Search

Background: Given advancements in adjuvant treatments for non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)-targeted therapies, it is important to consider postoperative targeted therapies for other early-stage oncogene-addicted NSCLC. Exploring baseline outcomes for early-stage NSCLC with these rare mutations is crucial. Objectives: This study aims to assess relapse-free survival (RFS) and overall survival (OS) in patients with resected early-stage NSCLC with rare targetable driver mutations. Methods: This retrospective single-center study identified stage I–III NSCLC patients with rare targetable mutations who underwent curative surgery. Tissue-based molecular profiling identified mutations in KRAS G12C, EGFR Exon20, Erb-B2 receptor tyrosine kinase 2 (ERBB2), ALK, ROS1, B-Raf proto-oncogene (BRAF) V600E, mesenchymal–epithelial transition factor (MET) exon14 skipping, and rearranged during transfection (RET). Baseline patient and tumor characteristics, mutation subtype, and TP53 co-mutation were correlated with RFS and OS using Cox regression. The KRAS G12C cohort was used as the reference for survival comparisons. Results: Among 225 patients, mutations included the following: KRAS G12C (n = 101, 45%), MET exon 14 skipping (n = 26, 12%), EGFR Exon 20 (n = 25, 11%), ERBB2 (n = 25, 11%), ALK fusion (n = 16, 7%), ROS1 fusion (n = 14, 6%), BRAF V600E mutation (n = 13, 6%), and RET fusion (n = 5, 2%). Five-year survival probabilities were 76% for stage I, 60% for stage II, and 58% for stage III. RFS was shorter across most mutation subgroups compared to KRAS G12C, with ROS1 mutations showing significantly poorer RFS (HR 2.70, p = 0.019). By contrast, all mutation subgroups were associated with better OS than KRAS G12C. The incidence of brain metastasis was highest in ERBB2 (22% at 5 years). TP53 co-mutation was associated with significantly worse OS (HR 2.35, p = 0.008). Conclusion: While RFS was poorer for most mutations compared to KRAS G12C, OS generally was better, suggesting a potential role for postoperative targeted therapies. These findings warrant further investigation through prospective studies and clinical trials to optimize adjuvant treatment strategies for patients with early-stage NSCLC harboring rare driver mutations. Plain language summary: Outcomes of patients with resected early-stage lung cancer with rare targetable driver mutations Early-stage non-small cell lung cancer (NSCLC) is often treated with surgery and sometimes chemotherapy after surgery. Recent advancement with discovery of mutations that drive cancer has led to improvement of outcomes in NSCLC with targeted therapies. Certain mutations in NSCLC are rare and how these mutations impact outcomes after surgery in early-stage NSCLC is less clear. Our study focused on patients with early-stage NSCLC who had surgery and specific rare mutations including EGFR Exon20 insertion, KRAS G12C, ALK, ROS1, BRAF, NTRK1/2/3, MET exon 14 skipping, RET, and ERBB2 mutations. We want to understand how presence of these mutations affects the chance of cancer returning (relapse-free survival) and overall survival after surgery. We found that most mutations had higher risk of cancer returning (relapse-free survival) compared to patients with KRAS mutation and ROS1 had highest risk of cancer returning in our study. However, for overall survival all mutations were linked to better overall survival than KRAS mutation. ERBB2 mutation had highest risk to develop brain metastasis when the cancer returns. Those with additional TP53 mutation, another genetic change had worse overall survival outcome. These results provide more evidence regarding the outcome of these patients with rare mutations in early-stage NSCLC. There might be a benefit of using targeted therapies early in the diagnosis of early-stage NSCLC. We hope our results help to inform potential studies in the future to show benefit of using targeted therapies after surgery in early-stage NSCLC. [ABSTRACT FROM AUTHOR]

Rationale: Chronic lung allograft dysfunction (CLAD) is the leading cause of death after lung transplant, and azithromycin has variable efficacy in CLAD. The lung microbiome is a risk factor for developing CLAD, but the relationship between lung dysbiosis, pulmonary inflammation, and allograft dysfunction remains poorly understood. Whether lung microbiota predict outcomes or modify treatment response after CLAD is unknown. Objectives: To determine whether lung microbiota predict post-CLAD outcomes and clinical response to azithromycin. Methods: Retrospective cohort study using acellular BAL fluid prospectively collected from recipients of lung transplant within 90 days of CLAD onset. Lung microbiota were characterized using 16S rRNA gene sequencing and droplet digital PCR. In two additional cohorts, causal relationships of dysbiosis and inflammation were evaluated by comparing lung microbiota with CLAD-associated cytokines and measuring ex vivo P. aeruginosa growth in sterilized BAL fluid. Measurements and Main Results: Patients with higher bacterial burden had shorter post-CLAD survival, independent of CLAD phenotype, azithromycin treatment, and relevant covariates. Azithromycin treatment improved survival in patients with high bacterial burden but had negligible impact on patients with low or moderate burden. Lung bacterial burden was positively associated with CLAD-associated cytokines, and ex vivo growth of P. aeruginosa was augmented in BAL fluid from transplant recipients with CLAD. Conclusions: In recipients of lung transplants with chronic rejection, increased lung bacterial burden is an independent risk factor for mortality and predicts clinical response to azithromycin. Lung bacterial dysbiosis is associated with alveolar inflammation and may be promoted by underlying lung allograft dysfunction. [ABSTRACT FROM AUTHOR]

Purpose While high body mass index (BMI) is a recognized risk factor for pulmonary complications in adults, its importance as a risk factor for complications following pediatric surgery is poorly described. We evaluated the association between BMI and severe pediatric perioperative pulmonary complications (PPCs). Methods In this retrospective cohort study, we evaluated pediatric patients (aged 2-17 years) undergoing elective procedures in the 2015 Pediatric National Surgical Quality Improvement Program (NSQIP-P). Severe PPCs were defined as either pneumonia/reintubation within 3 days of surgery, or pneumonia/reintubation as an index complication within 7 days. Univariate and multivariable logistic regression analyses adjusting for patient factors and surgical case-mix tested associations between BMI class-using the Centers for Disease Control age- and sex-dependent BMI percentiles-and severe PPCs. Results Among 40,949 patients, BMI class was distributed as follows: 2740 (6.7%) were underweight, 23,630 (57.7%) normal weight, 6161 (15.0%) overweight, and 8418 (20.6%) obese. Overweight BMI class was not associated with PPCs in univariate analyses, but became statistically significant after adjustment [OR 1.84 (95% CI 1.07-3.15), p = 0.03], and persisted across multiple adjustment approaches. Neither underweight [OR 1.01 (95% CI 0.53-1.94), p = 0.97] nor obesity [OR 1.10 (95% CI 0.63-1.94), p = 0.73] were associated with PPCs after adjustment. Conclusion Overweight pediatric patients have an elevated, previously underappreciated risk of severe PPCs. Contrary to prior studies, the present study found no greater risk in obese children, perhaps due to bias, confounding, or practice migration from 'availability bias'. Findings from the present study, taken with prior work describing pulmonary risks of obesity, suggest that both obese and overweight children may be evaluated for tailored perioperative care to improve outcomes., Author(s): Leanne Thalji [sup.1] , Yu Shi [sup.1] , Kristine T. Hanson [sup.2] , Elliot Wakeam [sup.3] , Elizabeth B. Habermann [sup.2] , Joseph A. Hyder [sup.1] [sup.2] [sup.4] Author [...]