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Since the initial US FDA approval of an immune checkpoint inhibitor (ICI) for the treatment of non-oncogene-driven non-small-cell lung cancer (NSCLC) nine years ago, this therapeutic strategy has been cemented as a crucial component of treatment for most of these patients. However, there is a clear efficacy–effectiveness gap whereby patients in the ‘real world’ seem to have more modest clinical outcomes compared to those enrolled in landmark clinical trials. This gap may be driven by the under-representation of important patient populations, including populations defined by clinical or molecular characteristics. In this review, we summarize the data outlining the evidence of ICIs in patients with poor Eastern Cooperative Oncology Group performance status (ECOG PS), underlying autoimmune disease (AID), older age, active brain metastases (BMs), and molecular aberrations such as EGFR mutations, ALK fusions, BRAF mutations and ROS1 fusions.

FISH cytogenetics, TP53 sequencing, and IGHV mutational status are increasingly used as prognostic and predictive markers in chronic lymphocytic leukemia (CLL), particularly as components of the CLL International Prognostic Index (CLL-IPI) and in directing therapy with novel agents. However, testing outside of clinical trials is not routinely available in Canada. As a centralized CLL clinic at CancerCare Manitoba, we are the first Canadian province to evaluate clinical outcomes and survivorship over a long period of time, incorporating the impact of molecular testing and the CLL-IPI score. We performed a retrospective analysis on 1315 patients diagnosed between 1960 and 2018, followed over a 12-year period, where 411 patients had molecular testing and 233 patients had a known CLL-IPI score at the time of treatment. Overall, 40.3% (n = 530) of patients received treatment, and 47.5% (n = 252) of patients received multiple lines of therapy. High-risk FISH and CLL-IPI (4-10) were associated with higher mortality (HR 2.03, p = 0.001; HR 2.64, p = 0.002), consistent with other studies. Over time, there was an increase in the use of targeted agents in treated patients. The use of Bruton’s tyrosine kinase inhibitors improved survival in patients with unmutated IGHV and/or TP53 aberrations (HR 2.20, p = 0.001). The major cause of death in patients who received treatment was treatment/disease-related (32%, n = 42) and secondary malignancies (57%, n = 53) in those who were treatment-naïve. Our data demonstrate the importance of molecular testing in determining survivorship in CLL and underpinning the likely immune differences in outcomes for those treated for CLL.

BackgroundAlthough therapy for limited-stage small-cell lung cancer (LS-SCLC) is administered with curative intent, most patients relapse and eventually die of recurrent disease. Chemotherapy (CT) with concurrent radiotherapy (RT) remains the standard of care for LS-SCLC; however, this could evolve in the near future. Therefore, understanding the current prognostic factors associated with survival is essential.ObjectiveThis real-world analysis examines factors associated with long-term survival in patients with LS-SCLC treated with CT in Manitoba, Canada.MethodsA retrospective cohort study was conducted using Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years and had cytologically confirmed LS-SCLC diagnosed between January 1, 2004, and December 31, 2018, for which they received CT ± RT. Baseline patient, disease, and treatment characteristics and survival duration, characterized as short (24 months), were extracted. Overall survival (OS) was estimated at one, two, and five years and assessed using Kaplan-Meier methods and Cox proportional hazards models.ResultsOver the 15-year study period, 304 patients met the eligibility criteria. Long-term survivors comprised 39.1% of the cohort; at diagnosis, this subgroup was younger, more likely to have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, and have normal lactate dehydrogenase, sodium, and hemoglobin levels. OS estimates for the entire cohort at one, two, and five years were 66%, 38%, and 18%, respectively. In the ECOG PS 0 subgroup, OS estimates at one, two, and five years were 85%, 52%, and 24%, respectively; OS estimates were 60%, 35%, and 17%, respectively, for ECOG PS 1−2 and were 47%, 23%, and 10%, respectively, for ECOG PS 3−4. OS was significantly higher among patients with normal serum sodium and hemoglobin levels than those with abnormal levels. Univariable hazard regression models found that ECOG PS, age at diagnosis, receipt of prophylactic cranial irradiation (PCI), and thoracic RT were associated with survival. On multivariable hazard regression, ECOG PS and receipt of PCI were associated with survival.ConclusionSurvival for greater than two years in patients with LS-SCLC treated with CT ± RT was associated with ECOG PS and receipt of PCI.

BackgroundExtensive-stage small-cell lung cancer (ES-SCLC) is an incurable cancer with poor prognosis in which characteristics predictive of long-term survival are debated. The utility of agents such as immune checkpoint inhibitors highlights the importance of identifying key characteristics and treatment strategies that contribute to long-term survival and could help guide therapeutic decisions.ObjectiveThis real-world analysis examines the characteristics, treatment patterns, and clinical outcomes of patients receiving chemotherapy without immunotherapy for ES-SCLC in Manitoba, Canada.MethodsA retrospective cohort study assessed patient characteristics, treatment, and survival duration (short: 24 months) using the Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years with cytologically confirmed ES-SCLC diagnosed between January 1, 2004, and December 31, 2018, and received cytotoxic chemotherapy (CT). The one-, two-, and five-year probabilities of overall survival (OS) were assessed relative to patient, disease, and treatment characteristics using Kaplan-Meier methods and Cox proportional hazards models.ResultsThis analysis included 537 patients. Cisplatin was used in 56.1% of patients, 45.6% received thoracic radiotherapy (RT), and few received prophylactic cranial irradiation (PCI). In the overall cohort, one-, two- and five-year OS rates were 26%, 8%, and 3%, respectively. For patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, OS rates at one, two, and five years were 43%, 17%, and 10%, respectively, vs. 27%, 8%, and 2% for those with ECOG PS 1–2, and 16%, 3%, and 3% for those with ECOG PS 3–4. In long-term survivors, ECOG PS scores were lower and abnormal laboratory test results were less frequent. Overall, 74.4% of long-term survivors received thoracic RT and 53.5% received PCI. Known poor prognostic factors – including brain/liver metastases, high lactate dehydrogenase (LDH), abnormal sodium, and low hemoglobin levels – were less common but still seen in long-term survivors.ConclusionAlthough rare, patients with ES-SCLC may experience long-term survival with CT ± thoracic RT ± PCI. Factors predicting long-term survival include traditional prognostic factors such as ECOG PS, LDH level, and receipt of thoracic RT or PCI. These findings support current treatment algorithms for ES-SCLC and provide baseline survival estimates to assess the real-world impact of adding immune checkpoint inhibitors in the future.

Abstract Background Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in North America. Previous studies have shown improved progression free survival (PFS) and response rates in unfit patients treated with obinutuzumab compared to other regimens. The aim of this study was to evaluate the obinutuzumab-chlorambucil regimen in the context of historical treatments and first-dose infusion reactions at CancerCare Manitoba (CCMB). Methods A retrospective chart review was conducted for patients treated with obinutuzumab from January 1, 2014 to December 31, 2017 at CCMB. A minimum data set was extracted for patients treated with other front-line therapies. Descriptive statistics were used to evaluate patient demographics, toxicity, duration and dosing of obinutuzumab treatment. Kaplan–Meier curves were used to evaluate time-to-next-treatment (TTNT), overall survival (OS) and PFS for patients treated with obinutuzumab. A multivariable logistic regression model was used to investigate associations between infusion related reactions (IRRs) and age at treatment, pre-treatment lymphocyte count, cumulative illness rating scale (CIRS) and receipt of prior chemotherapy. Results Forty seven percent of patients receiving frontline therapy received chlorambucil and obinutuzumab. Sixty-seven patients were treated with obinutuzumab and consisted of 36 males (53.7%) and 31 females (46.3%) with 29 patients (43.3%) over age 75 years. Rates of grade 3 and 4 obinutuzumab IRRs were lower (6%) compared to the CLL11 clinical trial (20%) due to local practices including slower infusion rates and using chlorambucil before starting obinutuzumab treatment. Many patients had difficulty tolerating the full dosage of chlorambucil. Only 26 patients (38.8%) had their dose of chlorambucil escalated to the full dose of 0.5 mg/kg. In addition, only 18 patients (26.9%) received all doses of obinutuzumab and all 12 doses of chlorambucil. Conclusions In summary, first dose infusion reactions with obinutuzumab can be markedly reduced by using chlorambucil to decrease the lymphocyte count before obinutuzumab and by using a very slow initial obinutuzumab infusion rate. Modifications in chlorambucil dosing and obinutuzumab administration can improve tolerance without significant loss in efficacy.

Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, resulting in a modest improvement in overall survival, but toxicity limits the eligible patient population. Few targeted agents beyond bevacizumab have demonstrated superior efficacy compared to placebos. With an improved understanding of the relationship between the immune system and cancer progression, immunotherapies are playing a greater role in the treatment of many cancers. Several early- and late-phase trials in malignant pleural mesothelioma, including assessments of the first-line efficacy of combination ipilimumab/nivolumab treatment, have now demonstrated promising results for both immune checkpoint inhibition and cell-based therapies. These immune therapies are likely to play a central role in the treatment of this disease going forward.

Background. Screening decreases non-small cell lung cancer (NSCLC) deaths and is recommended by the Canadian Task Force on Preventive Health Care. We investigated risk factor prevalence and NSCLC incidence at a small region level to inform resource allocation for lung cancer screening. Methods. NSCLC diagnoses were obtained from the Canadian Cancer Registry, then geocoded to 283 small geographic areas (SGAs) in Manitoba. Sociodemographic characteristics of SGAs were obtained from the 2006 Canadian Census and Canadian Community Health Survey. Geographical variation was modelled using a Bayesian spatial Poisson model. Results. NSCLC incidence in SGAs ranged from 1 to 343 cases per 100,000 population per year. The highest incidence rates were in the Southeastern, Southwestern, and Central regions of Manitoba, while most of Northern Manitoba had lower rates. Poisson regression suggested areas with higher proportions of Aboriginal people and higher average income, and immigrants had lower NSCLC incidence whereas areas with higher proportions of smokers had higher incidence. Conclusion. On an SGA level, smoking rates remain the most significant factor driving NSCLC incidence. Socioeconomic status and proportions of immigrants or Aboriginal peoples independently impact NSCLC rates. We have identified SGAs in Manitoba to target in policy and infrastructure planning for lung cancer screening.

An increasing proportion of patients with advanced NSCLC are over 70 years old, raising unique challenges for treatment decision-making. While these patients are underrepresented in clinical trials, there is an emerging body of evidence associated with this group. The lesson of comprehensive geriatric assessment is that chronological age does not always correlate with physiological age and a variety of important comorbidities and geriatric syndromes can go undetected in a typical history and physical. These comorbidities and expected physiologic changes due to aging complicate decision-making around appropriate treatment. This review discusses geriatric assessment in elderly cancer patients and evaluates the current evidence for chemotherapy and targeted therapy for patients with advanced non-small cell lung cancer aged ≥70 years.