Publications by authors named "Oliver Bucher"

31 Publications

Risk factors and prognostic implications of diagnosis of cancer within 30 days after an emergency hospital admission (emergency presentation): an International Cancer Benchmarking Partnership (ICBP) population-based study.

Lancet Oncol 2022 05 6;23(5):587-600. Epub 2022 Apr 6.

Cancer Registry of Norway, Oslo, Norway.

Background: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries.

Methods: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies.

Findings: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0).

Interpretation: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control.

Funding: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.
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http://dx.doi.org/10.1016/S1470-2045(22)00127-9DOI Listing
May 2022

The impact of the modified frailty index on clinical outcomes for patients with stage IV non-small cell lung cancer receiving chemotherapy.

J Geriatr Oncol 2022 Mar 3. Epub 2022 Mar 3.

Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Medical Oncology and Hematology, CancerCare Manitoba, Winnipeg, Manitoba, Canada; CancerCare Manitoba Research Institute, CancerCare Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address:

Introduction: Frailty impacts outcomes for patients with lung cancer, but no brief tools have been assessed in patients with metastatic disease. We evaluated the impact of the Modified Frailty Index (mFI) on clinical outcomes for patients with metastatic non-small cell lung cancer (NSCLC).

Methods: We conducted a retrospective cohort study of all patients with Stage IV NSCLC diagnosed in Manitoba between 2011 and 2016 who then received first-line cytotoxic chemotherapy. We assigned mFI scores based on documented comorbidities and collected data on toxicity, progression, and survival. Descriptive statistics characterized the cohort and toxicity experienced. Kaplan-Meier methods were used to evaluate progression-free survival (PFS) and overall survival (OS), followed by multivariable Cox proportional hazards models.

Results: Our cohort of 426 (mFI 0/1-2/3+ = 175/196/55) patients, showed no significant association between higher mFI score and incidence of overall chemotherapy toxicity. Patients with mFI 0 experienced more frequent thromboses (p=0.022) and a trend towards less nausea or vomiting (p = 0.059). There was no significant difference in PFS or OS among frailty groups. Poorer performance status, number of metastatic sites, and the absence of a driver mutation were independently associated with poorer PFS and OS. Male sex and not completing chemotherapy were also associated with worse OS.

Conclusion: This study is the first to investigate the use of the mFI as a frailty tool in patients with metastatic NSCLC receiving cytotoxic chemotherapy. The mFI does not appear to be strongly associated with treatment-related toxicities, PFS, or OS in patients with metastatic NSCLC receiving first-line cytotoxic chemotherapy.
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http://dx.doi.org/10.1016/j.jgo.2022.02.015DOI Listing
March 2022

Real world risk of infusion reactions and effectiveness of front-line obinutuzumab plus chlorambucil compared with other frontline treatments for chronic lymphocytic leukemia.

BMC Cancer 2022 Feb 6;22(1):148. Epub 2022 Feb 6.

Max Rady College of Medicine, 727 McDermot Ave, Winnipeg, MB, R3E 3P5, Canada.

Background: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in North America. Previous studies have shown improved progression free survival (PFS) and response rates in unfit patients treated with obinutuzumab compared to other regimens. The aim of this study was to evaluate the obinutuzumab-chlorambucil regimen in the context of historical treatments and first-dose infusion reactions at CancerCare Manitoba (CCMB).

Methods: A retrospective chart review was conducted for patients treated with obinutuzumab from January 1, 2014 to December 31, 2017 at CCMB. A minimum data set was extracted for patients treated with other front-line therapies. Descriptive statistics were used to evaluate patient demographics, toxicity, duration and dosing of obinutuzumab treatment. Kaplan-Meier curves were used to evaluate time-to-next-treatment (TTNT), overall survival (OS) and PFS for patients treated with obinutuzumab. A multivariable logistic regression model was used to investigate associations between infusion related reactions (IRRs) and age at treatment, pre-treatment lymphocyte count, cumulative illness rating scale (CIRS) and receipt of prior chemotherapy.

Results: Forty seven percent of patients receiving frontline therapy received chlorambucil and obinutuzumab. Sixty-seven patients were treated with obinutuzumab and consisted of 36 males (53.7%) and 31 females (46.3%) with 29 patients (43.3%) over age 75 years. Rates of grade 3 and 4 obinutuzumab IRRs were lower (6%) compared to the CLL11 clinical trial (20%) due to local practices including slower infusion rates and using chlorambucil before starting obinutuzumab treatment. Many patients had difficulty tolerating the full dosage of chlorambucil. Only 26 patients (38.8%) had their dose of chlorambucil escalated to the full dose of 0.5 mg/kg. In addition, only 18 patients (26.9%) received all doses of obinutuzumab and all 12 doses of chlorambucil.

Conclusions: In summary, first dose infusion reactions with obinutuzumab can be markedly reduced by using chlorambucil to decrease the lymphocyte count before obinutuzumab and by using a very slow initial obinutuzumab infusion rate. Modifications in chlorambucil dosing and obinutuzumab administration can improve tolerance without significant loss in efficacy.
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http://dx.doi.org/10.1186/s12885-022-09256-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818183PMC
February 2022

Evaluating the impact of the COVID-19 pandemic on cancer screening in a central Canadian province.

Prev Med 2022 02 19;155:106961. Epub 2022 Jan 19.

CancerCare Manitoba Research Institute, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada; Department of Epidemiology and Cancer Registry, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada.

We evaluated the impact of COVID-19 on cancer screening in Manitoba, Canada using an interrupted time series (ITS) design and data from Manitoba's population-based, organized cancer screening programs from April 2020 to August 2021. In June 2020 (breast screening was suspended during April and May 2020), there was a 54% decrease between the predicted (i.e., observed data produced from regression models) and expected (i.e., counterfactual values produced for the COVID-19 period by assuming COVID-19 did not occur) number of screening mammograms (ratio = 0.46, 95% Confidence Interval (CI) 0.28-0.64). By December 2020, there was no significant difference between predicted and expected number of screening mammograms (ratio = 0.95, 95% CI 0.80-1.10). In April 2020, there was an 83% decrease in the number of Pap tests (ratio = 0.17, 95% CI 0.04-0.30). By January 2021, there was no significant difference between predicted and expected number of Pap tests (ratio = 0.93, 95% CI 0.81-1.06). In April 2020, there was an 81% decrease in the number of screening program fecal occult blood tests (FOBTs) (ratio = 0.19, 95% CI 0.0-0.44). By September 2020, there was no significant difference between predicted and expected number of FOBTs (ratio = 0.95, 95% CI 0.65-1.24). The estimated cumulative deficit (i.e., backlog) from April 2020 to August 2021 was 17,370 screening mammograms, 22,086 Pap tests, and 5253 screening program FOBTs. Overall, screening programs adapted quickly to the COVID-19 pandemic. Additional strategies may be needed to address remaining backlogs.
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http://dx.doi.org/10.1016/j.ypmed.2022.106961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8769532PMC
February 2022

Impact of Pre-Treatment NLR and Other Hematologic Biomarkers on the Outcomes of Early-Stage Non-Small-Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy.

Curr Oncol 2022 01 4;29(1):193-208. Epub 2022 Jan 4.

Department of Radiation Oncology, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada.

Introduction: We evaluated the association of pre-treatment immunologic biomarkers on the outcomes of early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT).

Materials And Methods: In this retrospective study, all newly diagnosed early-stage NSCLC treated with SBRT between January 2010 and December 2017 were screened and included for further analysis. The pre-treatment neutrophil-lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan-Meier. Multivariable models were constructed to determine the impact of different biomarkers and the Akaike information criterion (AIC), index of adequacy, and scaled Brier scores were calculated.

Results: A total of 72 patients were identified and 61 were included in final analysis. The median neutrophil count at baseline was 5.4 × 10/L (IQR: 4.17-7.05 × 10/L). Median lymphocyte count was 1.63 × 10/L (IQR: 1.29-2.10 × 10/L), median monocyte count was 0.65 × 10/L (IQR: 0.54-0.83 × 10/L), median platelet count was 260.0 × 10/L (IQR: 211.0-302.0 × 10/L). The median NLR was 3.42 (IQR: 2.38-5.04), median MLR was 0.39 (IQR: 0.31-0.53), and median PLR was 156.4 (IQR: 117.2-197.5). On multivariable regression a higher NLR was associated with worse OS ( = 0.01; HR-1.26; 95% CI 1.04-1.53). The delta AIC between the two multivariable models was 3.4, suggesting a moderate impact of NLR on OS. On multivariable analysis, higher NLR was associated with poor RFS ( = 0.001; NLR^1 HR 0.36; 0.17-0.78; NLR^2 HR-1.16; 95% CI 1.06-1.26) with a nonlinear relationship. The delta AIC between the two multivariable models was 16.2, suggesting a strong impact of NLR on RFS. In our cohort, MLR and PLR were not associated with RFS or OS in multivariable models.

Conclusions: Our study suggests NLR, as a biomarker of systemic inflammation, is an independent prognostic factor for OS and RFS. The nonlinear relationship with RFS may indicate a suitable immunological environment is needed for optimal SBRT action and tumoricidal mechanisms. These findings require further validation in independent cohorts.
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http://dx.doi.org/10.3390/curroncol29010019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774597PMC
January 2022

International variation in oesophageal and gastric cancer survival 2012-2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study).

Gut 2021 Nov 25. Epub 2021 Nov 25.

Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France.

Objective: To provide the first international comparison of oesophageal and gastric cancer survival by stage at diagnosis and histological subtype across high-income countries with similar access to healthcare.

Methods: As part of the ICBP SURVMARK-2 project, data from 28 923 patients with oesophageal cancer and 25 946 patients with gastric cancer diagnosed during 2012-2014 from 14 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were included. 1-year and 3-year age-standardised net survival were estimated by stage at diagnosis, histological subtype (oesophageal adenocarcinoma (OAC) and oesophageal squamous cell carcinoma (OSCC)) and country.

Results: Oesophageal cancer survival was highest in Ireland and lowest in Canada at 1 (50.3% vs 41.3%, respectively) and 3 years (27.0% vs 19.2%) postdiagnosis. Survival from gastric cancer was highest in Australia and lowest in the UK, for both 1-year (55.2% vs 44.8%, respectively) and 3-year survival (33.7% vs 22.3%). Most patients with oesophageal and gastric cancer had regional or distant disease, with proportions ranging between 56% and 90% across countries. Stage-specific analyses showed that variation between countries was greatest for localised disease, where survival ranged between 66.6% in Australia and 83.2% in the UK for oesophageal cancer and between 75.5% in Australia and 94.3% in New Zealand for gastric cancer at 1-year postdiagnosis. While survival for OAC was generally higher than that for OSCC, disparities across countries were similar for both histological subtypes.

Conclusion: Survival from oesophageal and gastric cancer varies across high-income countries including within stage groups, particularly for localised disease. Disparities can partly be explained by earlier diagnosis resulting in more favourable stage distributions, and distributions of histological subtypes of oesophageal cancer across countries. Yet, differences in treatment, and also in cancer registration practice and the use of different staging methods and systems, across countries may have impacted the comparisons. While primary prevention remains key, advancements in early detection research are promising and will likely allow for additional risk stratification and survival improvements in the future.
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http://dx.doi.org/10.1136/gutjnl-2021-325266DOI Listing
November 2021

Comparison of liver cancer incidence and survival by subtypes across seven high-income countries.

Int J Cancer 2021 12 14;149(12):2020-2031. Epub 2021 Sep 14.

International Agency for Research on Cancer, Lyon, France.

International comparison of liver cancer survival has been hampered due to varying standards and degrees for morphological verification and differences in coding practices. This article aims to compare liver cancer survival across the International Cancer Benchmarking Partnership's (ICBP) jurisdictions whilst trying to ensure that the estimates are comparable through a range of sensitivity analyses. Liver cancer incidence data from 21 jurisdictions in 7 countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom) were obtained from population-based registries for 1995-2014. Cases were categorised based on histological classification, age-groups, basis of diagnosis and calendar period. Age-standardised incidence rate (ASR) per 100 000 and net survival at 1 and 3 years after diagnosis were estimated. Liver cancer incidence rates increased over time across all ICBP jurisdictions, particularly for hepatocellular carcinoma (HCC) with the largest relative increase in the United Kingdom, increasing from 1.3 to 4.4 per 100 000 person-years between 1995 and 2014. Australia had the highest age-standardised 1-year and 3-year net survival for all liver cancers combined (48.7% and 28.1%, respectively) in the most recent calendar period, which was still true for morphologically verified tumours when making restrictions to ensure consistent coding and classification. Survival from liver cancers is poor in all countries. The incidence of HCC is increasing alongside the proportion of nonmicroscopically verified cases over time. Survival estimates for all liver tumours combined should be interpreted in this context. Care is needed to ensure that international comparisons are performed on appropriately comparable patients, with careful consideration of coding practice variations.
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http://dx.doi.org/10.1002/ijc.33767DOI Listing
December 2021

Evaluating the Impact of the COVID-19 Pandemic on New Cancer Diagnoses and Oncology Care in Manitoba.

Curr Oncol 2021 08 12;28(4):3081-3090. Epub 2021 Aug 12.

Department of Community Health Sciences, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 750 Bannatyne Avenue, Winnipeg, MB R3E 0V9, Canada.

Individuals with cancer are vulnerable to infection with SARS-CoV-2, the virus causing COVID-19. Physical distancing, the reallocation of health care resources, and the implementation of procedures to reduce the spread of COVID-19 may also have serious consequences for people with cancer. We evaluated the impact of COVID-19 on new cancer diagnoses and oncology care in Manitoba, Canada using an interrupted time series design and data from the Manitoba Cancer Registry and CancerCare Manitoba's (CCMB) electronic medical record. In April 2020, there was a 23% decrease in new cancer diagnoses, a 21% decrease in pathology reports, and a 43% reduction in surgical resections. There was no difference in new cancer diagnoses by August 2020, surgery by July 2020, and pathology reports by September 2020. From April 2020 to June 2021, there was a 13% decrease in radiotherapy (RT) fractions, an 18% decrease in UCC visits, and a 52% decrease in in-person visits. There was no change in intravenous chemotherapy visits per month, first RT visits, or overall patient visits. The impact of COVID-19 on shifts in the stage at diagnosis and survival will be assessed in future analyses.
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http://dx.doi.org/10.3390/curroncol28040269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395519PMC
August 2021

International differences in lung cancer survival by sex, histological type and stage at diagnosis: an ICBP SURVMARK-2 Study.

Thorax 2022 04 19;77(4):378-390. Epub 2021 Jul 19.

Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France

Introduction: Lung cancer has a poor prognosis that varies internationally when assessed by the two major histological subgroups (non-small cell (NSCLC) and small cell (SCLC)).

Method: 236 114 NSCLC and 43 167 SCLC cases diagnosed during 2010-2014 in Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK were included in the analyses. One-year and 3-year age-standardised net survival (NS) was estimated by sex, histological type, stage and country.

Results: One-year and 3-year NS was consistently higher for Canada and Norway, and lower for the UK, New Zealand and Ireland, irrespective of stage at diagnosis. Three-year NS for NSCLC ranged from 19.7% for the UK to 27.1% for Canada for men and was consistently higher for women (25.3% in the UK; 35.0% in Canada) partly because men were diagnosed at more advanced stages. International differences in survival for NSCLC were largest for regional stage and smallest at the advanced stage. For SCLC, 3-year NS also showed a clear female advantage with the highest being for Canada (13.8% for women; 9.1% for men) and Norway (12.8% for women; 9.7% for men).

Conclusion: Distribution of stage at diagnosis among lung cancer cases differed by sex, histological subtype and country, which may partly explain observed survival differences. Yet, survival differences were also observed within stages, suggesting that quality of treatment, healthcare system factors and prevalence of comorbid conditions may also influence survival. Other possible explanations include differences in data collection practice, as well as differences in histological verification, staging and coding across jurisdictions.
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http://dx.doi.org/10.1136/thoraxjnl-2020-216555DOI Listing
April 2022

Predictors of Urgent Cancer Care Clinic and Emergency Department Visits for Individuals Diagnosed with Cancer.

Curr Oncol 2021 05 8;28(3):1773-1789. Epub 2021 May 8.

Department of Medical Oncology and Hematology, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada.

In 2013, CancerCare Manitoba (CCMB) launched an urgent cancer care clinic (UCC) to meet the needs of individuals diagnosed with cancer experiencing acute complications of cancer or its treatment. This retrospective cohort study compared the characteristics of individuals diagnosed with cancer that visited the UCC to those who visited an emergency department (ED) and determined predictors of use. Multivariable logistic mixed models were run to predict an individual's likelihood of visiting the UCC or an ED. Scaled Brier scores were calculated to determine how greatly each predictor impacted UCC or ED use. We found that UCC visits increased up to 4 months after eligibility to visit and then decreased. ED visits were highest immediately after eligibility and then decreased. The median number of hours between triage and discharge was 2 h for UCC visits and 9 h for ED visits. Chemotherapy had the strongest association with UCC visits, whereas ED visits prior to diagnosis had the strongest association with ED visits. Variables related to socioeconomic status were less strongly associated with UCC or ED visits. Future studies would be beneficial to planning service delivery and improving clinical outcomes and patient satisfaction.
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http://dx.doi.org/10.3390/curroncol28030165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161790PMC
May 2021

Brain Cancer Progression: A Retrospective Multicenter Comparison of Awake Craniotomy Versus General Anesthesia in High-grade Glioma Resection.

J Neurosurg Anesthesiol 2021 May 18. Epub 2021 May 18.

Department of Anesthesia and Pain Medicine, Toronto Western Hospital Section Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada Max Rady College of Medicine Department of Anesthesiology, Perioperative and Pain Medicine, University of Manitoba Department of Epidemiology and Cancer Registry, CancerCare Manitoba Department of Radiology, Radiation Oncologist, CancerCare, University of Manitoba, Winnipeg, MB, Canada Penn State College of Medicine, Penn State University Section Neurosurgery, Penn State Health, Penn State Health, Milton S. Hershey Medical Center, Hershey, PA Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH Outcomes and Clinical Research in Perioperative Medicine, School of Medicine, Stony Brook University, Health Sciences Center, Stony Brook, NY.

Background: High-grade gliomas impose substantial morbidity and mortality due to rapid cancer progression and recurrence. Factors such as surgery, chemotherapy and radiotherapy remain the cornerstones for treatment of brain cancer and brain cancer research. The role of anesthetics on glioma progression is largely unknown.

Methods: This multicenter retrospective cohort study compared patients who underwent high-grade glioma resection with minimal sedation (awake craniotomy) and those who underwent craniotomy with general anesthesia (GA). Various perioperative factors, intraoperative and postoperative complications, and adjuvant treatment regimens were recorded. The primary outcome was progression-free survival (PFS); secondary outcomes were overall survival (OS), postoperative pain score, and length of hospital stay.

Results: A total of 891 patients were included; 79% received GA, and 21% underwent awake craniotomy. There was no difference in median PFS between awake craniotomy (0.54, 95% confidence interval [CI]: 0.45-0.65 y) and GA (0.53, 95% CI: 0.48-0.60 y) groups (hazard ratio 1.05; P<0.553). Median OS was significantly longer in the awake craniotomy (1.70, 95% CI: 1.30-2.32 y) compared with that in the GA (1.25, 95% CI: 1.15-1.37 y) group (hazard ratio 0.76; P<0.009) but this effect did not persist after controlling for other variables of interest. Median length of hospital stay was significantly shorter in the awake craniotomy group (2 [range: 0 to 76], interquartile range 3 d vs. 5 [0 to 98], interquartile range 5 for awake craniotomy and GA groups, respectively; P<0.001). Pain scores were comparable between groups.

Conclusions: There was no difference in PFS and OS between patients who underwent surgical resection of high-grade glioma with minimal sedation (awake craniotomy) or GA. Further large prospective randomized controlled studies are needed to explore the role of anesthetics on glioma progression and patient survival.
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http://dx.doi.org/10.1097/ANA.0000000000000778DOI Listing
May 2021

Population-based cancer staging for oesophageal, gastric, and pancreatic cancer 2012-2014: International Cancer Benchmarking Partnership SurvMark-2.

Int J Cancer 2021 09 29;149(6):1239-1246. Epub 2021 May 29.

Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France.

Cancer stage at diagnosis is important information for management and treatment of individual patients as well as in epidemiological studies to evaluate effectiveness of health care system in managing cancer patients. Population-based studies to examine international disparities on cancer survival by stage, however, has been challenging due to the lack of international standardization on recording stage information and variation in stage completeness across regions and countries. The International Cancer Benchmarking Partnership (ICBP) previously assessed the availability and comparability of staging information for colorectal, lung, female breast and ovarian cancers. Stage conversion algorithms were developed to aggregate and map all stage information into a single staging system to allow international comparison by stage at diagnosis. In this article, we developed stage conversion algorithms for three additional cancers, namely oesophageal, gastric and pancreatic cancers. We examined all stage information available, evaluated stage completeness, applied each stage conversion algorithm, and assessed the magnitude of misclassification using data from six Canadian cancer registries (Alberta, Manitoba, Newfoundland, Nova Scotia, Prince Edward Island and Saskatchewan). In addition, we discussed five recommendations for registries to improve international cancer survival comparison by stage: (a) improve collection and completeness of staging data; (b) promote a comparable definition for stage at diagnosis; (c) promote the use of a common stage classification system; (d) record versions of staging classifications and (e) use multiple data sources for valid staging data.
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http://dx.doi.org/10.1002/ijc.33679DOI Listing
September 2021

The impact of excluding or including Death Certificate Initiated (DCI) cases on estimated cancer survival: A simulation study.

Cancer Epidemiol 2021 04 10;71(Pt A):101881. Epub 2021 Jan 10.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Health Sciences, University of Leicester, Leicester, United Kingdom.

Background: Population-based cancer registries strive to cover all cancer cases diagnosed within the population, but some cases will always be missed and no register is 100 % complete. Many cancer registries use death certificates to identify additional cases not captured through other routine sources, to hopefully add a large proportion of the missed cases. Cases notified through this route, who would not have been captured without death certificate information, are referred to as Death Certificate Initiated (DCI) cases. Inclusion of DCI cases in cancer registries increases completeness and is important for estimating cancer incidence. However, inclusion of DCI cases will generally lead to biased estimates of cancer survival, but the same is often also true if excluding DCI cases. Missed cases are probably not a random sample of all cancer cases, but rather cases with poor prognosis. Further, DCI cases have poorer prognosis than missed cases in general, since they have all died with cancer mentioned on the death certificates.

Methods: We performed a simulation study to estimate the impact of including or excluding DCI cases on cancer survival estimates, under different scenarios.

Results: We demonstrated that including DCI cases underestimates survival. The exclusion of DCI cases gives unbiased survival estimates if missed cases are a random sample of all cancer cases, while survival is overestimated if these have poorer prognosis.

Conclusion: In our most extreme scenarios, with 25 % of cases initially missed, the usual practice of including DCI cases underestimated 5-year survival by at most 3 percentage points.
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http://dx.doi.org/10.1016/j.canep.2020.101881DOI Listing
April 2021

Clinical Outcomes After Stereotactic Body Radiation Therapy for Early Stage Non-Small Cell Lung Cancer: A Single Institutional Study.

Cureus 2020 Dec 3;12(12):e11886. Epub 2020 Dec 3.

Department of Radiation Oncology, CancerCare Manitoba, University of Manitoba, Winnipeg, CAN.

Introduction The standard of care for early-stage non-small cell lung cancer (NSCLC) is surgery. However, for medical inoperable patients stereotactic body radiation therapy (SBRT) is an alternative method. The aim of the study is to assess the overall survival (OS), progression-free survival (PFS) and local control (LC) of patients diagnosed with NSCLC in Manitoba, Canada, between 2013 and 2017 and managed with SBRT. Materials and methods This retrospective study included a total of 158 patients (60.13% of the population were females) that were diagnosed with stage I-II NSCLC and were treated with lung SBRT between 2013 and 2017 in Manitoba. Demographics and clinical data were retrospectively extracted from the electronic patient record. Kaplan-Meier and Cumulative incidence curves were used to describe the OS, PFS, and LC outcomes. Results From the 158 patients, 32 patients were treated with 60 Gy in eight fractions, while 121 patients were treated with 48 Gy in four fractions. Only 85 patients had biopsy-proven NSCLC. The median OS was 2.87 years (95% confidence interval [CI] 2.16-3.43). OS rates at one and two years were 85% and 66%, respectively. The median PFS was 2.03 years (95% CI 1.65-2.77). Furthermore, one-year and two-year PFS rates were 77% and 51%, respectively. Only 10 patients progressed locally at one year and 17 at two years, making the LC rate 93% at the one-year and 87% at the two-year mark. Conclusion These findings add to a growing evidence base supporting SBRT in the treatment of clinically suspected and biopsy-proven early-stage NSCLC patients.
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http://dx.doi.org/10.7759/cureus.11886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719484PMC
December 2020

Exploring the impact of cancer registry completeness on international cancer survival differences: a simulation study.

Br J Cancer 2021 03 9;124(5):1026-1032. Epub 2020 Dec 9.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Background: Data from population-based cancer registries are often used to compare cancer survival between countries or regions. The ICBP SURVMARK-2 study is an international partnership aiming to quantify and explore the reasons behind survival differences across high-income countries. However, the magnitude and relevance of differences in cancer survival between countries have been questioned, as it is argued that observed survival variations may be explained, at least in part, by differences in cancer registration practice, completeness and the availability and quality of the respective data sources.

Methods: As part of the ICBP SURVMARK-2 study, we used a simulation approach to better understand how differences in completeness, the characteristics of those missed and inclusion of cases found from death certificates can impact on cancer survival estimates.

Results: Bias in 1- and 5-year net survival estimates for 216 simulated scenarios is presented. Out of the investigated factors, the proportion of cases not registered through sources other than death certificates, had the largest impact on survival estimates.

Conclusion: Our results show that the differences in registration practice between participating countries could in our most extreme scenarios explain only a part of the largest observed differences in cancer survival.
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http://dx.doi.org/10.1038/s41416-020-01196-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921088PMC
March 2021

Age disparities in stage-specific colon cancer survival across seven countries: An International Cancer Benchmarking Partnership SURVMARK-2 population-based study.

Int J Cancer 2021 04 14;148(7):1575-1585. Epub 2020 Oct 14.

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.

We sought to understand the role of stage at diagnosis in observed age disparities in colon cancer survival among people aged 50 to 99 years using population-based cancer registry data from seven high-income countries: Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom. We used colon cancer incidence data for the period 2010 to 2014. We estimated the 3-year net survival, as well as the 3-year net survival conditional on surviving at least 6 months and 1 year after diagnosis, by country and stage at diagnosis (categorised as localised, regional or distant) using flexible parametric excess hazard regression models. In all countries, increasing age was associated with lower net survival. For example, 3-year net survival (95% confidence interval) was 81% (80-82) for 50 to 64 year olds and 58% (56-60) for 85 to 99 year olds in Australia, and 74% (73-74) and 39% (39-40) in the United Kingdom, respectively. Those with distant stage colon cancer had the largest difference in colon cancer survival between the youngest and the oldest patients. Excess mortality for the oldest patients with localised or regional cancers was observed during the first 6 months after diagnosis. Older patients diagnosed with localised (and in some countries regional) stage colon cancer who survived 6 months after diagnosis experienced the same survival as their younger counterparts. Further studies examining other prognostic clinical factors such as comorbidities and treatment, and socioeconomic factors are warranted to gain further understanding of the age disparities in colon cancer survival.
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http://dx.doi.org/10.1002/ijc.33326DOI Listing
April 2021

International trends in oesophageal cancer survival by histological subtype between 1995 and 2014.

Gut 2021 02 17;70(2):234-242. Epub 2020 Jun 17.

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.

Introduction: Survival from oesophageal cancer remains poor, even across high-income countries. Ongoing changes in the epidemiology of the disease highlight the need for survival assessments by its two main histological subtypes, adenocarcinoma (AC) and squamous cell carcinoma (SCC).

Methods: The ICBP SURVMARK-2 project, a platform for international comparisons of cancer survival, collected cases of oesophageal cancer diagnosed 1995 to 2014, followed until 31 December 2015, from cancer registries covering seven participating countries with similar access to healthcare (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK). 1-year and 3-year age-standardised net survival alongside incidence rates were calculated by country, subtype, sex, age group and period of diagnosis.

Results: 111 894 cases of AC and 73 408 cases of SCC were included in the analysis. Marked improvements in survival were observed over the 20-year period in each country, particularly for AC, younger age groups and 1 year after diagnosis. Survival was consistently higher for both subtypes in Australia and Ireland followed by Norway, Denmark, New Zealand, the UK and Canada. During 2010 to 2014, survival was higher for AC compared with SCC, with 1-year survival ranging from 46.9% (Canada) to 54.4% (Ireland) for AC and 39.6% (Denmark) to 53.1% (Australia) for SCC.

Conclusion: Marked improvements in both oesophageal AC and SCC survival suggest advances in treatment. Less marked improvements 3 years after diagnosis, among older age groups and patients with SCC, highlight the need for further advances in early detection and treatment of oesophageal cancer alongside primary prevention to reduce the overall burden from the disease.
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http://dx.doi.org/10.1136/gutjnl-2020-321089DOI Listing
February 2021

Colon and rectal cancer survival in seven high-income countries 2010-2014: variation by age and stage at diagnosis (the ICBP SURVMARK-2 project).

Gut 2021 01 1;70(1):114-126. Epub 2020 Jun 1.

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France

Objectives: As part of the International Cancer Benchmarking Partnership (ICBP) SURVMARK-2 project, we provide the most recent estimates of colon and rectal cancer survival in seven high-income countries by age and stage at diagnosis.

Methods: Data from 386 870 patients diagnosed during 2010-2014 from 19 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were analysed. 1-year and 5-year net survival from colon and rectal cancer were estimated by stage at diagnosis, age and country, RESULTS: (One1-year) and 5-year net survival varied between (77.1% and 87.5%) 59.1% and 70.9% and (84.8% and 90.0%) 61.6% and 70.9% for colon and rectal cancer, respectively. Survival was consistently higher in Australia, Canada and Norway, with smaller proportions of patients with metastatic disease in Canada and Australia. International differences in (1-year) and 5-year survival were most pronounced for regional and distant colon cancer ranging between (86.0% and 94.1%) 62.5% and 77.5% and (40.7% and 56.4%) 8.0% and 17.3%, respectively. Similar patterns were observed for rectal cancer. Stage distribution of colon and rectal cancers by age varied across countries with marked survival differences for patients with metastatic disease and diagnosed at older ages (irrespective of stage).

Conclusions: Survival disparities for colon and rectal cancer across high-income countries are likely explained by earlier diagnosis in some countries and differences in treatment for regional and distant disease, as well as older age at diagnosis. Differences in cancer registration practice and different staging systems across countries may have impacted the comparisons.
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http://dx.doi.org/10.1136/gutjnl-2020-320625DOI Listing
January 2021

Effect of Hospitalization During First Chemotherapy and Performance Status on Small-cell Lung Cancer Outcomes.

Clin Lung Cancer 2020 09 26;21(5):e388-e404. Epub 2020 Feb 26.

Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada; Department of Hematology and Medical Oncology, CancerCare Manitoba, Winnipeg, MB, Canada; Research Institute in Oncology and Hematology, CancerCare Manitoba, Winnipeg, MB, Canada. Electronic address:

Introduction: Small-cell lung cancer (SCLC) is highly responsive to chemotherapy (CT) and one of the few malignancies treated in hospitalized patients with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS). Because of the little current information available on the outcomes experienced by hospitalized patients with SCLC receiving CT, we explored the outcomes for these patients to improve the evidence base for practice.

Materials And Methods: We conducted a retrospective cohort study to evaluate patients with a diagnosis of SCLC and treated with CT during a 10-year period. Progression-free survival (PFS) and overall survival (OS) were evaluated according to site of first CT (inpatient vs. outpatient) and PS. Multivariable analysis was completed to assess for independent survival predictors.

Results: A total of 530 patients with SCLC were treated, with 82 (15%) receiving their first CT in hospital. Inpatients had a greater burden of disease and poorer PS. Neutropenia, thrombocytopenia, nephrotoxicity, and fatigue were all experienced less often by the inpatient cohort (P < .001, P < .001, P < .001, and P = .007, respectively). For inpatients and outpatients, the OS rate at 12, 24, and 60 months was 22%, 9%, and 7% and 43%, 20%, and 9%, respectively (P < .001 for all). The median PFS and OS were longer for outpatients and highly functional patients. On multivariable analysis, ECOG PS was an independent predictor of the outcome and the site of first CT was not (P = .04 and P = .49, respectively).

Conclusion: Patients with SCLC initially treated as inpatients and those with poor functional status had shorter PFS and OS; however, some experienced long-term survival, including 5-year survival of 7% for the inpatient cohort and 5% for the ECOG PS 3-4 cohort. CT toxicities were less common in the inpatient cohort, validating that administration of CT in hospital should be considered for these patients because they could experience a meaningful long-term response to therapy.
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http://dx.doi.org/10.1016/j.cllc.2020.02.013DOI Listing
September 2020

Time intervals and routes to diagnosis for lung cancer in 10 jurisdictions: cross-sectional study findings from the International Cancer Benchmarking Partnership (ICBP).

BMJ Open 2019 11 27;9(11):e025895. Epub 2019 Nov 27.

Centre for Population Health Sciences, Edinburgh University, Edinburgh, UK.

Objective: Differences in time intervals to diagnosis and treatment between jurisdictions may contribute to previously reported differences in stage at diagnosis and survival. The International Cancer Benchmarking Partnership Module 4 reports the first international comparison of routes to diagnosis and time intervals from symptom onset until treatment start for patients with lung cancer.

Design: Newly diagnosed patients with lung cancer, their primary care physicians (PCPs) and cancer treatment specialists (CTSs) were surveyed in Victoria (Australia), Manitoba and Ontario (Canada), Northern Ireland, England, Scotland and Wales (UK), Denmark, Norway and Sweden. Using Wales as the reference jurisdiction, the 50th, 75th and 90th percentiles for intervals were compared using quantile regression adjusted for age, gender and comorbidity.

Participants: Consecutive newly diagnosed patients with lung cancer, aged ≥40 years, diagnosed between October 2012 and March 2015 were identified through cancer registries. Of 10 203 eligible symptomatic patients contacted, 2631 (27.5%) responded and 2143 (21.0%) were included in the analysis. Data were also available from 1211 (56.6%) of their PCPs and 643 (37.0%) of their CTS.

Primary And Secondary Outcome Measures: Interval lengths (days; primary), routes to diagnosis and symptoms (secondary).

Results: With the exception of Denmark (-49 days), in all other jurisdictions, the median adjusted total interval from symptom onset to treatment, for respondents diagnosed in 2012-2015, was similar to that of Wales (116 days). Denmark had shorter median adjusted primary care interval (-11 days) than Wales (20 days); Sweden had shorter (-20) and Manitoba longer (+40) median adjusted diagnostic intervals compared with Wales (45 days). Denmark (-13), Manitoba (-11), England (-9) and Northern Ireland (-4) had shorter median adjusted treatment intervals than Wales (43 days). The differences were greater for the 10% of patients who waited the longest. Based on overall trends, jurisdictions could be grouped into those with trends of reduced, longer and similar intervals to Wales. The proportion of patients diagnosed following presentation to the PCP ranged from 35% to 75%.

Conclusion: There are differences between jurisdictions in interval to treatment, which are magnified in patients with lung cancer who wait the longest. The data could help jurisdictions develop more focused lung cancer policy and targeted clinical initiatives. Future analysis will explore if these differences in intervals impact on stage or survival.
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http://dx.doi.org/10.1136/bmjopen-2018-025895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886977PMC
November 2019

Institutional review of glial tumors treated with chemotherapy: the first description of PCV-related pseudoprogression.

Neurooncol Pract 2019 Jan 21;6(1):22-29. Epub 2018 May 21.

Research Institute in Oncology and Hematology, CancerCare Manitoba, Winnipeg, MB, Canada.

Background: Pseudoprogression refers to areas of enhancement on MRI postadjuvant chemoradiation that arise as a result of treatment-related effects. Pseudoprogression has been well described with temozolomide-based chemoradiation but has not been studied in the setting of procarbazine, lomustine, and vincristine (PCV) chemotherapy. We reviewed patients treated with PCV to investigate the occurrence of pseudoprogression.

Methods: Adults diagnosed with World Health Organization grade II or III gliomas between 2010 and 2015 and treated with PCV or temozolomide were identified. Patient, tumor, treatment, and MRI data were retrospectively collected and analyzed. Pseudoprogression was defined as new enhancement seen on MRI within 6 months of completion of adjuvant radiotherapy or concurrent chemoradiation, which improved or remained stable on subsequent scans without therapeutic intervention. If MRI showed areas of new enhancement outside the 6-month post-treatment window, which resolved or remained stable without treatment, or in patients who did not receive adjuvant treatment, it was referred to as "atypical pseudoprogression."

Results: Fifty-seven patients were identified. Nine (16%) patients were identified as having pseudoprogression on MRI. Two (4%) of these patients were treated with PCV and 7 (12%) were treated with temozolomide. Seventeen (30%) patients had atypical pseudoprogression: 8 (14%) treated with temozolomide, 8 (14%) treated with PCV, and 1 (2%) treated with both types of chemotherapy.

Conclusions: We describe the first 2 cases of PCV-related pseudoprogression and 17 cases of atypical pseudoprogression. As the re-emergence of adjuvant PCV occurs in clinical practice, the occurrence of classical and atypical pseudoprogression could have a significant impact on clinical decision making.
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http://dx.doi.org/10.1093/nop/npy012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656297PMC
January 2019

Changes in colorectal cancer incidence in seven high-income countries: a population-based study.

Lancet Gastroenterol Hepatol 2019 07 16;4(7):511-518. Epub 2019 May 16.

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.

Background: The overall incidence of colorectal cancer is decreasing in many high-income countries, yet analyses in the USA and other high-income countries such as Australia, Canada, and Norway have suggested increasing incidences among adults younger than 50 years. We aimed to examine longitudinal and generational changes in the incidence of colon and rectal cancer in seven high-income countries.

Methods: We obtained data for the incidence of colon and rectal cancer from 21 population-based cancer registries in Australia, Canada, Denmark, Norway, New Zealand, Ireland, and the UK for the earliest available year until 2014. We used age-period-cohort modelling to assess trends in incidence by age group, period, and birth cohort. We stratified cases by tumour subsite according to the 10th edition of the International Classification of Diseases. Age-standardised incidences were calculated on the basis of the world standard population.

Findings: An overall decline or stabilisation in the incidence of colon and rectal cancer was noted in all studied countries. In the most recent 10-year period for which data were available, however, significant increases were noted in the incidence of colon cancer in people younger than 50 years in Denmark (by 3·1%), New Zealand (2·9%), Australia (2·9%), and the UK (1·8%). Significant increases in the incidence of rectal cancer were also noted in this age group in Canada (by 3·4%), Australia (2·6%), and the UK (1·4%). Contemporaneously, in people aged 50-74 years, the incidence of colon cancer decreased significantly in Australia (by 1·6%), Canada (1·9%), and New Zealand (3·4%) and of rectal cancer in Australia (2·4%), Canada (1·2%), and the UK (1·2%). Increases in the incidence of colorectal cancer in people younger than 50 years were mainly driven by increases in distal (left) tumours of the colon. In all countries, we noted non-linear cohort effects, which were more pronounced for rectal than for colon cancer.

Interpretation: We noted a substantial increase in the incidence of colorectal cancer in people younger than 50 years in some of the countries in this study. Future studies are needed to establish the root causes of this rising incidence to enable the development of potential preventive and early-detection strategies.

Funding: Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, the Cancer Society of New Zealand, NHS England, Norwegian Cancer Society, Public Health Agency Northern Ireland, Scottish Government, Western Australia Department of Health, and Wales Cancer Network.
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http://dx.doi.org/10.1016/S2468-1253(19)30147-5DOI Listing
July 2019

The impact of fellowship training on pathological outcomes following radical prostatectomy: a population based analysis.

BMC Urol 2014 Oct 23;14:82. Epub 2014 Oct 23.

CancerCare Manitoba, Winnipeg, Manitoba, Canada.

Background: Radical prostatectomy (RP) is a common treatment for prostate cancer (PCa). Morbidity, mortality and pathological outcomes may be superior in academic institutions. One explanation may be the involvement of oncology fellowship trained urologists within academic institutions. The literature examining pathological outcomes often lacks individual surgeon data. The objective of this study was to compare pathological outcomes following RP between fellowship trained and non-fellowship trained urologists.

Methods: Population-based, retrospective chart review of men diagnosed with PCa between 2003 and 2008, the majority treated with open approach RP (>99%). Pathological outcomes were compared between oncology fellowship trained academic (FTA), non-fellowship trained academic (NFTA) and non-academic (NA) urologists. Relationships with pathological outcomes were examined utilizing multivariable logistic regression.

Results: 83.1% of eligible patients were included in our analysis resulting in 1075 patients. In multivariable analysis, surgeon group was an independent predictor of positive surgical margin (PSM) (p < 0.0001). NFTA and NA urologists were more likely to have PSM compared to FTA urologists (OR 2.50; 95% CI: 1.44-4.35 and OR 2.10; 95% CI: 1.53-2.88, respectively). However, the proportion of PSM between NFTA and NA urologists was not significant (p = 0.492). In addition, pathological stage (p = 0.0004), Gleason sum (p < 0.0001), and surgeon volume (p = 0.017) were associated with PSM. Limitations include retrospective design and lack of clinical and functional outcomes.

Conclusions: Uro-oncology fellowship trained surgeons had significantly lower rates of PSM than non-fellowship trained surgeons in this population based cohort. This study demonstrates the importance of surgeon-related variables on pathological outcomes and highlights the value of additional urologic oncology fellowship training.
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http://dx.doi.org/10.1186/1471-2490-14-82DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216843PMC
October 2014

Population-based referrals for adjuvant radiotherapy after radical prostatectomy in men with prostate cancer: impact of randomized trials.

Clin Genitourin Cancer 2014 Feb;12(1):e1-5

Introduction: To examine the impact of published randomized controlled trial (RCT) data on referrals for adjuvant radiotherapy (RT) in patients who had high-risk pathologic features after radical prostatectomy (RP).

Methods: In this population-based, retrospective Canadian study, all patients who received a diagnosis of prostate adenocarcinoma and underwent RP from 2003-2008 were identified through the Manitoba Cancer Registry. Manual review of pathology reports was performed, and patients who had high-risk pathologic features of extracapsular extension, seminal vesicle invasion, or positive surgical margins were included. Referrals for adjuvant RT were examined before and after publication of RCT data to determine their influence on practice. Multivariable logistic regression was used to identify factors related to referral.

Results: Of the 1080 identified patients, 546 (50.6%) had ≥ 1 high-risk pathologic feature. Only 78 (14.3%) of the 546 patients were referred for adjuvant RT within 6 months of RP. Year of diagnosis, in relation to the publication of the RCT, was not significantly associated with referral (P =.60). Higher pT stage (P < .0001), Gleason score (P =.035), and increased distance from cancer center (P =.004) were associated with referral.

Conclusion: In patients who had high-risk pathologic features after RP, referral rates for adjuvant RT were low and did not increase after presentation of RCT. Men who had higher pT stage, Gleason score, and rural residence were more likely to be referred.
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http://dx.doi.org/10.1016/j.clgc.2013.07.010DOI Listing
February 2014

A systematic review-meta-analysis and meta-regression on the effect of selected competitive exclusion products on Salmonella spp. prevalence and concentration in broiler chickens.

Prev Vet Med 2013 Aug 31;111(1-2):112-25. Epub 2013 May 31.

Laboratory for Foodborne Zoonoses, Public Health Agency of Canada, 160 Research Lane, Guelph, ON N1G 5B2, Canada.

The effectiveness of various competitive exclusion (CE) products for reducing Salmonella colonization in broiler chickens was evaluated using systematic review-meta-analysis-meta-regression (SR-MA-MR). Relevance screening identified 201 relevant studies that were subjected to methodological assessment. Of these studies, 159 were suitable for data extraction, 66 were presented in a number of MAs and 130 were examined in a meta-regression (MR). Fourteen different CE products were identified, 9 of them commercial products, and the most common route of administration was oral gavage (63.7% of trials). Meta-analyses indicated that a number of CE products reduce Salmonella colonization in broilers, the most effective one being Preempt™ which was formerly known as CF-3. Five study characteristics (publication year, CE type, CE route, sample origin, and Salmonella serovar administered/recovered) and three methodological soundness characteristics (treatment assignment, intervention and laboratory methods description) were retained as statistically significant (p<0.05) in the final MR model. The MR analysis indicated that, undefined CE products outperformed all commercial products, except for: Preempt™ and Broilact(®). Both were considered comparable to the undefined chicken source CE culture products in effectiveness. The administration of CE through spraying the chicks at the hatchery was determined to be just as effective as the oral gavage treatment, and more practical for farmers to administer. The results of this study could be useful in decision-making concerning the on-farm use of CE products in broiler chickens, and as inputs for risk assessments as the industry pushes for more antibiotic-free alternatives. Out of the various interventions to reduce Salmonella colonization in broilers on-farm, CE was the most studied; its inability to be licenced in certain countries and proof of consistent efficacy remains a barrier.
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http://dx.doi.org/10.1016/j.prevetmed.2013.04.005DOI Listing
August 2013

The effectiveness of selected feed and water additives for reducing Salmonella spp. of public health importance in broiler chickens: a systematic review, meta-analysis, and meta-regression approach.

Prev Vet Med 2012 Oct 2;106(3-4):197-213. Epub 2012 Aug 2.

Laboratory for Foodborne Zoonoses, Public Health Agency of Canada, 160 Research Lane, Guelph, ON N1G 5B2, Canada.

Eating inappropriately prepared poultry meat is a major cause of foodborne salmonellosis. Our objectives were to determine the efficacy of feed and water additives (other than competitive exclusion and antimicrobials) on reducing Salmonella prevalence or concentration in broiler chickens using systematic review-meta-analysis and to explore sources of heterogeneity found in the meta-analysis through meta-regression. Six electronic databases were searched (Current Contents (1999-2009), Agricola (1924-2009), MEDLINE (1860-2009), Scopus (1960-2009), Centre for Agricultural Bioscience (CAB) (1913-2009), and CAB Global Health (1971-2009)), five topic experts were contacted, and the bibliographies of review articles and a topic-relevant textbook were manually searched to identify all relevant research. Study inclusion criteria comprised: English-language primary research investigating the effects of feed and water additives on the Salmonella prevalence or concentration in broiler chickens. Data extraction and study methodological assessment were conducted by two reviewers independently using pretested forms. Seventy challenge studies (n=910 unique treatment-control comparisons), seven controlled studies (n=154), and one quasi-experiment (n=1) met the inclusion criteria. Compared to an assumed control group prevalence of 44 of 1000 broilers, random-effects meta-analysis indicated that the Salmonella cecal colonization in groups with prebiotics (fructooligosaccharide, lactose, whey, dried milk, lactulose, lactosucrose, sucrose, maltose, mannanoligosaccharide) added to feed or water was 15 out of 1000 broilers; with lactose added to feed or water it was 10 out of 1000 broilers; with experimental chlorate product (ECP) added to feed or water it was 21 out of 1000. For ECP the concentration of Salmonella in the ceca was decreased by 0.61 log(10)cfu/g in the treated group compared to the control group. Significant heterogeneity (Cochran's Q-statistic p≤0.10) was observed among studies examining all organic acids (controlled or challenge experiments), butyric acid, formic acid, a formic/propionic acid mixture, fermented liquid feed, and D-mannose. Meta-regressions were conducted to examine the source of heterogeneity among studies. For prevalence outcomes, 36% and 60% of the total variance was within and between studies, respectively. For concentration outcomes, 39% and 33% of the total variance was within and between studies, respectively. Inadequate blinding and randomization was common, and no studies undergoing meta-analysis or meta-regression were conducted on a commercial farm. The strength of evidence of the effect of these additives was very low. Studies conducted under commercial conditions are needed to understand the potential benefit of these interventions for the poultry industry and to improve the strength of evidence of the effectiveness of these additives.
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http://dx.doi.org/10.1016/j.prevetmed.2012.07.007DOI Listing
October 2012

A systematic review-meta-analysis of chilling interventions and a meta-regression of various processing interventions for Salmonella contamination of chicken.

Prev Vet Med 2012 Jan 10;103(1):1-15. Epub 2011 Oct 10.

Department of Population Medicine, University of Guelph, Guelph, ON, Canada.

Context: The results of individual studies investigating the efficacy of chilling and other processing interventions on Salmonella prevalence or concentration in broiler chicken carcasses are inconsistent or contradictory.

Objective: Determine efficacy of chilling on reducing Salmonella prevalence or concentration on broiler carcasses using systematic review-meta-analysis, and explore sources of heterogeneity among studies investigating various processing interventions through meta-regression.

Data Sources: A comprehensive search included electronic search in six databases, manual search of reference lists of topic-related articles, and consultation with five topic experts to assure that all relevant intervention research was identified. STUDY INCLUSION: Primary intervention research, published in English, encompassing control, challenge, cohort, or before-and-after study designs investigating the efficacy of any chilling or other processing interventions on Salmonella prevalence or concentration in broiler chicken carcasses. RISK OF BIAS ASSESSMENT AND DATA EXTRACTION: Data pertaining to study methodology and reported results, chilling or other processing intervention parameters, populations sampled and outcomes measured were assessed for methodological soundness and extracted by two independent reviewers using pretested checklists.

Results: Random-effects meta-analyses of immersion chilling with chlorine (n=9 trials), acetic acid (n=16) and potable water (n=13) trended towards reductions in the odds or log(10)CFU/ml of Salmonella. Significant heterogeneity (P-value≤0.1 and I(2)>25%) precluded the reporting of pooled summary effect estimates. Meta-regression of all processing interventions indicated that serotype, disinfectant type and treatment time and pH were significantly associated with studies reporting reductions in concentration while study design, population sampled, study setting, publication date, intervention and disinfectant type, and treatment pH were significantly associated with studies reporting reductions in prevalence. Methodological and reporting flaws were consistently observed in relevant intervention research as well as a lack of studies conducted under commercial conditions and using Salmonella concentration outcomes.

Conclusions: Chilling may be effective at reducing Salmonella concentration and prevalence, but significant heterogeneity precluded reporting of pooled summary effect estimates for many chilling interventions. Investigations into potential sources of heterogeneity among all processing interventions found that the use of other chemical disinfectants, such as organic acids and surfactants might result in larger reductions in Salmonella contamination than more commonly utilized oxidizing agents like chlorine.
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http://dx.doi.org/10.1016/j.prevetmed.2011.09.017DOI Listing
January 2012

Thermal resistance of Salmonella serovars isolated from raw, frozen chicken nuggets/strips, nugget meat and pelleted broiler feed.

Int J Food Microbiol 2008 May 7;124(2):195-8. Epub 2008 Mar 7.

Department of Food Science, University of Manitoba, Winnipeg, Manitoba, Canada.

Raw, frozen chicken nuggets/strips available at retail and prepared at home before consumption have been identified as a significant risk factor in contracting food-borne salmonellosis. Cases of salmonellosis from consumption of these products may be due, in part, to Salmonella strains originating in broiler feed. In this study the thermal resistances of Salmonella strains isolated from chicken nuggets and strips, chicken nugget/strip meat and broiler feed were determined to assess whether they exhibited enhanced thermal resistance. Thermal resistances (D- and z- values) of 7 cocktails (25 isolates, 4 serovars) were determined in commercially prepared irradiation-treated chicken nugget/strip meat blend, and heated in a constant temperature waterbath. The thermal resistances found were lower than those reported for similar strains in the literature. D-values ranged from 6.93 to 0.12 min at 55 and 62 degrees C respectively, with z-values from 4.10 to 5.17 degrees C. Two strains of S. Enteritidis separately isolated from pelleted feed and chicken nugget meat blend, with indistinguishable geno- and phenotypes, had lower (and probably identical) thermal resistances than the other isolates. Results indicated that the strains of Salmonella isolated from raw, frozen chicken nuggets/strips and pelleted broiler feed did not exhibit unusually high thermal resistance, and that normal heating (71 degrees C) prior to consumption should eliminate these organisms from chicken nuggets/strips.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2008.03.002DOI Listing
May 2008
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