Comparing Time to Diagnosis and Treatment Between Younger and Older Adults With Colorectal Cancer: A Population-Based Study.

BACKGROUND & AIMS: Younger adults (aged <50 years) with colorectal cancer (CRC) may have prolonged delays to diagnosis and treatment that are associated with adverse outcomes. We compared delay intervals by age for patients with CRC in a large population. METHODS: This was a population-based study of adults diagnosed with CRC in Ontario, Canada, from 2003 to 2018. We measured the time between presentation and diagnosis (diagnostic interval), diagnosis and treatment start (treatment interval), and the time from presentation to treatment (overall interval). We compared interval lengths between adults aged <50 years, 50 to 74 years, and 75 to 89 years using multivariable quantile regression. RESULTS: Included were 90,225 patients with CRC. Of these, 6853 patients (7.6%) were aged <50 years. Younger patients were more likely to be women, present emergently, have stage IV disease, and have rectal cancer compared with middle-aged patients. Factors associated with significantly longer overall intervals included female sex (8.7 days; 95% confidence interval [CI], 6.6-10.9 days) and rectal cancer compared with proximal colon cancer (9.8 days; 95% CI, 7.4-2.2 days). After adjustment, adults aged <50 years had significantly longer diagnostic intervals (4.3 days; 95% CI. 1.3-7.3 days) and significantly shorter treatment intervals (-4.5 days; 95% CI, -5.3 to -3.7 days) compared with middle-aged patients. However, there was no significant difference in the overall interval (-0.6 days; 95% CI, -4.3 to 3.2 days). In stratified models, younger adults with stage IV disease who presented emergently and patients aged >75 years had longer overall intervals. CONCLUSIONS: Younger adults present more often with stage IV CRC but have overall similar times from presentation to treatment as screening-eligible older adults.

The Association Between Surgical Axillary Staging, Adjuvant Treatment Use and Survival in Older Women with Early Stage Breast Cancer: A Population-Based Study.

BACKGROUND: Choosing Wisely guidelines recommend against surgical axillary staging (AS) in women ≥70 years with ER+/HER2- early stage breast cancer (BC). This study examined the impact of AS omission on survival in older patients with BC. METHODS: This was a population-based cohort study using health administrative data in Ontario, Canada. We identified women aged 65-95 years who underwent surgery for Stage I/II BC between 2010 and 2016. Patients were weighted by propensity scores for receipt of AS that included patient and disease characteristics using overlap weights. Association with overall survival (OS) was calculated using weighted Cox models, and breast cancer-specific survival (BCSS) was calculated using weighted Fine and Gray models, adjusting for biomarkers and adjuvant treatments. Adjuvant treatment receipt was modelled with weighted log-binomial models. RESULTS: Among 17,370 older women, the 1771 (10.2%) who did not undergo AS were older, more comorbid, and less likely to undergo mastectomy. Women who did not undergo AS were less likely to receive adjuvant chemotherapy (RR 0.68, 95% CI 0.57-0.82), endocrine therapy (RR 0.85, 95% CI 0.81-0.89) or radiotherapy (RR 0.69, 95% CI 0.65-0.74). After weighting and adjustment, there was no significant difference in BCSS (sdHR 0.98, 95% CI 0.77-1.25), but women who did not undergo AS had worse OS (HR 1.14, 95% CI 1.04-1.25). The results among 6215 ER+/HER2- women ≥70 years undergoing SLNB vs no AS were similar. CONCLUSIONS: The omission of AS in older women with early stage BC was not associated with adverse BCSS, although OS was worse.

Long-term outcomes of women with large DCIS lesions treated with breast-conserving therapy.

PURPOSE: The paucity of data on women with large (≥ 40 mm) DCIS tumors lead to uncertainty on the safety of breast-conserving surgery (BCS) for these patients. We evaluated the impact of large tumor size on local recurrence (LR) among women with DCIS treated with BCS ± radiotherapy (RT). METHODS: Treatment and outcomes were ascertained through administrative databases for all women with DCIS in Ontario from 1994 to 2003 treated with BCS ± RT with negative margins; 82% had pathology review. Cox proportional hazards model was used to evaluate the impact of tumor size on LR. 10- and 15-year LR-free survival (LRFS) were calculated using Kaplan-Meier method. RESULTS: The cohort includes 2049 women treated by BCS (N = 1073 with RT). Median follow-up is 14 years (IQR 9-17 years). Referenced to tumors ≤ 10 mm, the risk of LR following BCS was significantly higher for larger tumors: HR ≥ 40 mm = 3.67 (95% CI 2.13, 6.33; p < 0.001), HR 26-39 mm = 2.27 (95% CI 1.47, 3.50, p < 0.001), and HR 11-25 mm = 1.42 (95% CI 1.06, 1.92, p = 0.02). However, for individuals with BCS + RT, large tumor size was not associated with a significantly increased risk of LR (HR ≥ 40 mm = 1.92 (95% CI 0.97, 3.79); HR 26-39 mm = 1.81 (95% CI 1.09-2.99)). For women with tumors ≥ 40 mm, 10-year LRFS risk for those treated by BCS alone, BCS + RT without boost, and BCS + RT with boost was 58.9%, 82.8%, and 83.9%. CONCLUSION: Large DCIS lesions ≥ 40 mm are associated with higher risks of LR following BCS, but high long-term LRFS rates can be achieved with the addition of breast RT.

The impact of marginalization on diffuse large B-cell lymphoma overall survival: a retrospective cohort study.

The aim of this study was to describe the impact of marginalization on DLBCL overall survival (OS) within the Canadian setting. We conducted a population-based retrospective cohort study of adult patients with newly diagnosed DLBCL in Ontario between 1 January 2005 and 31 December 2017 receiving a rituximab-containing chemotherapy regimen with curative intent followed until 1 March 2020. Our primary exposure of interest was the Ontario Marginalization Index (ON-Marg). The primary outcome was 2-year OS, accounting for patient age, sex, cancer characteristics, comorbidity burden, and rural dwelling status. While two-year overall survival was inferior for individuals in the most deprived marginalization quintile (70.4% Q5 vs. 76.0% Q1), after adjustment for relevant covariates neither the composite ON-Marg nor any of its dimensions had a significant effect. Within the Canadian context, among patients who receive chemotherapy, marginalization may not have a significant association with overall survival when accounting for key patient covariates, lending support for preserved outcomes.

Analysis of Time to Treatment and Survival Among Adults Younger Than 50 Years of Age With Colorectal Cancer in Canada.

Importance: Colorectal cancer (CRC) is uncommon in adults younger than 50 years of age, so this population may experience delays to treatment that contribute to advanced stage and poor survival. Objective: To investigate whether there is an association between time from presentation to treatment and survival in younger adults with CRC. Design, Setting, and Participants: This retrospective cohort study used linked population-based data in Ontario, Canada. Participants included patients with CRC aged younger than 50 years who were diagnosed in Ontario between 2007 and 2018. Analysis was performed between December 2019 and December 2022. Exposure: Administrative and billing codes were used to identify the number of days between the date of first presentation and treatment initiation (overall interval). Main Outcomes and Measures: The associations between increasing overall interval, overall survival (OS), and cause-specific survival (CSS) were explored with restricted cubic spline regression. Multivariable Cox proportional hazards models were also fit for OS and CSS, adjusted for confounders. Analyses were repeated in a subset of patients with lower urgency, defined as those who did not present emergently, did not have metastatic disease, did not have cross-sectional imaging or endoscopy within 14 days of first presentation, and had an overall interval of at least 28 days duration. Results: Among 5026 patients included, the median (IQR) age was 44.0 years (40.0-47.0 years); 2412 (48.0%) were female; 1266 (25.2%) had metastatic disease and 1570 (31.2%) had rectal cancer. The lower-urgency subset consisted of 2548 patients. The median (IQR) overall interval was 108 days (55-214 days) (15.4 weeks [7.9-30.6 weeks]). Patients with metastatic CRC had shorter median (IQR) overall intervals (83 days [39-183 days]) compared with those with less advanced disease. Five-year overall survival was 69.8% (95% CI, 68.4%-71.1%). Spline regression showed younger patients with shorter overall intervals (<108 days) had worse OS and CSS with no significant adverse outcomes of longer overall intervals. In adjusted Cox models, overall intervals longer than 18 weeks were not associated with significantly worse OS or CSS compared with those waiting 12 to 18 weeks (OS: HR, 0.83 [95% CI, 0.67-1.03]; CSS: HR, 0.90 [95% CI, 0.69-1.18]). Results were similar in the subset of lower-urgency patients, and when stratified by stage. Conclusions and relevance: In this cohort study of 5026 patients with CRC aged younger than 50 years of age in Ontario, time from presentation to treatment was not associated with advanced disease or poor survival. These results suggest that targeting postpresentation intervals may not translate to improved outcomes on a population level.

Mortality among patients with diffuse large B-cell lymphoma and mental disorders: a population-based study.

BACKGROUND: Mental disorders have been reported in patients with diffuse large B-cell lymphoma (DLBCL), but studies examining their association with mortality are lacking. METHODS: We conducted a population-based study using linked administrative health-care databases from Ontario, Canada. All patients with DLBCL 18 years of age or older treated with rituximab-based therapy between January 1, 2005, and December 31, 2017, were identified and followed until March 1, 2020. Mental disorders were defined as either preexisting or postdiagnosis (after lymphoma treatment initiation). Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) between mental disorders and 1-year and all-cause mortality while controlling for covariates. RESULTS: We identified 10 299 patients with DLBCL. The median age of the cohort was 67 years; 46% of patients were female, and 28% had a preexisting mental disorder. At 1-year follow-up, 892 (9%) had a postdiagnosis mental disorder, and a total of 2008 (20%) patients died. Preexisting mental disorders were not associated with 1-year mortality (adjusted HR = 1.06, 95% confidence interval [CI] = 0.96 to 1.17, P = .25), but postdiagnosis disorders were (adjusted HR = 1.51, 95% CI = 1.26 to 1.82, P = .0001). During a median follow-up of 5.2 years, 2111 (22%) patients had a postdiagnosis mental disorder, and 4084 (40%) patients died. Both preexisting and postdiagnosis mental disorders were associated with worse all-cause mortality (preexisting adjusted HR = 1.12, 95% CI = 1.04 to 1.20, P = .0024; postdiagnosis adjusted HR = 1.63, 95% CI = 1.49 to 1.79, P < .0001). CONCLUSIONS: Patients with DLBCL and mental disorders had worse short-term and long-term mortality, particularly those with postdiagnosis mental disorders. Further studies are needed to examine mental health service utilization and factors mediating the relationship between mental disorders and inferior mortality.

Measurement of clinical delay intervals among younger adults with colorectal cancer using health administrative data: a population-based analysis.

BACKGROUND: Clinical delays may be important contributors to outcomes among younger adults (<50 years) with colorectal cancer (CRC). We aimed to describe delay intervals for younger adults with CRC using health administrative data to understand drivers of delay in this population. METHODS: This was a population-based study of adults <50 diagnosed with CRC in Ontario, Canada from 2003 to 2018. Using administrative code-based algorithms (including billing codes), we identified four time points along the pathway to treatment-first presentation with a CRC-related symptom, first investigation, diagnosis date and treatment start. Intervals between these time points were calculated. Multivariable quantile regression was performed to explore associations between patient and disease factors with the median length of each interval. RESULTS: 6853 patients aged 15-49 were diagnosed with CRC and met the inclusion criteria. Males comprised 52% of the cohort, the median age was 45 years (IQR 40-47), and 25% had stage IV disease. The median time from presentation to treatment start (overall interval) was 109 days (IQR 55-218). Time between presentation and first investigation was short (median 5 days), as was time between diagnosis and treatment start (median 23 days). The greatest component of delay occurred between first investigation and diagnosis (median 78 days). Women, patients with distal tumours, and patients with earlier stage disease had significantly longer overall intervals. CONCLUSIONS: Some younger CRC patients experience prolonged times from presentation to treatment, and time between first investigation to diagnosis was an important contributor. Access to endoscopy may be a target for intervention.