Browsing by Author "Chernilo, Sara"
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Publication Beyond tobacco: genomic disparities in lung cancer between smokers and never-smokers(2024) Garrido, Javiera; Bernal, Yanara; González, Evelin; Blanco, Alejandro; Sepúlveda, Gonzalo; Freire, Matías; Oróstica, Karen; Rivas, Solange; Marcelain, Katherine; Owen, Gareth; Ibañez, Carolina; Corvalan, Alejandro; Garrido, Marcelo; Assar, Rodrigo; Lizana, Rodrigo; Cáceres, Javier; Ampuero, Diego; Ramos, Liliana; Pérez, Paola; Aren, Osvaldo; Chernilo, Sara; Fernández, Cristina; Spencer, María; Flores, Jacqueline; Bernal, Giuliano; Ahumada, Mónica; Rasse, Germán; Sánchez, Carolina; De Amorim, Maria; Bartelli, Thais; Noronha, Diana; Dias, Emmanuel; Freitas, Helano; Armisén, RicardoBackground: Tobacco use is one of the main risk factors for Lung Cancer (LC) development. However, about 10-20% of those diagnosed with the disease are never-smokers. For Non-Small Cell Lung Cancer (NSCLC) there are clear differences in both the clinical presentation and the tumor genomic profiles between smokers and never-smokers. For example, the Lung Adenocarcinoma (LUAD) histological subtype in never-smokers is predominately found in young women of European, North American, and Asian descent. While the clinical presentation and tumor genomic profiles of smokers have been widely examined, never-smokers are usually underrepresented, especially those of a Latin American (LA) background. In this work, we characterize, for the first time, the difference in the genomic profiles between smokers and never-smokers LC patients from Chile. Methods: We conduct a comparison by smoking status in the frequencies of genomic alterations (GAs) including somatic mutations and structural variants (fusions) in a total of 10 clinically relevant genes, including the eight most common actionable genes for LC (EGFR, KRAS, ALK, MET, BRAF, RET, ERBB2, and ROS1) and two established driver genes for malignancies other than LC (PIK3CA and MAP2K1). Study participants were grouped as either smokers (current and former, n = 473) or never-smokers (n = 200) according to self-report tobacco use at enrollment. Results: Our findings indicate a higher overall GA frequency for never-smokers compared to smokers (58 vs. 45.7, p-value < 0.01) with the genes EGFR, KRAS, and PIK3CA displaying the highest prevalence while ERBB2, RET, and ROS1 the lowest. Never-smokers present higher frequencies in seven out of the 10 genes; however, smokers harbor a more complex genomic profile. The clearest differences between groups are seen for EGFR (15.6 vs. 21.5, p-value: < 0.01), PIK3CA (6.8 vs 9.5) and ALK (3.2 vs 7.5) in favor of never-smokers, and KRAS (16.3 vs. 11.5) and MAP2K1 (6.6 vs. 3.5) in favor of smokers. Alterations in these genes are comprised almost exclusively by somatic mutations in EGFR and mainly by fusions in ALK, and only by mutations in PIK3CA, KRAS and MAP2K1. Conclusions: We found clear differences in the genomic landscape by smoking status in LUAD patients from Chile, with potential implications for clinical management in these limited-resource settings.Item Complicaciones asociadas a la broncoscopía flexible: análisis de registro post- procedimiento(Sociedad Médica de Santiago, 2014) Fernández-Bussy, Sebastián; Labarca, Gonzalo; Zagolin, Mónica; Oyonarte, Maite; Isamit, Dionis; Jalilie, Alfredo; Guerra, Carlos; Chernilo, SaraBackground: Flexible bronchoscopy is a useful diagnostic tool with a relative low rate of complications. Aim: To analyze post procedure risk of complications after flexible bronchoscopy with transbronchial or bronchial biopsy. Material and Methods: The electronic database of a bronchoscopy unit at a general Hospital was analyzed. All procedures performed between 2009 and 2011 were reviewed and complications recorded. The primary outcome measure was the risk for complications defined as the percentage of procedures complicated by hemorrhage, pneumothorax, desaturation < 80% and other complications. We used a logistic regression model to explore the association between each procedure characteristic and complication. Results: One thousand seventy nine procedures were included in the analysis. Eight percent had complications. Among these, the frequency of hemorrhage was 5.9% and pneumothorax was 0.3%. Factors associated with complications were exclusive use of topical anesthesia with an odds ratio (OR) of 1.72 (confidence intervals (CI): 1.04-2.86), regular or bad intolerance to the procedure with an OR 4.70 (CI: 3.00-7.38) and performing biopsies of the upper lobes with an OR of 1.76 (CI: 1.04-2.97). Conclusions: Exclusive use of topical anesthesia, performing biopsies of the upper lobes and procedure tolerance were risk factors associated with complications following bronchoscopic biopsies.Item Concordance analysis of ALK gene fusion detection methods in patients with Non– Small-Cell Lung Cancer from Chile, Brazil, and Peru(2021-06) Sepúlveda-Hermosilla, Gonzalo; Freire, Matías; Blanco, Alejandro; Cáceres, Javier; Lizana, Rodrigo; Ramos, Liliana; Assar, Rodrigo; Ampuero, Diego; Aren, Osvaldo; Chernilo, Sara; Spencer, María Loreto; Bernal, Giuliano; Flores, Jacqueline; Rasse, Germán; Sánchez, Carolina; Marcelain, Katherine; Rivas, Solange; Pereira Branco, Gabriela; Galli de Amorim, María; Noronha Nunes, Diana; Dias-Neto, Emmanuel; Freitas, Helano C.; Fernández, Cristina; Pérez, Paola; NIRVANA team; Armisén, RicardoAbout 4 to 7 % of the Non-small cell lung cancer patients have ALK rearrangements and specific target therapies improve patients’ outcomes significantly. ALK gene fusions are detected by immunohistochemistry (IHC) or Fluorescent in situ Hybridization (FISH) as gold standards in South America. Next Generation Sequencing (NGS) based assays are a reliable alternative, able to perform simultaneous detection of multiple events from a single sample. We analyzed 4,240 Non-small cell lung cancer samples collected in 37 hospitals from Chile, Brazil, and Peru; where ALK rearrangements were determined as part of their standard of care (SofC) using either IHC or FISH. A subset of 1450 samples was sequenced with the Oncomine Focus Assay (OFA), and the concordance with the SofC tests was measured. An orthogonal analysis was performed using a qPCR EML4-ALK fusion detection kit. ALK fusion prevalence is very similar for Chile (3.67%, N=2142), Brazil (4.05%, N=1013) and Peru (4.59%, N=675). Whereas a comparison between OFA and SofC assays showed similar sensitivity, OFA had significantly higher specificity and higher positive predictive value, which opens new opportunities for a more specific determination of ALK gene rearrangements.Item Rendimiento diagnóstico de la broncoscopia con biopsia transbronquial en el estudio de lesiones sugerentes de cáncer pulmonar(Sociedad Médica de Santiago, 2015) Fernández-Bussy, Sebastián; Labarca, Gonzalo; Canals, Sofía; Zagollín, Mónica; Oyonarte, Maite; Isamit, Dionis; Jalilie, Alfredo; Guerra, Carlos; Chernilo, SaraBackground: Bronchoscopy is a minimally invasive procedure used for the diagnosis of lung cancer. Aim: To report our experience with bronchoscopy and transbronchial biopsies for the diagnosis of potentially malignant pulmonary lesions. Material and Methods: Revision of electronic records from patients who underwent transbronchial biopsies seeking for lung cancer. The diagnostic yield of the procedure was evaluated using pathology reports or a 24 months follow up. Results: 261 patients were included. Bronchoscopy was diagnostic in 65% of cases. Lesions mean diameter was 51 mm (range 9-120 mm). Diagnostic yield for lesions less than 30 mm was 59%, for lesions less than 35 mm was 61%, and for lesions over 40 mm was 69%. The presence of malignant lesions and their location in the superior or middle lobe were associated with a better predictive value of the procedure. TNM staging was IIIB/IV in 80% of the patient at the time of diagnosis. Conclusions: The diagnostic yield of bronchoscopy is influenced by the etiology and location of lung lesions.