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Postoperative pulmonary complications (PPCs) significantly impact surgical outcome. We investigated the predictive ability of controlling nutritional status (CONUT) for PPC after lung resection in patients with non-small cell lung cancer (NSCLC). We retrospectively reviewed data of 922 patients with NSCLC who underwent complete resection from January 2016–December 2017. We analyzed the frequency and characteristics of PPCs and compared receiver operating characteristic (ROC) curves of various prognostic models to predict PPCs. A CONUT score higher than 1 was considered as a high CONUT score. Total incidence of PPCs was 8.6% (n = 79). The proportion of pneumonia was significantly larger in the high CONUT group (P < 0.05). The CONUT consistently had a higher area under curve (AUC) value (0.64) than other prognostic models (prognostic nutritional index (PNI): AUC = 0.61, Glasgow prognostic score (GPS): AUC = 0.57, and assessment of respiratory risk in surgical patients in Catalonia (ARISCAT): AUC = 0.54). Multivariate analysis identified underweight [Odds ratio (OR) = 4.57, P = 0.002] and high CONUT score (OR = 1.91, P = 0.009) as independent PPCs prognostic factors. One-year mortality rate for high CONUT score was significantly higher (hazard ratio = 7.97; 95% confidence interval, 1.78–35.59). Preoperative CONUT score is an independent predictor of PPCs and 1-year mortality in patients with resectable NSCLC. [ABSTRACT FROM AUTHOR]

• Frozen sections have low sensitivity for identifying STAS. • GGO percentage of ≥75% on CT predicts STAS negativity. • SUV T/L ratio ≤0.65 predicts STAS negativity. • A lepidic predominant pattern predicts STAS negativity. • Our flowchart is more suitable as it gives a stratified process. The sensitivity for tumor spread through air space (STAS), an independent risk factor for locoregional recurrence after sublobar resection for lung cancer, has been relatively low in frozen sections. We aimed to determine predictors with high negative predictive value for the presence of STAS and to provide the flowchart in combination with these predictors for the decision-making for sublobar resection. Between July 2015 and December 2017, 387 patients who underwent surgery for non-small cell lung cancer (NSCLC) with pathologic findings of the total masses measuring ≤ 2 cm were enrolled. The lesions were divided into two groups according to presence of STAS. We compared the preoperative characteristics, operative data, and developed a flowchart for STAS prediction using receiver operator characteristic curve analysis and multivariable logistic regression. The STAS-positive group (N = 111) had a significantly higher preoperative tumor size (1.70 [1.5] vs 1.50 [0.69], p < 0.001) and standardized uptake value tumor-to-liver (SUV T/L) ratio (1.40 [1.60] vs 0.60 [1.10], p < 0.001) and a significantly lower two-dimensional ground-glass opacity (GGO) percentage (35.86 [61.00] vs 78.14 [39.00], p < 0.001). Meanwhile, the STAS-negative group (N = 286) had higher lepidic predominance (41.6% vs. 1.8%, p < 0.001). We developed a flowchart for predicting STAS in combination with two-dimensional GGO percentage on computed tomography (CT), SUV T/L ratio on positron-emission CT, and lepidic predominant pattern. The sensitivity, specificity, and negative predictive value for STAS positivity were 79.3%, 68.5%, and 89.5%, respectively. The stepwise flowchart using two-dimensional GGO percentage on CT, maximum SUV, and lepidic predominance might be helpful in selecting patients with early NSCLC for sublobar resection. [ABSTRACT FROM AUTHOR]

• The positive highest mediastinal LN is one of the criteria of uncertain resection. • The positive highest or most distant mediastinal LN was not related to poor survival. • The subcategories of N2 and T stage were highly associated with overall survival. The positive highest nodal station after operation is one of the definitions of "uncertain resection" proposed by the International Association for the Study of Lung Cancer. This study was performed to determine the prognostic value of positive highest or the most distant nodal station in patients with N2 non-small-cell lung cancer (NSCLC). Three hundred thirty-nine patients who underwent complete anatomical resection and mediastinal lymph node (LN) dissection for N2 NSCLC between 2000 and 2015 were reviewed. Cases of operative mortality, extracapsular invasion of LN and incomplete resection were excluded from analysis. The mean age was 61.58 ± 9.43 years, and 235(69.3%) patients were male. The numbers of total dissected LNs and positive LNs were 29.90 ± 11.92 and 5.49 ± 5.90, respectively. The subcategory of N stage was divided as follows: N2a1, 91(26.8%); N2a2, 132(38.9%); and N2b, 116(34.2%). One hundred forty-two (41.9%) patients showed highest LN metastasis, and 162(47.8%) patients showed most distant LN metastasis. Kaplan–Meier analysis revealed no differences between distant LN negative and positive patients regarding 5-year overall survival (43.1% vs. 39.2%; p = 0.428) and between highest LN negative and positive patients regarding 5-year overall survival (42.1% vs. 40.0%; p = 0.539). On multivariable analysis, metastasis to the most distant mediastinal LN (hazard ratio (HR): 1.050; p = 0.755) and metastasis to the highest mediastinal LN (HR: 1.015; p = 0.924) were not related to overall survival. The current definition of uncertain resection based on metastasis of the highest or most distant LNs did not show survival differences in completely resected N2 NSCLC. [ABSTRACT FROM AUTHOR]

Highlights • We established 41 NSCLC PDXs by directly implanting tumor specimens of patients. • These established PDXs were genetically and clinically annotated. • The clinical response was recapitulated by PDXs. • PDXs is a robust tool for biomarker, therapeutic target, and drug discovery. Abstract Background Preclinical models that can better predict therapeutic activity in clinical trials are needed in this era of personalized cancer treatment. Herein, we established genomically and clinically annotated patient-derived xenografts (PDXs) from non-small-cell lung cancer (NSCLC) patients and investigated whether these PDXs would faithfully recapitulate patient responses to targeted therapy. Methods Patient-derived tumors were implanted in immunodeficient mice and subsequently expanded via re-implantation. Established PDXs were examined by light microscopy, genomic profiling, and in vivo drug testing, and the successful engraft rate was analyzed with the mutation profile, histology, or acquisition method. Finally, the drug responses of PDXs were compared with the clinical responses of the respective patients. Results Using samples from 122 patients, we established 41 NSCLC PDXs [30 adenocarcinoma (AD), 11 squamous cell carcinoma (SQ)], among which the following driver mutation were observed: 13 EGFR-mutant, 4 ALK-rearrangement, 1 ROS1-rearrangement, 1 PIK3CA-mutant, 1 FGFR1-amplification, and 2 KRAS-mutant. We rigorously characterized the relationship of clinical features to engraftment rate and latency rates. The engraft rates were comparable across histologic type. The AD engraft rate tended to be higher for surgically resected tissues relative to biopsies, whereas similar engraft rates was observed for SQ, irrespective of the acquisition method. Notably, EGFR-mutants demonstrated significantly longer latency time than EGFR-WT (86 vs. 37days, P = 0.007). The clinical responses were recapitulated by PDXs harboring driver gene alteration (EGFR, ALK, ROS1, or FGFR1) which regressed to their target inhibitors, suggesting that established PDXs comprise a clinically relevant platform. Conclusion The establishment of genetically and clinically annotated NSCLC PDXs can yield a robust preclinical tool for biomarker, therapeutic target, and drug discovery. [ABSTRACT FROM AUTHOR]

Background: The development of chemo-resistance in non-small lung cancer is a major obstacle in treating patients. Hypoxia is a commonly faced microenvironment in solid tumor and suggested to be related to both autophagy and chemo-resistance. Methods: In this study, we investigated the role of hypoxia-induced autophagy in acquiring chemo-resistance in both cancer cell (A549) and human cancer tissue Results: Hypoxic exposure (1 % O2) of A549 cell stimulated autophagic induction in cancer cells, shown by increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 in Western blot, increased GFP-LC puncta in confocal microscopy, and increased number of double-membrane autophagic vacuoles in electron micrographs. Hypoxic exposure also induced resistance of cancer cells to cisplatin, and LC3B siRNA restored the sensitivity of cancer cells to chemotherapy. Furthermore, Human lung cancer tissues that experienced chemotherapy showed increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 compared with chemo-naïve cancer tissue in Western blot. Conclusion: Autophagy may play an important role in acquiring resistance to chemotherapy in lung cancer and hypoxia related pathway seems to be involved in autophagy induction. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to determine prognostic factors associated with postrecurrence survival in cases with postoperative brain metastasis but with no extracranial metastasis in non-small cell lung cancer (NSCLC). Material and methods Between 1992 and 2012, a total of 2832 patients underwent surgical resection for NSCLC. Among those, 86 patients had postoperative brain metastasis as the initial recurrence. Those patients were retrospectively reviewed. Results The median follow-up time after the initial lung resection was 24.0 months (range, 2.0–126.0 months). The median overall survival after initial lung cancer resection was 25.0 months and the median overall postrecurrence survival was 11 months. An initial lesion of adenocarcinoma (hazard ratio, 0.548; 95% confidence interval, 0.318 to 0.946; p = 0.031), non-pneumonectomy, and a disease-free interval longer than 10.0 months (hazard ratio, 0.565; 95% confidence interval, 0.321–0.995; p = 0.048) from the initial lung resection to the diagnosis of brain metastasis positively related to a good postrecurrence survival. Solitary brain metastasis and a size of less than 3 cm for the largest brain lesion were also positive factors for postrecurrence survival. Systemic chemotherapy for brain metastasis (hazard ratio, 0.356; 95% confidence interval, 0.189–0.670; p = 0.001) and local treatment of surgery and/or stereotactic radiosurgery (SRS) for brain lesions (hazard ratio, 0.321; 95% confidence interval, 0.138–0.747; p = 0.008) were positive factors for better postrecurrence survival. Conclusion In patients with brain metastasis after resection for NSCLC with no extracranial metastasis, adenocarcinoma histologic type, longer disease-free interval, systemic chemotherapy for brain metastasis and local treatment of surgery and/or SRS for brain metastasis are independent positive prognostic factors for postrecurrence survival. [ABSTRACT FROM AUTHOR]