The tumor immune microenvironment (TIME) of lung cancer brain metastasis is largely unexplored. We carried out immune profiling and sequencing analysis of paired resected primary tumors and brain metastases of non-small-cell lung carcinoma (NSCLC). TIME profiling of archival formalin-fixed and paraffin-embedded specimens of paired primary tumors and brain metastases from 39 patients with surgically resected NSCLCs was carried out using a 770 immune gene expression panel and by T-cell receptor beta repertoire (TCRβ) sequencing. Immunohistochemistry was carried out for validation. Targeted sequencing was carried out to catalog hot spot mutations in cancer genes. Somatic hot spot mutations were mostly shared between both tumor sites (28/39 patients; 71%). We identified 161 differentially expressed genes, indicating inhibition of dendritic cell maturation, Th1, and leukocyte extravasation signaling pathways, in brain metastases compared with primary tumors (P < 0.01). The proinflammatory cell adhesion molecule vascular cell adhesion protein 1 was significantly suppressed in brain metastases compared with primary tumors. Brain metastases exhibited lower T cell and elevated macrophage infiltration compared with primary tumors (P < 0.001). T-cell clones were expanded in 64% of brain metastases compared with their corresponding primary tumors. Furthermore, while TCR repertoires were largely shared between paired brain metastases and primary tumors, T-cell densities were sparse in the metastases. We present findings that suggest that the TIME in brain metastases from NSCLC is immunosuppressed and comprises immune phenotypes (e.g. immunosuppressive tumor-associated macrophages) that may help guide immunotherapeutic strategies for NSCLC brain metastases.

The aim of this study was to demonstrate the feasibility and efficacy of a novel simulation software called, virtual segmentectomy. We developed the segmentectomy simulation system, which was programmed to analyse the detailed 3D bronchovascular structure and to predict the appropriate segmental surface and surgical margin, based on lung modelling from CT images. We have attempted this novel technique for 3 cases of pulmonary metastases and 1 case of multiple lung cancer. For validation, the predicted resection margin was compared with the actual resected specimen. The surgical surface, as estimated by the simulation, was compared with the surface of the specimen and a surgical video. To test its feasibility, the operation time, blood loss, durations of chest tube placement and hospitalization as well as pathological findings were assessed. Preoperative simulation and intraoperative guidance by virtual segmentectomy could contribute significantly to determining the most appropriate anatomical segmentectomy and curative resection.

The presence of ground glass opacity (GGO) on high-resolution computed tomography (HRCT) is well known to be pathologically closely associated with adenocarcinoma in situ. To determine whether it is more useful to evaluate the whole tumor size or only the solid component size to predict the pathologic high-grade malignancy and the prognostic outcome in lung adenocarcinoma. Using HRCT data of 232 patients with adenocarcinoma who underwent curative resection, we retrospectively measured the whole tumor and solid component sizes with lung window setting (WTLW and SCLW) and whole tumor sizes with a mediastinal window setting (WTMW). There was significant correlation between the WTLW and the measurements of pathological whole tumor (pWT) (r = 0.792, P < 0.0001). The SCLW and WTLW values significantly correlated with the area of pathological invasive component (pIVS) (r = 0.762, P < 0.0001 and r = 0.771, P < 0.0001, respectively). The receiver operating characteristics area under the curve for WTLW, SCLW, and WTMW used to identify lymph node metastasis or lymphatic or vascular invasion were 0.693, 0.817, and 0.824, respectively. Kaplan-Meier curves of disease-free survival (DFS) and overall survival (OS) were better divided according to SCLW and WTMW, compared with WTLW. Multivariate analysis of DFS and OS revealed that WTMW was an independent prognostic factor (HR = 0.72, 95% confidence interval [CI] = 0.58–0.90, P = 0.004 and HR = 0.74, 95% CI = 0.57–0.96, P = 0.022, respectively). The predictive values of the solid tumor size visualized on HRCT especially in the mediastinal window for pathologic high-grade malignancy and prognosis in lung adenocarcinoma were greater than those of whole tumor size.

Although an association between prognosis and lobar location of lung cancer, particularly the left lower lobe (LLL), has been suggested, the certainty of such association remains controversial. The purpose of this study was to evaluate the impact of tumour lobar location on surgical outcomes as an independent prognostic factor for survival in our non-small cell lung cancer (NSCLC) patient series. We retrospectively reviewed 978 NSCLC patients who underwent complete resection in our hospital between 2000 and 2007. We statistically analysed the association between clinicopathological factors and clinical outcomes. Among the 978 patients reviewed, the NSCLC was located in the LLL in 143 (14.6%) patients, and lymph node involvement was identified in 210 patients (21.5%). The 5-year overall survival rates of patients whose NSCLC was located in the LLL and in other lobes (non-LLL) were 73.1 and 74.3%, respectively, and showed no significant association (P = 0.86). On the other hand, the 5-year survival rates of patients whose NSCLC occurred in the LLL (n = 33) and non-LLL (n = 177) and with lymph node metastasis were 32.7 and 57.7%, respectively, and showed a significant association (P = 0.01). Therefore, we performed a more detailed analysis on the 210 NSCLC patients with lymph node metastasis. On multivariate analysis, we found that LLL tumour (P = 0.02), tumour size >3 cm (P = 0.02) and N status (P < 0.001) were significant independent predictors for survival. LLL tumours with lymph node metastasis are strongly associated with mortality in NSCLC patients. The location of the primary tumour may contribute in determining the optimal management strategy and accurate prediction of prognosis.