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Background: Electromagnetic navigation bronchoscopy (ENB) is an image-guided approach to access peripheral pulmonary lesions. ENB has been evaluated in a prospective global study (NAVIGATE, NCT02410837, Khandhar, BMC Pulm Med 2017;17:59). Practice patterns and safety specifically in the full European cohort have not yet been presented. The objective of this study is to evaluate ENB safety and usage in the NAVIGATE European sites. Methods: NAVIGATE is a global, prospective, multicenter study of ENB (superDimension TM navigation system) use in community and academic settings. A prespecified 1-month interim analysis was conducted of the European cohort. Results: Subjects (n ¼ 175) were enrolled at 8 European sites, with complete 1-month follow-up in 99.4%. ENB was used to aid in lung biopsy in 99.4% (174/175) and fiducial marking in 8.0% (14/175). Lymph node sampling was attempted in 12 procedures (9 using linear EBUS). General anesthesia was used in 57%, radial EBUS in 4.0%, conebeam CT in 9.7%, fluoroscopy in 41.7%, and rapid on-site evaluation (ROSE) in 17.9%. The median lesion size was 18.0 mm. Lesions were in the peripheral third of the lung in 72.7% and the upper lobe in 62.6%. A bronchus sign was present in 66.8%. Navigation was successful in 96.6% of biopsy cases. The median ENB planning time was 12.5 minutes. The median total procedure time (bronchoscope in to bronchoscope out) was 43.5 minutes, which included 32.9 minutes of ENB-specific navigation/sampling time (first entry to last exit of the locatable guide or extended working channel). The ENB-related pneumothorax rate was 7.4% (13/175), 5.1% requiring intervention or hospitalization. The ENB-related Common Terminology Criteria for Adverse Events Grade 2 bronchopulmonary hemorrhage and Grade 4 respiratory failures rates were 2.3% and 0.6%, respectively. Longer follow-up is required to assess diagnostic yield. Conclusions: The results from the European cohort of the NAVIGATE study suggest that ENB provides a safe platform to aid in lung lesion biopsy. ENB also allows multidimensional lung lesion biopsy, fiducial placement, and concurrent lymph node sampling during a single anesthetic event.

In this study, we recruited 119 patients with LARC receiving nCRT. 595 serial plasma samples were collected at d0, d15, d25 of radiotherapy as well before and 7 days post-surgery. The level of ctDNA was calculated by dynamic monitoring the mutant allele frequency of somatic mutations in plasma. Plasma and tissue samples were subjected to targeted-NGS using a 422 cancer-related genes panel. We followed up patients with concomitant CT until disease progression or death. Results: Serial samples' data analysis showed detection of pre-treatment mutations after completion of nCRT was significantly associated with worse disease-free survival (DFS) (P<0.05). Patients with ctDNA mutations clearance during nCRT significantly have a better DFS compare with patients with ctDNA non-clearance (PZ0.02). The presence of TP53 mutations is predictive of treatment outcome and shows a statistically significant worse DFS (2 years) (54.3% VS 87.0%, PZ0.0005). Predictive model based on support vector machine was developed for prediction of pCR achieving a mean AUC of 0.85 assessed by repeated cross validation. Through tracking clonal extinction, persistence and emergence, patients were grouped into four evolutionary subtypes with distinct TRG and DFS. Conclusion: Our data showed the prognostic value of ctDNA on DFS. In patients treated with nCRT, the presence of ctDNA after completion of nCRT was associated with an inferior DFS (PZ0.02). Dynamic monitoring of ctDNA can be used to predict TRG and prognosis in LARC patients receiving nCRT. ctDNA sequencing depicts the evolutionary trajectories of sensitive and resistant clones during nCRT in LARC. CtDNA could potentially be used to guide patient selection for nCRT.