Background: Leptomeningeal metastases (LM), associated with poor prognosis, are frequent complications of advanced non-small cell lung cancer (NSCLC) patients, especially in patients with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the mutational landscape of LM has not been comprehensively investigated in large cohorts and the underlining biology of LM remains elusive. Some studies have explored the potential of cerebrospinal fluid (CSF) in reflecting the molecular profile of LM but with limited number of patients enrolled. Methods: In this study, we performed capture-based targeted sequencing using a panel consisting of 168 lung cancer-related genes on matched CSF and plasma samples from 72 advanced NSCLC patients with confirmed LM to interrogate the potential of CSF as a source of liquid biopsy. Results: We revealed a rate of detection of 81.5% and 62.5% for CSF and plasma, respectively (p = 0.008). The maximum allelic fraction (MaxAF) was also significantly higher in CSF (43.6% vs. 4.6%) (p < 0.001). CSF, harboring a unique genomic profile by having a significant number of CSF-specific mutations, primarily copy number variations, is superior to plasma in reflecting the mutational profile of LM. Further pathway enrichment analysis revealed that most of CSF-specific mutations participated in pathways relevant to the tumorigenesis and the development of metastases. Moreover, our data also revealed that TP53 loss of heterozygosity (LOH) predominantly existed in CSF (p < 0.001). Conclusions: Collectively, we demonstrated that CSF provides a more comprehensive profile of LM than plasma in a large cohort, thus can be used as an alternative source of liquid biopsy for LM patients.

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Aim: Individual differences in chemosensitivity and clinical outcome in non-small cell lung cancer (NSCLC) patients treatment with platinum-based chemotherapy may be due to genetic factors. Our study aimed to investigate the prognostic role of GSTP1, XRCC1 and XRCC3 in NSCLC patients treated with chemotherapy.

Background: Limited resection has gradually become an acceptable treatment for lung adenocarcinomas (ADCs) presenting as ground-glass nodules (GGNs). However, its role in lung ADCs presenting as pure solid nodules (PSN) remains unclear. In this study, we aimed to identify potential candidates for limited resection in lung ADCs presenting as PSN. Methods: We retrospectively reviewed 772 patients from seven hospitals with lung ADCs ⩽2 cm, presenting as PSN on computed tomography scans, who had undergone surgery between 2009 and 2013. Histological subtypes were listed in 5% increments. To investigate the value of histological subtypes in surgical decision making, five pathologists prospectively evaluated the feasibility of identifying histological subtypes using frozen section (FS) in two cohorts. Results: The percentage of micropapillary (MIP) subtype had a striking impact on recurrence-free survival (RFS) and overall survival (OS) for lung ADCs ⩽2 cm presenting as PSNs. In multivariable Cox analysis, segmentectomy was significantly associated with worse RFS and OS in patients with MIP >5% than lobectomy, but not in those with MIP ⩽5%. With wedge resection, worse RFS and OS were observed in patients with MIP >5% and those with MIP ⩽5% than lobectomy. The sensitivity and specificity for detecting MIP by FS were 74.2% and 85.6%, respectively, with substantial inter-rater agreement. Conclusion: Segmentectomy and lobectomy had similar oncological outcomes in patients with lung ADCs ⩽2 cm presenting as PSN with MIP ⩽5%. Randomized trials are necessary to validate the feasibility of intraoperative FS to choose candidates for segmentectomy.