The large burden of COVID-19 on health care systems worldwide has raised concerns among medical oncologists about the impact of COVID-19 on the diagnosis and treatment of lung cancer patients. In this retrospective cohort study, we investigated the impact of COVID-19 on lung cancer diagnosis and treatment before and during the COVID-19 era. New lung cancer diagnoses decreased by 34.7% during the pandemic with slightly more advanced stages of disease, there was a significant increase in the utilization of radiosurgery as the first definitive treatment, and a decrease in both systemic treatment as well as surgery compared to the pre-COVID-19 era. There was no significant delay in starting chemotherapy and radiation treatment during the pandemic compared to pre-COVID-19 time. However, we observed a delay to lung cancer surgery during the pandemic time. COVID-19 seems to have had a major impact at our lung cancer center on the diagnoses and treatment patterns of lung cancer patients. Many oncologists fear that they will see an increase in newly diagnosed lung cancer patients in the coming year. This study is still ongoing and further data will be collected and analyzed to better understand the total impact of the COVID-19 pandemic on our lung cancer patient population.

Rearrangements in the anaplastic lymphoma kinase (ALK) gene are found in approximately 5% of non–small cell lung carcinoma (NSCLC). Here, we present a comprehensive genomic landscape of 11 patients with ALK+ NSCLC and investigate its relationship with response to crizotinib. Using whole-exome sequencing and RNAseq data, we identified four rare ALK fusion partners (HIP1, GCC2, ERC1, and SLC16A7) and one novel partner (CEP55). At the mutation level, TP53 was the most frequently mutated gene and was only observed in patients with the shortest progression-free survival (PFS). Of note, only 4% of the genes carrying mutations are present in more than 1 patient. Analysis of somatic copy number aberrations (SCNA) demonstrated that a gain in EML4 was associated with longer PFS, and a loss of ALK or gain in EGFR was associated with shorter PFS. This study is the first to report a comprehensive view of the ALK+ NSCLC copy number landscape and to identify SCNA regions associated with clinical outcome. Our data show the presence of TP53 mutation as a strong prognostic indication of poor clinical response in ALK+ NSCLC. Furthermore, new and rare ALK fusion partners were observed in this cohort, expanding our knowledge in ALK+ NSCLC.

Background: Immunotherapy with ICIs has revolutionized the treatment for NSCLC. The impact of sex on treatment outcomes remains unclear. The aim of this study was to evaluate sex-related differences in immunotherapy outcomes in a real-world population of NSCLC patients. Methods: Demographics, clinical, pathological characteristics, and treatment-related variables were analyzed to understand the differences in efficacy and safety outcomes in relation to sex. Results: 174 advanced NSCLC patients receiving first-line ICIs, either alone or in conjunction with chemotherapy, were included. No differences based on gender were observed in PFS and OS. Prognostic factors for OS and PFS included liver metastases and CRP levels at treatment discontinuation (TD). IrAE-related TD occurred at a significantly higher rate in females. GI toxicity, including hepatitis and colitis, was predominantly observed in females, whereas pneumonitis was the most frequent irAE leading to TD in males. Conclusions: Despite no significant differences based on gender being observed in survival outcomes, our study showed that female patients with advanced NSCLC receiving ICIs are at a substantially greater risk of severe symptomatic irAEs and TD. This finding indicates that broad-based sex differences could potentially exist and emphasizes the need for further investigations into the role played by gender in immunity and cancer immunotherapy treatment.

Background: We have recently reported a 35% drop in new lung cancer diagnoses and a 64% drop in lung cancer surgeries during the first year of the pandemic. Methods: The target population was divided into three cohorts: pre-COVID-19 (2019), first year of COVID-19 (2020), and second year of COVID-19 (2021). Results: The number of new lung cancer diagnoses during the second year of the pandemic increased by 75%, with more than 50% being in the advanced/metastatic stage. There was a significant increase in cases with multiple extrathoracic sites of metastases during the pandemic. During the first year of the pandemic, significantly more patients were treated with radiosurgery compared to the pre-COVID-19 year. During the second year, the number of radiosurgery and surgical cases returned to pre-COVID-19 levels. No significant changes were observed in systemic chemotherapy and targeted therapy. No statistical difference was identified in the mean wait time for diagnosis and treatment during the three years of observation. However, the wait time for surgery was prolonged compared to the pre-COVID-19 cohort. Conclusions: The significant drop in new diagnoses of lung cancer during the first year of the pandemic was followed by an almost two-fold increase in the second year, with the increased rate of metastatic disease with multiple extra-thoracic site metastases. Limited access to surgery resulted in the more frequent use of radiosurgery.

The discovery of EGFR tyrosine kinase inhibitors (TKI) for the treatment of EGFR mutant (EGFRm) metastatic NSCLC is regarded as a landmark in lung cancer. EGFR-TKIs have now become a standard first-line treatment for EGFRm NSCLC. The aim of this retrospective cohort study is to describe real-world patterns of treatment and treatment outcomes in patients with EGFRm metastatic NSCLC who received EGFR-TKI therapy outside of clinical trials. One hundred and seventy EGFRm metastatic NSCLC patients were diagnosed and initiated on first-line TKI therapy between 2004 and 2018 at the Peter Brojde Lung Cancer Centre in Montreal. Following progression of the disease, 137 (80%) patients discontinued first-line treatment. Moreover, 80/137 (58%) patients received second-line treatment, which included: EGFR-TKIs, platinum-based, or single-agent chemotherapy. At the time of progression on first-line treatment, 73 patients were tested for the T790M mutation. Moreover, 30/73 (41%) patients were found to be positive for the T790M mutation; 62/80 patients progressed to second-line treatment and 20/62 were started on third-line treatment. The median duration of treatment was 11.5 (95% CI; 9.62–13.44) months for first-line treatment, and 4.4 (95% CI: 1.47–7.39) months for second-line treatment. Median OS from the time of diagnosis of metastatic disease was 23.5 months (95% CI: 16.9–30.1) and median OS from the initiation of EGFR-TKI was 20.6 months (95% CI: 13.5–27.6). We identified that ECOG PS ≤ 2, presence of exon 19 deletion mutation, and absence of brain metastases were associated with better OS. A significant OS benefit was observed in patients treated with osimertinib in second-line treatment compared to those who never received osimertinib. Overall, our retrospective observational study suggests that treatment outcomes in EGFRm NSCLC in real-world practice, such as OS and PFS, reflect the result of RCTs. However, given the few observational studies on real-world treatment patterns of EGFR-mutant NSCLC, this study is important for understanding the potential impact of EGFR-TKIs on survival outside of clinical trials. Further real-world studies are needed to characterize patient outcomes for emerging therapies, including first-line osimertinib use and combination of osimertinib with chemotherapy and potential future combination of osimertinib and novel anticancer drug, outside of a clinical trial setting.