Treatment, healthcare utilization and outcomes in patients with glioblastoma in Ontario: a 10-year cohort study.

BACKGROUND AND PURPOSE: Glioblastoma (GBM) is the most common malignant primary brain tumour in adults. Receipt of adjuvant therapies has been shown to exert a significant positive effect on patient survival. Little is known however about how changes in standards of care and healthcare system factors, such as access, affect real-world outcomes. In this study, we provide an overview of GBM in Ontario and examine elements of care, including treatment patterns, healthcare utilization, and overall survival, from 2010 to 2019, to interpret the impact of the changes in practice standards and expansion of the care network within this period. METHODS: Using linked health-administrative databases from Ontario, Canada, we conducted a population-based cohort study to examine the clinical and biological characteristics, treatment, and healthcare utilization patterns of adult GBM patients diagnosed between 2010 and 2019. The primary outcomes were enrollment in adjuvant chemoradiation treatment and 1-, 2-, and 5-year survival. All analyses were performed using the Statistical Analysis Software (SAS). RESULTS: 5392 patients were diagnosed with GBM in Ontario from 2010 to 2019 (58% male, 42% female). The median age at diagnosis was 64. Receipt of adjuvant chemoradiation within one year of diagnosis increased from 51% in 2010 to 63% in 2019. 1-year, 2-year, and 5-year overall survival for all patients remained stable, ranging between 40 and 43%, 15-19%, and 5-7%, respectively. For patients above the age of 65, however, 1-year survival increased from 19% in 2010 to 26% in 2019. INTERPRETATION: Regionalization enabled access to treatment closer to home for many patients. Over the last decade, receipt of adjuvant chemoradiation increased among elderly patients, but the improvement in 1-year overall survival over time was accounted for by sociodemographic and clinical covariates. Our findings support the efforts for regionalization of services to improve accessibility. CONCLUSION: This Ontario-based study provides insight into the effect of practice evolution and healthcare utilization on the overall survival of patients with GBM. Overall survival for most patients with glioblastoma has remained stagnant over the past decade. Changes in treatment standards and expansion of access to treating centres have been associated with prolonged survival in elderly glioblastoma patients.

A cohort study of patients hospitalised with SARS-CoV-2 infection in Ontario: patient characteristics and outcomes by wave.

INTRODUCTION: Each wave of the COVID-19 pandemic exhibited a unique combination of epidemiological, social and structural characteristics. We explore similarities and differences in wave-over-wave characteristics of patients hospitalised with COVID-19. METHODS: This was a population-based study in Ontario province, Canada. Patients hospitalised with SARS-CoV-2 between 26 February 2020 and 31 March 2022 were included. An admission was considered related to SARS-CoV-2 infection if the provincial inpatient or outpatient hospital databases contained the ICD-10 diagnostic codes U071/U072 or the Ontario Laboratories Information System indicated a positive SARS-CoV-2 test result (PCR or rapid antigen testing) during the admission or up to two weeks prior. The primary outcome was 90-day mortality (modified Poisson regression). Secondary outcomes were use of critical care during the admission (logistic regression) and total length-of-stay (linear regression with heteroskedastic-consistent standard-error estimators). All models were adjusted for demographic characteristics, neighbourhood socioeconomic factors and indicators of illness severity. RESULTS: There were 73,201 SARS-CoV-2-related admissions: 6127 (8%) during wave 1 (wild-type), 14,371 (20%) during wave 2 (wild-type), 16,653 (23%) during wave 3 (Alpha), 5678 (8%) during wave 4 (Delta) and 30,372 (42%) during wave 5 (Omicron). SARS-CoV-2 was the most responsible diagnosis for 70% of admissions during waves 1-2 and 42% in wave 5. The proportion of admitted patients who were long-term care residents was 18% (n = 1111) during wave 1, decreasing to 10% (n = 1468) in wave 2 and <5% in subsequent waves. During waves 1-3, 46% of all admitted patients resided in a neighbourhood assigned to the highest ethnic diversity quintile, which declined to 27% during waves 4-5. Compared to wave 1, 90-day mortality was similar during wave 2 (adjusted risk ratio [aRR]: 1.00 [95% CI: 0.95-1.04]), but lower during wave 3 (aRR: 0.89 [0.85-0.94]), wave 4 (aRR: 0.85 [0.79-0.91]) and wave 5 (aRR: 0.83 [0.80-0.88]). Improvements in survival over waves were observed among elderly patients (p-interaction <0.0001). Critical care admission was significantly less likely during wave 5 than previous waves (adjusted odds ratio: 0.50 [0.47-0.54]). The length of stay was a median of 8.5 (3.6-23.8) days during wave 1 and 5.3 (2.2-12.6) during wave 5. After adjustment, the mean length of stay was on average -10.4 (-11.1 to -9.8) days, i.e. shorter, in wave 5 vs wave 1. CONCLUSION: Throughout the pandemic, sociodemographic characteristics of patients hospitalised with SARS-CoV-2 changed over time, particularly in terms of ethnic diversity, but still disproportionately affected patients from more marginalised regions. Improved survival and reduced use of critical care during the Omicron wave are reassuring.

Risk-based lung cancer screening performance in a universal healthcare setting.

Globally, lung cancer is the leading cause of cancer death. Previous trials demonstrated that low-dose computed tomography lung cancer screening of high-risk individuals can reduce lung cancer mortality by 20% or more. Lung cancer screening has been approved by major guidelines in the United States, and over 4,000 sites offer screening. Adoption of lung screening outside the United States has, until recently, been slow. Between June 2017 and May 2019, the Ontario Lung Cancer Screening Pilot successfully recruited 7,768 individuals at high risk identified by using the PLCOm2012noRace lung cancer risk prediction model. In total, 4,451 participants were successfully screened, retained and provided with high-quality follow-up, including appropriate treatment. In the Ontario Lung Cancer Screening Pilot, the lung cancer detection rate and the proportion of early-stage cancers were 2.4% and 79.2%, respectively; serious harms were infrequent; and sensitivity to detect lung cancers was 95.3% or more. With abnormal scans defined as ones leading to diagnostic investigation, specificity was 95.5% (positive predictive value, 35.1%), and adherence to annual recall and early surveillance scans and clinical investigations were high (>85%). The Ontario Lung Cancer Screening Pilot provides insights into how a risk-based organized lung screening program can be implemented in a large, diverse, populous geographic area within a universal healthcare system.

The impact of the COVID-19 pandemic on longitudinal trends of surgical mortality and inpatient quality of care in Ontario, Canada.

AIMS: Previous studies have shown the COVID-19 pandemic was associated with reductions in volume across a spectrum of non-SARS-CoV-2 hospitalizations. In the present study, we examine the impact of the pandemic on patient safety and quality of care. DESIGN: This is a retrospective population-based study of discharge abstracts. METHODS: We applied a set of nationally validated indicators for measuring the quality of inpatient care to hospitalizations in Ontario, Canada between January 2010 and December 2022. We measured 90-day mortality after selected types of higher risk admissions (such as cancer surgery and cardiovascular emergency) and the rate of patient harm events (such as delirium, pressure injuries and hospital-acquired infections) occurring during the hospital stay. RESULTS: A total 13,876,377 hospitalization episodes were captured. Compared with the pre-pandemic period, and independent of SARS-CoV-2 infection, the pandemic period was associated with higher rates of mortality after bladder cancer resection (adjusted risk ratio [aRR] 1.20 (1.07-1.34)) and open repair for abdominal aortic aneurysm (aRR 1.45 (1.06-1.99)). The pandemic was also associated with higher rates of delirium (adjusted odds ratio [aOR] 1.04 (1.02-1.06)), venous thromboembolism (aOR 1.10 (1.06-1.13)), pressure injuries (aOR 1.28 (1.24-1.33)), aspiration pneumonitis (aOR 1.15 (1.12-1.18)), urinary tract infections (aOR 1.02 (1.01-1.04)), Clostridiodes difficile infection (aOR 1.05 (1.02-1.09)), pneumothorax (aOR 1.08 (1.03-1.13)), and use of restraints (aOR 1.12 (1.10-1.14)), but was associated with lower rates of viral gastroenteritis (aOR 0.22 (0.18-0.28)). During the pandemic, SARS-CoV-2-positive admissions were associated with a higher likelihood of various harm events. CONCLUSION: The COVID-19 pandemic was associated with higher rates of patient harm for a wide range of non-SARS-CoV-2 inpatient populations. IMPACT: Understanding which quality measures are improving or deteriorating can help health systems prioritize quality improvement initiatives. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Choreographed expansion of services results in decreased patient burden without compromise of outcomes: An assessment of the Ontario experience.

Background: Neuro-oncology care in Ontario, Canada has been historically centralized, at times requiring significant travel on the part of patients. Toward observing the goal of patient-centered care and reducing patient burden, 2 additional regional cancer centres (RCC) capable of neuro-oncology care delivery were introduced in 2016. This study evaluates the impact of increased regionalization of neuro-oncology services, from 11 to 13 oncology centers, on healthcare utilization and travel burden for glioblastoma (GBM) patients in Ontario. Methods: We present a cohort of GBM patients diagnosed between 2010 and 2019. Incidence of GBM and treatment modalities were identified using provincial health administrative databases. A geographic information system and spatial analysis were used to estimate travel time from patient residences to neuro-oncology RCCs. Results: Among the 5242 GBM patients, 79% received radiation as part of treatment. Median travel time to the closest RCC was higher for patients who did not receive radiation as part of treatment than for patients who did (P = .03). After 2016, the volume of patients receiving radiation at their local RCC increased from 62% to 69% and the median travel time to treatment RCCs decreased (P = .0072). The 2 new RCCs treated 35% and 41% of patients within their respective catchment areas. Receipt of standard of care, surgery, and chemoradiation (CRT), increased by 11%. Conclusions: Regionalization resulted in changes in the healthcare utilization patterns in Ontario consistent with decreased patient travel burden for patients with GBM. Focused regionalization did not come at the cost of decreased quality of care, as determined by the delivery of a standard of care.

SARS-CoV-2 infection among physicians over time in Ontario, Canada: a population-based retrospective cohort study.

AIM: To assess this risk of SARS-CoV-2 infection among Ontario physicians by specialty and in comparison with non-physician controls during the COVID-19 pandemic. METHODS: In this retrospective cohort study, the primary outcome was incident SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR). Secondary outcomes were hospitalization, use of critical care, and mortality. RESULTS: From March 1, 2020 to December 31, 2022, 6172/30 617 (20%) active Ontario physicians tested positive for SARS-CoV-2. Infection was less likely if physicians were older (OR 0.78 [0.76-0.81] per 10 years), rural residents (OR 0.70 [0.59-0.83]), and lived in more marginalized neighborhoods (OR 0.74 [0.62-0.89]), but more likely if they were female (OR 1.14 [1.07-1.22]), worked in long-term care settings (OR 1.16 [1.02-1.32]), had higher patient volumes (OR 2.05 [1.82-2.30] for highest vs lowest), and were pediatricians (OR 1.25 [1.09-1.44]). Compared with community-matched controls (n=29 763), physicians had a higher risk of infection during the first two waves of the pandemic (OR 1.38 [1.20-1.59]) but by wave 3 the risk was no longer significantly different (OR 0.93 [0.83-1.05]). Physicians were less likely to be hospitalized within 14 days of their first positive PCR test than non-physicians (P<0.0001), but there was no difference in the use of critical care (P=0.48) or mortality (P=0.15). CONCLUSION: Physicians had higher rates of infection than community-matched controls during the first two waves of the pandemic in Ontario, but not from wave 3 onward. Physicians practicing in long-term care facilities and pediatricians were more likely to test positive for SARS-CoV-2 than other physicians.

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).

Scheduled and urgent inguinal hernia repair in Ontario, Canada between 2010 and 2022: Population-based cross sectional analysis of trends and outcomes.

INTRODUCTION: We examine trends in inguinal hernia repairs with respect to the COVID-19 pandemic and secular trends in Ontario, Canada. METHODS: This was a retrospective cohort study. Hernia repairs performed January 1, 2010-December 31, 2022 were captured from health administrative inpatient and outpatient databases. Patients managed in three clinical settings were examined: public hospital in-patient, semi-private hospital in-patient (Shouldice Hospital), and public hospital out-patient. We examined the effect of the COVID-19 pandemic on surgical volumes, clinical setting, patient characteristics by setting, time from diagnosis until surgery, hospital length-of-stay, and patient outcomes (90-day readmissions, 1-year reoperations). We used multivariable logistic regression to examine whether patient outcomes were comparable between the COVID-19 period and the pre-pandemic period, adjusted sociodemographic and clinical factors. Shouldice Hospital is the only semi-private hospital in Ontario specializing in hernia repair (patients pay for the mandated admission, but not for the procedure). RESULTS: During the pandemic (March 2020-December 2022), there were 8,162 fewer (15%) scheduled inguinal hernia repairs than expected, but the age-sex standardized rate of urgent repairs remained unchanged. Shouldice Hospital performed more surgeries in the COVID-19 era than pre-pandemic and had a shorter average LOS by 24 hours, despite treating more patients with older age, higher ASA score [adjusted odds ratio (aOR) 2.13 (1.93-2.35) III vs I-II] and greater comorbidity [aOR 1.36 (1.08-1.70) for 2 vs none] than pre-pandemic. Patients treated in the COVID-19 era experienced a longer time until surgery, being the longest in 2022 (median 133 days). Ninety-day readmissions and 1-year reoperations were lower in the COVID-19 era and lower for patients receiving surgery at Shouldice Hospital. CONCLUSION: During the COVID-19 pandemic, there were 8,162 fewer scheduled hernia repairs than expected, longer wait-times until surgery, shorter length-of-stay, and more patients with comorbidities, but outcomes were not worse compared with the pre-pandemic period.

The successful and safe conversion of joint arthroplasty to same-day surgery: A necessity after the COVID-19 pandemic.

INTRODUCTION: A key strategy to address system pressures on hip and knee arthroplasty through the COVID-19 pandemic has been to shift procedures to the outpatient setting. METHODS: This was a retrospective cohort and case-control study. Using the Discharge Abstract Database and the National Ambulatory Care Reporting System databases, we estimated the use of outpatient hip and knee arthroplasty in Ontario, Canada. After propensity-score matching, we estimated rates of 90-day readmission, 90-day emergency department (ED) visit, 1-year mortality, and 1-year infection or revision. RESULTS: 204,066 elective hip and 341,678 elective knee arthroplasties were performed from 2010-2022. Annual volumes of hip and knee arthroplasties increased steadily until 2020. Following the start of the COVID-19 pandemic (March 1, 2020) through December 31, 2022 there were 7,561 (95% CI 5,435 to 9,688) fewer hip and 20,777 (95% CI 17,382 to 24,172) fewer knee replacements performed than expected. Outpatient arthroplasties increased as a share of all surgeries from 1% pre-pandemic to 39% (hip) and 36% (knee) by 2022. Among inpatient arthroplasties, the tendency to discharge to home did not change since the start of the pandemic. During the COVID-19 era, patients receiving arthroplasty in the outpatient setting had a similar or lower risk of readmission than matched patients receiving inpatient arthroplasty [hip: RR 0.65 (0.56-0.76); knee: RR 0.86 (0.76-0.97)]; ED visits [hip: RR 0.78 (0.73-0.83); knee: RR 0.92 (0.88-0.96)]; and mortality, infection, or revision [hip: RR 0.65 (0.45-0.93); knee: 0.90 (0.64-1.26)]. CONCLUSION: Following the start of the COVID-19 pandemic in Ontario, the volume of outpatient hip and knee arthroplasties performed increased despite a reduction in overall arthroplasty volumes. This shift in surgical volumes from the inpatient to outpatient setting coincided with pressures on hospitals to retain inpatient bed capacity. Patients receiving arthroplasty in the outpatient setting had relatively similar outcomes to those receiving inpatient surgery after matching on known sociodemographic and clinical characteristics.

Changes in hospitalizations and emergency department respiratory viral diagnosis trends before and during the COVID-19 pandemic in Ontario, Canada.

INTRODUCTION: Population-level surveillance systems have demonstrated reduced transmission of non-SARS-CoV-2 respiratory viruses during the COVID-19 pandemic. In this study, we examined whether this reduction translated to reduced hospital admissions and emergency department (ED) visits associated with influenza, respiratory syncytial virus (RSV), human metapneumovirus, human parainfluenza virus, adenovirus, rhinovirus/enterovirus, and common cold coronavirus in Ontario. METHODS: Hospital admissions were identified from the Discharge Abstract Database and exclude elective surgical admissions and non-emergency medical admissions (January 2017-March 2022). Emergency department (ED) visits were identified from the National Ambulatory Care Reporting System. International Classification of Diseases (ICD-10) codes were used to classify hospital visits by virus type (January 2017-May 2022). RESULTS: At the onset of the COVID-19 pandemic, hospitalizations for all viruses were reduced to near-trough levels. Hospitalizations and ED visits for influenza (9,127/year and 23,061/year, respectively) were nearly absent throughout the pandemic (two influenza seasons; April 2020-March 2022). Hospitalizations and ED visits for RSV (3,765/year and 736/year, respectively) were absent for the first RSV season during the pandemic, but returned for the 2021/2022 season. This resurgence of hospitalizations for RSV occurred earlier in the season than expected, was more likely among younger infants (age ≤6 months), more likely among older children (aged 6.1-24 months), and less likely to comprise of patients residing in higher areas of ethnic diversity (p<0.0001). CONCLUSION: During the COVID-19 pandemic, there was a reduced the burden of other respiratory infections on patients and hospitals. The epidemiology of respiratory viruses in the 2022/23 season remains to be seen.

The effect of the COVID-19 pandemic on hospital admissions and outpatient visits in Ontario, Canada.

INTRODUCTION: The wave-over-wave effect of the COVID-19 pandemic on hospital visits for non-COVID-19-related diagnoses in Ontario, Canada remains unknown. METHODS: We compared the rates of acute care hospitalizations (Discharge Abstract Database), emergency department (ED) visits, and day surgery visits (National Ambulatory Care Reporting System) during the first five "waves" of Ontario's COVID-19 pandemic with prepandemic rates (since January 1, 2017) across a spectrum of diagnostic classifications. RESULTS: Patients admitted in the COVID-19 era were less likely to reside in long-term-care facilities (OR 0.68 [0.67-0.69]), more likely to reside in supportive housing (OR 1.66 [1.63-1.68]), arrive by ambulance (OR 1.20 [1.20-1.21]) or be admitted urgently (OR 1.10 [1.09-1.11]). Since the start of the COVID-19 pandemic (February 26, 2020), there were an estimated 124,987 fewer emergency admissions than expected based on prepandemic seasonal trends, representing reductions from baseline of 14% during Wave 1, 10.1% in Wave 2, 4.6% in Wave 3, 2.4% in Wave 4, and 10% in Wave 5. There were 27,616 fewer medical admissions to acute care, 82,193 fewer surgical admissions, 2,018,816 fewer ED visits, and 667,919 fewer day-surgery visits than expected. Volumes declined below expected rates for most diagnosis groups, with emergency admissions and ED visits associated with respiratory disorders exhibiting the greatest reduction; mental health and addictions was a notable exception, where admissions to acute care following Wave 2 increased above prepandemic levels. CONCLUSIONS: Hospital visits across all diagnostic categories and visit types were reduced at the onset of the COVID-19 pandemic in Ontario, followed by varying degrees of recovery.

Association of Brain Metastases With Survival in Patients With Limited or Stable Extracranial Disease: A Systematic Review and Meta-analysis.

Importance: Intracranial metastatic disease (IMD) is a severe complication of cancer with profound prognostic implications. Patients with IMD in the setting of limited or stable extracranial disease (IMD-SE) may represent a unique and understudied subset of patients with IMD with superior prognosis. Objective: To evaluate overall survival (OS), progression-free survival (PFS), and intracranial PFS (iPFS) in patients with IMD-SE secondary to any primary cancer. Data Sources: Records were identified from MEDLINE, EMBASE, CENTRAL, and gray literature sources from inception to June 21, 2021. Study Selection: Studies in English reporting OS, PFS, or iPFS in patients with IMD-SE (defined as IMD and ≤2 extracranial metastatic sites) and no prior second-line chemotherapy or brain-directed therapy were selected. Data Extraction and Synthesis: Author, year of publication, type of study, type of primary cancer, and outcome measures were extracted. Random-effects meta-analyses were performed to estimate effect sizes, and subgroup meta-analysis and metaregression were conducted to measure between-study differences in February 2022. Main Outcomes and Measures: The primary end point was OS described as hazard ratios (HRs) and medians for comparative and single-group studies, respectively. Secondary end points were PFS and iPFS. Results: Overall, 68 studies (5325 patients) were included. IMD-SE was associated with longer OS (HR, 0.52; 95% CI, 0.39-0.70) and iPFS (HR, 0.63; 95% CI, 0.52-0.76) compared with IMD in the setting of progressive extracranial disease. The weighted median OS estimate for patients with IMD-SE was 17.9 months (95% CI, 16.4-22.0 months), and for patients with IMD-PE it was 8.0 months (95% CI, 7.2-12.8 months). Pooled median OS for all patients with IMD-SE was 20.9 months (95% CI, 16.35-25.98 months); for the subgroup with breast cancer it was 20.2 months (95% CI, 10.43-38.20 months), and for non-small cell lung cancer it was 27.5 months (95% CI, 18.27-49.66 months). Between-study heterogeneity for OS and iPFS were moderate (I2 = 56.5%) and low (I2 = 0%), respectively. Conclusions and Relevance: In this systematic review and meta-analysis of patients with IMD-SE, limited systemic disease was associated with improved OS and iPFS. Future prospective trials should aim to collect granular information on the extent of extracranial disease to identify drivers of mortality and optimal treatment strategies in patients with brain metastases.

Estimating the incidence of breast cancer recurrence using administrative data.

BACKGROUND: Breast cancer is the most common cancer among women, but most cancer registries do not capture recurrences. We estimated the incidence of local, regional, and distant recurrences using administrative data. METHODS: Patients diagnosed with stage I-III primary breast cancer in Ontario, Canada from 2013 to 2017 were included. Patients were followed until 31/Dec/2021, death, or a new primary cancer diagnosis. We used hospital administrative data (diagnostic and intervention codes) to identify local recurrence, regional recurrence, and distant metastasis after primary diagnosis. We used logistic regression to explore factors associated with developing a distant metastasis. RESULTS: With a median follow-up 67 months, 5,431/45,857 (11.8%) of patients developed a distant metastasis a median 23 (9, 42) months after diagnosis of the primary tumor. 1086 (2.4%) and 1069 (2.3%) patients developed an isolated regional or a local recurrence, respectively. Patients with distant metastatic disease had a median overall survival of 15.4 months (95% CI 14.4-16.4 months) from the time recurrence/metastasis was identified. In contrast, the median survival for all other patients was not reached. Patients were more likely to develop a distant metastasis if they had more advanced stage, greater comorbidity, and presented with symptoms (p < 0.0001). Trastuzumab halved the risk of recurrence [OR 0.53 (0.45-0.63), p < 0.0001]. CONCLUSION: Distant metastasis is not a rare outcome for patients diagnosed with breast cancer, translating to an annual incidence of 2132 new cases (17.8% of all breast cancer diagnoses). Overall survival remains high for patients with locoregional recurrences, but was poor following a diagnosis of a distant metastasis.

Erythroblastic oncogene B-2 status and intracranial metastatic disease in patients with gastrointestinal cancer: a systematic review.

PURPOSE: The incidence of intracranial metastatic disease (IMD) in patients with gastrointestinal (GI) cancers is rising. Expression of the erythroblastic oncogene B-2 (ERBB2) is associated with an in increased risk of IMD in patients with breast cancer. The implications of ERBB2 expression for IMD risk in patients with GI cancers is less clear. The objective of this systematic review was to determine the incidence of IMD and OS in patients with ERBB2+ gastrointestinal cancers. METHODS: A literature search of MEDLINE, EMBASE, CENTRAL, and grey literature sources was conducted from date of database inception to July 2021. Included studies reported outcomes on patients with IMD secondary to ERBB2 GI cancers. RESULTS: Fourteen cohort studies met inclusion criteria, of which thirteen were retrospective. Eleven studies reported on gastric, esophageal, or gastroesophageal junction cancers. Three studies directly compared incidence of IMD based on ERBB2 status and among these, ERBB2+ patients had a higher incidence of IMD. One study indicated that ERBB2+ patients had significantly longer OS from the times of primary cancer (P = .015) and IMD diagnosis (P = .01), compared with patients with ERBB2- disease. CONCLUSIONS: In this systematic review, patients with ERBB2+ GI cancer were more likely to develop IMD. Future study is required on the prognostic and predictive value of ERBB2 status in patients with GI cancers.

The effect of age on the opportunity to receive cancer treatment.

INTRODUCTION: Older adults with cancer may not receive the same opportunities for treatment as younger patients. In this retrospective population-based cohort study, we explored whether age was an independent predictor of receiving specialist consultation and treatment. METHODS: Patients age 45-99 were identified from the Ontario Cancer Registry having a primary solid tumor diagnosed between 01/Jan/2010 and 31/Dec/2019. We used logistic regression adjusted sociodemographic and clinical characteristics to compare the likelihood of consultation or receipt of treatment using linear splines at critical ages of 65, 80, and 90 years. RESULTS: A total 168,232 (42%), 165,205 (41%), 57,360 (14%), and 7810 (2%) patients were diagnosed age 45-64, 65-79, 80-89, and 90-99, respectively. The likelihood of surgical consultation decreased as patients reached 65 years [adjusted odds ratio (aOR) 0.86 (0.84-0.89)], which decreased further among octogenarians [aOR 0.63 (0.59-0.67)]. Similar results were observed for consultation with a medical oncologist and radiation oncologist. Receipt of surgery also decreased with age. Three-month post-operative mortality was higher among older patients [aRR 1.38 (1.26-1.50) per 10 years, p < 0.0001], an effect that remained similar as patients reached age 65 + years of age (p = 0.09 for change). For stage I patients, 3-month post-operative survival was high across all age groups, ranging from 99.8% in 45-64 year-olds, 99.4% in 65-79 year-olds, and 98.1% among octogenarians and nonagenarians (lung, colorectal, breast, cervical cancer patients). CONCLUSION: Older patients were less likely to have specialist consultations. More comprehensive data collection on clinical factors and referral patterns is needed to improve care for elderly cancer patients.

Comparison of Use of Neoadjuvant Systemic Treatment for Breast Cancer and Short-term Outcomes Before vs During the COVID-19 Era in Ontario, Canada.

Importance: In response to an increase in COVID-19 infection rates in Ontario, several systemic treatment (ST) regimens delivered in the adjuvant setting for breast cancer were temporarily permitted for neoadjuvant-intent to defer nonurgent breast cancer surgical procedures. Objective: To examine the use and compare short-term outcomes of neoadjuvant-intent vs adjuvant ST in the COVID-19 era compared with the pre-COVID-19 era. Design, Setting, and Participants: This was a retrospective population-based cohort study in Ontario, Canada. Patients with cancer starting selected ST regimens in the COVID-19 era (March 11, 2020, to September 30, 2020) were compared to those in the pre-COVID-19 era (March 11, 2019, to March 10, 2020). Patients were diagnosed with breast cancer within 6 months of starting systemic therapy. Main Outcomes and Measures: Estimates were calculated for the use of neoadjuvant vs adjuvant ST, the likelihood of receiving a surgical procedure, the rate of emergency department visits, hospital admissions, COVID-19 infections, and all-cause mortality between treatment groups over time. Results: Among a total of 10 920 patients included, 7990 (73.2%) started treatment in the pre-COVID-19 era and 7344 (67.3%) received adjuvant ST; the mean (SD) age was 61.6 (13.1) years. Neoadjuvant-intent ST was more common in the COVID-19 era (1404 of 2930 patients [47.9%]) than the pre-COVID-19 era (2172 of 7990 patients [27.2%]), with an odds ratio of 2.46 (95% CI, 2.26-2.69; P < .001). This trend was consistent across a range of ST regimens, but differed according to patient age and geography. The likelihood of receiving surgery following neoadjuvant-intent chemotherapy was similar in the COVID-19 era compared with the pre-COVID-19 era (log-rank P = .06). However, patients with breast cancer receiving neoadjuvant-intent hormonal therapy were significantly more likely to receive surgery in the COVID-19 era (log-rank P < .001). After adjustment, there were no significant changes in the rate of emergency department visits over time between patients receiving neoadjuvant ST, adjuvant ST, or ST only during the ST treatment period or postoperative period. Hospital admissions decreased in the COVID-19 era for patients who received neoadjuvant ST compared with adjuvant ST or ST alone (P for interaction = .01 for both) in either setting. Conclusions and Relevance: In this cohort study, patients were more likely to start neoadjuvant ST in the COVID-19 era, which varied across the province and by indication. There was limited evidence to suggest any substantial impact on short-term outcomes.

Inverse optimization on hierarchical networks: an application to breast cancer clinical pathways.

Clinical pathways are standardized processes that outline the steps required for managing a specific disease. However, patient pathways often deviate from clinical pathways. Measuring the concordance of patient pathways to clinical pathways is important for health system monitoring and informing quality improvement initiatives. In this paper, we develop an inverse optimization-based approach to measuring pathway concordance in breast cancer, a complex disease. We capture this complexity in a hierarchical network that models the patient's journey through the health system. A novel inverse shortest path model is formulated and solved on this hierarchical network to estimate arc costs, which are used to form a concordance metric to measure the distance between patient pathways and shortest paths (i.e., clinical pathways). Using real breast cancer patient data from Ontario, Canada, we demonstrate that our concordance metric has a statistically significant association with survival for all breast cancer patient subgroups. We also use it to quantify the extent of patient pathway discordances across all subgroups, finding that patients undertaking additional clinical activities constitute the primary driver of discordance in the population.

Real-World Cost-Effectiveness of First-Line Gemcitabine Plus Nab-Paclitaxel vs FOLFIRINOX in Patients With Advanced Pancreatic Cancer.

BACKGROUND: There are no randomized control trials (RCTs) comparing gemcitabine and nab-paclitaxel (Gem-Nab) and fluorouracil, folinic acid, irinotecan, oxaliplatin (FOLFIRINOX) for advanced pancreatic cancer (APC). Although it is well known that RCT-based efficacy often does not translate to real-world effectiveness, there is limited literature investigating comparative cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC. We aimed to examine the real-world cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC in Ontario, Canada. METHODS: This study compared patients treated with first-line Gem-Nab or FOLFIRINOX for APC in Ontario from April 2015 to March 2019. Patients were linked to administrative databases. Using propensity scores and a stabilizing weights method, an inverse probability of treatment weighted cohort was developed. Mean survival and total costs were calculated over a 5-year time horizon, adjusted for censoring, and discounted at 1.5%. Incremental cost-effectiveness ratio and net monetary benefit were computed to estimate cost-effectiveness from the public health-care payer's perspective. Sensitivity analysis was conducted using the propensity score matching method. RESULTS: A total of 1988 patients were identified (Gem-Nab: n = 928; FOLFIRINOX: n = 1060). Mean survival was lower for patients in the Gem-Nab than the FOLFIRINOX group (0.98 vs 1.26 life-years; incremental effectiveness = -0.28 life-years [95% confidence interval = -0.47 to -0.13]). Patients in the Gem-Nab group incurred greater mean 5-year total costs (Gem-Nab: $103 884; FOLFIRINOX: $101 518). Key cost contributors include ambulatory cancer care, acute inpatient hospitalization, and systemic therapy drug acquisition. Gem-Nab was dominated by FOLFIRINOX, as it was less effective and more costly. Results from the sensitivity analysis were similar. CONCLUSIONS: Gem-Nab is likely more costly and less effective than FOLFIRINOX and therefore not considered cost-effective at commonly accepted willingness-to-pay thresholds.

Delivery of Cancer Care in Ontario, Canada, During the First Year of the COVID-19 Pandemic.

Importance: The COVID-19 pandemic has impacted cancer systems worldwide. Quantifying the changes is critical to informing the delivery of care while the pandemic continues, as well as for system recovery and future pandemic planning. Objective: To quantify change in the delivery of cancer services across the continuum of care during the COVID-19 pandemic. Design, Setting, and Participants: This population-based cohort study assessed cancer screening, imaging, diagnostic, treatment, and psychosocial oncological care services delivered in pediatric and adult populations in Ontario, Canada (population 14.7 million), from April 1, 2019, to March 1, 2021. Data were analyzed from May 1 to July 31, 2021. Exposures: COVID-19 pandemic. Main Outcomes and Measures: Cancer service volumes from the first year of the COVID-19 pandemic, defined as April 1, 2020, to March 31, 2021, were compared with volumes during a prepandemic period of April 1, 2019, to March 31, 2020. Results: During the first year of the pandemic, there were a total of 4 476 693 cancer care services, compared with 5 644 105 services in the year prior, a difference of 20.7% fewer services of cancer care, representing a potential backlog of 1 167 412 cancer services. While there were less pronounced changes in systemic treatments, emergency and urgent imaging examinations (eg, 1.9% more parenteral systemic treatments) and surgical procedures (eg, 65% more urgent surgical procedures), major reductions were observed for most services beginning in March 2020. Compared with the year prior, during the first pandemic year, cancer screenings were reduced by 42.4% (-1 016 181 screening tests), cancer treatment surgical procedures by 14.1% (-8020 procedures), and radiation treatment visits by 21.0% (-141 629 visits). Biopsies to confirm cancer decreased by up to 41.2% and surgical cancer resections by up to 27.8% during the first pandemic wave. New consultation volumes also decreased, such as for systemic treatment (-8.2%) and radiation treatment (-9.3%). The use of virtual cancer care increased for systemic treatment and radiation treatment and psychosocial oncological care visits, increasing from 0% to 20% of total new or follow-up visits prior to the pandemic up to 78% of total visits in the first pandemic year. Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, large reductions in cancer service volumes were observed. While most services recovered to prepandemic levels at the end of the first pandemic year, a substantial care deficit likely accrued. The anticipated downstream morbidity and mortality associated with this deficit underscore the urgent need to address the backlog and recover cancer care and warrant further study.