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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. [ABSTRACT FROM AUTHOR]

• Nd model ages indicate a Grenvillian tectonic window near Chalk River, Ontario. • The main ramp of Ottawan orogenic thrusting was located southeast of Chalk River. • This strongly supports a ramp-flat thrusting model for the SW Grenville province. • It removes the basis for pervasive SE-directed orogenic collapse across the gneiss belt. Over forty new Nd isotope determinations are presented for granitoid orthogneisses from the Chalk River area, on the border between Ontario and Quebec in the SW Grenville Province. TDM model ages provide evidence for a tectonic window through the allochthonous belt into the Grenvillian parautochthon in the Chalk River area. This tectonic window constrains the location of the main ramp of the Allochthon Boundary Thrust southeast of the Chalk River area. However, the structure of the tectonic window has been complicated by down-faulting on the Ontario side of the Ottawa River, due to reactivation of late Precambrian normal faulting associated with the Ottawa–Bonnechere graben. Thus, on the Ontario side of the border, the surface expression of the tectonic window is represented by a strongly sheared tectonic duplex that underlies the main allochthon. However, the lower section of a 1 km-deep borehole drilled by Canadian Nuclear Laboratories has TDM model ages indicating penetration into the underlying parautochthon. The new data, combined with previous Nd isotope mapping and Lithoprobe seismic reflection results, point to a relatively constant thickness for the exhumed Muskoka allochthon. By showing that this exhumation occurred immediately below the Central Metasedimentary Belt boundary, this evidence strongly supports a ramp-flat thrusting model for the SW Grenville province. This model greatly reduces the likelihood of major crustal exhumation to the NW of Parry Sound domain, thus removing the theoretical basis for pervasive southeast directed orogenic collapse across the Ontario gneiss belt. [ABSTRACT FROM AUTHOR]