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Rates of colorectal cancer diagnosed before age 50 (early-onset colorectal cancer) are increasing in many countries. Many regions have lowered the age of screening initiation to 45 in response. Although early studies suggest increases in early cancer detection and improved outcomes among newly eligible individuals, some of the fastest increases are among those below 45, particularly for rectal cancers. In those below 45, population-wide screening is not likely to be cost-effective. Research to understand the factors driving the increases is essential in these younger groups. Recent data suggest that both novel and known exposures play a role. Novel initiators such as colibactin-producing Escherichia coli have been identified, and known promoters such as obesity, poor diet, and inactivity, among others, are increasing in prevalence among younger generations. Data from Baek and colleagues reinforce the role of metabolic and lifestyle factors, with differences observed between sexes. Their findings support the concept that early exposure to known promoters increases the risk of carcinogenesis. Future studies that incorporate biomarkers along with purposefully collected early-life data will be integral to identifying causal exposures and informing targeted cancer prevention strategies. See related article by Baek et al., p. 647.
The objectives of this study were to systematically identify studies that (i) quantified the prevalence of breast cancer screening among female survivors of a prior cancer other than breast cancer and (ii) compared the likelihood of undergoing breast cancer screening between cancer survivors and cancer-free controls. Effect estimates were pooled using random-effects meta-analyses. Stratified analyses were performed across primary cancer sites with three or more studies. Sixty-two studies were included in this review. The prevalence of breast cancer screening among female cancer survivors was 0.67 [95% confidence interval (CI), 0.62-0.71], ranging from 0.49 (lung) to 0.75 (cervical) across primary cancer sites. The prevalence of breast cancer screening was higher among studies that ascertained screening through self-report and studies conducted in North America. The odds of undergoing breast cancer screening were significantly greater among cancer survivors compared with cancer-free controls (odds ratio: 1.24; 95% CI, 1.13-1.36). Although cancer survivors had higher rates of breast cancer screening compared with cancer-free controls, overall rates were below population-based screening targets. Given that cancer survivors are at an elevated risk of subsequent breast cancer, future studies should evaluate predictors of screening nonadherence and explore targeted approaches to improve participation in breast cancer screening among cancer survivors.
OBJECTIVES: To characterize real-world evidence (RWE) in Canada's Drug Agency (CDA-AMC) submissions, describe its designs and purposes, and summarize the agency/committee views on its use. METHODS: We conducted a comprehensive environmental scan of the CDA-AMC website to retrieve all reports and recommendations of reimbursement review submissions published between January 2020 and June 2024. RWE utilization was classified by therapeutic area, study design, geographic data source, and intended purpose. Reviewer and committee comments were thematically coded. RESULTS: Of the 294 submissions screened, 274 were included in this study. A total of 70 submissions (25.5%) contained RWE. These submissions cited 113 distinct real-world data/RWE sources, namely: retrospective cohorts (58%), prospective cohorts (20%), and other designs (22%). Geographic origin was predominantly the United States (39%) or Europe (38%); only 12 sources (11%) were Canadian. RWE often informed comparative effectiveness (54%) and evidence gaps (52%). Reviewer critiques focused on data quality (70%) and generalizability (61%); lack of Canadian data was identified in 50% of submissions. Within the Canadian subgroup, generalizability concerns decreased (40%), but data quality issues remained common (70%). A total of 83% of submissions received "reimburse with conditions" recommendations. CONCLUSIONS: RWE has become routine in CDA-AMC submissions, yet remains largely non-Canadian and limited in its applicability. More formal guidance on transportability analyses, quantitative bias assessment, and improved standards across clinical and economic domains could enhance evidence generation, submission quality, and health technology assessment confidence in clinical and pharmacoeconomic information. These findings may inform ongoing refinement of RWE checklists and expectations, providing a benchmark against which future use of RWE can be measured and tracked.
BACKGROUND: In East-Asian predominant populations, multiple reports identify East-Asian ancestry as prognostic of improved outcome in EGFRmut+ non-small cell lung cancer (NSCLC) populations when treated with first/second generation tyrosine kinase inhibitor (TKI). Generalizability to more heterogeneous populations is less understood. OBJECTIVE: To identify clinical characteristics associated with long-term survival (LTS) in patients from heterogeneous Canadian populations with advanced NSCLC with EGFRmut+ treated with first-line TKIs. METHODS: De novo advanced EGFRmut+ NSCLC diagnoses receiving a first/second generation epidermal growth factor receptor-TKI between 2004 and 2016 were included. Demographic, clinical, treatment, and outcome details were extracted from three sources: two province-wide, multi-center registries, the Alberta Glans-Look Lung Cancer Research Database (GLR), and the British Columbia Cancer (BCC), along with data from Princess Margaret Cancer Center (PM), a single-center, urban, tertiary hospital. Survival time from TKI initiation was divided into LTS, patients surviving longer than the upper quartile (34.4 months), and the remaining patients described as 'non-long-term survivors' (non-LTS). RESULTS: Of 577 patients (GLR: 246, PM: 112, and BCC: 219), median overall survival was 20.3 months. From initiation of TKI, LTS-median survival was 48.5 months, whereas non-LTS was 15.7 months. The LTS cohort differed significantly from non-LTS in many clinical and pathologic characteristics, including being significantly more likely to be of East-Asian ancestry (50% vs. 39%, p = 0.02), Female (74% vs. 64%, p = 0.04), and more likely to harbor exon19del-mutation (60% vs. 46%, p = 0.004). In multivariate analysis, exon19del (hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.63-0.93, p = 0.01) and East-Asian ethnicity (HR = 0.75, 95% CI 0.69-0.94, p = 0.02) were independently associated with longer survival. Male sex (HR = 1.36, 95% CI 1.12-1.66, p < 0.01) was associated with shorter survival, while smoking status, treatment site, and age > 70 years were not independent prognostic factors. CONCLUSION: This study confirmed previously known prognosticators within a real-world multicenter Canadian cohort. This included East-Asian ancestry, female sex, and exon19del, which were associated with better overall survival. Future work to better understand the impact of socioeconomic factors and biological reasons for ancestry resulting in different prognosis are needed to better guide treatment management.
BACKGROUND: Low-dose computed tomography (LDCT) screening reduces lung cancer mortality, the leading cause of cancer deaths globally. Segmentation-free deep learning (DL) models such as Sybil can improve screening efficiency but require extensive validation and possible improvement. RESEARCH QUESTION: Can the integration of deep learning based on LDCT scans and clinical data improve lung cancer risk prediction? STUDY DESIGN AND METHODS: Retrospective cohort data from 4 different screening programs, one used for model training and three for external validation. Data collected between the years 2002 and 2021. The median follow-up period was 7 years. All participants had a history of either current or former smoking, with at least 10 pack-years or who smoked over 20 years. The area under the receiver operating characteristic curve (AUC) was calculated for lung cancer risk within 1 to 6 years, stratified by pulmonary nodule presence and size. Key clinical and epidemiological factors were evaluated for their added predictive value. RESULTS: This analysis uses 52,482 LDCT series from 22,469 participants. Sybil's AUC ranged from 0.93 in year 1 and reduced to 0.79 in year 6 in the independent cohorts. The predictive performance was suboptimal in the absence of documented nodules (AUC=0.64), and for small nodules (AUC=0.61) in year 6. Our new model, Sybil-Epi, trained with baseline scans, achieved higher predictive performance (AUC=0.83, 95% CI 0.81 to 0.85) compared to Sybil (AUC=0.80, 95% CI 0.78 to 0.82) in year 6. The difference is most notable when nodules are absent, with Sybil-Epi AUC of 0.76 (95% CI 0.70 to 0.82) and Sybil AUC of 0.64 (95% CI 0.57 to 0.70). INTERPRETATION: Sybil performs better for short-term lung cancer risk, but the predictive accuracy was suboptimal when nodules were absent. Our integrated Sybil-Epi model with deep learning and clinical-epidemiological factors significantly improved model predictive performance.
INTRODUCTION: The treatment landscape for human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) in Canada is rapidly evolving. This retrospective cohort study described real-world historical treatment patterns and clinical outcomes for patients with HER2- mBC. METHODS: Adults enrolled in the pan-Canadian 'Personalize My Treatment' cancer registry and diagnosed with stage IV HER2- mBC (01/01/2015-03/01/2022) were eligible and followed until 03/01/2023. Hormone receptor-positive (HR+)/HER2- mBC and triple-negative mBC (mTNBC) were analyzed separately and further stratified by line of therapy. Main study outcomes included treatment patterns, PIK3CA/AKT1/PTEN alteration testing/positivity rates, and overall survival (OS), all analyzed descriptively. RESULTS: A total of 507 patients with HER2- mBC were included (HR+/HER2- mBC: 387; mTNBC: 120; median follow-up: 54.1 months). The most common HR+/HER2- mBC treatments were cyclin‑dependent kinase 4/6 inhibitors (CDK4/6is) plus endocrine therapy (ET) in first line (1L; 55.0%), targeted therapies (22.9%) and CDK4/6i + ET (22.0%) in second line (2L), and chemotherapy (CT) monotherapy (42.7%) in third line (3L). CT monotherapy was the most common mTNBC treatment in 1L (35.1%), 2L (50.6%), and 3L (54.8%). Attrition was similar for HR+/HER2- mBC and mTNBC from 1L-2L (16.9% and 16.3%, respectively) but was lower for HR+/HER2- mBC from 2L-3L (33.2% and 38.6%) and 3L-4L (48.1% and 62.1%). PIK3CA/AKT1/PTEN alteration testing was performed in 31.8% of patients with HR+/HER2- mBC and 50.0% with mTNBC, with alterations identified in 15.4% and 20.0% of patients, respectively. Median OS (65.9 and 31.4 months, respectively), OS rates (1 year: 94.8% and 79.8%; 5 years: 56.0% and 21.7%), and time to next treatment (1L-2L: 24.5 and 8.1 months; 2L-3L: 10.1 and 5.1 months) were greater for HR+/HER2- mBC than mTNBC. CONCLUSIONS: These findings describe historical HER2- mBC treatment patterns and associated outcomes in Canada. Ongoing research is needed to optimize therapeutic strategies, expand novel treatment access, and improve patient outcomes.
Real-world data on patients with ROS1-positive advanced non-small cell lung cancer (NSCLC) remain scarce. In this descriptive observational retrospective cohort study, we describe characteristics, treatments, and real-world progression-free survival (rwPFS) and overall survival (OS) among patients with ROS1-positive advanced NSCLC (de novo or recurrent) using secondary data pooled from clinical sites in Canada, France, Germany, Portugal, and Spain as part of the Oncology Evidence Network. Site-specific patient inclusion periods occurred between 2009 and 2023, with follow-up to 2024, allowing ≥1 year of potential follow-up at each site. In total, 108 patients were included, with most (n = 105; 97.2%) having a de novo diagnosis of advanced NSCLC. 103 patients (95.4%) received ≥1 line of systemic anticancer therapy (SACT), of which 65 (63.1%) received first-line targeted therapy, mostly crizotinib monotherapy (n = 45) or crizotinib-based regimens (n = 10), with a median (95% CI) rwPFS and OS of 14.0 (8.3-19.8) and 47.9 (27.3-not estimable) months, respectively. Thirty-eight of the 103 SACT-treated patients (36.9%) received first-line non-targeted therapy, mostly platinum-based chemotherapy (n = 26); median (95% CI) rwPFS and OS were 9.0 (7.5-11.0) and 29.3 (17.7-65.7) months, respectively. Results from this study indicated a tendency for longer survival using currently available ROS1-targeted versus non-targeted therapy for patients with ROS1-positive advanced NSCLC. Nevertheless, survival outcomes were limited, highlighting the importance of more effective emerging treatments for ROS1-positive disease.
Choosing Wisely (CW) campaign addresses the global challenge of reducing waste in healthcare by discouraging unnecessary interventions, minimizing harm, and promoting evidence-based care. Barriers like limited awareness among healthcare professionals and the lack of global mapping of recommendations hinder its implementation. We conducted a comprehensive scoping review mapping the literature on CW recommendations in oncology from 2012 to 2024. A total of 220 recommendations were gathered from 19 studies and 20 recognized international websites. These recommendations explored the importance of personalizing screening, staging, and treatment based on individual risk factors, such as life expectancy and biomarker status. The findings suggest a global shift toward patient-centered oncology care, focusing on personalized, evidence-based treatments and minimizing unnecessary interventions. Developing recommendations based on resource-stratified guidelines is vital for improving the adoption of CW, particularly in low- and middle-income countries, as it ensures that recommendations are aligned with local healthcare needs and available resources.
BACKGROUND: Adults aged ≥ 70 years represent approximately half of all patients diagnosed with colon cancer, but undertreatment in this population persists. Recent guidelines have aimed to reduce age-related biases in the treatment of colon cancer. We evaluated the age-related disparities in the receipt of curative-intent surgical and medical treatment of colon cancer, and their changes over time. METHODS: This was a population-based cohort study of adult patients diagnosed with colon adenocarcinoma between 2010 and 2018 in Alberta, Canada. Surgery receipt was assessed in patients with stage I-III disease, while systemic therapy receipt was assessed in stage III to IV disease. Patients were stratified by age at diagnosis (< 70 and ≥ 70 years). Cox proportional hazard models were used to evaluate interactions between age and treatment status, and their associations with cancer-specific survival (CSS). Time trends associated with treatment receipt were identified with multivariable logistic regression. RESULTS: Among the 10,838 patients included, 48% were aged ≥ 70 years. For surgery recipients, 5-year CSS was 0.90 (95% CI, 0.88-0.91) and 0.79 (95% CI, 0.77-0.80) for patients < 70 and patients ≥ 70 years of age respectively. Systemic therapy recipients aged < 70 years had a 5-year CSS of 0.57 (95% CI, 0.55-0.60), while individuals aged ≥ 70 years had a 5-year CSS of 0.51 (95% CI, 0.49-0.55). The association between treatment receipt and CSS was independent of age for both treatment modalities (P = .17). Treatment receipt trends remained consistent between 2010 and 2018. CONCLUSION: Despite evolving practice guidelines and non-age-dependent survival benefits, disparities persist in the receipt of treatment for older adults with colon adenocarcinoma.
INTRODUCTION: Exercise interventions improve quality of life and survival for individuals living with and beyond cancer (ILWBC), yet equitable access remains limited. Evidence on characteristics of who enrolls in exercise oncology programs is scarce, leaving gaps for equity-focused recruitment and scale-up, particularly in rural and underserved settings. The EXercise for Cancer to Enhance Living Well (EXCEL) study offers a unique opportunity to examine these issues across a Canada-wide cohort. METHODS: EXCEL is an 8-12-week tailored exercise intervention delivered primarily to ILWBC in rural/remote communities, with additional enrollment of urban participants lacking exercise oncology resources. Adults with any cancer type or stage were eligible if pre-treatment, receiving treatment, or within 3 years post-treatment. This analysis describes baseline demographic, lifestyle, medical, and fitness factors by rural versus urban residence using descriptive statistics. RESULTS: Of 1495 participants enrolled in the EXCEL program (rural n = 1085; urban n = 400), baseline characteristics differed modestly by geography. Age did not differ significantly between rural and urban participants. Rural participants were more often male, had lower educational attainment, and demonstrated higher BMI than urban participants. Urban participants exhibited greater ethnic diversity and higher levels of education. Physical activity levels were similar with 78% classified as physically active at baseline. CONCLUSION: This Canada-wide baseline analysis reveals rural-urban variations in age, treatment status, disease burden, education, and lifestyle, yet comparable physical activity and functional capacity levels. These findings provide descriptive evidence to inform recruitment strategies and considerations for exercise oncology program delivery across geographic settings.