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.

Adaptation and qualitative evaluation of the BETTER intervention for chronic disease prevention and screening by public health nurses in low income neighbourhoods: views of community residents.

BACKGROUND: The BETTER intervention is an effective comprehensive evidence-based program for chronic disease prevention and screening (CDPS) delivered by trained prevention practitioners (PPs), a new role in primary care. An adapted program, BETTER HEALTH, delivered by public health nurses as PPs for community residents in low income neighbourhoods, was recently shown to be effective in improving CDPS actions. To obtain a nuanced understanding about the CDPS needs of community residents and how the BETTER HEALTH intervention was perceived by residents, we studied how the intervention was adapted to a public health setting then conducted a post-visit qualitative evaluation by community residents through focus groups and interviews. METHODS: We first used the ADAPT-ITT model to adapt BETTER for a public health setting in Ontario, Canada. For the post-PP visit qualitative evaluation, we asked community residents who had received a PP visit, about steps they had taken to improve their physical and mental health and the BETTER HEALTH intervention. For both phases, we conducted focus groups and interviews; transcripts were analyzed using the constant comparative method. RESULTS: Thirty-eight community residents participated in either adaptation (n = 14, 64% female; average age 54 y) or evaluation (n = 24, 83% female; average age 60 y) phases. In both adaptation and evaluation, residents described significant challenges including poverty, social isolation, and daily stress, making chronic disease prevention a lower priority. Adaptation results indicated that residents valued learning about CDPS and would attend a confidential visit with a public health nurse who was viewed as trustworthy. Despite challenges, many recipients of BETTER HEALTH perceived they had achieved at least one personal CDPS goal post PP visit. Residents described key relational aspects of the visit including feeling valued, listened to and being understood by the PP. The PPs also provided practical suggestions to overcome barriers to meeting prevention goals. CONCLUSIONS: Residents living in low income neighbourhoods faced daily stress that reduced their capacity to make preventive lifestyle changes. Key adapted features of BETTER HEALTH such as public health nurses as PPs were highly supported by residents. The intervention was perceived valuable for the community by providing access to disease prevention. TRIAL REGISTRATION: #NCT03052959, 10/02/2017.

Impact of non-adherence to endocrine therapy on recurrence risk in older women with stage I breast cancer after breast-conserving surgery.

PURPOSE: We examined the impact of non-adherence to adjuvant endocrine therapy (ET) on the risk and site of recurrence among older women with early stage, hormone receptor positive (HR+) breast cancer (EBC). METHODS: A population-based cohort of women age ≥ 65 years with T1N0 HR + EBC who were diagnosed between 2010 and 2016 and treated with breast-conserving surgery (BCS) + ET was identified. Treatment and outcomes were ascertained through linkage with administrative databases. ET non-adherence was examined as a time-dependent covariate in multivariable cause-specific Cox regression models to evaluate its effect on the risks of ipsilateral local recurrence (LR), contralateral breast cancer, and distant metastases. RESULTS: The population cohort includes 2637 women; 73% (N = 1934) received radiation (RT) + ET and 27% (N = 703) received ET alone. At a median follow-up of 8.14 years, the first event was LR in 3.6% of women treated with ET alone and 1.4% for those treated with RT + ET (p < 0.001); the risk of distant metastases was < 1% in both groups. The proportion of time adherent to ET was 69.0% among those treated with RT + ET and 62.8% for those treated with ET alone. On multivariable analysis, increasing proportion of time non-adherent to ET was associated with increased risk of LR ((HR = 1.52 per 20% increase in time; 95%CI 1.25, 1.85; p < 0.001), contralateral BC (HR = 1.55; 95%CI 1.30, 1.84; p < 0.001), and distant metastases (HR = 1.44; 95%CI 1.08, 1.94; p = 0.01) but absolute risks were low. CONCLUSION: Non-adherence to adjuvant ET was associated with an increased risk of recurrence, but absolute recurrence rates were low.

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.

Effect of Chronic Comorbidities on Follow-up Colonoscopy After Positive Colorectal Cancer Screening Results: A Population-Based Cohort Study.

INTRODUCTION: Fecal occult blood tests (FOBTs) are colorectal cancer screening tests used to identify individuals requiring further investigation with colonoscopy. Delayed colonoscopy after positive FOBT (FOBT+) is associated with poorer cancer outcomes. We assessed the effect of comorbidity on colonoscopy receipt within 12 months after FOBT+. METHODS: Population-based healthcare databases from Ontario, Canada, were linked to assemble a cohort of 50-74-year-old individuals with FOBT+ results between 2008 and 2017. The associations between comorbidities and colonoscopy receipt within 12 months after FOBT+ were examined using multivariable cause-specific hazard regression models. RESULTS: Of 168,701 individuals with FOBT+, 80.5% received colonoscopy within 12 months. In multivariable models, renal failure (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.62-0.82), heart failure (HR 0.77, CI 0.75-0.80), and serious mental illness (HR 0.88, CI 0.85-0.92) were associated with the lowest colonoscopy rates, compared with not having each condition. The number of medical conditions was inversely associated with colonoscopy uptake (≥4 vs 0: HR 0.64, CI 0.58-0.69; 3 vs 0: HR 0.75, CI 0.72-0.78; and 2 vs 0: HR 0.87, CI 0.85-0.89). Having both medical and mental health conditions was associated with a lower colonoscopy uptake relative to no comorbidity (HR 0.88, CI 0.87-0.90). DISCUSSION: Persons with medical and mental health conditions had lower colonoscopy rates after FOBT+ than those without these conditions. Better strategies are needed to optimize colorectal cancer screening and follow-up in individuals with comorbidities.

Long-term survival in elderly women receiving chemotherapy for non-metastatic breast cancer: a population-based analysis.

BACKGROUND: Older women are poorly represented in trials evaluating chemotherapy for breast cancer (BC). This study aimed to describe survival and associated factors among elderly women receiving chemotherapy for non-metastatic BC. METHODS: This was a population-based cohort study including women ≥ 70 years old diagnosed with invasive, non-metastatic BC from 2010 to 2017 in SEER. Among those who received chemotherapy, overall survival (OS) was determined using Kaplan-Meier curves and hazard ratios were reported with 95% confidence intervals (CIs). Adjustment was made for available confounders. Co-morbidity is not available in SEER. BC-specific survival (BCSS) and subdistribution hazard ratios were determined using competing risks analysis. RESULTS: The cohort consisted of 109,239 women aged 70+, of whom 17,961 (16%) received chemotherapy. Chemotherapy patients were younger (median 73.0 years vs. 77.0), had more advanced disease (25% stage III vs. 5.2%), and were more likely to receive mastectomy (50% vs. 33%). Among chemotherapy patients, 5-year OS was 77.8% (95% CI 76.9-78.6%), and for women 80+ was 60.2% (95% CI 57.5-63.1%). More recent diagnoses, no previous history of cancer, and receipt of radiotherapy were all associated with improved BCSS. Conversely, older age, higher tumour grade, advanced stage, and human epidermal growth factors receptor (HER)2 negative tumours were associated with worse BCSS. 56% of deaths were due to BC, and women aged 80+ had worse BCSS compared to those aged 70-79 (adjusted sdHR 1.62, 95% CI 1.43-1.84). CONCLUSIONS: Elderly women with advanced disease can achieve good survival after chemotherapy for non-metastatic BC. Those with HER2+ disease have superior survival, reinforcing benefit in this population.

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.

Periodic screening for breast and cervical cancer in women with diabetes: a population-based cohort study.

PURPOSE: Diabetes is associated with poorer cancer outcomes. Screening for breast and cervical cancer is recommended by clinical guidelines; however, utilization of these tests in people with diabetes has been unclear due to methodological limitations in the evidence base. We used administrative data to determine the association between diabetes and the rates of becoming up-to-date with periodic breast and cervical cancer screening over a 20-year period. METHODS: Healthcare databases from Ontario, Canada, were linked to assemble two population-based cohorts of 50-70 and 21-70 year-olds between 1994 and 2011, eligible for breast and cervical cancer screening, respectively. Using age as the time scale, multivariable recurrent events models were implemented to examine the association between the presence of diabetes and the rates of becoming up-to-date with the recommended cancer screenings. RESULTS: In each of the breast and cervical cancer screening cohorts, there were, respectively, 1,516,302 (16% had diabetes at baseline) and 4,751,220 (9.5% had diabetes at baseline) screen-eligible women. In multivariable models, prevalent diabetes (duration ≥ 2 years) was associated with lower rates of becoming up-to-date with cervical (hazard ratio, HR 0.85, 95% confidence interval, CI 0.84-0.85) and breast (HR 0.94, CI 0.93-0.94) cancer screening, compared to no diabetes. CONCLUSIONS: Having diabetes is associated with decreased rates of becoming up-to-date with two recommended periodic cancer screenings, with a bigger reduction in the rates of becoming up-to-date with cervical cancer screening. Greater attention to cervical cancer preventive services is needed in women with diabetes.

Two randomized controlled trials for colorectal cancer screening invitations developed using a behavioral science approach.

The effectiveness of behaviorally informed, targeted invitations to standard invitations and to no invitation (control arm, primary analysis) were compared in the context of an organized colorectal cancer (CRC) screening program. Two multi-arm, pragmatic randomized controlled trials in men (arms: male-specific, unisex, standard invitation, or no invitation) and in women (arms: unisex, standard invitation, or no invitation), were conducted in Ontario, Canada. Eligible persons aged 50-74, due for CRC screening, were randomized. Primary and secondary outcomes were completion of the guaiac fecal occult blood test (gFOBT) and uptake of any colorectal test, respectively, within 5 months of mailing. Impact of invitation type was assessed using logistic regression. Letters were mailed to 75,810 men and women; 38,673 males and 34,453 females were included in the analyses. Men who received the male-specific letter were most likely to screen with gFOBT compared to controls (odds ratio (OR) 7·24, 95% CI: 5·77, 9·09), followed by those receiving the unisex letter (OR 6·75, 95% CI: 5·37, 8·47) and the standard letter (OR 5·99, 95% CI: 4·76, 7·53). Women who received the unisex letter were most likely to be screened with gFOBT compared to controls (OR 7·07, 95% CI: 5·83, 8·59), followed by those receiving the standard letter (OR 6·76, 95% CI: 5·56, 8·21). In both trials, the findings were similar for the secondary outcome. Mailed invitations were effective for both men and women. With greater targeting using the behaviorally informed invitations, the magnitude of benefit relative to no invitation appeared to increase. (ClinicalTrials.gov, NCT02364895).

Calculation of Stop Ages for Colorectal Cancer Screening Based on Comorbidities and Screening History.

BACKGROUND & AIMS: Routine screening for colorectal cancer typically is recommended until age 74 years. Although it has been proposed that a screening stop age could be determined based on sex and comorbidity, less is known about the impact of screening history. We investigated the effects of screening history on the selection of an optimal age to stop screening. METHODS: We used the Microsimulation Screening Analysis-Colon model to estimate the harms and benefits of screening with biennial fecal immunochemical tests by sex, comorbidity status, and screening history. The optimal screening stop age was determined based on the incremental number needed for 1 additional life-year per 1000 screened individuals compared with the threshold provided by stopping screening at 76 years in the average-health population with a perfect screening history (attended all required screening, diagnostic, and follow-up tests) to biennial fecal immunochemical testing from age 50 years. RESULTS: For persons age 76 years, 157 women and 108 men with a perfect screening history would need to be screened to gain 1 life-year per 1000 screened individuals. Previously unscreened women with no comorbid conditions and no history of screening could undergo an initial screening through 90 years, whereas unscreened men could undergo initial screening through 88 years, before this balance is reached. As screening adherence improved or as comorbidities increased, the optimal age to stop screening decreased to a point that, regardless of sex, individuals with severe comorbidities and a perfect screening history should stop screening at age 66 years or younger. CONCLUSIONS: Based on the harm-benefit balance, the optimal stop age for colorectal cancer screening ranges from 66 years for unhealthy individuals with a perfect screening history to 90 years for healthy individuals without prior screening. These findings can be used to assist patients and clinicians in making decisions about screening participation.

A Pragmatic Randomized Controlled Trial of an Endoscopist Audit and Feedback Report for Colonoscopy.

INTRODUCTION: Variation in endoscopist performance contributes to poor-quality colonoscopy. Audit and feedback (A/F) can be used to improve physician performance, particularly among lower performing physicians. In this large pragmatic randomized controlled trial, we compared A/F to improve endoscopists' colonoscopy performance to usual practice. METHODS: Endoscopists practicing in Ontario, Canada, in 2014 were randomly assigned in October 2015 (index date) to receive (intervention group, n = 417) or not receive (control group, n = 416) an A/F report generated centrally using health administrative data. Colonoscopy performance was measured in both groups over two 12-month periods: prereport and postreport (relative to the index date). The primary outcome was polypectomy rate (PR). Secondary outcomes were cecal intubation rate, bowel preparation, and premature repeat after normal colonoscopy. A post hoc analysis used adenoma detection rate as the outcome. Outcomes were compared between groups for all endoscopists and for lower performing endoscopists using Poisson regression analyses under a difference-in-difference framework. RESULTS: Among all endoscopists, PR did not significantly improve from prereport to postreport periods for those receiving the intervention (relative rate [RR], intervention vs control: 1.07 vs 1.05, P = 0.09). Among lower performing endoscopists, PR improved significantly (RR, intervention vs control 1.34 vs 1.11, P = 0.02) in the intervention group compared with controls. In this subgroup, adenoma detection rate also improved but not significantly (RR, intervention vs control 1.12 vs 1.04, P = 0.12). There was no significant improvement in secondary outcomes between the intervention and control groups. DISCUSSION: A/F reports for colonoscopy improve performance in lower performing endoscopists (ClinicalTrials.gov: NCT02595775).

Clinical and endoscopist factors associated with post-colonoscopy colorectal cancer in a population-based sample.

AIM: Factors associated with verified post-colonoscopy colorectal cancers (PCCRC) have not been well defined and survival for these patients is not well described. We aimed to assess the association of patient, tumour and endoscopist characteristics with PCCRC. METHODS: Using population-based data, we identified individuals diagnosed with CRC from 1 January 2000 to 31 December 2005 who underwent a colonoscopy within 3 years prior to diagnosis. Detected cancers were those diagnosed ≤6 months following colonoscopy; PCCRC were diagnosed >6 months to ≤3 years following colonoscopy. Post-colonoscopy and detected cancers were verified through chart review using a hospital-based simple random sampling frame. We used multivariable conditional logistic regression to determine the association of patient, tumour and endoscopist factors with PCCRC and compared overall survival using Cox proportional hazard models. RESULTS: Using the random sampling frame, we identified 498 patients with PCCRC and 498 with detected CRC; we obtained records and confirmed 367 patients with PCCRC and 412 with detected cancers. In multivariable analysis, patient age (OR 1.01; 95% CI 1.00-1.03) and tumour location (distal vs. proximal OR 0.36; 95% CI 0.25-0.53) were associated with PCCRC; endoscopist quality measures were not significantly associated with PCCRC. We did not find significant differences in overall survival between PCCRC and detected cancers (hazard ratio 1.12; 95% CI 0.92-1.32). CONCLUSION: Although endoscopic quality measures are important for CRC prevention, endoscopist factors were not associated with PCCRC. This study highlights the need for further research into the role of tumour biology in PCCRC development.

Cost-effectiveness of Active Identification and Subsequent Colonoscopy Surveillance of Lynch Syndrome Cases.

BACKGROUND & AIMS: The province of Ontario, Canada is considering immunohistochemical followed by cascade analyses of all patients who received a diagnosis of colorectal cancer (CRC) at an age younger than 70 years to identify individuals with Lynch syndrome. We evaluated the costs and benefits of testing for Lynch syndrome and determined the optimal surveillance interval for first-degree relatives (FDRs) found to have Lynch syndrome. METHODS: We developed a patient flow diagram to determine costs and yield of immunohistochemical testing for Lynch syndrome in CRC cases and, for those found to have Lynch syndrome, their FDRs, accounting for realistic uptake. Subsequently, we used the MISCAN-colon model to compare costs and benefits of annual, biennial, and triennial surveillance in FDRs identified with Lynch syndrome vs colonoscopy screening every 10 years (usual care for individuals without a diagnosis of Lynch syndrome). RESULTS: Testing 1000 CRC cases was estimated to identify 20 CRC index cases and 29 FDRs with Lynch syndrome at a cost of $310,274. Despite the high cost of Lynch syndrome tests, offering the FDRs with Lynch syndrome biennial colonoscopy surveillance was cost-effective at $8785 per life-year gained compared with usual care because of a substantial increase in life-years gained (+122%) and cost savings in CRC care. Triennial surveillance was more costly and less effective, and annual surveillance showed limited additional benefit compared with biennial surveillance. CONCLUSIONS: Immunohistochemical testing for Lynch syndrome in persons younger than 70 years who received a diagnosis of CRC and then testing FDRs of those found to have Lynch syndrome provide a good balance between costs and long-term benefits. Colonoscopy surveillance every 2 years is the optimal surveillance interval for patients with Lynch syndrome.

The impact of ductal carcinoma in situ on health services utilization.

PURPOSE: To determine the intermediate-term impact of diagnosis and treatment of ductal carcinoma in situ of the breast (DCIS) on health services utilization, we compared utilization by cases of DCIS to unaffected controls. METHODS: We identified a population-based cohort of Ontario females diagnosed with DCIS between 2010 and 2015. We matched 5 controls without any history of cancer to each case, on the date of diagnosis of the case (the index date), by age, annual mammography history, socioeconomic status, and comorbidity. We identified billing claims and hospital records, during the interval 13 to 60 months prior to, and subsequent to the index date, and computed rates per 100 person-years during both intervals, to conduct a difference-in-differences analysis. We used negative binomial regression to test if the change in rates in health services differed between cases and controls. RESULTS: Visits with a breast diagnosis code, and claims for breast surgery and imaging, were significantly increased among cases compared to controls (all p values < 0.0001) after DCIS;however, there was no increase in visits for anxiety or depression (RR 1.13 (95% CI 0.97, 1.32, p = 0.11), visits to psychiatrists (RR 1.07 (95% CI 0.82, 1.40) p = 0.6), or hospital procedures other than breast surgery (RR 1.10 (95% CI 0.88, 1.37) p = 0.4). CONCLUSIONS: DCIS is associated with more visits and procedures related to the breast compared to controls following diagnosis and treatment, but other health services utilization and visits related to anxiety and depression were not increased.

Fractionation in adjuvant radiotherapy for invasive breast cancer and ductal carcinoma in situ in Ontario, Canada from 2009 to 2015.

The use of hypofractionated radiotherapy (HFRT) in patients with breast cancer and ductal carcinoma in situ (DCIS) in Ontario, Canada, from 2009 to 2015 was reported. A retrospective cohort study was conducted using data from the Institute for Clinical Evaluative Sciences (ICES). Patients with a breast cancer or DCIS diagnosis between 2009 and 2015 who received adjuvant breast or chest wall radiation were included. Trends in HFRT use (≤16 fractions) and factors associated with HFRT use in a multivariable logistic regression model with physician-level random effect were reported. The approximate number of hours that could be saved if all patients were to receive HFRT was calculated. A total of 42 072 patients were included. All included characteristics were significantly associated with HFRT use. Hypofractionated radiotherapy use in patients with breast cancer and DCIS increased to around 75% in 2015. In stage I/II patients with mastectomy and chest wall radiation, HFRT use increased to 40% in 2015. Hypofractionated radiotherapy use in patients with regional nodal radiation or reconstruction has increased but remains under 20%. For breast cancer patients with breast-conserving surgery (BCS) and breast radiation, 56 265 visits corresponding to 7200 hours of treatment or 3500 additional HFRT courses could have been saved. In conclusion, HFRT use in Ontario has increased in all patient populations but is nonuniform among physicians and institutions. Use of HFRT in chest wall and regional nodal radiation remains relatively lower than in breast cancer and DCIS patients with BCS.

Anesthesia Assistance in Outpatient Colonoscopy and Risk of Aspiration Pneumonia, Bowel Perforation, and Splenic Injury.

BACKGROUND & AIMS: The increase in use of anesthesia assistance (AA) to achieve deep sedation with propofol during colonoscopy has significantly increased colonoscopy costs without evidence for increased quality and with possible harm. We investigated the effects of AA on colonoscopy complications, specifically bowel perforation, aspiration pneumonia, and splenic injury. METHODS: In a population-based cohort study using administrative databases, we studied adults in Ontario, Canada undergoing outpatient colonoscopy from 2005 through 2012. Patient, endoscopist, institution, and procedure factors were derived. The primary outcome was bowel perforation, defined using a validated algorithm. Secondary outcomes were splenic injury and aspiration pneumonia. Using a matched propensity score approach, we matched persons who had colonoscopy with AA (1:1) with those who did not. We used logistic regression models under a generalized estimating equations approach to explore the relationship between AA and outcomes. RESULTS: Data from 3,059,045 outpatient colonoscopies were analyzed; 862,817 of these included AA. After propensity matching, a cohort of 793,073 patients who had AA and 793,073 without AA was retained for analysis (51% female; 78% were age 50 years or older). Use of AA did not significantly increase risk of perforation (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.84-1.16) or splenic injury (OR, 1.09; 95% CI, 0.62-1.90]. Use of AA was associated with an increased risk of aspiration pneumonia (OR, 1.63; 95% CI, 1.11-2.37). CONCLUSIONS: In a population-based cohort study, AA for outpatient colonoscopy was associated with a significantly increased risk of aspiration pneumonia, but not bowel perforation or splenic injury. Endoscopists should warn patients, especially those with respiratory compromise, of this risk.

Patterns of adjuvant care and outcomes of elderly women with stage I breast cancer after breast-conserving surgery: a population-based analysis.

PURPOSE: Randomized trials studying endocrine therapy (ET) with and without radiation therapy (RT) following breast-conserving surgery (BCS) have detected differences in local recurrence (LR) but not survival among elderly women with hormone receptor positive stage I breast cancer (BC). We assembled a population-based cohort of such women to examine the use and outcomes associated with or without the administration of adjuvant radiotherapy (RT) or ET. METHODS: Women aged ≥ 65 years with stage I BC treated with BCS in Ontario between 2010 and 2016, their treatments and outcomes were ascertained using deterministic linkages of administrative databases. Multivariable Cox regression models were used to evaluate risks of ipsilateral LR and of any first in-breast event, categorizing women by their treatment. RESULTS: 5076 women were treated with BCS followed by RT + ET (n = 1964), RT alone (n = 1325), ET alone (n = 719), or no adjuvant treatment (n = 1068). Median follow-up was 5 years. LR occurred in 0.9% after adjuvant RT + ET, 1.4% after RT alone, 3.1% after ET alone, and 9.4% after BCS alone (p < 0.001). The adjusted risk of LR was increased in those who received no adjuvant therapy (HR = 13.43, CI: 7.89, 22.85), or ET alone (HR = 4.03, CI: 2.14, 7.59). The adjusted risk of any first in-breast event was greatest among those without any adjuvant therapy (HR = 7.61, 95%CI: 5.21, 11.11, p < 0.0001). Absolute and adjusted risks of any first in-breast event were comparable between those with ET alone (HR = 2.09, 95%CI: 1.27, 3.43, p = 0.0038) and those with RT alone (HR = 1.91, 95% CI: 1.25, 2.91, p = 0.0028). CONCLUSIONS: Older women with stage I BC who receive no adjuvant therapy have a significant absolute risk of LR and any first in-breast event, whereas the absolute risk of these events among those with either RT alone or ET alone is only slightly higher than among those treated with both.

The time-varying effect of radiotherapy after breast-conserving surgery for DCIS.

BACKGROUND: A better understanding underlying radiation (RT) response after breast-conserving surgery (BCS) is needed to mitigate over-treatment of DCIS. The hazard ratio (HR) measures the effect of RT but assumes the effect is constant over time. We examined the hazard function adjusted for adherence to surveillance mammography to examine variations in LR risk and the effect of RT over time. METHODS: Crude hazard estimates for the development of LR in a population cohort of DCIS treated by BCS ± RT were computed. Multivariable extended Cox models and hazard plots were used to examine the association between receipt of RT and risk of each outcome adjusted for baseline covariates and adherence to mammography. RESULTS: Population cohort includes 3262 women treated by BCS; 1635 received RT. Median follow-up was 13 years. LR developed in 364 women treated by BCS alone and 274 treated with RT. LR risk peaked at 2 years, declined until year 7, and then remained steady. The peak hazard of LR was associated with adverse features of DCIS. Early LR risk was attenuated in patients treated with RT but late annual risks of LR and invasive LR were similar among the two treatment groups. On multivariate analysis, RT was associated with a reduction in early LR risk (HR = 0.52, 95% CI 0.43-0.63, p < 0.0001) but did not reduce the risk of late LR (HR = 0.89, 95% CI: 0.67, 1.19, p = 0.44) (interaction, p = 0.002). CONCLUSIONS: The effect of RT is not uniform over time and greatest in the first 7 years after BCS for DCIS, which can guide future research to understand mechanisms underlying RT response and optimize future management of DCIS.

Multiple foci of microinvasion is associated with an increased risk of invasive local recurrence in women with ductal carcinoma in situ treated with breast-conserving surgery.

PURPOSE: The impact of Ductal Carcinoma in Situ (DCIS) with multiple foci of microinvasion (MI) (≤ 1 mm) on the risks of local recurrence (LR) and invasive LR is unknown, leading to uncertainty if DCIS with multiple foci of MI requires more aggressive treatment. We report a population-based analysis of the impact of multiple foci of MI, confirmed by pathology review, on the 15-year risks of LR and invasive LR treated with breast-conserving surgery (BCS) ± radiotherapy (RT). METHODS: Cohort includes all women diagnosed with DCIS ± MI from 1994 to 2003 treated with BCS ± RT. Cox proportional hazards model was used to evaluate the impact of multiple foci of MI on the risks of LR and invasive LR, adjusting for covariates. The 15-year local and invasive local recurrence-free survival rates were calculated using the Kaplan-Meier method with differences compared by log-rank test. RESULTS: The cohort includes 2988 women treated by BCS; 2721 had pure DCIS (51% received RT), 267 had DCIS with one or more foci of MI (58% had RT). Median follow-up was 13 years. Median age at diagnosis was 58 years. On multivariable analyses, the presence of multiple foci of MI was associated with an increased risk of invasive LR (HR = 1.59, 95% CI 1.01-2.49, p = 0.04) but not DCIS LR (HR = 0.89, 95% CI 0.46, 1.76, p = 0.7). The 15-year invasive LRFS risks for cases with pure DCIS, with 1 focus or multiple foci of MI were 85.7%, 85.6%, 74.7% following treatment by BCS alone, 87.2%, 89.9%, and 77% for those treated with BCS + RT without boost and 89.2%, 91.3%, and 95% for women treated with BCS + RT and boost. CONCLUSIONS: The presence of multiple foci of MI in DCIS is associated with higher 15-year risks of invasive LR after breast-conserving therapy compared to women with pure DCIS but treatment with whole breast and boost RT can mitigate this risk.

Economic Analysis of Adjuvant Chemoradiotherapy Compared with Chemotherapy in Resected Pancreas Cancer.

BACKGROUND: Population-based survival and costs of pancreas adenocarcinoma patients receiving adjuvant chemoradiation and chemotherapy following pancreaticoduodenectomy are poorly understood. METHODS: This retrospective cohort study used linked administrative and pathological datasets to identify all patients diagnosed with pancreas adenocarcinoma and undergoing pancreaticoduodenectomy in Ontario between April 2004 and March 2014, who received postoperative chemoradiation or chemotherapy. Stage and margin status were defined by using pathology reports. Kaplan-Meier and Cox proportional hazards regression survival analyses were used to determine associations between adjuvant treatment approach and survival, while stratifying by margin status. Median overall health system costs were calculated at 1 and 3 years for chemoradiation and chemotherapy, and differences were tested using the Kruskal-Wallis test. RESULTS: Among 709 patients undergoing pancreaticoduodenectomy for pancreas cancer during the study period, the median survival was 21 months. Median survival was 19 months for chemoradiation and 22 months for chemotherapy. Patients receiving chemoradiation were more likely to have positive margins: 47.7% compared with 19.2% in chemotherapy. After stratifying by margin status and controlling for confounders, adjusted hazard ratio of death were not statistically different between chemotherapy and chemoradiation [margin positive, hazard ratio (HR) = 0.99, 95% confidence interval (CI) = 0.88-1.27; margin negative, HR 0.95, 95% CI 0.91-1.18]. Overall 1-year health system costs were significantly higher for chemoradiation (USD $70,047) than chemotherapy (USD $54,005) (p ≤ 0.001). CONCLUSIONS: Chemotherapy and chemoradiation yielded similar survival, but chemoradiation resulted in higher costs. To create more sustainable healthcare systems, both the efficacy and costs of therapies should be considered.