Outcomes and Healthcare Utilization Among New Persistent Opioid Users and Nonopioid Users After Curative-intent Surgery for Cancer.

OBJECTIVE: The aim of the study was to compare the health outcomes and resource use of cancer patients who were new persistent opioid users with those who were not, after undergoing curative intent surgery for cancer. BACKGROUND: Little is known about long-term health outcomes (overdose, mortality) and resource utilization of new persistent opioid users among cancer patients undergoing curative-intent surgery. METHODS: This retrospective cohort study included all adults with a diagnosis of solid cancers who underwent curative-intent surgery during the study period (2011-2015) in Alberta, Canada and were opioid-naïve before surgery, with a follow-up period until December 31, 2019. The key exposure, "new persistent opioid user," was defined as a patient who was opioid-naive before surgery and subsequently filled at least 1 opioid prescription between 60 and 180 days after surgery. The primary outcome was opioid overdose that occurred within 3 years of surgery. All-cause death, noncancer caused death, and department visit (yes vs. no), and hospitalization (yes vs. no) in the follow-up periods were also included as outcomes. RESULTS: In total, 19,219 patients underwent curative intent surgery with a median follow-up of 47 months, of whom 1530 (8.0%) were identified as postoperative new persistent opioid users. In total, 101 (0.5%) patients experienced opioid overdose within 3 years of surgery. Compared with nonopioid users, new persistent opioid users experienced a higher rate of opioid overdose (OR = 2.37, 95% CI: 1.44-3.9) within 3 years of surgery. New persistent opioid use was also associated with a greater likelihood of being hospitalized (OR = 2.03, 95% CI: 1.76-2.33) and visiting an emergency room (OR = 1.83, 95% CI: 1.62-2.06) in the first year after surgery, and a higher overall (HR = 1.28, 95% CI: 1.1-1.49) and noncancer caused mortality (HR = 1.33, 95% CI: 1.12-1.58), when compared with nonopioid users. CONCLUSION: Postoperative new persistent opioid use among cancer patients undergoing curative-intent surgery is associated with subsequent opioid overdose, worse survival, and more health resource utilization.

Investigating Factors Associated with Postmastectomy Emergency Department Visits: A Population-Based Analysis.

BACKGROUND: In 2016, a multi-pronged pathway was implemented across 13 hospitals to improve the mastectomy perioperative care experience with one objective being to safely allow same day surgery mastectomy. While the pathway successfully increased same day mastectomy rates from 1.7 to 73.0%, the rate of postoperative emergency department (ED) visits remained high at > 20%, despite focused interventions to enhance perioperative support. AIM: To investigate potential factors associated with high postoperative ED visits following mastectomies in Alberta, Canada. METHODS: Data was collected using the Discharge Abstract Database and the National Ambulatory Care Reporting System database. Eligible patients included all women over 18 years old who underwent a mastectomy province-wide between 2004 and 2020. Patient demographics were collected. Primary outcome of interest was ED visit within 30 days of mastectomy. Univariate and multivariable analyses were performed to identify independent predictors for post-operative ED visits. RESULTS: A total of 19,974 patients had mastectomy during the study period, of which 4590 (23%) had an ED visit within 30 days of surgery. Independent factors associated with ED visits were increasing age, overnight stay mastectomy, reconstruction, certain comorbidities, and living rurally. CONCLUSIONS: Post-operative ED visits remain high despite initiating a province-wide surgical pathway in 2016 which emphasizes patient education and improved perioperative care and supports. Currently, the majority of ED visits are manageable in non-emergent settings. Patient populations at higher risk for ED visits groups may benefit from additional targeted support and resources to reduce unplanned ED visits.

Patient and disease characteristics, treatment practices and oncologic outcomes among patients with colorectal cancer: a population-based analysis.

BACKGROUND: The incidence of colorectal cancer (CRC) is increasing among young adults. We sought to report on patient and disease characteristics, treatment practice patterns and outcomes in this population. METHODS: We conducted a retrospective cohort study using administrative health data from the Alberta Cancer Registry (2004-2015), including demographic and tumour characteristics, and treatment received. Outcome measures included overall and cancer-specific deaths. We used Cox regression and Kaplan-Meier curves to assess for factors associated with survival. RESULTS: We included 18 070 patients with CRC (n = 1583 [8.8%] < 50 yr, n = 16 487 [91.2 %] ≥ 50 yr). Younger patients were more likely to present with locally advanced disease (21.0% v. 18.0%, p < 0.0001), stage III (16.4 % v. 14.6%, p < 0.0001) or metastatic (16.7% v. 13.8%, p < 0.0001) involvement. Younger patients were more likely to receive surgery (87.2% v. 80.9%, p < 0.0001), chemotherapy (59.6% v. 34.1%, p < 0.0001) or radiation therapy (49.5% v. 37.2%, p < 0.001). At 5 years, overall and cancer-specific survival was better among younger patients than older patients (30.6% v. 51.5% overall deaths, 27.5% v. 38.4% cancer-specific deaths, p < 0.0001). CONCLUSION: Despite higher stage and higher grade disease, young patients with CRC had more favourable oncologic outcomes than stage-matched older patients, which may be related to younger patients receiving more aggressive treatment. Further investigation should focus on optimal treatment patterns for young patients with CRC.

Associations Between Physician Prescribing Behavior and Persistent Postoperative Opioid Use Among Cancer Patients Undergoing Curative-intent Surgery: A Population-based Cohort Study.

OBJECTIVE: This study aimed to evaluate the association between prescribers' opioid prescribing history and persistent postoperative opioid use in cancer patients undergoing curative-intent surgery. BACKGROUND: Study has shown that patients may be over-prescribed analgesics after surgery. However, whether and how the prescriber's opioid prescribing behavior impacts persistent opioid use is unclear. METHODS: All adults with a diagnosis of solid cancers who underwent surgery during the study period (2009-2015) in Alberta, Canada and were opioid-naïve were included. The key exposure was the historical opioid-prescribing pattern of a patient's most responsible prescriber. The primary outcome was "new persistent postoperative opioid user," was defined as a patient who was opioid-naïve before surgery and subsequently filled at least 1 opioid prescription between 60 and 180 days after surgery. RESULTS: We identified 24,500 patients. Of these, 2106 (8.6%) patients became a new persistent opioid user after surgery. Multivariate analysis demonstrated that patients with most responsible prescribers that historically prescribed higher daily doses of opioids (≥50 vs <50 mg oral morphine equivalent) had an increased risk of new persistent opioid use after surgery (odds ratio = 2.41, P < 0.0001). In addition to the provider's prescribing pattern, other factors including younger age, comorbidities, presurgical opioid use, chemotherapy, type of tumor/surgical procedure were also found to be independently associated with new persistent postoperative opioid use. CONCLUSIONS: Our results suggest that prescriber with a history of prescribing a higher opioid dose is an important predictor of persistent postoperative opioid use among cancer patients undergoing curative-intent surgery.

Risk factors for psychological morbidity and the protective role of coping self-efficacy in young women with breast cancer early in diagnosis: a national multicentre cohort study.

PURPOSE: Young women with breast cancer (YWBC) are an understudied population and there are limited data on risk factors for psychological morbidity early in diagnosis. We examined psychological morbidity (anxiety, depression, stress symptoms), well-being and associated risk factors. METHODS: A total of 845 women from a pan-Canadian, multicentre inception cohort study of YWBC (age ≤ 40) who completed Patient Reported Outcome Measures (PROMs) after their initial surgical consultation and prior to surgical or other treatments were included. Multivariate regression analyses identified risk factors (i.e. parenting young children) associated with psychological morbidity and whether coping self-efficacy was protective. RESULTS: Rates of clinically significant anxiety (n = 683, 69.1%) and depression (n = 422, 42.7%) were high but lower for stress symptoms (n = 67, 6.8%). Probability of anxiety was high for women with a previous history of depression (OR 2.02, P = 0.03, CI 1.09-3.74) and working full-time (OR 1.76, P = 0.05 CI 1.02-2.77). Whereas, pre-existing depression (OR 2.91, P = 0.01, CI 1.36-6.01), younger children (age ≤ 10) (OR 1.69, P = 0.05, CI 1.01-2.93), and income > $100,000 (OR 2.06, P = 0.02, CI 1.18-3.64) were risk factors for depression. Coping self-efficacy was protective with a decreased risk of anxiety (OR 0.11, P ≤ 0.01 CI 0.04-0.28), depression (OR 0.03, P ≤ .01, CI 0.01-0.16), stress symptoms (OR 0.17, P ≤ .01, CI 0.04-0.65) and higher psychosocial well-being with a gain of 19.68 points (P < 0.01) for high levels of CSE (> mean plus 1 SD). Those with lower levels of neurosis had less negative outcomes. CONCLUSION: Young women with breast cancer are vulnerable to psychological morbidity early in diagnosis, particularly those with low coping self-efficacy and may benefit from earlier supportive care.

New method for determining breast cancer recurrence-free survival using routinely collected real-world health data.

BACKGROUND: In cancer survival analyses using population-based data, researchers face the challenge of ascertaining the timing of recurrence. We previously developed algorithms to identify recurrence of breast cancer. This is a follow-up study to detect the timing of recurrence. METHODS: Health events that signified recurrence and timing were obtained from routinely collected administrative data. The timing of recurrence was estimated by finding the timing of key indicator events using three different algorithms, respectively. For validation, we compared algorithm-estimated timing of recurrence with that obtained from chart-reviewed data. We further compared the results of cox regressions models (modeling recurrence-free survival) based on the algorithms versus chart review. RESULTS: In total, 598 breast cancer patients were included. 121 (20.2%) had recurrence after a median follow-up of 4 years. Based on the high accuracy algorithm for identifying the presence of recurrence (with 94.2% sensitivity and 79.2% positive predictive value), the majority (64.5%) of the algorithm-estimated recurrence dates fell within 3 months of the corresponding chart review determined recurrence dates. The algorithm estimated and chart-reviewed data generated Kaplan-Meier (K-M) curves and Cox regression results for recurrence-free survival (hazard ratios and P-values) were very similar. CONCLUSION: The proposed algorithms for identifying the timing of breast cancer recurrence achieved similar results to the chart review data and were potentially useful in survival analysis.

Trends in treatment patterns and survival outcomes in advanced non-small cell lung cancer: a Canadian population-based real-world analysis.

BACKGROUND: As part of the multi-country I-O Optimise research initiative, this population-based study evaluated real-world treatment patterns and overall survival (OS) in patients treated for advanced non-small cell lung cancer (NSCLC) before and after public reimbursement of immuno-oncology (I-O) therapies in Alberta province, Canada. METHODS: This study used data from the Oncology Outcomes (O2) database, which holds information for ~ 4.5 million residents of Alberta. Eligible patients were adults newly diagnosed with NSCLC between January 2010 and December 2017 and receiving first-line therapy for advanced NSCLC (stage IIIB or IV) either in January 2010-March 2016 (pre-I-O period) or April 2016-June 2019 (post-I-O period). Time periods were based on the first public reimbursement of I-O therapy in Alberta (April 2017), with a built-in 1-year lag time before this date to allow progression to second-line therapy, for which the I-O therapy was indicated. Kaplan-Meier methods were used to estimate OS. RESULTS: Of 2244 analyzed patients, 1501 (66.9%) and 743 (33.1%) received first-line treatment in the pre-I-O and post-I-O periods, respectively. Between the pre-I-O and post-I-O periods, proportions of patients receiving chemotherapy decreased, with parallel increases in proportions receiving I-O therapies in both the first-line (from < 0.5% to 17%) and second-line (from 8% to 47%) settings. Increased use of I-O therapies in the post-I-O period was observed in subgroups with non-squamous (first line, 15%; second line, 39%) and squamous (first line, 25%; second line, 65%) histology. First-line use of tyrosine kinase inhibitors also increased among patients with non-squamous histology (from 26% to 30%). In parallel with these evolving treatment patterns, median OS increased from 10.2 to 12.1 months for all patients (P < 0.001), from 11.8 to 13.7 months for patients with non-squamous histology (P = 0.022) and from 7.8 to 9.4 months for patients with squamous histology (P = 0.215). CONCLUSIONS: Following public reimbursement, there was a rapid and profound adoption of I-O therapies for advanced NSCLC in Alberta, Canada. In addition, OS outcomes were significantly improved for patients treated in the post-I-O versus pre-I-O periods. These data lend support to the emerging body of evidence for the potential real-world benefits of I-O therapies for treatment of patients with advanced NSCLC.

The influence of adjuvant chemotherapy dose intensity on overall survival in resected colon cancer: a multicentered retrospective analysis.

BACKGROUND: Colorectal cancer remains the second leading cause of cancer death in North America. Fluorouracil and oxaliplatin based adjuvant chemotherapy for resected colon cancer (CC) reduces cancer recurrence, but also causes significant toxicity requiring dose reductions. The effect of dose intensity on survival outcomes is not fully understood and strengthening the evidence supports informed decision making between patients and oncologists. METHODS: Patients treated with adjuvant chemotherapy, between 2006 and 2011, for resected colon cancer at four Canadian academic cancer centers were retrospectively analyzed. All patients must have received oxaliplatin with either capecitabine (CAPOX) or 5-FU (FOLFOX). Dose intensity (DI) was calculated as total delivered dose of an individual chemotherapy agent divided by the cumulative intended dose of that agent. The influence of DI on overall survival was examined. RESULTS: Five hundred thirty-one patients with high-risk stage II or stage III resected CC were eligible and included in the analysis. FOLFOX was the most common regimen (69.6%) with 29.7% of patients receiving CAPOX and 0.7% receiving both therapies. Median follow-up was 36.7 months. The median DI for 5-FU and capecitabine was 100% and 100% with 13.6% and 9.8% of patients receiving ≤ 80% DI, respectively. The median DI of oxaliplatin was 70% with 56.8% of patients receiving ≤ 80% DI. A DI of > 80% for each chemotherapy component was associated with a significant improvement in overall survival compared to those with a DI of ≤ 80% (5-FU HR = 0.23, 95% CI = 0.08-0.65, p = 0.006; capecitabine HR = 0.56, 95% CI = 0.33-0.94, p = 0.026; oxaliplatin HR = 0.52, 95% CI = 0.33-0.82, p = 0.005). Patients with T2 and/or N2 disease with an oxaliplatin DI > 80% had a trend towards improved survival (HR = 0.62, 95% CI = 0.38-1.02, p = 0.06). CONCLUSIONS: In resected CC an adjuvant chemotherapy DI of > 80%, of each chemotherapy agent, is associated with improved overall survival.

Factors associated with the initiation of chemotherapy within 90 days of death in metastatic colorectal cancer patients: a population-based study.

INTRODUCTION: Initiation of chemotherapy in patients with cancer near end-of-life (EOL) has become more frequent due to an increasing number of treatment options. We aimed to analyze the proportion of metastatic colorectal cancer patients (mCRC) in Alberta, Canada, who were started on a new chemotherapy regimen within 90 days of death. METHODS: This was a retrospective, population-based study using data from the cancer measurement outcomes and evaluation (C-MORE) database. All patients who received chemotherapy for mCRC in a large Canadian province from January 1, 2011, to December 31, 2016, were included in the current analysis. We identified the proportion of patients who initiated chemotherapy near EOL. Further, we analyzed the associations of baseline factors with initiation of chemotherapy near EOL. RESULTS: We identified 511 patients with mCRC who received chemotherapy. Of these, 132 (25.8%) initiated chemotherapy near EOL. Charlson's comorbidity index (CCI) score (score 1: OR, 0.524; 95% CI, 0.279-0.985; P = 0.045; CCI score > 1: OR, 0.366; 95% CI, 0.180-0.746; P = 0.006) and Eastern cooperative oncology group performance status (ECOG PS) (ECOG PS 2: OR, 4.457; 95% CI 2.518-7.890; P < 0.0001; ECOG PS > 2: OR 7.725; 95% CI 3.465-17.222; P < 0.0001) were predictive of initiation of chemotherapy near EOL. The most frequent chemotherapy regimens initiated were FOLFIRI (17%), capecitabine (15%), and panitumumab (15%), respectively. CONCLUSIONS: Chemotherapy is frequently initiated near EOL in patients with mCRC. Routine clinical assessments including ECOG PS and comorbid medical conditions can help select patients with mCRC who are unlikely to benefit from palliative chemotherapy and prevent the adverse events and healthcare costs associated with such interventions near EOL.

Anti-PD1-Induced Immune-Related Adverse Events and Survival Outcomes in Advanced Melanoma.

INTRODUCTION: Objective response rates (ORR) appear to be higher in melanoma patients who develop immune-related adverse events (irAEs), but whether there is a similar association between irAEs and survival remains unknown. MATERIALS AND METHODS: Patients with advanced melanoma treated with single-agent pembrolizumab or nivolumab in the province of Alberta from June 2014 to May 2017 were identified through the provincial pharmacy database. Chart review identified and categorized all irAEs that occurred while on anti-programmed cell death protein 1 (PD-1) checkpoint inhibitors. The primary objective was to compare overall survival (OS) with patients who developed any irAEs versus those who did not. Secondary outcomes included progression-free survival (PFS) and ORR. RESULTS: Among 186 patients, any-grade and grade ≥3 irAEs occurred in 88 (47%) and 27 (15%) patients, respectively; one patient died of pneumonitis. In a landmark analysis excluding patients who died within the first 12 weeks, the median follow-up was 24 months, 20 months in patients without any irAEs and 26 months in patients with irAEs (p = .006). Median OS was 39 versus 23 months (hazard ratio [HR], 0.46; p = .001) for any irAE and no irAE, respectively, and median OS not reached versus 29 months for grade ≥3 irAEs and no grade ≥3 irAEs, respectively. In multivariate analysis, elevated lactate dehydrogenase correlated with reduced OS (HR, 2.34; p = .001), whereas each additional cycle of treatment received (HR, 0.94; p < .001) and development of grade ≥3 irAEs (HR, 0.29, p = .024) were significantly associated with longer OS. CONCLUSION: Anti-PD-1-associated grade ≥3 irAEs in patients with advanced melanoma is associated with better patient outcomes, including overall survival. IMPLICATIONS FOR PRACTICE: Previous prospective randomized clinical trials demonstrate improved response rates in patients with melanoma who develop select adverse events. The current population-based real-world study in advanced melanoma reports an association with anti-programmed cell death protein 1 (PD-1)-induced grade ≥3 immune-related adverse events (irAEs) and better patient outcomes, including overall survival. These results suggest that irAEs may be a manifestation of a patient's ability to mount a systemic immune response from PD-1-directed therapies, which may be associated with therapeutic benefit. The finding of irAEs coinciding with clinical benefit from these therapies supposes that these events are, by and large, unavoidable, and the critical management of irAEs remains essential for optimizing patient outcomes.

Breast Biopsy During Post-treatment Surveillance of Screen-Detected Breast Cancer Patients Yields High Rates of Benign Findings.

BACKGROUND: The incidence of breast biopsy following treatment for breast cancer is not well-characterized. We sought to determine the frequency and outcomes of breast biopsy and the need for subsequent surgery in patients treated with breast-conserving surgery (BCS). METHODS: Using a prospective database, we identified patients in Alberta, Canada, treated with BCS for screen-detected breast cancer or ductal carcinoma in situ (DCIS) from 2010 to 2014. Post-treatment breast procedures were identified from physician claims data. Multivariable analysis was performed to identify factors associated with biopsy. RESULTS: We included 2065 patients with a median of 6.4 years of follow-up; most had DCIS (n = 426, 20.6%) or stage I disease (n = 1385, 67.1%). Post-treatment core biopsy was performed in 389 (18.8%, 95% confidence interval [CI] 17.2-20.6%) patients, and excisional biopsy was performed in 19 (0.9%, 95% CI 0.6-1.4%) patients. The per-patient benign-to-malignant biopsy ratio was 3.2 to 1, and the overall malignancy rate was 6.1% (95% CI 5.1-7.2%). Younger age, proximity to a cancer center, positive margins, and the use of magnetic resonance imaging were associated with biopsy (p < 0.05). Additional surgery was performed in 150 (7.3%, 95% CI 6.2-8.5%) patients; 93 (4.5%, 95% CI 3.6-5.4%) patients underwent mastectomy. Surgery was performed for local recurrence/ipsilateral cancer in 62 (3.0%) patients, contralateral breast cancer in 60 (2.9%) patients, bilateral breast cancer in 3 (0.1%) patients, and benign indications/prophylaxis in 25 (1.2%) patients. CONCLUSIONS: One in five patients required breast biopsy during post-treatment surveillance following BCS and most revealed benign findings. Rates of additional surgery, especially subsequent mastectomy due to ipsilateral or contralateral malignancy, were low. Patients can be reassured of these findings during pre-treatment counseling and post-treatment surveillance.

Impact of pre-existing cardiovascular disease on treatment patterns and survival outcomes in patients with lung cancer.

BACKGROUND: Baseline cardiovascular disease (CVD) can impact the patterns of treatment and hence the outcomes of patients with lung cancer. This study aimed to characterize treatment trends and survival outcomes of patients with pre-existing CVD prior to their diagnosis of lung cancer. METHODS: We conducted a retrospective, population-based cohort study of patients with lung cancer diagnosed from 2004 to 2015 in a large Canadian province. Multivariable logistic regression and Cox regression models were constructed to determine the associations between CVD and treatment patterns, and its impact on overall (OS) and cancer-specific survival (CSS), respectively. A competing risk multistate model was developed to determine the excess mortality risk of patients with pre-existing CVD. RESULTS: A total of 20,689 patients with lung cancer were eligible for the current analysis. Men comprised 55%, and the median age at diagnosis was 70 years. One-third had at least one CVD, with the most common being congestive heart failure in 15% of patients. Pre-existing CVD was associated with a lower likelihood of receiving chemotherapy (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.48-0.58; P < .0001), radiotherapy (OR, 0.76; 95% CI, 0.7-0.82; P < .0001), and surgery (OR, 0.56; 95% CI, 0.44-0.7; P < .0001). Adjusting for measured confounders, the presence of pre-existing CVD predicted for inferior OS (hazard ratio [HR], 1.1; 95% CI, 1.1-1.2; P < .0001) and CSS (HR, 1.1; 95% CI, 1.1-1.1; P < .0001). However, in the competing risk multistate model that adjusted for baseline characteristics, prior CVD was associated with increased risk of non-cancer related death (HR, 1.48; 95% CI, 1.33-1.64; P < 0.0001) but not cancer related death (HR, 0.98; 95% CI, 0.94-1.03; P = 0.460). CONCLUSIONS: Patients with lung cancer and pre-existing CVD are less likely to receive any modality of cancer treatment and are at a higher risk of non-cancer related deaths. As effective therapies such as immuno-oncology drugs are introduced, early cardio-oncology consultation may optimize management of lung cancer.

Patient-level factors associated with chronic opioid use in cancer: a population-based cohort study.

PURPOSE: Concerns around chronic opioid use (COU), misuse, and harms have led to increased scrutiny of opioid prescribing in oncology. There is lack of research examining patient-level factors associated with COU. Our aim was to examine patient-level factors associated with COU in newly diagnosed cancer patients. METHODS: Population-based retrospective cohort study using administrative health data of patients in Alberta, Canada, diagnosed between February 2016 and October 2017. Adult cancer patients who completed a symptom survey within ± 60 days of diagnosis were included. Patients were divided into two groups: COU (defined as continuous opioid prescriptions for at least 90 days post-diagnosis) and non-chronic opioid use (NCOU). Logistic regression was used to evaluate factors associated with COU. RESULTS: We included 694 patients (mean age 65 years; 51% female). Most had breast (20%), colorectal (13%), and lung (33%) cancers. Of the 14% with COU, 79% were opioid naïve at diagnosis. Those in the COU group were more often diagnosed with advanced cancer (66% versus 40%), had lung cancer (47%), and were opioid tolerant (> 90 days of continuous opioids within one-year pre-diagnosis). A total of 64% of COU versus 27% of NCOU had moderate to severe pain at diagnosis (p < 0.001). Irrespective of treatment type or stage, those with moderate to severe pain, were opioid tolerant at diagnosis, or had multiple prescribers were at greater risk for COU. CONCLUSIONS: Specific patient groups were at increased risk of COU and should be the focus of adaptive prescribing approaches to ensure that opioid use is appropriate.

Development and validation of case-finding algorithms for recurrence of breast cancer using routinely collected administrative data.

BACKGROUND: Recurrence is not explicitly documented in cancer registry data that are widely used for research. Patterns of events after initial treatment such as oncology visits, re-operation, and receipt of subsequent chemotherapy or radiation may indicate recurrence. This study aimed to develop and validate algorithms for identifying breast cancer recurrence using routinely collected administrative data. METHODS: The study cohort included all young (≤ 40 years) breast cancer patients (2007-2010), and all patients receiving neoadjuvant chemotherapy (2012-2014) in Alberta, Canada. Health events (including mastectomy, chemotherapy, radiation, biopsy and specialist visits) were obtained from provincial administrative data. The algorithms were developed using classification and regression tree (CART) models and validated against primary chart review. RESULTS: Among 598 patients, 121 (20.2%) had recurrence after a median follow-up of 4 years. The high sensitivity algorithm achieved 94.2% (95% CI: 90.1-98.4%) sensitivity, 93.7% (91.5-95.9%) specificity, 79.2% (72.5-85.8%) positive predictive value (PPV), and 98.5% (97.3-99.6%) negative predictive value (NPV). The high PPV algorithm had 75.2% (67.5-82.9%) sensitivity, 98.3% (97.2-99.5%) specificity, 91.9% (86.6-97.3%) PPV, and 94% (91.9-96.1%) NPV. Combining high PPV and high sensitivity algorithms with additional (7.5%) chart review to resolve discordant cases resulted in 94.2% (90.1-98.4%) sensitivity, 98.3% (97.2-99.5%) specificity, 93.4% (89.1-97.8%) PPV, and 98.5% (97.4-99.6%) NPV. CONCLUSION: The proposed algorithms based on routinely collected administrative data achieved favorably high validity for identifying breast cancer recurrences in a universal healthcare system in Canada.

'Driving' Rates Down: A Population-Based Study of Opening New Radiation Therapy Centers on the Use of Mastectomy for Breast Cancer.

BACKGROUND: Two new cancer centers providing radiation therapy opened in Alberta, Canada, in 2010 and 2013, respectively. We aimed to assess whether opening the new RT centers influenced mastectomy rates for breast cancer. METHOD: Breast cancer patients who underwent surgery from 2004 through 2015 were identified from the Alberta Cancer Registry. Mastectomy rates for 64 predefined health status areas (HSAs) were calculated after adjusting for patient and system factors. Variations in mastectomy rates among the HSAs were quantified using weighted coefficient of variation (CV). Multivariable logistic regressions were performed to determine associations between driving time and mastectomy use in the entire cohort and in subgroups. RESULTS: Of the 21,872 patients, the proportion of patients who lived a ≤ 60 min drive from the nearest RT center significantly increased from 68.8% (95% CI 67.7-69.9%) to 80.7% (95% CI 79.5-81.9%) during the study period. Concurrently, the crude provincial mastectomy rate decreased from 56.2% (95% CI 55.3-57.1%) to 45.3% (95% CI 44.1-46.5%). However, variation in adjusted mastectomy rates (weighted CV) across the 64 HSAs increased from 9.5 to 14.6. Factors associated with mastectomy included age, larger tumor size, lymph node involvement, higher tumor grade, molecular subtype, lobular histology type, more comorbidities, academic institution, region, earlier period of diagnosis, and longer driving time to the nearest RT center. CONCLUSIONS: Opening new RT centers in previously underserved regions reduced driving times to the nearest center, and was associated with a reduction in mastectomy rates; however, these reductions among regions across the province were not uniform.

A Population-Based Study to Evaluate the Associations of Nodal Stage, Lymph Node Ratio and Log Odds of Positive Lymph Nodes with Survival in Patients with Small Bowel Adenocarcinoma.

PURPOSE: This study aimed to determine the real-world prognostic significance of lymph node ratio (LNR) and log odds of positive lymph nodes (LOPLN) in patients with non-metastatic small bowel adenocarcinoma. METHODS: Patients diagnosed with early-stage small bowel adenocarcinoma between January 2007 and December 2018 from a large Canadian province were identified. We calculated the LNR by dividing positive over total lymph nodes examined and the LOPLN as log ([positive lymph nodes + 0.5]/[negative lymph nodes + 0.5]). The LNR and LOPLN were categorized at cut-offs of 0.4 and -1.1, respectively. Multivariable Cox proportional hazards models were constructed for each nodal stage, LNR and LOPLN, adjusting for measured confounding factors. Harrell's C-index and Akaike's Information Criterion (AIC) were used to calculate the prognostic discriminatory abilities of the different models. RESULTS: We identified 141 patients. The median age was 67 years and 54.6% were men. The 5-year overall survival rates for patients with stage I, II and III small bowel adenocarcinoma were 50.0%, 56.6% and 47.5%, respectively. The discriminatory ability was generally comparable for LOPLN, LNR and nodal stage in the prognostication of all patients. However, LOPLN had higher discriminatory ability among patients with at least one lymph node involvement (Harrell's C-index, 0.75, 0.77 and 0.82, and AIC, 122.91, 119.68 and 110.69 for nodal stage, LNR and LOPLN, respectively). CONCLUSION: The LOPLN may provide better prognostic information when compared to LNR and nodal stage in specific patients.

Developing a Prediction Model for Pathologic Complete Response Following Neoadjuvant Chemotherapy in Breast Cancer: A Comparison of Model Building Approaches.

PURPOSE: The optimal characteristics among patients with breast cancer to recommend neoadjuvant chemotherapy is an active area of clinical research. We developed and compared several approaches to developing prediction models for pathologic complete response (pCR) among patients with breast cancer in Alberta. METHODS: The study included all patients with breast cancer who received neoadjuvant chemotherapy in Alberta between 2012 and 2014 identified from the Alberta Cancer Registry. Patient, tumor, and treatment data were obtained through primary chart review. pCR was defined as no residual invasive tumor at surgical excision in breast or axilla. Two types of prediction models for pCR were built: (1) expert model: variables selected on the basis of oncologists' opinions and (2) data-driven model: variables selected by trained machine. These model types were fit using logistic regression (LR), random forests (RF), and gradient-boosted trees (GBT). We compared the models using area under the receiver operating characteristic curve and integrated calibration index, and internally validated using bootstrap resampling. RESULTS: A total of 363 cases were included in the analyses, of which 86 experienced pCR. The RF and GBT fits yielded higher optimism-corrected area under the receiver operating characteristic curves compared with LR for the expert (RF: 0.70; GBT: 0.69; LR: 0.65) and data-driven models (RF: 0.71; GBT: 0.68; LR: 0.64). The LR fit yielded the lowest integrated calibration indices for the expert (LR: 0.037; GBT: 0.05; RF: 0.10) and data-driven models (LR: 0.026; GBT: 0.06; RF: 0.099). CONCLUSION: Our models demonstrated predictive ability for pCR using routinely collected clinical and demographic variables. We show that machine learning fit methods can be used to optimize models for pCR prediction. We also show that additional variables beyond clinical expertise do not considerably improve predictive ability and may not be of value on the basis of the burden of data collection.

Understanding real-world treatment patterns and clinical outcomes in AL amyloidosis patients diagnosed in Canada: A population-based cohort study.

Amyloid light chain (AL) amyloidosis is a rare and chronic bone marrow disorder. Existing claims data can be used to help understand the real-world treatment patterns and outcomes of this patient population. Various population-based administrative databases in Alberta, Canada were queried from 2010 to mid-2019 to identify cases of AL amyloidosis. Baseline patient and disease characteristics, sequencing of pharmacologic therapies, overall survival, and healthcare resource utilization were evaluated. A total of 215 individuals with AL amyloidosis were included. Among patients diagnosed between 2012 and 2019, 149 (85.1%) initiated first-line, 67 (38.3%) initiated second-line, 22 (12.6%) initiated third-line, and 11 (6.3%) initiated fourth-line systemic therapy. In the first-line setting, 99/149 (66.4%) received bortezomib, cyclophosphamide, and dexamethasone (CyBorD) and 21/149 (14.1%) received another bortezomib-based regimen. Survival from time of diagnosis improved over time, with a median overall survival of 25.8 months (95% CI: 9.8, 57.1) for individuals diagnosed in 2010-2011 versus 52.1 months (95% CI: 25.6, NA) for those diagnosed in 2012-2019. Despite this improvement, the proportion of individuals diagnosed in 2012-2019 who survived beyond five-years remained low (5-year survival: 48.4%; 95% CI: 40.9, 57.2) which highlights an unmet need for more efficacious therapies.

Geographic and temporal variation in the treatment and outcomes of atrial fibrillation: a population-based analysis of national quality indicators.

BACKGROUND: Assessment of potential geographic variation in quality indicators of atrial fibrillation care may identify opportunities for improvement in the quality of atrial fibrillation care. The objective of this study was to assess for potential geographic variation in the quality of atrial fibrillation care in Alberta, Canada. METHODS: In a population-based cohort of adults (age ≥ 18 yr) with incident nonvalvular atrial fibrillation (NVAF) diagnosed between Apr. 1, 2008, and Mar. 31, 2016, in Alberta, we investigated the variation in national quality indicators of atrial fibrillation care developed by the Canadian Cardiovascular Society. Specifically, we assessed the geographic and temporal variation in the proportion of patients with initiation of oral anticoagulant therapy, persistence with therapy, ischemic stroke and major bleeding outcomes 1 year after atrial fibrillation diagnosis using linked administrative data sets. We defined stroke risk using the CHADS2 score. We assessed geographic variation using small-area variation statistics and geospatial data analysis. RESULTS: Of the 64 093 patients in the study cohort (35 019 men [54.6%] and 29 074 women [45.4%] with a mean age of 69 [standard deviation 15.9] yr), 36 199 were at high risk for stroke and 14 411 were at moderate risk. Within 1 year of NVAF diagnosis, 20 180 patients (55.7%) in the high-risk group and 6448 patients (44.7%) in the moderate-risk group were prescribed anticoagulation. A total of 2187 patients (3.4%) had an ischemic stroke, and 2996 patients (4.7%) experienced a major bleed. There was substantial regional variation observed in initiation of oral anticoagulant therapy but not in the proportion of patients with ischemic stroke or major bleeding. Among the 64 Health Status Areas in Alberta, therapy initiation rates ranged from 22.6% to 71.2% among patients at high stroke risk and from 22.7% to 55.8% among those at moderate stroke risk, with clustering of lower therapy initiation rates in rural northern regions. INTERPRETATION: The rate of initiation of oral anticoagulant therapy among adults with incident atrial fibrillation was less than 60% in patients in whom oral anticoagulant therapy would be considered guideline-appropriate care. The large geographic variation in oral anticoagulant prescribing warrants additional study into patient, provider and health care system factors that contribute to variation and drive disparities in high-quality, equitable atrial fibrillation care.

Associations of Socioeconomic Status and Rurality With New-Onset Cardiovascular Disease in Cancer Survivors: A Population-Based Analysis.

PURPOSE: Patients with cancer are predisposed to develop new-onset cardiovascular disease (CVD). We aimed to assess if rural residence and low socioeconomic status modify such a risk. METHODS: Patients diagnosed with solid organ cancers without any baseline CVD and on a follow-up of at least 1 year in a large Canadian province from 2004 to 2017 were identified using the population-based registry. We performed logistic regression analyses to examine the associations of rural residence and low socioeconomic status with the development of CVD. RESULTS: We identified 81,418 patients eligible for the analysis. The median age was 62 years, and 54.3% were women. At a median follow-up of 68 months, 29.4% were diagnosed with new CVD. The median time from cancer diagnosis to CVD diagnosis was 29 months. Rural patients (32.3% v 28.5%; P < .001) and those with low income (30.4% v 25.9%; P < .001) or low educational attainment (30.7% v 27.6%; P < .001) experienced higher rates of CVD. After adjusting for baseline factors and treatment, rural residence (odds ratio [OR], 1.07; 95% CI, 1.04 to 1.11; P < .001), low income (OR, 1.17; 95% CI, 1.12 to 1.21; P < .001), and low education (OR, 1.08; 95% CI, 1.04 to 1.11; P < .001) continued to be associated with higher odds of CVD. A multivariate Cox regression model showed that patients with low socioeconomic status were more likely to die, but patients residing rurally were not. CONCLUSION: Despite universal health care, marginalized populations experience different CVD risk profiles that should be considered when operationalizing lifestyle modification strategies and cardiac surveillance programs for the growing number of cancer survivors.