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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. [ABSTRACT FROM AUTHOR]

In this analysis, we describe population-based outcomes for first-line treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) combined with an aromatase inhibitor (AI). All patients who were prescribed CDK4/6i + AI from January 2016 through June 2019 were included. Patient demographics, tumour and treatment characteristics were collected and described. Survival distributions were estimated using the Kaplan–Meier method. Multivariate analysis (MVA) was constructed to examine associations between potentially prognostic clinical variables and progression-free survival (PFS). In total, 316 patients were included. The median age was 61 years. After a median follow-up of 28.1 months, the median PFS was 37.9 months (95% CI, 26.7–NR). In the MVA, PR-negative tumour (HR, 2.37; 95% CI, 1.45–3.88; p = 0.001) and CDK4/6i dose reduction (HR, 1.51; 95% CI, 1.06–2.16; p = 0.022) predicted worse PFS. Median overall survival (OS) was not reached. The 30-month and 36-month OS rates were 74% and 68%, respectively. Of patients who progressed, 89% received second-line treatment. Median time to progression on second-line chemotherapy was 9.0 (5.8–17.6) months, and median time to progression on second-line hormonal therapy +/− targeted agent was 4.0 (3.4–8.6) months (p = 0.012). CDK4/6i + AI as first-line treatment for HR-positive, HER2-negative MBC in Alberta is justified based on favourable PFS and early OS outcomes. [ABSTRACT FROM AUTHOR]

Background: Patients dying with cancer can experience various physical and psychological symptoms. We aimed to determine the type and severity of symptoms within the last 6 months of life in a large real-world cohort of patients with cancer. Methods: We examined prospectively collected patient-reported outcomes of patients with lung, colorectal, breast, prostate or pancreatic cancer using the revised Edmonton Symptom Assessment System (ESASr) questionnaire from a large province in Canada from 2016 to 2017. The ESASr was categorized into physical and psychological symptom subscores and total symptom score, and each was classified as none to mild (0–3) or moderate to severe (4–10) based on intensity. Multivariable logistic regression analyses were performed to evaluate the relationship between clinical characteristics and symptom scores. Results: We identified 1159 patients eligible for analysis, of whom 52.2% were men and median age was 68 years. There were 613, 192, 149, 111 and 94 patients with lung, colorectal, breast, prostate and pancreatic cancer, respectively. While approximately half of patients reported moderate to severe physical symptom subscores and total symptom scores, only one-third reported moderate to severe psychological subscores. On multivariable logistic regression analyses, women were more likely to report moderate to severe physical (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.08–2.12; P = 0.016), psychological (OR, 1.60; 95% CI, 1.14–2.26; P = 0.006) and total symptom scores (OR, 1.80; 95% CI, 1.28–2.51; P = 0.001). Patients with lung cancer were also more likely to report moderate to severe physical and psychological subscores (OR, 1.95; 95% CI, 1.28–2.96; P = 0.002 and OR, 1.78; 95% CI, 1.13–2.81; P = 0.013) and total symptom scores (OR, 1.83; 95% CI, 1.20–2.81; P = 0.005). Finally, those closer to death were more likely to report moderate to severe physical symptom subscores (OR, 2.07; 95% CI, 1.33–3.23; P = 0.001) and total symptom scores (OR, 2.29; 95% CI, 1.46–3.60; P < 0.001), but not psychological symptom scores (OR, 1.34; 95% CI, 0.84–2.14; P = 0.210). Conclusions: There is significant symptom burden in patients with cancer near the end-of-life. Further, physical symptoms appear to be more intense than psychological symptoms. Symptom-directed care is still needed to improve the quality of end-of-life. [ABSTRACT FROM AUTHOR]

Background: Treatment strategies for metastatic non-small cell lung cancer (NSCLC) are evolving rapidly and can be highly variable. Real-world evidence of treatment patterns and outcomes can provide an understanding of our current practice and offer insights on ways to incorporate emerging therapies into our treatment paradigm. In this population-based study, we investigated treatments and outcomes of stage IV NSCLC patients from a large Canadian province., Methods: Patients diagnosed with de novo stage IV NSCLC from April 1, 2010 to March 31, 2015 were identified. Data for baseline characteristics, treatments, and outcomes were obtained from provincial data sources, including the cancer registry and electronic medical records. We classified systemic treatments as chemotherapy, targeted therapy (anti-epidermal growth factor receptor, and anti-anaplastic lymphoma kinase) and immunotherapy (checkpoint inhibitors) and characterized clinical outcomes by treatment type., Results: A total of 6438 patients were identified with NSCLC, of whom 3606 (56%) had de novo stage IV disease. The median age of diagnosis was 69 (range: 20 to 100) years and 52.4% were men. First-line palliative treatments included: chemotherapy in 19.5% (n=703), targeted agents in 5.7% (n=204), immunotherapy in 1% (n=1), radiotherapy in 6.8% (n=246), and best supportive care in 74.8% (n=2,698). Median overall survival (mOS) from diagnosis for the whole cohort was 3.8 months. Within subgroups, mOS was 18.0 months for targeted therapies, 9.4 months for chemotherapy, and 2.5 months for best supportive care. Only 1.0% of patients (n=34) received immunotherapy at any line., Conclusions: Survival benefit was dependent on type of treatment received, with significantly better mOS observed with the use of small-molecule targeted therapy against epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements, as compared with best supportive care., Competing Interests: M.H. and R.N.W. are affiliated with AstraZeneca, which manufactures, distributes, or markets immunotherapy and targeted therapy that have obtained regulatory approval for the indication of advanced NSCLC (durvalumab, gefinitib, and osimertinib). W.Y.C. and D.Y. have indirectly received honoraria or grants from the manufacturers of the drugs investigated in this study. The remaining authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Background: Use of fluoropyrimidine-based therapy in patients with metastatic colorectal cancer is associated with significant toxicities. This study aimed to assess the safety and efficacy of raltitrexed use in patients with metastatic colorectal cancer who developed significant toxicities after fluoropyrimidine-based treatment., Patients and Methods: We identified patients with metastatic colorectal cancer who were treated with raltitrexed-based systemic therapy after developing serious adverse events with fluoropyrimidine-based treatment in a large Canadian province from 2004 to 2018. Demographic, tumor, and treatment characteristics were retrieved from the electronic medical records. Progression-free and overall survival were assessed from the start of raltitrexed-based therapy., Results: A total of 86 patients were identified for the study. The median age was 66.5 years, and 58.1% of patients were men. The primary cancer site was right, left, and transverse colon in 38.4%, 27.9%, and 9.3%, respectively. The remaining 24.4% had rectal cancer. Among all patients, 43.0% had received more than 2 prior systemic therapies, and 37.6% had developed previous cardiotoxicity to fluoropyrimidine-based treatment. The median progression-free and overall survival were 8.5 and 10.2 months, respectively. On multivariable Cox regression model, patients with left-sided colon cancer (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.12-0.97; P = .044) and the Eastern Cooperative Oncology Group performance status of 0/1 (HR, 0.10; 95% CI, 0.01-0.82; P = .032) had a longer progression-free survival, whereas left-sidedness of colon cancer was the only factor that predicted overall survival (HR, 0.30; 95% CI, 0.10-0.88; P = .029). Raltitrexed was well-tolerated with common adverse events that included anemia in 41.7% of patients and chemotherapy-induced nausea and vomiting in 27.4%. Most toxicities were grade 1/2, but 16.7% of patients experienced grade 3. There were no cardiac events and treatment-related deaths., Conclusions: Raltitrexed in patients with colorectal cancer who were previously treated with fluoropyrimidine-based systemic therapy is effective and well-tolerated., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: There are limited data on patient-reported outcomes near the end of life in patients with gynaecologic cancers. This study aimed to assess the symptom burden in the last 6 months of life in a real-world cohort., Methods: Patients diagnosed with metastatic gynaecologic malignancies from 2016 to 2019 who completed the revised Edmonton Symptom Assessment System (ESASr) questionnaire within 6 months of death in a large Canadian province were identified. Patient-reported symptom scores were categorized as none to mild (0-3) and moderate to severe (4-10). Individual symptoms were subsequently grouped into physical, psychological, and total subscores. The severity of symptoms was further analyzed for any associations with age, time to death, and primary tumour site (ovarian vs. uterocervical and vulvovaginal)., Results: We identified 107 patients with gynaecologic malignancies including 59 ovarian, 29 uterocervical, and 19 vulvovaginal cancers. The median ages at diagnosis and questionnaire completion were 64 and 65 years, respectively. The median time from completing the ESASr questionnaire to death was 65 days. Overall, physical and psychological symptoms were moderate to severe in 57.9% and 40.2% of patients, respectively. Among the individual symptoms, tiredness was the most commonly reported moderate to severe symptom (74.9%), while shortness of breath was least commonly reported (31.6%). While physical (P < 0.001) and total symptom (P = 0.009) subscores were more likely to be moderate to severe in intensity as death approached, the psychological subscore (P = 0.744) had no relationship with time to death. Longer time to death was predictive of lower physical (P = 0.002) and total symptom (P = 0.002) subscores, while a primary uterocervical cancer site was associated with a lower psychological symptom subscore (P = 0.042)., Conclusions: In the real-world setting, unique symptom trajectories can emerge for patients with gynaecologic cancer near the end of life. Knowledge of these specific symptom patterns can help inform the development and delivery of targeted palliative interventions to improve quality of life for these patients., (Copyright © 2020 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Introduction: The results of adjuvant chemotherapy trials in stage II and III colon cancer are often extrapolated to real-world patients. This study was conducted to determine the proportion of real-world patients with stage II/III colon cancer who would be eligible for adjuvant chemotherapy trials and to compare the outcomes among eligible versus ineligible patients., Patients and Methods: We identified all patients diagnosed with stage II/III colon cancer between 2004 and 2015 from a large province in Canada. Patients meeting any one of the following criteria were considered ineligible: age > 75 years, anemia, comorbid conditions (heart disease, uncontrolled diabetes, kidney disease, liver disease), and a history of malignancy or immunosuppression. Cox regression models were constructed to determine the factors predicting overall and cancer-specific survival., Results: A total of 7841 patients with stage II/III colon cancer were identified, of whom 52.0% were men and median age at diagnosis was 71 years. Approximately 58.6% of patients were deemed trial ineligible; the most common reasons for ineligibility included advanced age (36.2%), renal dysfunction (26.9%), and cardiac disease (17.4%). In the real-world setting, 54.0% of eligible patients received adjuvant chemotherapy compared to 23.2% of ineligible patients (odds ratio, 3.89; 95% confidence interval, 3.53-4.28; P < .0001). The 5-year overall and cancer-specific survival of trial-ineligible patients who received adjuvant chemotherapy was significantly better than those treated with surgery alone., Conclusion: The eligibility criteria of adjuvant chemotherapy trials in colon cancer should be broadened to be more representative of real-world patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The results of clinical trials in metastatic breast cancer (MBC) are generalized to real-world patients. This study determines the proportion of real-world patients who would be eligible for clinical trials and compares outcomes in eligible versus ineligible patients., Methods: Patients diagnosed with MBC from 2004 to 2015 in a large Canadian province were included. Patients with one of the following criteria were considered ineligible: the presence of comorbid conditions (anemia, uncontrolled diabetes, heart disease, liver disease, and kidney disease) or a history of immunosuppression or prior malignancy. The likelihood of receiving cancer therapy was analysed using logistic regression models and factors affecting overall survival (OS) were assessed by Cox proportional hazards models., Results: A total of 1585 patients with MBC were identified. The median age at diagnosis was 63 years. Of these, 512 (32.3%) patients were deemed ineligible in whom the two most common reasons for ineligibility were renal dysfunction (17.2%), and previous immunosuppression (7.8%). In the real world, ineligible patients were less likely to receive chemotherapy (29.5% vs 45.8%; P < 0.001) but not radiation treatment (7.6% vs 9.6%; P = 0.196) or hormonal therapy (57.6% vs 60.6%; P = 0.261). The 5-year OS of ineligible patients who received systemic therapy in the real-world was significantly better than those who did not., Conclusions: Despite being ineligible for clinical trials based on common eligibility criteria, many real-world patients receive systemic treatment and derive possible benefit. Broadening of inclusion criteria in clinical trials will enhance the representation of real-world patients and increase the generalizability of results., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)