline estimates of overall survival in cT3-4 prostate cancer patients (PCa).

Methods And Materials: In 1997, the BC Cancer Agency adopted as standard a policy of prolonged ADT (>18months) with EBRT for locally advanced PCa. Two cohorts of cT3-T4 PCa treated with EBRT were selected: 1993-1995 (early: N=725) and 1999-2001 (late: N=584). Duration of ADT and baseline prognostic factors (age, clinical stage, grade, presenting PSA, and Charlson index (CCI)) were abstracted from charts. Estimates of 10-year (E10) survival using an age-adjusted CCI were calculated and patients were grouped into low (<60%), medium (60-90%) and high (>90%) E10. In each E10 group, actual overall survivals were compared by era using log rank test.

Results: There were 318 low, 544 medium, and 447 high E10 patients with median follow-up of 11.1years. Gleason grade and T stage were not statistically different between E10 groups. As expected, median age and baseline CCI were higher in lower E10 groups (p<0.0001). Overall survival was higher in the late era, but varied with E10 group: low (43% vs. 49%, p=0.54), medium (55% vs. 64%, p=0.02) and high (66% vs. 77%, p=0.01).

Conclusion: The policy of prolonged ADT with EBRT provides a survival benefit that varies with baseline risk of death from other causes. Absolute benefit from ADT is largest in those with medium or high E10.
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http://dx.doi.org/10.1016/j.radonc.2017.04.028DOI Listing
August 2017

External validation of the ProCaRS nomograms and comparison of existing risk-stratification tools for localized prostate cancer.

Can Urol Assoc J 2017 Mar-Apr;11(3-4):94-100

Department of Radiation Oncology, Centre Hospitalier de l'Université de Montréal (CHUM), Hôpital Notre-Dame, Montreal, QC, Canada.

Introduction: The purpose of this study was to perform a direct comparison of several existing risk-stratification tools for localized prostate cancer in terms of their ability to predict for biochemical failure-free survival (BFFS). Two large databases were used and an external validation of two recently developed nomograms on an independent cohort was also performed in this analysis.

Methods: Patients who were treated with external beam radiotherapy (EBRT) and/or brachytherapy for localized prostate cancer were selected from the multi-institutional Genitourinary Radiation Oncologists of Canada (GUROC) Prostate Cancer Risk Stratification (ProCaRS) database (n=7974) and the Centre Hospitalier de l'Université de Montréal (CHUM) validation database (n=2266). The primary outcome was BFFS using the Phoenix definition. Concordance index (C-index) reported from Cox proportional hazards regression using 10-fold cross validation and decision curve analysis (DCA) were used to predict BFFS.

Results: C-index identified Cancer of the Prostate Risk Assessment (CAPRA) score and ProCaRS as superior to the historical GUROC and National Comprehensive Cancer Network (NCCN) risk-stratification systems. CAPRA modeled as five and three categories were superior to GUROC and NCCN only for the CHUM database. C-indices for CAPRA score, ProCaRS, GUROC, and NCCN were 0.72, 0.72, 0.71, and 0.72, respectively, for the ProCaRS database, and 0.66, 0.63, 0.57, and 0.60, respectively, for the CHUM database. However, many of these comparisons did not demonstrate a clinically meaningful difference. DCA identified minimal differences across the different risk-stratification systems, with no system emerging with optimal net benefit. External validation of the ProCaRS nomograms yielded favourable calibrations of R=0.778 (low-dose rate [LDR]-brachytherapy) and R=0.868 (EBRT).

Conclusions: This study externally validated two ProCaRS nomograms for BFFS that may help clinicians in treatment selection and outcome prediction. A direct comparison between existing risk-stratification tools demonstrated minimal clinically significant differences in discriminative ability between the systems, favouring the CAPRA and ProCaRS systems. The incorporation of novel prognostic variables, such as genomic markers, is needed.
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http://dx.doi.org/10.5489/cuaj.4084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434512PMC
May 2017

Maximal testosterone suppression in the management of recurrent and metastatic prostate cancer.

Can Urol Assoc J 2017 Jan-Feb;11(1-2):E62-E63. Epub 2017 Feb 20.

Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.

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http://dx.doi.org/10.5489/cuaj.4494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403685PMC
February 2017

Maximal testosterone suppression in the management of recurrent and metastatic prostate cancer.

Can Urol Assoc J 2017 Jan-Feb;11(1-2):16-23

Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.

Introduction: Testosterone suppression, or androgen-deprivation therapy (ADT), is an established treatment for recurrent and metastatic prostate cancer (PCa). Based on the accuracy and sensitivity of early assays (c. 1960-1970), the castrate testosterone level was set at ≤1.7 nmol/l. Improved sensitivity of testosterone assays shows that both surgical and medical castration can achieve levels <0.7 nmol/l. However, the clinical implications and importance of maximum testosterone suppression remains a subject of controversy. This evidence-based review assesses prospective and retrospective clinical data, linking maximum suppression of testosterone with improved outcomes from ADT.

Methods: PubMed and conference proceedings were searched for studies assessing the impact of low testosterone on clinical outcomes from ADT. The key search terms included combinations of prostate cancer and testosterone, predictive/prognostic, and androgen deprivation. Results were limited to studies investigating the relationship between testosterone levels and clinical outcomes.

Results: Both prospective and retrospective data support a relationship between testosterone levels below the historical standard of 1.7 nmol/l and improved outcomes. Eight studies showed significant improvements in survival-related outcomes, with the majority of data supporting a testosterone level cutoff of ≤0.7 nmol/l.

Conclusions: Tracking both testosterone and prostate-specific antigen (PSA) levels has significant clinical benefits, and the serum testosterone threshold of ≤0.7 nmol/l is a practical goal. The relative levels of testosterone and PSA may indicate continued hormone responsiveness or progression toward castration-resistant prostate cancer (CRPC) and should, therefore, inform treatment strategy. Standardization of assay methods and clinical coordination to facilitate widespread access to state-of the art laboratory equipment is necessary to ensure accurate decision-making.
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http://dx.doi.org/10.5489/cuaj.4303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403681PMC
April 2017

Expert consensus document: Semantics in active surveillance for men with localized prostate cancer - results of a modified Delphi consensus procedure.

Nat Rev Urol 2017 May 14;14(5):312-322. Epub 2017 Mar 14.

Department of Urology, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, Netherlands.

Active surveillance (AS) is broadly described as a management option for men with low-risk prostate cancer, but semantic heterogeneity exists in both the literature and in guidelines. To address this issue, a panel of leading prostate cancer specialists in the field of AS participated in a consensus-forming project using a modified Delphi method to reach international consensus on definitions of terms related to this management option. An iterative three-round sequence of online questionnaires designed to address 61 individual items was completed by each panel member. Consensus was considered to be reached if ≥70% of the experts agreed on a definition. To facilitate a common understanding among all experts involved and resolve potential ambiguities, a face-to-face consensus meeting was held between Delphi survey rounds two and three. Convenience sampling was used to construct the panel of experts. In total, 12 experts from Australia, France, Finland, Italy, the Netherlands, Japan, the UK, Canada and the USA participated. By the end of the Delphi process, formal consensus was achieved for 100% (n = 61) of the terms and a glossary was then developed. Agreement between international experts has been reached on relevant terms and subsequent definitions regarding AS for patients with localized prostate cancer. This standard terminology could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making.
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http://dx.doi.org/10.1038/nrurol.2017.26DOI Listing
May 2017

Secondary Breast Cancer Risk by Radiation Volume in Women With Hodgkin Lymphoma.

Int J Radiat Oncol Biol Phys 2017 01 13;97(1):35-41. Epub 2016 Oct 13.

Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Purpose: To determine whether the risk of secondary breast cancer (SBC) is reduced in women with Hodgkin lymphoma (HL) treated with smaller field radiation therapy (SFRT) versus mantle field radiation therapy (MRT).

Methods And Materials: We used the BC Cancer Agency (BCCA) Lymphoid Cancer Database to identify female patients treated for HL between January 1961 and December 2009. Radiation therapy volumes were categorized as MRT or SFRT, which included involved field, involved site, or involved nodal radiation therapy. SBC risk estimates were compared using competing risk analysis and Fine and Gray multivariable model: MRT ± chemotherapy, SFRT ± chemotherapy, or chemotherapy-only.

Results: Of 734 eligible patients, 75% of the living patients have been followed up for more than 10 years, SBC has developed in 54, and 15 have died of breast cancer. The 20-year estimated risks (competing risk cumulative incidence) for SBC differed significantly: MRT 7.5% (95% confidence interval [CI] 4.4%-11.5%), SFRT 3.1% (95% CI 1.0%-7.7%), and chemotherapy-only 2.2% (95% CI 1.0%-4.8%) (P=.01). Using a Fine and Gray model to control for death and patients lost to follow-up, MRT was associated with a higher risk of SBC (hazard ratio [HR] = 2.9; 95% CI 1.4%-6.0%; P=.004) compared with chemotherapy-only and with SFRT (HR = 3.3; 95% CI 1.3%-8.4%; P=.01). SFRT was not associated with a greater risk of SBC compared with chemotherapy-only (HR = 0.87; 95% CI 0.28%-2.66%; P=.80).

Conclusion: This study confirms that large-volume MRT is associated with a markedly increased risk of SBC; however, more modern small-volume RT is not associated with a greater risk of SBC than chemotherapy alone.
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http://dx.doi.org/10.1016/j.ijrobp.2016.10.004DOI Listing
January 2017

Outcome of primary cutaneous anaplastic large cell lymphoma: a 20-year British Columbia Cancer Agency experience.

Br J Haematol 2017 Jan 21;176(2):234-240. Epub 2016 Oct 21.

Department of Medical Oncology, Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada.

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare CD30 lymphoproliferative disorder with excellent outcomes reported despite frequent cutaneous relapses. Limited information exists on the development of systemic lymphoma. The British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database was searched to identify all adults diagnosed with PCALCL from 1993 to 2013. From 2005, the BCCA endorsed radiotherapy (RT) alone for limited stage with data failing to support chemotherapy. Forty-seven patients were identified with a male predominance (n = 31, 66%), median age of 64 years and predominantly limited stage (n = 40, 85%). Median follow-up was 8·4 years. The 5-year time to progression (TTP) was 58% (64% limited versus 29% advanced stage). The 5-year disease-specific survival (DSS) and overall survival was 86% and 75%, respectively. In an as-treated analysis, the 5-year DSS for limited stage patients was similar comparing RT to combined modality treatment or chemotherapy alone but the 5-year TTP favoured RT (82% vs. 33%, P = 0·004). The 5-year cumulative risk of developing systemic lymphoma was 14%. Our results confirm the favourable prognosis of PCALCL despite a high relapse rate. Limited stage patients treated with RT alone have excellent outcomes. There is a small risk of systemic lymphoma in PCALCL.
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http://dx.doi.org/10.1111/bjh.14404DOI Listing
January 2017

Secondary malignancy following radiotherapy for thyroid eye disease.

Rep Pract Oncol Radiother 2016 May-Jun;21(3):156-61. Epub 2016 Feb 8.

Division of Radiation Oncology and Developmental Radiotherapeutics, University of British Columbia, Vancouver, BC, Canada; Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada; Division of Neurosurgery, Department of Surgery, University of British Columbia, Vancouver, BC, Canada.

Aim: To describe the first case of a secondary meningioma in a patient after radiation treatment for thyroid eye disease (TED). Secondarily to identify any additional cases of secondary malignancy resulting from radiotherapy for thyroid eye disease from our institutional experience.

Background: Thyroid eye disease (TED) is a self-limiting auto-immune disorder causing expansion of orbital soft tissue from deposition of glycosaminoglycans and collagen, leading to significant cosmetic and functional morbidity. Established management options for TED include: glucocorticosteroids, orbital radiotherapy, and surgical orbital decompression. Two large series on radiotherapy for TED have been reported without any cases of secondary malignancy.

Materials And Methods: The case of a patient with visual failure, found to have a sphenoid wing meningioma after previous TED radiotherapy is described. We then reviewed 575 patients with at least 3-year follow-up receiving radiotherapy for TED at British Columbia Cancer Agency to identify other possible secondary malignancies.

Results: The patient had postoperative improvement in her vision without any identified complications. Three additional cases of hematologic malignancy were identified. The calculated risk in our population of developing a radiation-induced meningioma after TED with at least 3 years of follow-up of is 0.17% (1/575); with hematopoetic malignancies the risk for secondary malignancy is 0.7% (4/575).

Conclusions: Our calculated risk for secondary malignancy (0.17%, 0.7%) is similar to the reported theoretical risk published in the literature (0.3-1.2%). There is real risk for the development of a secondary malignancy after radiotherapy treatment of TED and treatment options should include consideration for this potential.
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http://dx.doi.org/10.1016/j.rpor.2016.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002015PMC
September 2016

A Decade of Active Surveillance in the PRIAS Study: An Update and Evaluation of the Criteria Used to Recommend a Switch to Active Treatment.

Eur Urol 2016 12 19;70(6):954-960. Epub 2016 Jun 19.

Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background: The Prostate Cancer Research International Active Surveillance (PRIAS) study was initiated a decade ago to study the most optimal selection and follow-up of men on active surveillance (AS).

Objective: We report on 10 yr of follow-up of men on AS in the PRIAS study and evaluate if criteria used to recommend a switch to active treatment truly predict unfavorable outcome on subsequent radical prostatectomy (RP).

Design, Setting, And Participants: Men with low-risk prostate cancer were included and followed prospectively on AS. Follow-up consisted of regular prostate-specific antigen (PSA) tests, digital rectal examinations, and biopsies. Men with Gleason >3+3, more than two positive biopsy cores, or stage higher than cT2 were advised to switch to active treatment (until 2014, a PSA doubling time [PSA DT] of 0-3 yr was also used).

Outcome Measurements And Statistical Analysis: Reclassification rates, treatment after discontinuation, and outcome on RP after discontinuing AS were reported. Regression analysis on the outcome of RP was used to evaluate the predictive value of criteria currently used to recommend a switch to active treatment. Kaplan-Meier and competing risk analysis were used to report discontinuation rates over time and long-term oncologic end points.

Results And Limitations: A total of 5302 men were included in PRIAS across 18 countries. Reclassification rates remained stable on all subsequent biopsies, with 22-33% of men having either Gleason >3+3 or more than two positive cores on any repeat biopsy. At 5 and 10 yr of follow-up, 52% and 73% of men, respectively, had discontinued AS, most of them because of protocol-based reclassification. A third of men undergoing subsequent RP had favorable pathologic tumor features (Gleason 3+3 and pT2). Of the criteria used to recommend a switch to active treatment, more than two positive cores and a PSA DT of 0-3 yr were not predictive of unfavorable pathologic outcome on RP.

Conclusions: A substantial group of men discontinued AS without subsequent unfavorable tumor features on RP; therefore, we propose Gleason upgrading and cT3 as the only indicators for an immediate switch to active treatment. Surrogate indicators (eg, more than two positive cores and a fast-rising PSA) should not trigger immediate active treatment but rather further investigation to confirm the suspicion of higher risk disease.

Patient Summary: We confirmed the safety of active surveillance as a treatment option for men with low-risk prostate cancer; however, some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance.
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http://dx.doi.org/10.1016/j.eururo.2016.06.007DOI Listing
December 2016

Evaluation of the Risk of Relapse in Classical Hodgkin Lymphoma at Event-Free Survival Time Points and Survival Comparison With the General Population in British Columbia.

J Clin Oncol 2016 07 6;34(21):2493-500. Epub 2016 Jun 6.

Greg Hapgood, Laurie H. Sehn, Diego Villa, Richard Klasa, Alina S. Gerrie, Tamara Shenkier, David W. Scott, Randy D. Gascoyne, Graham W. Slack, Joseph M. Connors, and Kerry J. Savage, British Columbia Cancer Agency Centre for Lymphoid Cancer; Yvonne Zheng, Cancer Surveillance and Outcomes, Population Oncology; Christina Parsons, James Morris, and Tom Pickles, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

Purpose: Studies in classical Hodgkin lymphoma (cHL) typically measure the time to events from diagnosis. We evaluated the risk of relapse at event-free survival time points in cHL and compared the risk of death to expected mortality rates in British Columbia (BC).

Methods: The BC Cancer Agency Lymphoid Cancer Database was screened to identify all patients age 16 to 69 years diagnosed with cHL between 1989 and 2012 treated with the chemotherapy regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (or equivalent). We compared the observed mortality to the general population using age-, sex-, and calendar period-generated expected mortality rates from BC life-tables. Relative survival was calculated using a conditional approach and expressed as a standardized mortality ratio of observed-to-expected deaths.

Results: One thousand four hundred two patients were identified; 749 patients were male (53%), the median age was 32 years, and 68% had advanced-stage disease. The median follow-up time was 8.4 years. Seventy-two percent of relapses occurred within the first 2 years of diagnosis. For all patients, the 5-year risk of relapse from diagnosis was 18.1% but diminished to 5.6% for patients remaining event free at 2 years. For advanced-stage patients who were event free at 2 years, the 5-year risk of relapse was only 7.6%, and for those who were event free at 3 years, it was comparable to that of limited-stage patients (4.1% v 2.5%, respectively; P = .07). Furthermore, international prognostic score ≥ 4 and bulky disease were no longer prognostic in patients who were event free at 1 year. Although the relative survival improved as patients remained in remission, it did not normalize compared with the general population.

Conclusion: Patients with cHL who are event free at 2 years have an excellent outcome regardless of baseline prognostic factors. All patients with cHL had an enduring increased risk of death compared with the general population.
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http://dx.doi.org/10.1200/JCO.2015.65.4194DOI Listing
July 2016

Outcomes of Proton Beam Radiotherapy for Large Non-Peripapillary Choroidal and Ciliary Body Melanoma at TRIUMF and the BC Cancer Agency.

Ocul Oncol Pathol 2015 Sep 9;2(1):29-35. Epub 2015 Jul 9.

Radiation Oncology, British Columbia Cancer Agency and University of British Columbia, Vancouver, B.C., Canada.

Background And Purpose: To report outcomes and toxicity after proton beam radiotherapy for non-peripapillary choroidal and ciliary body melanoma considered unsuitable for other eye-sparing therapies.

Materials And Methods: An existing database of 77 patients with non-peripapillary tumors treated at TRIUMF, Canada, including patient, tumor, and treatment characteristics, was updated with ocular complications and follow-up status from chart reviews.

Results: Most of the patients had large tumors: 61% were T3/T4 tumors (AJCC classification), while 48% were large by the Collaborative Ocular Melanoma Study classification. The median thickness was 7.1 mm, and the ciliary body was involved in 35%. After 5 and 10 years, the actuarial ocular tumor control rate was 85 and 85%, metastasis-free survival was 72 and 57%, overall survival was 77 and 63%, the enucleation rate was 22 and 22%, and complete blindness was found in 38 and 38%, respectively. On univariate analysis, patients with ciliary body involvement had significantly worse metastasis-free survival and overall survival rates compared to patients without ciliary body involvement (p < 0.001).

Conclusions: Proton therapy for large anteriorly located tumors resulted in acceptable ocular tumor control and survival rates. The risk of blindness and severe toxicity requiring enucleation was low, and a substantial proportion of patients maintained useful vision.
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http://dx.doi.org/10.1159/000433546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847687PMC
September 2015

Joint modelling of longitudinal and multi-state processes: application to clinical progressions in prostate cancer.

Stat Med 2016 09 18;35(22):3933-48. Epub 2016 Apr 18.

INSERM U1219, ISPED, Université de Bordeaux, Bordeaux, France.

Joint modelling of longitudinal and survival data is increasingly used in clinical trials on cancer. In prostate cancer for example, these models permit to account for the link between longitudinal measures of prostate-specific antigen (PSA) and time of clinical recurrence when studying the risk of relapse. In practice, multiple types of relapse may occur successively. Distinguishing these transitions between health states would allow to evaluate, for example, how PSA trajectory and classical covariates impact the risk of dying after a distant recurrence post-radiotherapy, or to predict the risk of one specific type of clinical recurrence post-radiotherapy, from the PSA history. In this context, we present a joint model for a longitudinal process and a multi-state process, which is divided into two sub-models: a linear mixed sub-model for longitudinal data and a multi-state sub-model with proportional hazards for transition times, both linked by a function of shared random effects. Parameters of this joint multi-state model are estimated within the maximum likelihood framework using an EM algorithm coupled with a quasi-Newton algorithm in case of slow convergence. It is implemented under R, by combining and extending mstate and JM packages. The estimation program is validated by simulations and applied on pooled data from two cohorts of men with localized prostate cancer. Thanks to the classical covariates available at baseline and the repeated PSA measurements, we are able to assess the biomarker's trajectory, define the risks of transitions between health states and quantify the impact of the PSA dynamics on each transition intensity. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/sim.6972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012926PMC
September 2016

Population-based 10-year event-free survival after radical prostatectomy for patients with prostate cancer in British Columbia.

Can Urol Assoc J 2015 Nov-Dec;9(11-12):409-13. Epub 2015 Dec 14.

Department of Radiation Oncology, Vancouver Cancer Centre, BC Cancer Agency, Vancouver, BC.

Introduction: We determined (1) the 10-year survival outcomes after radical treatment of prostate cancer and (2) the 10-year event-free survival following radical prostatectomy (RP) at a population-level in British Columbia (BC), Canada.

Methods: We identified all men with a new diagnosis of prostate cancer in BC between 1999 and 2000. Those treated with RP, external beam radiotherapy (EBRT) or brachytherapy (BT) were identified. Overall survival, and prostate cancer specific survival (PCSS) were calculated from diagnosis using the Kaplan-Meier method. For those men treated with RP, we calculated the 10-year event-free survival (freedom from salvage EBRT or androgen ablation, or death from prostate cancer). Reasons for initiating androgen therapy were unknown and may include symptomatic metastatic disease or asymptomatic biochemical recurrence. An important limitation was the absence of prostate-specific antigen data for staging or follow-up.

Results: Among 6028 incident cases, RP was the curative-intent treatment within 1 year in 1360 (22.6%) patients, EBRT in 1367 (22.7%), and BT in 357 (5.9%). The 10-year PCSS was 98% for RP, 95% for EBRT and 98% for BT (log rank p < 0.0001). The 10-year overall survival was 87%. The 10-year event-free survival for those treated with RP was 79% and varied with Gleason grade: 87%, 74%, and 52% for Gleason 2-6, 7, and 8-10, respectively (p < 0.0001).

Conclusions: This population-based study provides outcomes which can inform patient decision-making and provide a benchmark to which other therapies can be compared. Event-free rates for patients treated with RP vary with Gleason score. There is room for improvement in the outcomes of patients with high Gleason score treated with RP.
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http://dx.doi.org/10.5489/cuaj.3288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707893PMC
January 2016
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