Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
Primary graft dysfunction is associated with an increased risk of bronchiolitis obliterans syndrome independent of acute rejection, lymphocytic bronchitis, and community-acquired respiratory viral infections, and this risk is directly related to the severity of primary graft dysfunction.
Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. Early detection of lung cancer is an important opportunity for decreasing mortality. Data support using low-dose computed tomography (LDCT) of the chest to screen select patients who are at high risk for lung cancer. Lung screening is covered under the Affordable Care Act for individuals with high-risk factors. The Centers for Medicare & Medicaid Services (CMS) covers annual screening LDCT for appropriate Medicare beneficiaries at high risk for lung cancer if they also receive counseling and participate in shared decision-making before screening. The complete version of the NCCN Guidelines for Lung Cancer Screening provides recommendations for initial and subsequent LDCT screening and provides more detail about LDCT screening. This manuscript focuses on identifying patients at high risk for lung cancer who are candidates for LDCT of the chest and on evaluating initial screening findings.
Patients undergoing video-assisted lobectomy had fewer respiratory complications and shorter length of stay. These data suggest video-assisted thoracoscopic lobectomy is safe in patients with resectable lung cancer. Longer follow-up is needed to determine the oncologic equivalency of video-assisted versus open lobectomy.
The recognition of diaphragmatic rupture is important because of the frequency and severity of associated injuries. The difficulties in reaching the diagnosis require an aggressive search in patients at risk.
In an unmatched comparison of clinical stage IA disease, surgical patients were healthier and had better local tumor control compared with those receiving stereotactic body radiation therapy. Propensity analysis in clinical stage IA/B non-small cell lung cancer revealed similar rates of local recurrence and disease-specific survival in patients treated with surgery compared with stereotactic body radiation therapy.
Background
Conflicting evidence currently exists regarding the causes and effects of delay of care in non-small cell lung cancer (NSCLC). We hypothesized that delayed surgery in early-stage NSCLC is associated with worse short- and long-term outcomes.
Methods
Treatment data of clinical stage I NSCLC patients undergoing surgical resection was obtained from the National Cancer Database (NCDB). Treatment delay was defined as resection 8 weeks or more after diagnosis. Propensity score matching for patient and tumor characteristics was performed to create comparable groups of patients receiving early (less than 8 weeks from diagnosis) and delayed surgery. Multivariable regression models were fitted to evaluate variables influencing delay of surgery.
Results
From 1998-2010, 39,995 patients with clinical stage I NSCLC received early surgery, while 15,658 patients received delayed surgery. Of these 27,022 propensity-matched patients were identified. Those with a delay in care were more likely to be pathologically upstaged (18.3% stage 2 or higher vs. 16.6%, p<0.001), have an increased 30-day mortality (2.9% vs. 2.4%, p = 0.01), and have decreased median survival (57.7 ± 1.0 months versus 69.2 ± 1.3 months, p <0.001). Delay in surgery was associated with increasing age, non-Caucasian race, treatment at an academic center, urban location, income less than $35,000 and increasing Charlson comorbidity score (p<0.0001 for all). Delayed patients were more likely to receive a sublobar resection (17.2% vs. 13.1%, p <0.001).
Conclusions
Patients receiving delayed resection for clinical stage I NSCLC have higher comorbidity scores that may affect ability to perform lobectomy and result in higher peri-operative mortality. However, delay in resection is independently associated with increased rates of upstaging and decreased median survival. Strategies to minimize delay while medically optimizing higher risk patients are needed.
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