A population-based analysis of the management of symptoms of depression among patients with stage IV non-small cell lung cancer (NSCLC) in Ontario, Canada.

PURPOSE: Patients with lung cancer can experience significant psychological morbidities including depression. We characterize patterns and factors associated with interventions for symptoms of depression in stage IV non-small cell lung cancer (NSCLC). METHODS: We conducted a population-based cohort study using health services administrative data in Ontario, Canada of stage IV NSCLC diagnosed from January 2007 to September 2018. A positive symptom of depression score was defined by reporting at least one ESAS (Edmonton Symptom Assessment System) depression score ≥ 2 following diagnosis until the end of follow-up (September 2019). Patient factors included age, sex, comorbidity burden, rurality of residence, and neighbourhood income quintile. Interventions included psychiatry assessment, psychology referral, social work referral and anti-depressant medical therapy (for patients ≥ 65 years with universal drug coverage). Multivariable modified Poisson regression models were used to examine the association between patient factors and intervention use for patients who reported symptoms of depression. RESULTS: In the cohort of 13,159 patients with stage IV NSCLC lung cancer, symptoms of depression were prevalent (71.4%, n = 9,397). Patients who reported symptoms of depression were more likely to receive psychiatry assessment/psychology referral (7.8% vs 3.5%; SD [standardized difference] 0.19), social work referral (17.4% vs 11.9%; SD 0.16) and anti-depressant prescriptions (23.8% vs 13.8%; SD 0.26) when compared to patients who did not report symptoms of depression respectively. In multivariable analyses, older patients were less likely to receive any intervention. Females were more likely to obtain a psychiatry assessment/psychology referral or social work referral. In addition, patients from non-major urban or rural residences were less likely to receive psychiatry assessment/psychology referral or social work referral, however patients from rural residences were more likely to be prescribed anti-depressants. CONCLUSIONS: There is high prevalence of symptoms of depression in stage IV NSCLC. We identify patient populations, including older patients and rural patients, who are less likely to receive interventions that will help identifying and screening for symptoms of depression.

Impact on costs and outcomes of multi-gene panel testing for advanced solid malignancies: a cost-consequence analysis using linked administrative data.

Background: To date, economic analyses of tissue-based next generation sequencing genomic profiling (NGS) for advanced solid tumors have typically required models with assumptions, with little real-world evidence on overall survival (OS), clinical trial enrollment or end-of-life quality of care. Methods: Cost consequence analysis of NGS testing (555 or 161-gene panels) for advanced solid tumors through the OCTANE clinical trial (NCT02906943). This is a longitudinal, propensity score-matched retrospective cohort study in Ontario, Canada using linked administrative data. Patients enrolled in OCTANE at Princess Margaret Cancer Centre from August 2016 until March 2019 were matched with contemporary patients without large gene panel testing from across Ontario not enrolled in OCTANE. Patients were matched according to 19 patient, disease and treatment variables. Full 2-year follow-up data was available. Sensitivity analyses considered alternative matched cohorts. Main Outcomes were mean per capita costs (2019 Canadian dollars) from a public payer's perspective, OS, clinical trial enrollment and end-of-life quality metrics. Findings: There were 782 OCTANE patients with 782 matched controls. Variables were balanced after matching (standardized difference <0.10). There were higher mean health-care costs with OCTANE ($79,702 vs. $59,550), mainly due to outpatient and specialist visits. Publicly funded drug costs were less with OCTANE ($20,015 vs. $24,465). OCTANE enrollment was not associated with improved OS (restricted mean survival time [standard error]: 1.50 (±0.03) vs. 1.44 (±0.03) years, log-rank p = 0.153), varying by tumor type. In five tumor types with ≥35 OCTANE patients, OS was similar in three (breast, colon, uterus, all p > 0.40), and greater in two (ovary, biliary, both p < 0.05). OCTANE was associated with greater clinical trial enrollment (25.4% vs. 9.5%, p < 0.001) and better end-of-life quality due to less death in hospital (10.2% vs. 16.4%, p = 0.003). Results were robust in sensitivity analysis. Interpretation: We found an increase in healthcare costs associated with multi-gene panel testing for advanced cancer treatment. The impact on OS was not significant, but varied across tumor types. OCTANE was associated with greater trial enrollment, lower publicly funded drug costs and fewer in-hospital deaths suggesting important considerations in determining the value of NGS panel testing for advanced cancers. Funding: T.P H holds a research grant provided by the Ontario Institute for Cancer Research through funding provided by the Government of Ontario (#IA-035 and P.HSR.158) and through funding of the Canadian Network for Learning Healthcare Systems and Cost-Effective 'Omics Innovation (CLEO) via Genome Canada (G05CHS).

Healthcare and Cancer Treatment Costs of Breast Screening Outcomes among Higher than Average Risk Women.

Concurrent cohorts of 644,932 women aged 50-74 screened annually due to family history, dense breasts or biennially in the Ontario Breast Screening Program (OBSP) from 2011-2014 were linked to provincial administrative datasets to determine health system resource utilization and costs. Age-adjusted mean and median total healthcare costs (2018 CAD) and incremental cost differences were calculated by screening outcome and compared by recommendation using regression models. Healthcare costs were compared overall and 1 year after a false positive (n = 46,081) screening mammogram and 2 years after a breast cancer diagnosis (n = 6011). Mean overall healthcare costs by age were highest for those 60-74, particularly with annual screening for family/personal history (CAD 5425; 95% CI: 5308 to 5557) compared to biennial. Although the mean incremental cost difference was higher (23.4%) by CAD 10,235 (95% CI: 6141 to 14,329) per breast cancer for women screened annually for density ≥ 75% compared to biennially, the cost difference was 12.0% lower (-CAD 461; 95% CI: -777 to -114) per false positive result. In contrast, for women screened annually for family/personal history, the mean cost difference per false positive was 19.7% higher than for biennially (CAD 758; 95% CI: 404 to 1118); however, the cost difference per breast cancer was only slightly higher (2.5%) by CAD 1093 (95% CI: -1337 to CAD 3760). Understanding that associated costs of annual compared to biennial screening may balance out by age and outcome can assist decision-making regarding the use of limited healthcare resources.

Changes in Health Care Costs, Survival, and Time Toxicity in the Era of Immunotherapy and Targeted Systemic Therapy for Melanoma.

Importance: Melanoma treatment has evolved during the past decade with the adoption of adjuvant and palliative immunotherapy and targeted therapies, with an unclear impact on health care costs and outcomes in routine practice. Objective: To examine changes in health care costs, overall survival (OS), and time toxicity associated with primary treatment of melanoma. Design, Setting, and Participants: This cohort study assessed a longitudinal, propensity score (PS)-matched, retrospective cohort of residents of Ontario, Canada, aged 20 years or older with stages II to IV cutaneous melanoma identified from the Ontario Cancer Registry from January 1, 2018, to March 31, 2019. A historical comparison cohort was identified from a population-based sample of invasive melanoma cases diagnosed from the Ontario Cancer Registry from January 1, 2007, to December 31, 2012. Data analysis was performed from October 17, 2022, to March 13, 2023. Exposures: Era of melanoma diagnosis (2007-2012 vs 2018-2019). Main Outcomes and Measures: The primary outcomes were mean per-capita health care and systemic therapy costs (Canadian dollars) during the first year after melanoma diagnosis, time toxicity (days with physical health care contact) within 1 year of initial treatment, and OS. Standardized differences were used to compare costs and time toxicity. Kaplan-Meier methods and Cox proportional hazards regression were used to compare OS among PS-matched cohorts. Results: A PS-matched cohort of 731 patients (mean [SD] age, 67.9 [14.8] years; 437 [59.8%] male) with melanoma from 2018 to 2019 and 731 patients (mean [SD] age, 67.9 [14.4] years; 440 [60.2%] male) from 2007 to 2012 were evaluated. The 2018 to 2019 patients had greater mean (SD) health care (including systemic therapy) costs compared with the 2007 to 2012 patients ($47 886 [$55 176] vs $33 347 [$31 576]), specifically for stage III ($67 108 [$57 226] vs $46 511 [$30 622]) and stage IV disease ($117 450 [$79 272] vs $47 739 [$37 652]). Mean (SD) systemic therapy costs were greater among 2018 to 2019 patients: stage II ($40 823 [$40 621] vs $10 309 [$12 176]), III ($55 699 [$41 181] vs $9764 [$12 771]), and IV disease ($79 358 [$50 442] vs $9318 [$14 986]). Overall survival was greater for the 2018 to 2019 cohort compared with the 2007 to 2012 cohort (3-year OS: 74.2% [95% CI, 70.8%-77.2%] vs 65.8% [95% CI, 62.2%-69.1%], hazard ratio, 0.72 [95% CI, 0.61-0.85]; P < .001). Time toxicity was similar between eras. Patients with stage IV disease spent more than 1 day per week (>52 days) with physical contact with the health care system by 2018 to 2019 (mean [SD], 58.7 [43.8] vs 44.2 [26.5] days; standardized difference, 0.40; P = .20). Conclusions and Relevance: This cohort study found greater health care costs in the treatment of stages II to IV melanoma and substantial time toxicity for patients with stage IV disease, with improvements in OS associated with the adoption of immunotherapy and targeted therapies. These health system-wide data highlight the trade-off with adoption of new therapies, for which there is a greater economic burden to the health care system and time burden to patients but an associated improvement in survival.

Hospital encounters and associated costs of prostate evaluation for clinically important disease MRI vs. standard evaluation procedures (PRECISE) study from a provincial-payer perspective.

INTRODUCTION: Systematic transrectal ultrasonography (TRUS) biopsy has been the standard diagnostic tool for prostate cancer (PCa) but is subject to limitations, such as a high false-negative rate of cancer detection. Multiparametric magnetic resonance imaging (mpMRI) prior to biopsy is emerging as an alternative diagnostic procedure for PCa. The PRECISE study found that MRI followed by a targeted biopsy was more accurately able to identify clinically significant cancer than TRUS biopsy. METHODS: PRECISE study patients recruited in Ontario between January 2017 and November 2019 were linked to various Ontario provincial administrative databases available at the Institute for Clinical and Evaluative Sciences (ICES ) to determine health resources used, associated costs, and hospitalizations in the 14 days after biopsy. Costs are presented in 2021 CAD. RESULTS: A total of 281 males were included in this study, with 48.4% of the patients in the TRUS biopsy group, 28.1% in the MRI+, and 23.5% in the MRI- group. Twenty-one patients (15%) from the TRUS biopsy group were seen at a hospital in the 14 days after their biopsy compared to fewer than five patients (6%) from the MRI+ group. The mean per person per year (PPPY) costs for the TRUS and all MRI groups (MRI- and MRI+) were $7828 and $8525, respectively. CONCLUSIONS: Patients in the TRUS biopsy group experienced more hospital encounters compared to patients who received an MRI prior to their biopsy. This economic analysis suggests that MRI imaging prior to biopsy is not associated with a significant increase in costs.

Pain and Interventions in Stage IV Non-Small Cell Lung Cancer: A Province-Wide Analysis.

Pain is a common symptom in stage IV non-small cell lung cancer (NSCLC). The objective of the study was to examine the use of interventions and factors associated with interventions for pain. A population-based cohort study in Ontario, Canada was conducted with patients diagnosed with stage IV NSCLC from January 2007 to September 2018. An Edmonton Symptom Assessment System (ESAS) score of ≥4 defined moderate-to-severe pain following diagnosis. The study cohort included 13,159 patients, of which 68.5% reported at least one moderate-to-severe pain score. Most patients were assessed by a palliative care team (85.4%), and the majority received radiation therapy (73.2%). The use of nerve block was rare (0.8%). For patients ≥65 years of age who had drug coverage, 59.6% received an opiate prescription. Patients with moderate-to-severe pain were more likely to receive palliative assessment or radiation therapy compared to patients with none or mild pain. Patients aged ≥70 years and with a greater comorbidity burden were associated with less likelihood to receive radiation therapy. Patients from rural/non-major urban residence and with a greater comorbidity burden were also less likely to receive palliative care assessment. Factors associated with interventions for pain are described to inform future symptom management in this population.

Dyspnea in patients with stage IV non-small cell lung cancer: a population-based analysis of disease burden and patterns of care.

Background: Patients with metastatic non-small cell lung cancer (NSCLC) experience significant morbidity with dyspnea being a common symptom with a prevalence of 70%. The objective of this study was to determine factors associated with a moderate-to-severe dyspnea score based on the Edmonton Symptom Assessment System (ESAS), as well as resultant patterns of intervention and factors correlated to intervention receipt. Methods: Using health services administrative data, we conducted a population-based study of all patients diagnosed with metastatic NSCLC treated from January 2007 to September 2018 in the province of Ontario. The primary outcomes of interest are the prevalence of moderate-to-severe dyspnea scores, and the receipt of dyspnea-directed intervention. Differences in baseline characteristic between moderate-to-severe dyspnea and low dyspnea score cohorts were assessed by comparative statistics. Predictors of intervention receipt for patients with moderate-to-severe dyspnea scores were estimated using multivariable modified Poisson regression. Results: The initial study cohort included 13,159 patients diagnosed with metastatic NSCLC and of these, 9,434 (71.7%) reported a moderate-to-severe dyspnea score. Compared to patients who did not report moderate-to-severe dyspnea scores, those who reported a moderate-to-severe dyspnea score were more likely to complete a greater number of ESAS surveys, be male, have a higher Elixhauser comorbidity index (ECI) score, and receive subsequent systemic therapy after diagnosis. Most patients with a moderate-to-severe dyspnea score received intervention (96%), of which the most common were palliative care management (87%), thoracic radiotherapy (56%) and thoracentesis (37%). Multivariable regression identified older patients to be less likely to undergo pleurodesis. Thoracentesis was less common for patients living in rural and non-major urban areas, lower income areas, and earlier year of diagnosis. Receipt of thoracic radiotherapy was less common for older patients, females, those with ECI ≥4, patients living in major urban areas, and those with later year of diagnosis. Finally, palliative care referrals were less frequent for patients with ECI ≥4, age 60-69, residence outside of major urban areas, earlier year of diagnosis, and lower income areas. Conclusions: Dyspnea is a prevalent symptom amongst patients with metastatic NSCLC. Subpopulations of patients with moderate-to-severe dyspnea scores were in which inequities may exist in access to care that require further attention and evaluation.

Cost-effectiveness of second-line ipilimumab for metastatic melanoma: A real-world population-based cohort study of resource utilization.

BACKGROUND: The efficacy-effectiveness gap between randomized trial and real-world evidence regarding the clinical benefit of ipilimumab for metastatic melanoma (MM) has been well characterized by previous literature, consistent with initial concerns raised by health technology assessment agencies (HTAs). As these differences can significantly impact cost-effectiveness, it is critical to assess the real-world cost-effectiveness of second-line ipilimumab versus non-ipilimumab treatments for MM. METHODS: This was a population-based retrospective cohort study of patients who received second-line non-ipilimumab therapies between 2008 and 2012 versus ipilimumab treatment between 2012 and 2015 (after public reimbursement) for MM in Ontario. Using a 5-year time horizon, censor-adjusted and discounted (1.5%) costs (from the public payer's perspective in Canadian dollars) and effectiveness were used to calculate incremental cost-effectiveness ratios (ICERs) in life-years gained (LYGs) and quality-adjusted life years (QALYs), with bootstrapping to capture uncertainty. Varying the discount rate and reducing the price of ipilimumab were done as sensitivity analyses. RESULTS: In total, 329 MM were identified (Treated: 189; Controls: 140). Ipilimumab was associated with an incremental effectiveness of 0.59 LYG, incremental cost of $91,233, and ICER of $153,778/LYG. ICERs were not sensitive to discounting rate. Adjusting for quality of life using utility weights resulted in an ICER of $225,885/QALY, confirming the original HTA estimate prior to public reimbursement. Reducing the price of ipilimumab by 100% resulted in an ICER of $111,728/QALY. CONCLUSION: Despite its clinical benefit, ipilimumab as second-line monotherapy for MM patients is not cost-effective in the real world as projected by HTA under conventional willingness-to-pay thresholds.

Impact of Frailty on Health Care Resource Utilization and Costs of Care in Myelodysplastic Syndromes.

PURPOSE: The role of frailty in affecting survival in myelodysplastic syndromes (MDS) is increasingly recognized. Despite this, a paucity of data exists on the association between frailty and other clinically meaningful outcomes including health care resource utilization and costs of care. METHODS: We linked the Ontario subset of the prospective Canadian MDS registry (including baseline patient/disease characteristics) to population-based health system administrative databases. Baseline frailty was calculated from the 15-item MDS-specific frailty scale (FS-15). Primary outcomes were public health care utilization and 30-day standardized costs of care (2019 Canadian dollars) determined for each phase of disease (initial, continuation, and terminal phases). Negative binomial regression was used to assess the association between frailty and health care costs with Poisson regression to explore predictors of hospitalization. RESULTS: Among 461 patients with complete FS-15 scores, 374 (81.1%) had a hospitalization with a mean length of stay of 10.6 days. Controlling for age, comorbidities, Revised International Prognostic Scoring System, and transfusion dependence, the FS-15 was independently associated with hospitalization during the initial (P = .02) and continuation (P = .01) phases but not the terminal disease phase (P = .09). The mean 30-day standardized cost per patient was $8,499 (median, $6,295; interquartile range, $2,798-$11,996), largely driven by cancer clinic visits and hospitalization. On multivariable analysis, the FS-15 was independently associated with costs of care during the initial disease phase (P = .02). CONCLUSION: We demonstrate an association between frailty and clinically meaningful outcomes including hospitalization and costs of care in patients with MDS. Our results suggest that baseline frailty may help to inform patients and physicians of expected outcomes.

Using Real-World Data to Determine Health System Costs of Ontario Women Screened for Breast Cancer.

Our study was to determine breast cancer screening costs in Ontario, Canada for screenings conducted through a formal (Ontario Breast Screening Program, OBSP) and informal (non-OBSP) screening program using administrative databases. Included women were 49-74 years of age when receiving screening mammograms between 1 January 2013 to 31 December 2019. Each woman was followed for a screening episode with screening and diagnostic components, and costs were calculated as an average cost per woman per month in 2021 Canadian dollars. The final cohort of 1,546,386 women screened had a mean age of 59.4 ± 7.1 years and ~87% were screened via OBSP. The average total cost per woman per month was $136 ± $103, $134 ± $103 and $155 ± $104 for the entire, OBSP and non-OBSP cohorts, respectively. This was further disaggregated into the average total screening cost per month, which was $103 ± $8, $100 ± $4 and $117 ± $9 per woman, and the average total diagnostic cost per woman per month at $219 ± $166, $228 ± $165 and $178 ± $159. for the entire, OBSP and non-OBSP cohorts, respectively. These results indicate similar screening costs across the different cohorts, but higher diagnostic costs for the OBSP cohort.

Real-World Cost-Effectiveness of First-Line Gemcitabine Plus Nab-Paclitaxel vs FOLFIRINOX in Patients With Advanced Pancreatic Cancer.

BACKGROUND: There are no randomized control trials (RCTs) comparing gemcitabine and nab-paclitaxel (Gem-Nab) and fluorouracil, folinic acid, irinotecan, oxaliplatin (FOLFIRINOX) for advanced pancreatic cancer (APC). Although it is well known that RCT-based efficacy often does not translate to real-world effectiveness, there is limited literature investigating comparative cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC. We aimed to examine the real-world cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC in Ontario, Canada. METHODS: This study compared patients treated with first-line Gem-Nab or FOLFIRINOX for APC in Ontario from April 2015 to March 2019. Patients were linked to administrative databases. Using propensity scores and a stabilizing weights method, an inverse probability of treatment weighted cohort was developed. Mean survival and total costs were calculated over a 5-year time horizon, adjusted for censoring, and discounted at 1.5%. Incremental cost-effectiveness ratio and net monetary benefit were computed to estimate cost-effectiveness from the public health-care payer's perspective. Sensitivity analysis was conducted using the propensity score matching method. RESULTS: A total of 1988 patients were identified (Gem-Nab: n = 928; FOLFIRINOX: n = 1060). Mean survival was lower for patients in the Gem-Nab than the FOLFIRINOX group (0.98 vs 1.26 life-years; incremental effectiveness = -0.28 life-years [95% confidence interval = -0.47 to -0.13]). Patients in the Gem-Nab group incurred greater mean 5-year total costs (Gem-Nab: $103 884; FOLFIRINOX: $101 518). Key cost contributors include ambulatory cancer care, acute inpatient hospitalization, and systemic therapy drug acquisition. Gem-Nab was dominated by FOLFIRINOX, as it was less effective and more costly. Results from the sensitivity analysis were similar. CONCLUSIONS: Gem-Nab is likely more costly and less effective than FOLFIRINOX and therefore not considered cost-effective at commonly accepted willingness-to-pay thresholds.

A comparative study of patient-reported outcomes after contemporary radiation techniques for prostate cancer.

PURPOSE: We aim to compare health-related quality of life (HRQoL) deterioration at 12 months in low-and intermediate-risk prostate cancer (PCa) patients treated with stereotactic ablative radiotherapy (SABR), high dose-rate brachytherapy (HDR) monotherapy and HDR boost. MATERIAL AND METHODS: Patients treated as part of 7 prospective clinical trials were included. All patients had low-or intermediate-risk PCa. Three strategies were considered: SABR, HDR monotherapy and HDR boost. HRQoL was prospectively measured at baseline and 12 months in all trials, using the Expanded Prostate Index Composite (EPIC). A minimally important difference (MID) was defined as a deterioration of HRQoL scores at 12 months compared to baseline ≥0.5 standard deviation of baseline score. Univariate and multivariable logistic regression using generalized estimating equations were used to compare the proportion of patients having MID between groups. A set of sensitivity analyses was conducted. RESULTS: 648 patients were included: 288, 173 and 187 respectively in the SABR, HDR monotherapy and HDR boost group. On univariate and multivariable analyses, SABR and HDR monotherapy compared to HDR boost, were associated with less deterioration in the urinary (38%, 40% vs. 55%; OR:0.543, 95%CI:0.320-0.922, p = 0.024; OR:0.468, 95%CI:0.432-0.507, p < 0.001) and sexual domains (38%, 42% vs. 47%; OR:0.762, 95%CI:0.645-0.900, p = 0.001; OR: 0.786, 95%CI:0.650-0.949, p = 0.012). These findings wererobust to a variety ofsensitivity analyses. CONCLUSION: Recent monotherapeutic approaches for low- and intermediate-risk PCa are associated with the preservation of patients HRQoL. Ultimately, the questions of efficacy, toxicity, and HRQoL will be best answered by a randomized clinical trial.

The impact of oral hypoglycemics and statins on outcomes in myelodysplastic syndromes.

Observational studies suggest an anti-neoplastic effect associated with statins, metformin, and dipeptidyl peptidase-4 inhibitors (DPP4i), while sulfonylureas may have a neutral or detrimental effect. We linked the Ontario subset of a prospective Canadian myelodysplastic syndromes (MDS) registry with provincial administrative databases. We assessed the impact of statin/oral hypoglycemic medication exposure on overall survival (OS) using Cox regression analysis, controlling for comorbidities and sociodemographic factors. Five hundred thirty-three patients aged ≥ 66 years were included: 49.3% used statins, 18.9% used metformin, 9.0% used sulfonylureas, and 6.4% used DPP4i. Three hundred ninety-five patients were lower-risk based on the International Prognostic Scoring System. On univariate analysis, we identified a marginal improvement in OS in the lower-risk group using DPP4i (HR 0.98, 95% CI 0.95-1.00, P = 0.05), while there was no impact on mortality for higher-risk DPP4i users (HR 1.03, CI 0.99-1.07, P = 0.21). There was no mortality difference for statins (HR 1.00, CI 1.00-1.01, P = 0.93), metformin (HR 1.00, CI 0.99-1.01, P = 0.81), or sulfonylureas (HR 1.00, CI 0.99-1.02, P = 0.43) in the entire cohort, as well as when stratified into lower/higher-risk groups. On multivariable analysis in the lower-risk group, there was no association between DPP4i and OS (HR 0.98, CI 0.95-1.00, P = 0.06). Prospective studies with larger cohorts of patients and longer follow-up are required to further study the impact of DPP4i in MDS.

Annual Mammographic Screening Reduces the Risk of Interval or Higher Stage Invasive Breast Cancers Among Postmenopausal Women in the Ontario Breast Screening Program.

Purpose: In the Ontario Breast Screening Program (OBSP) annual screening improved breast cancer detection for women 50-74 years with a family/personal history compared to biennial, while detection was equivalent for women screened annually for mammographic density ≥75%. This study compares the risk of interval or higher stage invasive cancers among postmenopausal women screened annually vs biennially by age and estrogen use. Methods: A retrospective design identified 4247 invasive breast cancers diagnosed among concurrent cohorts of women 50-74 screened in the OBSP with digital mammography between 2011 and 2014, followed until 2016. Polytomous logistic regression estimated the risk of interval or higher stage breast cancers by age and estrogen use between women screened annually because of first-degree relative with breast or ovarian cancer or personal history of ovarian cancer, or mammographic density ≥75%, and those screened biennially. Results: The risk of interval vs screen-detected cancers was significantly reduced in women screened annually for family/personal history (OR=.64; 95%CI:0.51-.80), particularly those 60-74 years (OR=.59; 95%CI:0.45-.77) or not currently using estrogen (OR=.66; 95%CI:0.52-.83) compared to those screened biennially. The risk of stage II-IV vs stage I tumors was also lower in women 60-74 years screened annually for family/personal history (OR=.79; 95%CI:0.64-.97) and in those screened annually for mammographic density ≥75% currently using estrogen (OR=.51; 95%CI:0.26-1.01) compared to women screened biennially. Conclusion: Postmenopausal women at increased risk screened annually had equivalent or reduced risks of interval or higher stage invasive breast cancers than those screened biennially, further supporting risk-based screening in this population.

The Cost of Patient Education Materials Development: Opportunities to Identify Value and Priorities.

The study aim was to evaluate the costs associated with developing and reviewing patient education materials (pamphlets) across Ontario cancer centers. While patient education often produces a positive return on investment, limited efforts have been dedicated to optimizing the personnel, time, and capital dedicated to this feat across healthcare systems. Patient education leaders at 14 cancer centers completed a survey measure, estimating the number of hours spent developing and reviewing pamphlets and identifying the personnel involved in each procedural step. The time expended per center in each step was then combined with average salary data for the identified personnel to derive total cost estimates. Cancer centers spend on average $5672 (SD = $3180) developing (M = $4560, SD = $2620) and reviewing (M = $1112, SD = $654) one pamphlet. This cumulates to an average per annum spending of $65,401 (SD = $75,494) for pamphlet development and $19,819 (SD = $28,524) for annual pamphlet review at each cancer center. The cost and number of hours spent developing and reviewing pamphlets varied substantially between cancer centers. While the security of budgets for patient education varies across cancer centers, opportunities to optimize human capital and monetary resources should be considered. Results of the study can be used to advocate for sustainable investment into cancer education programs, improve the coordination of educational materials production and review, and ensure that resource quality and access are consistent across the province.

The Past, Present, and Future of Economic Evaluations of Precision Medicine at the Committee for Economic Analyses of the Canadian Cancer Trials Group.

Precision medicine in oncology poses unique challenges to the generation of clinical and economic evidence used for cost-effectiveness analyses that can inform health technology assessment. The conduct of randomized controlled trials for biomarker-specific therapies targeted towards small populations has limitations in regard to feasibility, timeliness, and cost. These limitations result in associated challenges for groups involved in the generation of economic evidence to inform treatment-related decision making, including the Committee of Economic Analysis (CEA) at the Canadian Cancer Trials Group (CCTG). We provide a high-level description and vision about the new paradigm of clinical trial design, generation of economic evidence, and novel approaches to economic evaluations necessary in the space of precision medicine in oncology in Canada. The CEA's previous approach to precision medicine, including master protocol designs and single-arm studies, is reviewed. Methods and approaches currently under consideration by the CEA and national collaborators, such as the role of real-world and clinical trial evidence in enabling life-cycle assessment of therapies, are explored. Finally, future initiatives being planned in the space of precision medicine at CCTG, such as the incorporation of correlative studies to identify and test high-performing biomarkers in trials, are discussed.

A Prospective Economic Analysis of Early Outcome Data From the Alliance A041202/ CCTG CLC.2 Randomized Phase III Trial Of Bendamustine-Rituximab Compared With Ibrutinib-Based Regimens in Untreated Older Patients With Chronic Lymphocytic Leukemia.

INTRODUCTION: The Alliance A041202/CCTG CLC.2 trial demonstrated superior progression-free survival with ibrutinib-based therapy compared to chemoimmunotherapy with bendamustine-rituximab (BR) in previously untreated older patients with chronic lymphocytic leukemia. We completed a prospective trial-based economic analysis of Canadian patients to study the direct medical costs and quality-adjusted benefit associated with these therapies. METHODS: Mean survival was calculated using the restricted mean survival method from randomization to the study time-horizon of 24 months. Health state utilities were collected using the EuroQOL EQ-5D instrument with Canadian tariffs applied to calculate quality-adjusted life years (QALYs). Costs were applied to resource utilization data (expressed in 2019 US dollars). We examined costs and QALYs associated ibrutinib, ibrutinib with rituximab (IR), and BR therapy. RESULTS: A total of 55 patients were enrolled; two patients were excluded from the analysis. On-protocol costs (associated with protocol-specified resource use) were higher for patients receiving ibrutinib (mean $189,335; P < 0.0001) and IR (mean $219,908; P < 0.0001) compared to BR (mean $51,345), driven by higher acquisition costs for ibrutinib. Total mean costs (over 2-years) were $192,615 with ibrutinib, $223,761 with IR, and $55,413 with BR (P < 0.0001 for ibrutinib vs. BR and P < 0.0001 for IR vs. BR). QALYs were similar between the three treatment arms: 1.66 (0.16) for ibrutinib alone, 1.65 (0.24) for IR, and 1.66 (0.17) for BR; therefore, a formal cost-utility analysis was not conducted. CONCLUSIONS: Direct medical costs are higher for patients receiving ibrutinib-based therapies compared to chemoimmunotherapy in frontline chronic lymphocytic leukemia, with the cost of ibrutinib representing a key driver.

Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation (PERSPECTIVE I&I).

Early detection of breast cancer through screening reduces breast cancer mortality. The benefits of screening must also be considered within the context of potential harms (e.g., false positives, overdiagnosis). Furthermore, while breast cancer risk is highly variable within the population, most screening programs use age to determine eligibility. A risk-based approach is expected to improve the benefit-harm ratio of breast cancer screening programs. The PERSPECTIVE I&I (Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation) project seeks to improve personalized risk assessment to allow for a cost-effective, population-based approach to risk-based screening and determine best practices for implementation in Canada. This commentary describes the four inter-related activities that comprise the PERSPECTIVE I&I project. 1: Identification and validation of novel moderate to high-risk susceptibility genes. 2: Improvement, validation, and adaptation of a risk prediction web-tool for the Canadian context. 3: Development and piloting of a socio-ethical framework to support implementation of risk-based breast cancer screening. 4: Economic analysis to optimize the implementation of risk-based screening. Risk-based screening and prevention is expected to benefit all women, empowering them to work with their healthcare provider to make informed decisions about screening and prevention.

Province-Wide Analysis of Patient-Reported Outcomes for Stage IV Non-Small Cell Lung Cancer.

BACKGROUND: In Ontario, Canada, patient-reported outcome (PRO) evaluation through the Edmonton Symptom Assessment System (ESAS) has been integrated into clinical workflow since 2007. As stage IV non-small cell lung cancer (NSCLC) is associated with substantial disease and treatment-related morbidity, this province-wide study investigated moderate to severe symptom burden in this population. MATERIALS AND METHODS: ESAS collected from patients with stage IV NSCLC diagnosed between 2007 and 2018 linked to the Ontario provincial health care system database were studied. ESAS acquired within 12 months following diagnosis were analyzed and the proportion reporting moderate to severe scores (ESAS ≥4) in each domain was calculated. Predictors of moderate to severe scores were identified using multivariable Poisson regression models with robust error variance. RESULTS: Of 22,799 patients, 13,289 (58.3%) completed ESAS (84,373 assessments) in the year following diagnosis. Patients with older age, with high comorbidity, and not receiving active cancer therapy had lower ESAS completion. The majority (94.4%) reported at least one moderate to severe symptom. The most prevalent were tiredness (84.1%), low well-being (80.7%), low appetite (71.7%), and shortness of breath (67.8%). Most symptoms peaked at diagnosis and, while declining, remained high in the following year. On multivariable analyses, comorbidity, low income, nonimmigrants, and urban residency were associated with moderate to severe symptoms. Moderate to severe scores in all ESAS domains aside from anxiety were associated with radiotherapy within 2 weeks prior, whereas drowsiness, low appetite and well-being, nausea, and tiredness were associated with systemic therapy within 2 weeks prior. CONCLUSION: This province-wide PRO analysis showed moderate to severe symptoms were prevalent and persistent among patients with metastatic NSCLC, underscoring the need to address supportive measures in this population especially around treatments. IMPLICATIONS FOR PRACTICE: In this largest study of lung cancer patient-reported outcomes (PROs), stage IV non-small cell lung cancer patients had worse moderate-to-severe symptoms than other metastatic malignancies such as breast or gastrointestinal cancers when assessed with similar methodology. Prevalence of moderate-to-severe symptoms peaked early and remained high during the first year of follow-up. Symptom burden was associated with recent radiation and systemic treatments. Early and sustained PRO collection is important to detect actionable symptom progression, especially around treatments. Vulnerable patients (e.g., older, high comorbidity) who face barriers in attending in-person clinic visits had lower PRO completion. Virtual PRO collection may improve completion.

Phase-specific risks of outpatient visits, emergency visits, and hospitalizations during Children's Oncology Group-based treatment for childhood acute lymphoblastic leukemia: A population-based study.

BACKGROUND: Therapy for childhood acute lymphoblastic leukemia (ALL) is associated with substantial health care utilization and burden on families. Little is known about health care utilization during specific treatment phases. PROCEDURES: We identified children with ALL diagnosed during 2002-2012 in Ontario, Canada and treated according to Children's Oncology Group (COG) protocols. Disease and treatment data were chart abstracted. Population-based health care databases identified all outpatient visits, emergency department (ED) visits, and hospitalizations. In addition to comparing standard and intensified versions of treatment phases, we compared patients receiving different steroids (dexamethasone vs. prednisone) and different versions of interim maintenance (IM) (Capizzi vs. high-dose methotrexate [HD-MTX]). RESULTS: Six hundred thirty-seven children met inclusion criteria. During intensified consolidation, 76.2% of patients were hospitalized at least once, compared to only 32.3% of patients receiving standard consolidation (p < .0001). Similarly, 72.9% of patients receiving intensified delayed intensification (DI) were hospitalized during this phase compared to 50.3% of patients receiving standard DI (p < .0001). Among patients receiving a four-drug induction, those receiving dexamethasone had an 85% higher rate of ED visits (adjusted rate ratio [aRR] 1.85, 95th confidence interval [95CI] 1.14-3.00; p = .01) and a 44% higher rate of hospitalization (aRR 1.44, 95CI 1.24-1.68) compared to those receiving prednisone. Among high-risk B-ALL and T-ALL patients in IM, Capizzi MTX was not associated with an increased rate of ED visits versus HD-MTX. CONCLUSIONS: These results can be used to inform anticipatory guidance for families, particularly those undergoing intensified therapy. Our results also suggest that increased toxicity rates associated with dexamethasone during Induction seen in clinical trials reflect real-world practice.