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\"In proving the existence of stem cells, Ernest Armstrong McCulloch and James Edgar Till formed the most important partnership in Canadian medical research since Frederick Banting and Charles Best, the discoverers of insulin. Together, Till and McCulloch instructed, influenced, and inspired successive generations of researchers who have used their findings to make huge advances against disease. Thousands of people who would have died from leukemia and immunological disorders now owe their lives to therapies supported by their seminal discoveries\"-- Dust jacket flap.

To achieve this goal the institute divided its operation into four strands: two of the strands were the research areas - the study of advanced radiation therapy and biology, which worked separatively but cooperatively; a third was patient care; and the fourth element was leadership, provided by the clinical chiefs, the heads of the research divisions, and the administration, in particular the institute's first administrator, John Law. Together these strands helped create a philosophy that made the Ontario Cancer Institute unique and provided the basis for its national and international success. Essential to these successes was a new graduate department, Medical Biophysics, based in the University of Toronto School of Graduate Studies. This department, which provided an innovative, research-based doctoral and masters program, meant that the OCI could accurately be described as a centre for cancer treatment, research, and education. McCulloch describes how the first quantitative assay for stem cells played a major role in bringing OCI research to the international stage as well as influencing other science and much of the clinical thinking in the Institute. Other major advances that brought international recognition have been the identification of the mechanisms that allow cancer cells to resist death from the effects of a variety of different tumours and the isolation of the gene that encodes the T cell receptor, a critical part of the immune apparatus for dealing with foreign cells and viruses. McCulloch also details how lack of space to meet growing demands was a continuing source of frustration and disagreement, and how sometimes serious interpersonal problems hindered the forward thrust of development. Describing these events as well as institute's successes, he provides an insight into the history of Canada's premier cancer research centre.

Immune checkpoint inhibitor (ICI) therapy for patients undergoing cancer treatment carries a risk of severe immune-related adverse events (IRAEs). Questions remain about whether seasonal influenza vaccination might increase the risk of developing IRAEs among these patients given that vaccines are immunomodulatory. Previous vaccine safety studies on patients with cancer prescribed ICI therapy have demonstrated conflicting results. Using health administrative data from Ontario, Canada among adults diagnosed with cancer who had been prescribed ICI therapy and who had received an influenza vaccine from 2012 to 2019, we conducted a self-controlled case series study. The pre-vaccination control period started 42-days post-ICI initiation until 14-days prior to vaccination, the risk period was 1–42 days post-vaccination, and the post-vaccination control period was after the risk period until ICI discontinuation or a maximum period of two years. Emergency department (ED) visit(s) and/or hospitalization for any cause after ICI initiation was used to identify severe IRAEs. We fitted a fixed-effects Poisson regression model accounting for seasonality and calendar time to estimate relative incidence of IRAEs between risk and control periods. We identified 1133 records of cancer patients who received influenza vaccination while prescribed ICI therapy. Most were aged ≥ 66 years (73 %), were male (63 %), had lung cancer (54 %), and had received ICI therapy with a programmed cell death protein 1(PD-1) inhibitor (91 %). A quarter (26 %) experienced an ED visit and/or hospitalization during the observation period. Rates of ED visits and/or hospitalizations in the risk vs. control periods were similar, with an incidence rate ratio of 1.04 (95 % CI: 0.75–1.45). Subgroup and sensitivity analyses yielded similar results. Seasonal influenza vaccination was not associated with an increased incidence of ED visit or hospitalization among adults with cancer treated with ICI therapy and our results support further evidence of vaccine safety.

ObjectiveTo describe the clinical, pathological and genomic characteristics of pancreatic cancer with DNA mismatch repair deficiency (MMRD) and proficiency (MMRP).DesignWe identified patients with MMRD and MMRP pancreatic cancer in a clinical cohort (N=1213, 519 with genetic testing, 53 with immunohistochemistry (IHC)) and a genomic cohort (N=288 with whole-genome sequencing (WGS)).Results12 out of 1213 (1.0%) in the clinical cohort were MMRD by IHC or WGS. Of the 14 patients with Lynch syndrome, 3 (21.4%) had an MMRP pancreatic cancer by IHC, and 4 (28.6%) were excluded because tissue was unavailable for testing. MMRD cancers had longer overall survival after surgery (weighted HR after coarsened exact matching 0.11, 95% CI 0.02 to 0.78, p=0.001). One patient with an unresectable MMRD cancer has an ongoing partial response 3 years after starting treatment with PD-L1/CTLA-4 inhibition. This tumour showed none of the classical histopathological features of MMRD. 9 out of 288 (3.1%) tumours with WGS were MMRD. Despite markedly higher tumour mutational burden and neoantigen loads, MMRD cancers were significantly less likely to have mutations in usual pancreatic cancer driver genes like KRAS and SMAD4, but more likely to have mutations in genes that drive cancers with microsatellite instability like ACV2RA and JAK1. MMRD tumours were significantly more likely to have a basal-like transcriptional programme and elevated transcriptional markers of immunogenicity.ConclusionsMMRD pancreatic cancers have distinct clinical, pathological and genomic profiles. Patients with MMRD pancreatic cancer should be considered for basket trials targeting enhanced immunogenicity or the unique genomic drivers in these malignancies.

Purpose There has been an alarming increase in colorectal cancer (CRC) incidence among young adults aged < 50 years, and factors driving this upward trend are unknown. This study investigated associations between various medical, lifestyle, and dietary factors and risk of early-onset CRC (EO-CRC). Methods A population-based case–control study was conducted in Ontario, Canada during 2018–2019. EO-CRC cases aged 20–49 years ( n  = 175) were identified from the Ontario Cancer Registry; sex- and age group-matched controls ( n  = 253) were recruited through random digit dialing. Data on potential a priori risk factors were collected using a web-based self-reported questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. Results Family history of CRC in a first- or second-degree relative (OR 2.37; 95% CI 1.47–3.84), longer sedentary time (≥ 10 vs. < 5 h/day, OR 1.93; 95% CI 1.02–3.65), greater consumption of sugary drinks (≥ 7 vs. < 1 drinks/week, OR 2.99; 95% CI 1.57–5.68), and a more Westernized dietary pattern (quartile 4 vs. 1, OR 1.92; 95% CI 1.01–3.66) were each associated with an increased risk of EO-CRC. Conversely, calcium supplement use (OR 0.53; 95% CI 0.31–0.92), history of allergy or asthma (OR 0.62; 95% CI 0.39–0.98), and greater parity in females (≥ 3 vs. nulliparity, OR 0.29; 95% CI 0.11–0.76) were each associated with a reduced risk. Conclusion Modifiable factors, particularly sedentary behavior and unhealthy diet including sugary drink consumption, may be associated with EO-CRC risk. Our findings, if replicated, may help inform prevention strategies targeted at younger persons.

ObjectiveFirefighters and police often work in high-stress, complex environments with known and suspected carcinogenic exposures. We aimed to characterise cancer incidence among firefighters and police.MethodsThe Occupational Disease Surveillance System (ODSS) was used to identify workers employed as firefighters or police in Ontario. A cohort of workers were identified using lost-time workers’ compensation claims data and followed for cancer in the Ontario Cancer Registry (1983–2020). Cox proportional hazard models were used to estimate HRs and 95% CIs for primary site-specific cancer diagnoses adjusted for age at start of follow-up, birth year and sex.ResultsA total of 13 642 firefighters and 22 595 police were identified in the cohort. Compared with all other workers in the ODSS, firefighters and police had increased risk of prostate cancer (firefighters: HR=1.43, 95% CI 1.31 to 1.57; police: HR=1.47, 95% CI 1.35 to 1.59), colon cancer (firefighters: HR=1.39, 95% CI 1.19 to 1.63; police: HR=1.39, 95% CI 1.21 to 1.60) and skin melanoma (firefighters: HR=2.38, 95% CI 1.99 to 2.84; police: HR=2.27, 95% CI 1.96 to 2.62). Firefighters also had increased risk of cancer of the pancreas, testis and kidney, as well as non-Hodgkin’s lymphoma and leukaemia. Police had increased risk of thyroid, bladder and female breast cancer. When compared directly with the police, firefighters had an elevated risk of mesothelioma and testicular cancer.ConclusionsFirefighters and police demonstrated some similar as well as some unique cancer risks. Findings from this larger worker population may have important implications for workplace and policy-level changes to improve preventative measures and reduce potential exposures to known carcinogenic hazards.

Background Immunotherapy in the presence of COVID-19 infections raises concerns because of potential overlapping clinical complications and immune system enhancement. Further investigation is warranted to establish its safety and to improve clinical decisions. Methods We conducted a retrospective cohort study using linked health administrative data from Ontario, Canada to assess 30-day mortality in patients with solid tumors who were treated with immunotherapy within 120 days before testing positive for COVID-19. A stepwise multivariable logistic regression model was used to identify clinical factors associated with 30-day mortality. Results Between January 2020 and April 2023, 281 patients tested positive for COVID-19 and were included in our study. The mean age was 68 (Standard Deviation: 10.3), 45% (127/281) were females and 58% (163/281) had lung cancer. 59% of patients (167/281) were treated with single agent immunotherapy, and almost 80% received at least one dose of COVID-19 vaccine. The 30-day mortality was 22% (63/281) and < 5% of patients were admitted to ICU or required ventilation. Factors associated with higher mortality were older age (Odds Ratio (OR) 1.60, 95% confidence interval (CI) 1.07–2.39), prior radiation therapy (OR 2.38, 95%CI 1.08–5.28), lower hemoglobin (< 10 g/dl) (OR 4.08, 95%CI 1.89–8.82) and higher leucocytes count (> 11,000/mm 3 ) (OR 3.63, 95%CI 1.55–8.52). Conclusions Immunotherapy does not seem to increase the risk of 30-day mortality in patients with COVID-19 infections compared to published outcomes of patients with cancer and COVID-19. Mortality was associated with certain clinical characteristics that need to be carefully examined when prescribing immunotherapy during future comparable pandemics.

The National Lung Screening Trial (NLST) results indicate that computed tomography (CT) lung cancer screening for current and former smokers with three annual screens can be cost-effective in a trial setting. However, the cost-effectiveness in a population-based setting with >3 screening rounds is uncertain. Therefore, the objective of this study was to estimate the cost-effectiveness of lung cancer screening in a population-based setting in Ontario, Canada, and evaluate the effects of screening eligibility criteria. This study used microsimulation modeling informed by various data sources, including the Ontario Health Insurance Plan (OHIP), Ontario Cancer Registry, smoking behavior surveys, and the NLST. Persons, born between 1940 and 1969, were examined from a third-party health care payer perspective across a lifetime horizon. Starting in 2015, 576 CT screening scenarios were examined, varying by age to start and end screening, smoking eligibility criteria, and screening interval. Among the examined outcome measures were lung cancer deaths averted, life-years gained, percentage ever screened, costs (in 2015 Canadian dollars), and overdiagnosis. The results of the base-case analysis indicated that annual screening was more cost-effective than biennial screening. Scenarios with eligibility criteria that required as few as 20 pack-years were dominated by scenarios that required higher numbers of accumulated pack-years. In general, scenarios that applied stringent smoking eligibility criteria (i.e., requiring higher levels of accumulated smoking exposure) were more cost-effective than scenarios with less stringent smoking eligibility criteria, with modest differences in life-years gained. Annual screening between ages 55-75 for persons who smoked ≥40 pack-years and who currently smoke or quit ≤10 y ago yielded an incremental cost-effectiveness ratio of $41,136 Canadian dollars ($33,825 in May 1, 2015, United States dollars) per life-year gained (compared to annual screening between ages 60-75 for persons who smoked ≥40 pack-years and who currently smoke or quit ≤10 y ago), which was considered optimal at a cost-effectiveness threshold of $50,000 Canadian dollars ($41,114 May 1, 2015, US dollars). If 50% lower or higher attributable costs were assumed, the incremental cost-effectiveness ratio of this scenario was estimated to be $38,240 ($31,444 May 1, 2015, US dollars) or $48,525 ($39,901 May 1, 2015, US dollars), respectively. If 50% lower or higher costs for CT examinations were assumed, the incremental cost-effectiveness ratio of this scenario was estimated to be $28,630 ($23,542 May 1, 2015, US dollars) or $73,507 ($60,443 May 1, 2015, US dollars), respectively. This scenario would screen 9.56% (499,261 individuals) of the total population (ever- and never-smokers) at least once, which would require 4,788,523 CT examinations, and reduce lung cancer mortality in the total population by 9.05% (preventing 13,108 lung cancer deaths), while 12.53% of screen-detected cancers would be overdiagnosed (4,282 overdiagnosed cases). Sensitivity analyses indicated that the overall results were most sensitive to variations in CT examination costs. Quality of life was not incorporated in the analyses, and assumptions for follow-up procedures were based on data from the NLST, which may not be generalizable to a population-based setting. Lung cancer screening with stringent smoking eligibility criteria can be cost-effective in a population-based setting.

In Canada, patients who move may choose to stay on their original family physician’s roster, creating long distances to seek primary care. We sought to explore how distance to primary care affected health care use and quality of care. We conducted a population-based study in Ontario, Canada, including urban and suburban patients enrolled with a family physician as of Mar. 31, 2023. The primary exposure was patients’ travel distance to their physician. Outcomes included emergency department visits, primary care visits, continuity of care, and cancer screening rates. We included 9 967 955 patients. Of these, 1 261 112 (12.7%) patients lived farther than 30 km from their family physician. These patients had greater odds of having nonurgent emergency department visits in the past year (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.42 to 1.44); having no visits with any family physician in the previous 2 years (OR 1.28, 95% CI 1.27 to 1.28); and not having had screening for colon cancer (OR 1.17, 95% CI 1.16 to 1.18), breast cancer (OR 1.24, 95% CI 1.23 to 1.25), and cervical cancer (OR 1.17, 95% CI 1.16 to 1.18). Among Ontario patients living in urban or suburban areas and rostered to a family physician within a patient enrolment model, more than 10% of patients resided farther than 30 km from their family physician. Proximity to primary care was associated with higher use of primary care, reduced emergency department use, and increased uptake of recommended cancer screening, underscoring the importance of reforms that enhance access to care close to home.