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. 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. 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. 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.
The prognosis for extensive-stage small cell lung cancer (ES-SCLC) is poor. Real-world evidence can highlight the unmet clinical need within this population. We conducted a population-based cohort study of ES-SCLC patients diagnosed in a large Canadian province (2010–2018) using electronic medical records and administrative claims data. In all, 1941 ES-SCLC patients were included, of which 476 (25%) were recurrent cases. Median age at diagnosis was 70 years (range: 39–94) and 50.2% were men. Of the 1941 ES-SCLC patients, 29.5% received chemotherapy and radiotherapy, 17.0% chemotherapy alone, 8.7% radiotherapy alone, and 44.8% received best supportive care. Chemotherapy was initiated by 46.5%, 8.5%, and 1.4% of first-, second-, and third-line patients, with lower uptake for recurrent cases. Median survival from first-, second-, and third-line chemotherapy was 7.82 months (95% CI: 7.50–8.22), 5.72 months (95% CI: 4.90–6.87), and 3.83 months (95% CI: 2.99–4.60). Among patients who received first-line therapy, the 2-year and 5-year survival was 7.3% (95% CI: 5.7–9.2) and 2.9% (95% CI: 1.8–4.5). In conclusion, initiation of first-line treatment in ES-SCLC was low with significant attrition in subsequent lines. These results underscore the need for effective front-line treatments and highlight the potential for novel therapies to improve patient outcomes.
The emergence of immunotherapy revolutionized the treatment of non-small-cell-lung cancer (NSCLC), with multiple landmark clinical trials establishing the efficacy of these agents. However, many patients who receive immunotherapy in clinical practice would be considered clinical trial ineligible. One such population that is often under-represented in clinical trials is older adults. In the current study, we evaluated clinical and safety outcomes in this population. Overall, older adults (>70 years of age) and younger adults had comparable clinical outcomes with an equivalent objective response rate (ORR), time to treatment failure (TTF), and median overall survival (p = 0.67, p = 0.98, and p = 0.91, respectively). Furthermore, the safety outcomes were equivalent between the cohorts with similar rates of immune-related adverse events (irAEs), irAE-related hospitalizations, and all-cause hospitalization (p = 0.99, p = 0.63, and p = 0.74, respectively). While older age was not found to impact overall survival, multivariant analysis revealed that a poor Eastern Cooperative Oncology Group (ECOG) status, low body-mass-index (BMI), and poor/intermediate lung immune prognostic index (LIPI) were all associated with worse survival. In conclusion, age does not impact the efficacy or safety of pembrolizumab in NSCLC, and therefore advanced age should not be a deterrent for treating these patients with pembrolizumab. Physicians and care providers can thus focus on other factors that may influence therapeutic outcomes.
Canada’s healthcare system, like others worldwide, is immersed in a process of evolution, attempting to adapt conventional frameworks of health technology assessment (HTA) and funding models to a new landscape of precision medicine in oncology. In particular, the need for real-world evidence in Canada is not matched by the necessary infrastructure and technologies required to integrate genomic and clinical data. Since healthcare systems in many developed nations face similar challenges, we adopted a solutions-based approach and conducted a search of worldwide programs in personalized medicine, with an emphasis on precision oncology. This search strategy included review articles published between 1 January 2016 and 1 March 2021 and hand-searches of their reference lists for relevant publications back to 1 December 2005. Thirty-nine initiatives across 37 countries in Europe, Australasia, Africa, and the Americas had the potential to lead to real-world data (RWD) on the clinical utility of oncology biomarkers. We highlight four initiatives with helpful lessons for Canada: Genomic Medicine France 2025, UNICANCER, the German Medical Informatics Initiative, and CANCER-ID. Among the 35 other programs evaluated, the main themes included the need for collaboration and systems to support data harmonization across multiple jurisdictions. In order to generate RWD in precision oncology that will prove acceptable to HTA bodies, Canada must take a national approach to biomarker strategy and unite all stakeholders at the highest level to overcome jurisdictional and technological barriers.
Early-onset diagnosis, defined by age 60 years. The pooled odds of achieving pCR were significantly higher in early-onset patients. Future studies should evaluate the role of locoregional management of TNBC and the implementation of novel therapies such as PARP inhibitors in real-world settings, and whether they improve outcomes.
Real-world evidence surrounding EGFR positive NSCLC patients in Canada is limited. Administrative databases in Alberta, Canada were used to evaluate EGFR testing and mutation prevalence in de novo metastatic NSCLC, as well as the characteristics, treatment patterns, and outcomes of individuals with Exon 19, L858R and Exon20ins mutations. Between 2013–2019, 2974 individuals underwent EGFR testing, of which 451 (15.2%) were EGFR positive. Among EGFR positive individuals, 221 (49.0%) had an Exon 19 mutation, 159 (35.3%) had an L858R mutation, and 18 (4%) had an Exon20ins mutation. The proportion of individuals who initiated 1L systemic therapy was 89.1% for Exon19, 85.5% for L858R, and 72.2% for Exon20ins carriers. The primary front-line systemic therapy was gefitinib or afatinib monotherapy for individuals with Exon 19 (93.4%) and L858R (94.1%) mutations versus platinum combination therapy for individuals with Exon20ins mutations (61.5%). The Exon20ins cohort had worse median overall survival from initiation of 1L systemic therapy (10.5 months [95% CI: 8.0-not estimable]) than the Exon19 (20.6 months [95% CI: 18.4–24.9]), and L858R cohorts (19.1 months [95% CI: 14.5–23.1]). These findings highlight that Exon20ins mutations represent a rare subset of NSCLC in which treatment options are limited and survival outcomes are worse relative to individuals with more common types of EGFR mutations.