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(1) Background: The immune checkpoint blockade (ICB) has shown promising efficacy in non-small-cell lung cancer (NSCLC) patients with significant clinical benefits and durable responses, but the overall response rate to ICBs is only 20%. The lack of responsiveness to ICBs is currently a central problem in cancer immunotherapy. (2) Methods: Four public cohorts comprising 2986 patients with NSCLC were included in the study. We screened 158 patients with NSCLC with no durable clinical benefit (NDB) to ICBs in the Rizvi cohort and identified NDB-related gene mutations in these patients using univariate and multivariate Cox regression analyses. Programmed death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB), neoantigen load, tumor-infiltrating lymphocytes, and immune-related gene expression were analyzed for identifying gene mutations. A comprehensive predictive classifier model was also built to evaluate the efficacy of ICB therapy. (3) Results: Mutations in FAT1 and KEAP1 were found to correlate with NDB in patients with NSCLC to ICBs; however, the analysis suggested that only mutation in FAT1 was valuable in predicting the efficacy of ICB therapy, and that mutation in KEAP1 acted as a prognostic but not a predictive biomarker for NSCLC. Mutations in FAT1 were associated with a higher TMB and lower multiple lymphocyte infiltration, including CD8 (T-Cell Surface Glycoprotein CD8)+ T cells. We established a prognostic model according to PD-L1 expression, TMB, smoking status, treatment regimen, treatment type, and FAT1 mutation, which indicated good accuracy by receiver operating characteristic (ROC) analysis (area under the curve (AUC) for 6-months survival: 0.763; AUC for 12-months survival: 0.871). (4) Conclusions: Mutation in FAT1 may be a predictive biomarker in patients with NSCLC who exhibit NDB to ICBs. We proposed an FAT1 mutation-based model for screening more suitable NSCLC patients to receive ICBs that may contribute to individualized immunotherapy.
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CONTEXT: Tracheobronchomalacia (TBM) results from structural and functional abnormalities of the respiratory system. It is characterized by excessive collapse: at least 50 percent of the cross-sectional area of the trachea and main bronchi. In this paper, we present a rare case of a patient with TBM who first presented with stridor and respiratory failure due to exacerbation of chronic bronchitis. CASE REPORT: An 81-year-old Caucasian man was admitted presenting coughing, purulent sputum, stridor and respiratory failure. He had a medical history of chronic obstructive pulmonary disease (COPD) and silicosis and was a former smoker. Axial computed tomography on the chest revealed marked collapse of the trachea in its middle third. Bronchoscopy showed characteristics compatible with TBM. He was treated with noninvasive ventilation, without any good response. Subsequently, a Dumon Y stent was placed by means of rigid bronchoscopy. After the procedure, he was discharged with a clinical improvement. CONCLUSION: TBM is fatal and often underdiagnosed. In COPD patients, stridor and respiratory failure may be helpful signs that should alert physicians to consider TBM as an early diagnosis. Thus, these signs may be important for optimizing the treatment and evolution of such patients.
CONTEXTO: Traqueobroncomalácia (TBM) é resultado de alterações funcionais e estruturais do aparelho respiratório. É caracterizada pelo colapso excessivo de pelo menos 50 por cento da área de secção transversal da traqueia e dos brônquios principais. Neste trabalho, descrevemos um raro caso de paciente com TBM que primeiro apresentou estridor e insuficiência respiratória devido à exacerbação da bronquite crônica. RELATO DE CASO: Homem de 81 anos de idade, caucasiano, foi admitido apresentando tosse, expectoração purulenta, estridor e falência respiratória. Ele apresentava história médica prévia de doença pulmonar obstrutiva crônica (DPOC), silicose e era ex-tabagista. A tomografia axial computadorizada de tórax revelou marcado colapso da traqueia em seu terço médio. A broncoscopia mostrou aspectos compatíveis com TBM. Foi submetido a ventilação não invasiva, sem boa resposta. Na sequência, foi colocado stent Dumon em Y por broncoscopia rígida. Após o procedimento, o paciente teve alta com melhora clínica. CONCLUSÃO: TBM é uma entidade fatal e muitas vezes subdiagnosticada. Em pacientes com DPOC, o estridor e a insuficiência respiratória podem ser sinais úteis que devem alertar os médicos a considerar TBM como diagnóstico precoce. Assim, pode ser importante para otimizar o tratamento e a evolução dos pacientes.