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Abstract Background Recommendations for improved survival after cancer through physical activity (PA) exist, although the evidence is still emerging. Our primary objective was to conduct a systematic review and meta-analysis of the association between prediagnosis and postdiagnosis PA and survival (cancer-specific, all-cause, and cardiovascular disease mortality) for all cancers and by tumor site. Secondary objectives were to examine the associations within population subgroups, by PA domain, and to determine the optimal dose of PA related to survival. Methods PubMed, EMBASE, and SportsDiscus databases were searched from inception to November 1, 2018. DerSimonian-Laird random-effects models were used to estimate the summary hazard ratios (HRs) and 95% confidence intervals (CI) for primary and secondary analyses and to conduct dose-response analyses. Results Evidence from 136 studies showed improved survival outcomes with highest vs lowest levels of prediagnosis or postdiagnosis total or recreational PA for all-cancers combined (cancer specific mortality: HR = 0.82, 95% CI = 0.79 to 0.86, and HR = 0.63, 95% CI = 0.53 to 0.75, respectively) as well as for 11 specific cancer sites. For breast and colorectal cancers, greater reductions were observed for postdiagnosis PA (HR = 0.58–0.63) compared with prediagnosis PA (HR = 0.80–0.86) for cancer-specific and all-cause mortality. Survival benefits through PA were observed in most subgroups (within sex, body mass index, menopausal status, colorectal subtypes, and PA domain) examined. Inverse dose-response relationships between PA and breast cancer-specific and all-cause mortality were observed, with steep reductions in hazards to 10–15 metabolic equivalent hours per week. Conclusion Higher prediagnosis and postdiagnosis levels of PA were associated with improved survival outcomes for at least 11 cancer types, providing support for global promotion of PA guidelines following cancer.

Background Outcomes-based agreements (OBAs) have the potential to provide more timely patient access to novel therapies, although they are not suitable for every new medication or reimbursement scenario. The authors of this paper studied how to operationalize an OBA in oncology by leveraging existing real-world data (RWD) infrastructure in the province of Alberta. Objective The main objectives were to (1) evaluate which health outcomes in oncology are suitable for OBAs and whether they can be tracked with existing infrastructure, and (2) determine how RWD in oncology can be used to implement an OBA and the expected timing for delivery. Methods Using the Oncology Outcomes (O2) Group infrastructure and Alberta administrative data, a review of five key oncology outcomes was performed to determine suitability to support an OBA. Results Overall survival and time-to-next-treatment were determined as potentially suitable oncology outcomes for OBAs; progression-free survival, patient-reported outcomes, and return to work were deemed inadequate for OBAs at the current time due to data limitations. Conclusions Results indicate that it is feasible to leverage RWD to support OBAs in oncology in Alberta, with minimal additional data, resources, and infrastructure. The operational processes and steps to collect and analyze RWD for OBAs were identified, starting with performing an RWD feasibility study. The expected timeframe to fulfill the real-world evidence (RWE) requirements for an OBA is approximately 3 years for cancers with short trajectories.

The COVID-19 pandemic is suspected to have affected cancer care and outcomes among patients in Canada. In this study, we evaluated the impact of the state of emergency period during the COVID-19 pandemic (Mar. 17 to June 15, 2020) on cancer diagnoses, stage at diagnosis and 1-year survival in Alberta. We included new diagnoses of the 10 most prevalent cancer types from Jan. 1, 2018, to Dec. 31, 2020. We followed patients up to Dec. 31, 2021. We used interrupted time series analysis to examine the impact of the first COVID-19–related state of emergency in Alberta on the number of cancer diagnoses. We used multivariable Cox regression to compare 1-year survival of the patients who received a diagnosis during 2020 after the state of emergency with those who received a diagnosis during 2018 and 2019. We also performed stage-specific analyses. We observed significant reductions in diagnoses of breast cancer (incidence rate ratio [IRR] 0.67, 95% confidence interval [CI] 0.59–0.76), prostate cancer (IRR 0.64, 95% CI 0.56–0.73) and colorectal cancer (IRR 0.64, 95% CI 0.56– 0.74) and melanoma (IRR 0.57, 95% CI 0.47–0.69) during the state of emergency period compared with the period before it. These decreases largely occurred among early-stage rather than late-stage diagnoses. Patients who received a diagnosis of colorectal cancer, non-Hodgkin lymphoma and uterine cancer in 2020 had lower 1-year survival than those diagnosed in 2018; no other cancer sites had lower survival. The results from our analyses suggest that health care disruptions during the COVID-19 pandemic in Alberta considerably affected cancer outcomes. Given that the largest impact was observed among early-stage cancers and those with organized screening programs, additional system capacity may be needed to mitigate future impact.

Purpose Opioid misuse is increasingly recognized as a relevant problem among patients with cancer. However, the applicability of these concerns for patients with metastatic disease is complicated by shorter prognoses and greater symptom burden. This study aimed to investigate whether nonmedical opioid use (NMOU) was identified as contributing to opioid-related healthcare encounters among patients with metastatic cancer receiving long-term prescribing. Methods The study included patients with stage IV cancer diagnosed from 2004–2017 in Alberta, Canada who 1) received long-term opioid prescribing and 2) experienced ≥ 1 hospitalization or emergency department visit relating to opioid overdose or use disorder. Records from visits to cancer centres and opioid-related hospital encounters were reviewed to identify any documentation of NMOU. Patient characteristics were compared between those with and without documented NMOU. Results Charts of 46 patients were reviewed. Although NMOU contributed to opioid-related encounters, these events were often related to poorly controlled pain, declining functional status, and disease progression. NMOU behaviors were documented for 16 (35%) patients. The most common NMOU behaviour was overuse of prescribed medications, which was documented for 12 patients. For 7 patients, there were indications of use of opioids for psychological coping, including 3 encounters caused by intentional overdoses with suicidal intent. Patients with NMOU were significantly more likely to have a history of substance use and limited social support. Conclusion Approximately 1-in-3 patients experiencing opioid-related hospitalizations/emergency department visits had indications of NMOU. Further psychosocial care and interdisciplinary pain management are warranted to improve safe prescribing for these patients.

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.

Colorectal cancer is the second most common malignancy diagnosed in Canada. Despite declining incidence and mortality rates in recent years, there is still a significant number of cases that are metastatic at presentation. Fluoropyrimidine-based chemotherapy was the backbone of colorectal cancer treatment, but the addition of irinotecan and oxaliplatin to form combination regimens has significantly improved overall survival. In the past decade, the development of novel biologic agents including therapies directed against vascular endothelial growth factor and epidermal growth factor receptor has further altered the landscape of metastatic colorectal cancer treatment. However, clinical trials have demonstrated that not all patients respond to these therapies similarly and consideration must be given to individual patient- and tumor-related factors. A more tailored and biomarker driven approach to treatment selection can optimize outcomes and avoid unnecessary adverse effects. In this review article, we offer a comprehensive overview of the panel of clinical- and tumor-associated characteristics that influence treatment decisions in metastatic colorectal cancer and how this sets the foundation for a more personalized treatment strategy in oncology.

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.

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.

Background A standard therapy for locally advanced rectal cancer (LARC) includes fluoropyrimidine (FP)-based neoadjuvant chemoradiation (nCRT). Previous studies have inconsistently demonstrated that baseline neutrophil- and platelet-to-lymphocyte ratios (NLR and PLR) are predictive of response to nCRT or prognostic of outcomes in LARC. Methods We reviewed patients with LARC undergoing nCRT followed by surgery from 2005 to 2013 across 8 Canadian cancer centres. Outcome measures of interest were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Logistic regression and Cox proportional hazard models were used to assess for associations between baseline hematologic variables and outcomes. Results Of 1527 identified patients, 1237 (81%) were included in the DFS/OS analysis. Median age was 62 (range 23–88), 69% were male, and 80% had performance status (PS) 0–1. Twenty-six percent had elevated NLR (≥ 4), and 66% had elevated PLR (≥ 150). Ninety-seven percent of patients received FP-based nCRT, with 96% receiving ≥44 Gy. 81% completed neoadjuvant chemotherapy and 95% completed neoadjuvant radiotherapy, with a pCR rate of 18%. After a median follow-up time of 71 months, 8% developed local recurrence, 22% developed distant recurrence and 24% died. 5-year DFS and OS were 69% (95% CI 66–72%) and 79% (95% CI 77–82%), respectively. In multivariate analyses, elevated baseline NLR and PLR were neither prognostic for DFS and OS nor predictive of pCR. Conclusions NLR and PLR were not found to be independently prognostic for DFS or OS and did not predict for pCR in patients with LARC undergoing nCRT followed by surgery.

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.