Use of chemotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There are few data on international variation in chemotherapy use, despite it being a key treatment type for some patients with cancer. Here, we aimed to examine the presence and size of such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), eight Canadian provinces (Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring from within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in chemotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 893 461 patients with a new diagnosis of one of the studied cancers, 111 569 (12·5%) did not meet the inclusion criteria, and 781 892 were included in the analysis. There was large interjurisdictional variation in chemotherapy use for all studied cancers, with wide 95% PIs: 47·5 to 81·2 (pooled estimate 66·4%) for ovarian cancer, 34·9 to 59·8 (47·2%) for oesophageal cancer, 22·3 to 62·3 (40·8%) for rectal cancer, 25·7 to 55·5 (39·6%) for stomach cancer, 17·2 to 56·3 (34·1%) for pancreatic cancer, 17·9 to 49·0 (31·4%) for lung cancer, 18·6 to 43·8 (29·7%) for colon cancer, and 3·5 to 50·7 (16·1%) for liver cancer. For patients with stage 3 colon cancer, the interjurisdictional variation was greater than that for all patients with colon cancer (95% PI 38·5 to 78·4; 60·1%). Patients aged 85-99 years had 20-times lower odds of chemotherapy use than those aged 65-74 years, with very large interjurisdictional variation in this age difference (odds ratio 0·05; 95% PI 0·01 to 0·19). There was large variation in median time to first chemotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation, particularly for rectal cancer (95% PI -15·5 to 193·9 days; pooled estimate 89·2 days). Patients aged 85-99 years had slightly shorter median time to first chemotherapy compared with those aged 65-74 years, consistently between jurisdictions (-3·7 days, 95% PI -7·6 to 0·1). INTERPRETATION: Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the 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, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Use of radiotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There is little evidence on variation in radiotherapy use in different countries, although it is a key treatment modality for some patients with cancer. Here we aimed to examine such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), nine Canadian provinces (Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in radiotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data, or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 902 312 patients with a new diagnosis of one of the studied cancers, 115 357 (12·8%) did not meet inclusion criteria, and 786,955 were included in the analysis. There was large interjurisdictional variation in radiotherapy use, with wide 95% PIs: 17·8 to 82·4 (pooled estimate 50·2%) for oesophageal cancer, 35·5 to 55·2 (45·2%) for rectal cancer, 28·6 to 54·0 (40·6%) for lung cancer, and 4·6 to 53·6 (19·0%) for stomach cancer. For patients with stage 2-3 rectal cancer, interjurisdictional variation was greater than that for all patients with rectal cancer (95% PI 37·0 to 84·6; pooled estimate 64·2%). Radiotherapy use was infrequent but variable in patients with pancreatic (95% PI 1·7 to 16·5%), liver (1·8 to 11·2%), colon (1·6 to 5·0%), and ovarian (0·8 to 7·6%) cancer. Patients aged 85-99 years had three-times lower odds of radiotherapy use than those aged 65-74 years, with substantial interjurisdictional variation in this age difference (odds ratio [OR] 0·38; 95% PI 0·20-0·73). Women had slightly lower odds of radiotherapy use than men (OR 0·88, 95% PI 0·77-1·01). There was large variation in median time to first radiotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation (eg, oesophageal 95% PI 11·3 days to 112·8 days; pooled estimate 62·0 days; rectal 95% PI 34·7 days to 77·3 days; pooled estimate 56·0 days). Older patients had shorter median time to radiotherapy with appreciable interjurisdictional variation (-9·5 days in patients aged 85-99 years vs 65-74 years, 95% PI -26·4 to 7·4). INTERPRETATION: Large interjurisdictional variation in both use and time to radiotherapy initiation were observed, alongside large and variable age differences. To guide efforts to improve patient outcomes, underlying reasons for these differences need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the 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, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Measuring the impact of COVID-19 on cancer survival using an interrupted time series analysis.

BACKGROUND: Few studies have investigated the impact of the COVID-19 pandemic on cancer survival. Those studies that have included pandemic vs prepandemic comparisons can mask differences during different periods of the pandemic such as COVID-19 waves. The objective of this study was to investigate the impact of the COVID-19 pandemic on cancer survival using an interrupted time series analysis and to identify time points during the pandemic when observed survival deviated from expected survival. METHODS: A retrospective population-based cohort study that included individuals diagnosed with cancer between January 2015 and September 2021 from Manitoba, Canada, was performed. Interrupted time series analyses with Royston-Parmar models as well as Kaplan-Meier survival estimates and delta restricted mean survival times at 1 year were used to compare survival rates for those diagnosed before and after the pandemic. Analyses were performed for 11 cancer types. RESULTS: Survival at 1 year for most cancer types was not statistically different during the pandemic compared with prepandemic except for individuals aged 50-74 years who were diagnosed with lung cancer from April to June 2021 (delta restricted mean survival times = -31.6 days, 95% confidence interval [CI] = -58.3 to -7.2 days). CONCLUSIONS: With the exception of individuals diagnosed with lung cancer, the COVID-19 pandemic did not impact overall 1-year survival in Manitoba. Additional research is needed to examine the impact of the pandemic on long-term cancer survival.

Real-world predictors of survival in patients with limited-stage small-cell lung cancer in Manitoba, Canada.

Background: Although therapy for limited-stage small-cell lung cancer (LS-SCLC) is administered with curative intent, most patients relapse and eventually die of recurrent disease. Chemotherapy (CT) with concurrent radiotherapy (RT) remains the standard of care for LS-SCLC; however, this could evolve in the near future. Therefore, understanding the current prognostic factors associated with survival is essential. Objective: This real-world analysis examines factors associated with long-term survival in patients with LS-SCLC treated with CT in Manitoba, Canada. Methods: A retrospective cohort study was conducted using Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years and had cytologically confirmed LS-SCLC diagnosed between January 1, 2004, and December 31, 2018, for which they received CT ± RT. Baseline patient, disease, and treatment characteristics and survival duration, characterized as short (<6 months), medium (6-24 months), and long term (>24 months), were extracted. Overall survival (OS) was estimated at one, two, and five years and assessed using Kaplan-Meier methods and Cox proportional hazards models. Results: Over the 15-year study period, 304 patients met the eligibility criteria. Long-term survivors comprised 39.1% of the cohort; at diagnosis, this subgroup was younger, more likely to have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, and have normal lactate dehydrogenase, sodium, and hemoglobin levels. OS estimates for the entire cohort at one, two, and five years were 66%, 38%, and 18%, respectively. In the ECOG PS 0 subgroup, OS estimates at one, two, and five years were 85%, 52%, and 24%, respectively; OS estimates were 60%, 35%, and 17%, respectively, for ECOG PS 1-2 and were 47%, 23%, and 10%, respectively, for ECOG PS 3-4. OS was significantly higher among patients with normal serum sodium and hemoglobin levels than those with abnormal levels. Univariable hazard regression models found that ECOG PS, age at diagnosis, receipt of prophylactic cranial irradiation (PCI), and thoracic RT were associated with survival. On multivariable hazard regression, ECOG PS and receipt of PCI were associated with survival. Conclusion: Survival for greater than two years in patients with LS-SCLC treated with CT ± RT was associated with ECOG PS and receipt of PCI.

Hematopoietic Cell Transplantation Trends and Outcomes in Canada: A Registry-Based Cohort Study.

Background: Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centres in Canada. In Canada, the quantity, indications, temporal trends, and outcomes of patients receiving HCT are not known. Methods: A retrospective cohort study of first transplants reported to the Cell Therapy Transplant Canada (CTTC) registry between 2000 and 2019. We determined overall survival (OS) and non-relapse mortality (NRM), categorizing the cohort into early (2000-2009) and later (2010-2019) eras to investigate temporal changes. Results: Of 18,046 transplants, 7571 were allogeneic and 10,475 were autologous. Comparing the two eras, allogeneic transplants increased in number by 22.3%, with greater use of matched unrelated donors in the later era. Autologous transplants increased by 10.9%. Temporal improvements in NRM were observed in children and adults. OS improved in pediatric patients and in adults receiving autologous HCT. In adults receiving allogeneic HCT, OS was stable despite the substantially older age of patients in the later era. Interpretation: HCT is an increasingly frequent procedure in Canada which has expanded to serve older adults. Noted improvements in NRM and OS reflect progress in patient and donor selection, preparation for transplant, and post-transplant supportive care. In allogeneic HCT, unrelated donors have become the most frequent donor source, highlighting the importance of the continued growth of volunteer donor registries. These results serve as a baseline measure for quality improvement and health services planning in Canada.

Cancer incidence during the COVID-19 pandemic by region of residence in Manitoba, Canada: A cancer registry-based interrupted time series study.

INTRODUCTION: Health care in Manitoba, Canada is divided into five regions, each with unique geographies, demographics, health care access, and health status. COVID-19-related restrictions and subsequent responses also differed by region. To understand the impact of the pandemic on cancer incidence in the context of these differences, we examined age-standardized cancer incidence rates by region over time before and after the COVID-19 pandemic. METHODS: We used a population-based quasi-experimental study design, population-based data, and an interrupted time series analysis to examine the rate of new cancer diagnoses before (January 2015 until December 2019) and after the start of COVID-19 and the interventions implemented to mitigate its impact (April 2020 until December 2021) by region. RESULTS: Overall cancer incidence differed by region and remained lower than expected in Winnipeg (4.6% deficit, 447 cases), Prairie Mountain (6.9% deficit, 125 cases), and Southern (13.0% deficit, 238 cases). Southern was the only region that had a significantly higher deficit in cases compared to Manitoba (ratio 0.92, 95% CI 0.86, 0.99). Breast and colorectal cancer incidence decreased at the start of the pandemic in all regions except Northern. Lung cancer incidence decreased in the Interlake-Eastern region and increased in the Northern region. Prostate cancer incidence increased in Interlake-Eastern. CONCLUSIONS: The impact of the COVID-19 pandemic on cancer incidence differed by region. The deficit in the number of cases was largest in the southern region and was highest for breast and prostate cancers. Cancer incidence did not significantly decrease in the most northern, remote region.

Real-world predictors of survival in patients with extensive-stage small-cell lung cancer in Manitoba, Canada: a retrospective cohort study.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is an incurable cancer with poor prognosis in which characteristics predictive of long-term survival are debated. The utility of agents such as immune checkpoint inhibitors highlights the importance of identifying key characteristics and treatment strategies that contribute to long-term survival and could help guide therapeutic decisions. Objective: This real-world analysis examines the characteristics, treatment patterns, and clinical outcomes of patients receiving chemotherapy without immunotherapy for ES-SCLC in Manitoba, Canada. Methods: A retrospective cohort study assessed patient characteristics, treatment, and survival duration (short: <6 months; medium: 6-24 months; long: >24 months) using the Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years with cytologically confirmed ES-SCLC diagnosed between January 1, 2004, and December 31, 2018, and received cytotoxic chemotherapy (CT). The one-, two-, and five-year probabilities of overall survival (OS) were assessed relative to patient, disease, and treatment characteristics using Kaplan-Meier methods and Cox proportional hazards models. Results: This analysis included 537 patients. Cisplatin was used in 56.1% of patients, 45.6% received thoracic radiotherapy (RT), and few received prophylactic cranial irradiation (PCI). In the overall cohort, one-, two- and five-year OS rates were 26%, 8%, and 3%, respectively. For patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, OS rates at one, two, and five years were 43%, 17%, and 10%, respectively, vs. 27%, 8%, and 2% for those with ECOG PS 1-2, and 16%, 3%, and 3% for those with ECOG PS 3-4. In long-term survivors, ECOG PS scores were lower and abnormal laboratory test results were less frequent. Overall, 74.4% of long-term survivors received thoracic RT and 53.5% received PCI. Known poor prognostic factors - including brain/liver metastases, high lactate dehydrogenase (LDH), abnormal sodium, and low hemoglobin levels - were less common but still seen in long-term survivors. Conclusion: Although rare, patients with ES-SCLC may experience long-term survival with CT ± thoracic RT ± PCI. Factors predicting long-term survival include traditional prognostic factors such as ECOG PS, LDH level, and receipt of thoracic RT or PCI. These findings support current treatment algorithms for ES-SCLC and provide baseline survival estimates to assess the real-world impact of adding immune checkpoint inhibitors in the future.

New Cancer Diagnoses Before and During the COVID-19 Pandemic.

Importance: Disruptions to health care during the COVID-19 pandemic may have led to missed cancer diagnoses. It is critical to evaluate the association between the COVID-19 pandemic and cancer incidence to address public and patient anxiety, inform recovery efforts, and identify strategies to reduce the system's vulnerability to future disruptions. Objective: To examine the association between the COVID-19 pandemic and cancer incidence in Manitoba, Canada. Design, Setting, and Participants: A population-based cross-sectional study design was conducted using data from the Manitoba Cancer Registry and an interrupted time-series analysis. All individuals diagnosed with cancer in Manitoba, Canada, from January 1, 2015, until December 31, 2021, were included. Individuals diagnosed with breast, colon, rectal, or lung cancer were grouped by age as follows: younger than 50 years, 50 to 74 years, and 75 years and older. Exposures: COVID-19 pandemic. Main Outcomes and Measures: Age-standardized cancer incidence rates and the estimated cumulative difference between the number of cases in the absence of COVID-19 and observed (fitted) number of cancer cases. Results: A total of 48 378 individuals were included. The median (IQR) age at diagnosis was 68 (59-77) years and 23 972 participants (49.6%) were female. In April 2020, there was a 23% decrease in overall cancer incidence. Cancer incidence decreased by 46% for breast, 35% for colon, 47% for rectal, 50% for head and neck, 65% for melanoma, and 33% for endocrine cancer diagnoses and increased by 12% for hematological cancer diagnoses and 8% for diagnoses of cancers with an unknown primary site. Lung cancer incidence remained stable until December 2020 when it decreased by 11%. Brain and central nervous system and urinary cancer diagnoses decreased consistently over time from April 2020 to December 2021 by 26% and 12%, respectively. No association was observed with gynecologic (1% increase), other digestive (1% decrease), or pancreatic (7% increase) cancer incidence. As of December 2021, Manitoba had an estimated deficit of 692 (5.3%) cancers. The largest estimated deficits were for breast (273 cases, 14.1% deficit), colon (133 cases, 12.2% deficit), and lung cancers (132 cases, 7.6% deficit). Conclusions and Relevance: In this study, the COVID-19 pandemic was associated with an initial decrease in cancer diagnosis incidence followed by a recovery for most cancer sites. However, the cumulative deficit for some cancers with high fatality needs immediate attention.

Clinical Outcomes in a Large Canadian Centralized CLL Clinic Based on Treatment and Molecular Factors over a Decade.

FISH cytogenetics, TP53 sequencing, and IGHV mutational status are increasingly used as prognostic and predictive markers in chronic lymphocytic leukemia (CLL), particularly as components of the CLL International Prognostic Index (CLL-IPI) and in directing therapy with novel agents. However, testing outside of clinical trials is not routinely available in Canada. As a centralized CLL clinic at CancerCare Manitoba, we are the first Canadian province to evaluate clinical outcomes and survivorship over a long period of time, incorporating the impact of molecular testing and the CLL-IPI score. We performed a retrospective analysis on 1315 patients diagnosed between 1960 and 2018, followed over a 12-year period, where 411 patients had molecular testing and 233 patients had a known CLL-IPI score at the time of treatment. Overall, 40.3% (n = 530) of patients received treatment, and 47.5% (n = 252) of patients received multiple lines of therapy. High-risk FISH and CLL-IPI (4-10) were associated with higher mortality (HR 2.03, p = 0.001; HR 2.64, p = 0.002), consistent with other studies. Over time, there was an increase in the use of targeted agents in treated patients. The use of Bruton's tyrosine kinase inhibitors improved survival in patients with unmutated IGHV and/or TP53 aberrations (HR 2.20, p = 0.001). The major cause of death in patients who received treatment was treatment/disease-related (32%, n = 42) and secondary malignancies (57%, n = 53) in those who were treatment-naïve. Our data demonstrate the importance of molecular testing in determining survivorship in CLL and underpinning the likely immune differences in outcomes for those treated for CLL.

Evaluation of the Impact of the Urgent Cancer Care Clinic on Emergency Department Visits, Primary Care Clinician Visits, and Hospitalizations in Winnipeg, Manitoba.

The urgent cancer care (UCC) clinic at CancerCare Manitoba (CCMB) opened in 2013 to provide care to individuals diagnosed with cancer and serious blood disorders experiencing complications from the underlying disorder or its treatment. This study examined the impact of the UCC clinic on other health care utilization in Winnipeg, Manitoba, Canada. An interrupted time series study design was used to compare the rates of emergency department (ED) visits, primary care clinician (PCC) visits, and hospitalizations from 1 January 2010 to 31 December 2015. Rates of ED visits were also stratified by ED location, severity, and cancer type. We found a 6% (95% CI 1.00-1.13, p-value = 0.0389) increase in PCC visits, a 7% (95% CI 0.99-1.15, p-value = 0.0737) increase in hospitalizations, a 4% (95% CI 0.86-1.08, p-value = 0.5053) decrease in the rate of ED visits, and a 3% (95% CI 0.92-1.17, p-value = 0.5778) increase in the rate of ED visits during the UCC clinic hours after the UCC clinic opened. The implementation of the UCC clinic had minimal impact on health care utilization. Future work should examine the impact of the UCC clinic on other aspects of healthcare utilization (e.g., number of tests ordered and time spent waiting in CCMB's main clinics) and patient quality of life and patient and health care provider experience.

Access to Hematopoietic Stem Cell Transplant in Canada for Patients with Acute Myeloid Leukemia.

Hematopoietic stem cell transplant is a complicated intervention only offered in specialized centers. Access to transplants may vary based on the location of primary residence, income levels, age, and reported race or ethnicity. Using data from the Canadian Institute of Health (CIH) Discharge abstract database (DAD), all non-Quebec Canadians under the age of 65 with a diagnosis of AML between 2004 and 2015 were included in this study. Descriptive statistics were produced for the variables of interest: time period, age, sex, rurality, transplant status, proportion of visible minorities, proportion identifying as indigenous, and proportion of low-income families. Transplant rates were compared and reported using univariable and multivariable analysis. In multivariable analysis, time period, province of residence, gender, and age were significantly associated with the receipt of an allogeneic hematopoietic stem cell transplant. However, differences in transplant rates observed in indigenous patients, low-income families, and visible minorities were not found to be statistically significant. In non-Quebec Canada, transplant rates vary significantly with province of residence, with the highest rates recorded in Alberta. Contrary to findings previously reported in studies exploring access to transplant in the United States, a low-income level was not associated with lower rates of transplants. This might suggest that Canada's universal health care insurance program is protective against socioeconomic barriers that impact access to health care services.

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.

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 (I2=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.

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

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.

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

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.

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.

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 × 109/L (IQR: 4.17-7.05 × 109/L). Median lymphocyte count was 1.63 × 109/L (IQR: 1.29-2.10 × 109/L), median monocyte count was 0.65 × 109/L (IQR: 0.54-0.83 × 109/L), median platelet count was 260.0 × 109/L (IQR: 211.0-302.0 × 109/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 (p = 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 (p = 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.

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

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.

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

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.

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

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.

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).

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.

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

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.