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Article ; Online: Next Generation Weight Loss Drugs for the Prevention of Cancer?

Carbonell, Chantelle / Mathew Stephen, Mariet / Ruan, Yibing / Warkentin, Matthew T / Brenner, Darren R

Cancer control : journal of the Moffitt Cancer Center

2024 Volume 31, Page(s) 10732748241241158

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Male ; Female ; Humans ; Anti-Obesity Agents/therapeutic use ; Obesity/complications ; Obesity/epidemiology ; Risk Factors ; Neoplasms/epidemiology ; Neoplasms/prevention & control ; Weight Loss
Chemical Substances	Anti-Obesity Agents
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1328503-8
ISSN	1526-2359 ; 1073-2748
ISSN (online)	1526-2359
ISSN	1073-2748
DOI	10.1177/10732748241241158
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Zs.A 4467: Show issues

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Article ; Online: Progress in site-specific cancer mortality in Canada over the last 70 years.

Warkentin, Matthew T / Ruan, Yibing / Ellison, Larry F / Billette, Jean-Michel / Demers, Alain / Liu, Fei-Fei / Brenner, Darren R

Scientific reports

2024 Volume 14, Issue 1, Page(s) 5688

Abstract: In Canada, the absolute number of cancer deaths has been steadily increasing, however, age-standardized cancer mortality rates peaked decades ago for most cancers. The objective of this study was to estimate the reduction in deaths for each cancer type ... ...

Abstract	In Canada, the absolute number of cancer deaths has been steadily increasing, however, age-standardized cancer mortality rates peaked decades ago for most cancers. The objective of this study was to estimate the reduction in deaths for each cancer type under the scenario where peak mortality rates had remained stable in Canada. Data for this study were obtained the Global Cancer Observatory and Statistics Canada. We estimated age-standardized mortality rates (ASMR, per 100,000) from 1950 to 2022, standardized to the 2011 Canadian standard population. We identified peak mortality rates and applied the age-specific mortality rates from the peak year to the age-specific Canadian population estimates for subsequent years (up to 2022) to estimate the number of expected deaths. Avoided cancer deaths were the difference between the observed and expected number of cancer deaths. There have been major reductions in deaths among cancers related to tobacco consumption and other modifiable lifestyle habits (417,561 stomach; 218,244 colorectal; 186,553 lung; 66,281 cervix; 32,732 head and neck; 27,713 bladder; 22,464 leukemia; 20,428 pancreas; 8863 kidney; 3876 esophagus; 290 liver). There have been 201,979 deaths avoided for female-specific cancers (breast, cervix, ovary, uterus). Overall, there has been a 34% reduction in mortality for lung cancer among males and a 9% reduction among females. There has been a significant reduction in cancer mortality in Canada since site-specific cancer mortality rates peaked decades ago for many cancers. This shows the exceptional progress made in cancer control in Canada due to substantial improvements in prevention, screening, and treatment. This study highlights priority areas where more attention and investment are needed to achieve progress.
MeSH term(s)	Male ; Humans ; Female ; Canada/epidemiology ; Neoplasms ; Lung Neoplasms ; Leukemia ; Breast ; Life Style ; Mortality ; Incidence
Language	English
Publishing date	2024-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-56150-x
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Article ; Online: Probability of lung cancer in a population excluded from screening due to low PLCO

MacEachern, Paul / Warkentin, Matthew T / Brenner, Darren R / Bedard, Eric L R / Tremblay, Alain

Cancer epidemiology

2023 Volume 84, Page(s) 102368

Abstract: Background: Several randomized trials demonstrated have reduced lung cancer mortality with screening using computed tomography. However, there remains debate about the optimal approach for determining screening eligibility, and no evidence yet exists ... ...

Abstract	Background: Several randomized trials demonstrated have reduced lung cancer mortality with screening using computed tomography. However, there remains debate about the optimal approach for determining screening eligibility, and no evidence yet exists reporting lung cancer rates in those excluded from screening due to too low of a personalized risk. Methods: This study was based on the Alberta Lung Cancer Screening Study, which received 1737 applicants and enrolled 850 based on the NLST criteria or a PLCO Results: We observed 30 and 8 lung cancers in the screened and unscreened groups, respectively. Only 1 of 8 lung cancers were among those considered too low risk (0.14%), while the remaining 7 were among those excluded for other reasons, including symptoms requiring more immediate workup. No NLST eligible but PLCO risk < 1.5% screened individual had a lung cancer detected as part of the study, so that of all applicants contacting the program with risk estimates less than 1.5%, only 1/857 (0.12%) developed lung cancer. Conclusion: Our findings indicate that a risk-based approach for screening eligibility is unlikely to miss many lung cancers.
MeSH term(s)	Humans ; Early Detection of Cancer/methods ; Lung Neoplasms/diagnosis ; Lung Neoplasms/epidemiology ; Tomography, X-Ray Computed/methods ; Probability ; Alberta ; Mass Screening/methods
Language	English
Publishing date	2023-04-21
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2508729-0
ISSN	1877-783X ; 1877-7821
ISSN (online)	1877-783X
ISSN	1877-7821
DOI	10.1016/j.canep.2023.102368
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Zs.A 1427: Show issues

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Article ; Online: Comment on Yakovlev, S. & Downing, K.H. (2011) Crystalline ice as a cryoprotectant: theoretical calculation of cooling speed in capillary tubes. J. Microsc. 243, 8-14.

Warkentin, Matthew

Journal of microscopy

2012 Volume 246, Issue 3, Page(s) 322

MeSH term(s)	Cryopreservation/methods ; Cryoprotective Agents/chemistry ; Ice
Chemical Substances	Cryoprotective Agents ; Ice
Language	English
Publishing date	2012-06
Publishing country	England
Document type	Comment ; Letter
ZDB-ID	219263-9
ISSN	1365-2818 ; 0022-2720
ISSN (online)	1365-2818
ISSN	0022-2720
DOI	10.1111/j.1365-2818.2012.03612.x
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Zs.A 838: Show issues

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Article ; Online: Progress in cancer control leads to a substantial number of cancer deaths avoided in Canada.

Warkentin, Matthew T / Ruan, Yibing / Ellison, Larry F / Billette, Jean-Michel / Demers, Alain A / Liu, Fei-Fei / Brenner, Darren R

JNCI cancer spectrum

2023 Volume 7, Issue 6

Abstract: It is currently not known how many more cancer deaths would have occurred among Canadians if cancer mortality rates were unchanged following various modern human interventions. The objective of this study was to estimate the number of cancer deaths that ... ...

Abstract	It is currently not known how many more cancer deaths would have occurred among Canadians if cancer mortality rates were unchanged following various modern human interventions. The objective of this study was to estimate the number of cancer deaths that have been avoided in Canada since the age-standardized overall cancer mortality rate peaked in 1988. We applied the age-specific overall cancer mortality rates from 1988 to the Canadian population for all subsequent years to estimate the number of expected deaths. Avoided cancer deaths were estimated as the difference between the observed and expected number of cancer deaths for each year. Since 1988, there have been 372 584 (standardized mortality ratio = 0.77) and 120 045 (standardized mortality ratio = 0.90) avoided cancer deaths in males and females, respectively (492 629 total). Nearly half a million cancer deaths have been avoided in Canada since the overall cancer mortality rate peaked, which demonstrates the exceptional progress made in modern cancer control in Canada.
MeSH term(s)	Female ; Humans ; Male ; Canada/epidemiology ; Neoplasms/mortality ; Neoplasms/prevention & control
Language	English
Publishing date	2023-12-12
Publishing country	England
Document type	Journal Article
ISSN	2515-5091
ISSN (online)	2515-5091
DOI	10.1093/jncics/pkad105
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Article ; Online: Determinants of impaired lung function and lung cancer prediction among never-smokers in the UK Biobank cohort.

Warkentin, Matthew T / Lam, Stephen / Hung, Rayjean J

EBioMedicine

2019 Volume 47, Page(s) 58–64

Abstract: Background: Impaired lung health represents a significant burden on global health, including chronic obstructive pulmonary disease (COPD) and lung cancer. Given its global health impact, it is important to understand the determinants of impaired lung ... ...

Abstract	Background: Impaired lung health represents a significant burden on global health, including chronic obstructive pulmonary disease (COPD) and lung cancer. Given its global health impact, it is important to understand the determinants of impaired lung function and its relation to lung cancer risk independent of smoking. However, to date, no study has evaluated determinants of impaired lung function in a cohort exclusively of never-smokers, who also represent a growing proportion of all lung cancers. Methods: A total of 222,274 never-smokers with reproducible spirograms were identified in the UK Biobank population-based cohort and included in the analysis. Baseline volumetric measures of lung function, including forced expiratory volume in 1-s (FEV1) and forced vital capacity (FVC), were used to define lung function impairment. Determinants of impaired lung function were evaluated using Poisson regression with robust variance estimation. The added value of lung function in lung cancer prediction was evaluated using Fine and Gray regression accounting for the competing risk of all-cause mortality. Findings: Lung function impairment was associated with low birthweight, ambient air pollution (PM Interpretation: We identified several modifiable risk factors associated with increased risk of lung function impairment among lifetime never-smokers in UKB. We achieved moderate discrimination for lung cancer risk-prediction for never-smokers, and found modest improvement with the inclusion of lung function. FUND: This study was supported by a Canada Research Chair to RJH.
MeSH term(s)	Adult ; Aged ; Biological Specimen Banks ; Biomarkers ; Female ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/epidemiology ; Lung Neoplasms/physiopathology ; Male ; Middle Aged ; Prognosis ; Respiratory Function Tests/methods ; Respiratory Function Tests/statistics & numerical data ; Smokers ; Tomography, X-Ray Computed
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-09-05
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2019.08.058
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Zs.A 7090: Show issues

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Article ; Online: Radiomics analysis to predict pulmonary nodule malignancy using machine learning approaches.

Warkentin, Matthew T / Al-Sawaihey, Hamad / Lam, Stephen / Liu, Geoffrey / Diergaarde, Brenda / Yuan, Jian-Min / Wilson, David O / Atkar-Khattra, Sukhinder / Grant, Benjamin / Brhane, Yonathan / Khodayari-Moez, Elham / Murison, Kiera R / Tammemagi, Martin C / Campbell, Kieran R / Hung, Rayjean J

Thorax

2024 Volume 79, Issue 4, Page(s) 307–315

Abstract: Background: Low-dose CT screening can reduce lung cancer-related mortality. However, most screen-detected pulmonary abnormalities do not develop into cancer and it often remains challenging to identify malignant nodules, particularly among indeterminate ...

Abstract	Background: Low-dose CT screening can reduce lung cancer-related mortality. However, most screen-detected pulmonary abnormalities do not develop into cancer and it often remains challenging to identify malignant nodules, particularly among indeterminate nodules. We aimed to develop and assess prediction models based on radiological features to discriminate between benign and malignant pulmonary lesions detected on a baseline screen. Methods: Using four international lung cancer screening studies, we extracted 2060 radiomic features for each of 16 797 nodules (513 malignant) among 6865 participants. After filtering out low-quality radiomic features, 642 radiomic and 9 epidemiological features remained for model development. We used cross-validation and grid search to assess three machine learning (ML) models (eXtreme Gradient Boosted Trees, random forest, least absolute shrinkage and selection operator (LASSO)) for their ability to accurately predict risk of malignancy for pulmonary nodules. We report model performance based on the area under the curve (AUC) and calibration metrics in the held-out test set. Results: The LASSO model yielded the best predictive performance in cross-validation and was fit in the full training set based on optimised hyperparameters. Our radiomics model had a test-set AUC of 0.93 (95% CI 0.90 to 0.96) and outperformed the established Pan-Canadian Early Detection of Lung Cancer model (AUC 0.87, 95% CI 0.85 to 0.89) for nodule assessment. Our model performed well among both solid (AUC 0.93, 95% CI 0.89 to 0.97) and subsolid nodules (AUC 0.91, 95% CI 0.85 to 0.95). Conclusions: We developed highly accurate ML models based on radiomic and epidemiological features from four international lung cancer screening studies that may be suitable for assessing indeterminate screen-detected pulmonary nodules for risk of malignancy.
MeSH term(s)	Humans ; Lung Neoplasms/diagnosis ; Early Detection of Cancer ; Radiomics ; Tomography, X-Ray Computed ; Canada ; Multiple Pulmonary Nodules/pathology ; Machine Learning ; Retrospective Studies
Language	English
Publishing date	2024-03-15
Publishing country	England
Document type	Journal Article
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thorax-2023-220226
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Article ; Online: Lung Cancer Absolute Risk Models for Mortality in an Asian Population using the China Kadoorie Biobank.

Warkentin, Matthew T / Tammemägi, Martin C / Espin-Garcia, Osvaldo / Budhathoki, Sanjeev / Liu, Geoffrey / Hung, Rayjean J

Journal of the National Cancer Institute

2022 Volume 114, Issue 12, Page(s) 1665–1673

Abstract: Background: Lung cancer is the leading cause of cancer mortality globally. Early detection through risk-based screening can markedly improve prognosis. However, most risk models were developed in North American cohorts of smokers, whereas less is known ... ...

Abstract	Background: Lung cancer is the leading cause of cancer mortality globally. Early detection through risk-based screening can markedly improve prognosis. However, most risk models were developed in North American cohorts of smokers, whereas less is known about risk profiles for never-smokers, which represent a growing proportion of lung cancers, particularly in Asian populations. Methods: Based on the China Kadoorie Biobank, a population-based prospective cohort of 512 639 adults with up to 12 years of follow-up, we built Asian Lung Cancer Absolute Risk Models (ALARM) for lung cancer mortality using flexible parametric survival models, separately for never and ever-smokers, accounting for competing risks of mortality. Model performance was evaluated in a 25% hold-out test set using the time-dependent area under the curve and by comparing model-predicted and observed risks for calibration. Results: Predictors assessed in the never-smoker lung cancer mortality model were demographics, body mass index, lung function, history of emphysema or bronchitis, personal or family history of cancer, passive smoking, and indoor air pollution. The ever-smoker model additionally assessed smoking history. The 5-year areas under the curve in the test set were 0.77 (95% confidence interval = 0.73 to 0.80) and 0.81 (95% confidence interval = 0.79 to 0.84) for ALARM-never-smokers and ALARM-ever smokers, respectively. The maximum 5-year risk for never and ever-smokers was 2.6% and 12.7%, respectively. Conclusions: This study is among the first to develop risk models specifically for Asian populations separately for never and ever-smokers. Our models accurately identify Asians at high risk of lung cancer death and may identify those with risks exceeding common eligibility thresholds who may benefit from screening.
MeSH term(s)	Adult ; Humans ; Prospective Studies ; Biological Specimen Banks ; Smoking/adverse effects ; Smoking/epidemiology ; Lung Neoplasms/epidemiology ; Lung ; Risk Factors
Language	English
Publishing date	2022-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djac176
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Uh III Zs.131: Show issues

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Article ; Online: Efficacy and Safety of First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis.

Bosma, Nicholas A / Warkentin, Matthew T / Gan, Chun Loo / Karim, Safiya / Heng, Daniel Y C / Brenner, Darren R / Lee-Ying, Richard M

European urology open science

2022 Volume 37, Page(s) 14–26

Abstract: Context: Considerable advances have been made in the first-line treatment of metastatic renal cell carcinoma (mRCC), with immunotherapy-based combinations including immunotherapy-tyrosine kinase inhibitors (IO-TKIs) and dual immunotherapy (IO-IO) ... ...

Abstract	Context: Considerable advances have been made in the first-line treatment of metastatic renal cell carcinoma (mRCC), with immunotherapy-based combinations including immunotherapy-tyrosine kinase inhibitors (IO-TKIs) and dual immunotherapy (IO-IO) favored. A lack of head-to-head clinical trials comparing these treatments means that there is uncertainty regarding their use in clinical practice. Objective: To compare and rank the efficacy and safety of first-line systemic treatments for mRCC with a focus on IO-based combinations. Evidence acquisition: MEDLINE (Ovid), EMBASE, Cochrane Library, Web of Science, and abstracts of recent major scientific meetings were searched to identify the most up-to-date phase 3 randomized controlled trials (RCTs) of first-line IO-based combinations for mRCC up to June 2021. A systematic review and network meta-analysis were completed using the Bayesian framework. Primary endpoints included overall survival (OS) and progression-free survival (PFS). Secondary endpoints included the objective response rate (ORR), complete response (CR), grade 3-4 treatment-related adverse events (TRAEs), treatment-related drug discontinuation (TRDD), and health-related quality of life (HRQoL). The analysis was performed for the intention-to-treat (ITT) population as well as by clinical risk group. Evidence synthesis: A total of six phase 3 RCTs were included involving a total of 5121 patients. Nivolumab plus cabozantinib (NIVO-CABO) had the highest likelihood of an OS benefit in the ITT population (surface under the cumulative ranking curve 82%). Avelumab plus axitinib (AVEL-AXI) had the highest likelihood of an OS benefit for patients with favorable risk (65%). Pembrolizumab plus AXI (PEMBRO-AXI) had the highest likelihood of an OS benefit for patients with intermediate risk (78%). PEMBRO plus lenvatinib (PEMBRO-LENV) had the highest likelihood of an OS benefit for patients with poor risk (89%). PEMBRO-LENV was associated with a superior PFS benefit across all risk groups (89-98%). Maximal ORR was achieved with PEMBRO-LENV (97%). The highest likelihood for CR was attained with NIVO plus ipilimumab (NIVO-IPI; 85%) and PEMBRO-LENV (83%). The highest grade 3-4 TRAE rate occurred with PEMBRO-LENV (95%) and NIVO-CABO (83%), but the latter was associated with the lowest TRDD rate (2%). By contrast, NIVO-IPI had the lowest grade 3-4 TRAE rate (6%) and the highest likelihood of TRDD (100%). HRQoL consistently favored NIVO-CABO (66-75%), PEMBRO-LENV (44-85%), and NIVO-IPI (65-93%) in comparison to the other treatments. Conclusions: IO-TKI drug combinations are associated with consistent improvements in clinically relevant outcomes for all mRCC risk groups. This benefit may be at the cost of higher TRAE rates; however, lower TRDD rates suggest a manageable side-effect profile. Longer follow-up is required to determine if the benefits of IO-TKIs will be sustained and if they should be favored in the first-line treatment of mRCC. Patient summary: Combination treatments based on immunotherapy agents continue to show meaningful benefits in the first-line treatment of metastatic kidney cancer. Our review and network meta-analysis shows that immunotherapy combined with another class of agents called tyrosine kinase inhibitors is promising. However, longer follow-up is needed for this treatment strategy to clarify if the benefits are long-lasting.
Language	English
Publishing date	2022-01-22
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	3040546-4
ISSN	2666-1683 ; 2058-4881
ISSN (online)	2666-1683
ISSN	2058-4881
DOI	10.1016/j.euros.2021.12.007
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Article ; Online: Estimating the Maximum Capacity of COVID-19 Cases Manageable per Day Given a Health Care System's Constrained Resources.

Giannakeas, Vasily / Bhatia, Deepit / Warkentin, Matthew T / Bogoch, Isaac I / Stall, Nathan M

Annals of internal medicine

2020 Volume 173, Issue 5, Page(s) 407–410

MeSH term(s)	Betacoronavirus ; COVID-19 ; Catchment Area, Health ; Coronavirus Infections/epidemiology ; Coronavirus Infections/therapy ; Health Resources/statistics & numerical data ; Hospital Bed Capacity/statistics & numerical data ; Humans ; Length of Stay/statistics & numerical data ; Models, Statistical ; Ontario/epidemiology ; Pandemics ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/therapy ; SARS-CoV-2 ; Ventilators, Mechanical/supply & distribution
Keywords	covid19
Language	English
Publishing date	2020-04-16
Publishing country	United States
Document type	Letter
ZDB-ID	336-0
ISSN	1539-3704 ; 0003-4819
ISSN (online)	1539-3704
ISSN	0003-4819
DOI	10.7326/M20-1169
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