Background: Ki-67 expression has been established as a predictive marker for recurrence in breast cancer. The insulin-like growth factor 1 receptor (IGF1R) is a transmembrane heterotetrameric protein implicated in promoting the oncogenic transformation, growth and survival of cancer cells. However, no useful data are presently available regarding the biological significance of both molecules in lung cancer. Therefore, we investigated the relationship between the expression of Ki-67 and IGF1R. This is the first molecular analysis of the correlation between the expression of Ki-67 and IGF1R in a Japanese population of primary lung adenocarcinoma patients. Methods: Tumor specimens were collected from 183 consecutive patients who underwent a complete resection for lung adenocarcinoma from 2003 to 2007 in our department. We analyzed the Ki-67 and IGF1R expression levels in the primary lung adenocarcinomas by immunohistochemistry. Results: The positive expression of Ki-67 and IGF1R was identified in 41 (22.4%) and 43 (23.6%) patients, respectively. The positive expression of Ki-67 was identified in 14 (50.0%) of 28 patients and 27 (18.1%) of 155 patients with and without recurrence, respectively (p< 0.001). The positive expression of Ki-67 was associated with a poorer disease-free survival (DFS) according to the survival analysis. A multivariate analysis also demonstrated that Ki-67 expression was independently associated with an increased risk of a poor DFS. On the other hand, a significant relationship was also observed between the expression levels of Ki-67 and IGF1R in NSCLC. However, in the subgroup analysis, no significant correlation was not observed. Conclusions: The expression of Ki-67, but not IGF1R, may be a useful marker for predicting postoperative recurrence in patients with the primary lung adenocarcinoma following complete resection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1149. doi:1538-7445.AM2012-1149

Background: Although immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) have been established as one of standard therapy, the prognostic factors of ICIs remain unclear, aside from the programed cell death-ligand 1 (PD-L1) expression of tumor cells. The aim of this study was to determine the prognostic factors of ICIs. Methods: We analyzed the clinicopathological data of 44 cases of advanced NSCLC targeted with ICIs in our hospital, between February 2016 and February 2018, in order to determine the prognostic factors of ICIs. We also reviewed the literature regarding ICIs. Result: We retrospectively analyzed the 44 cases (26 nivolumab and 18 pembrolizumab cases). These patients were 38 men and 6 women, comprising 13 cases of adenocarcinoma, 29 squamous cell carcinoma and 2 unclassified types. Seven patients were using first-line therapy and while the others were using secondline therapy or later. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) mutations were negative in all the cases. The response rate and disease control rate were 20.5% and 51.3%, respectively. The median progression-free survival time and median survival time were 146 days and 257 days, respectively. We observed five severe adverse effects (AEs) (three cases of interstitial pneumonia, one of liver dysfunction and one of adrenal failure), that were resolved by steroid pulse therapy. In multivariate analyses, the Eastern Cooperative Oncology Group performance status (ECOG PS), pathological type, standardized uptake value (SUV) on positron emission tomography (PET), white blood cell (WBC) count, neutrophil, neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and albumin were independently prognostic factors. There were no significant differences in the prognosis between nivolumab and pembrolizumab. Conclusions: ICIs were effective in 44 treated NSCLC cases. Our analysis suggests that while ICIs are effective in treating patients, candidates must be carefully selected and cautiously observed.

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Early removal of chest tube on the day after thoracoscopic lobectomy, independently of the drainage volume, appears to be safe in well-selected patients.

A lobectomy with a resection of the pulmonary artery is less invasive than a pneumonectomy. However, it seems to be extremely difficult to perform this technique using video-assisted thoracic surgery with technical limitations because this technique is associated with an increased operative risk even in an open thoracotomy. Between April 2002 and December 2006, a curative video-assisted thoracic surgery lobectomy including a mediastinal lymphadenectomy was performed in 121 patients with primary non-small cell lung cancer. Five of those patients underwent a thoracoscopic lobectomy with the partial removal and reconstruction of the pulmonary artery. The causes of the pulmonary artery resection included two direct invasions of the artery, two invasions of the arterial branch, and one calcified lymphadenopathy involving the branch. No patients required a blood transfusion. No complications attributable to the technique or mortality were seen. No patients showed an abnormal blood flow through the reconstructed vessel. There were no local recurrences on the pulmonary artery. A video-assisted thoracic surgery lobectomy including a partial resection and reconstruction of the pulmonary artery is a complex procedure for patients with non-small cell lung cancer. It is feasible when all associated technical issues are properly addressed.

Detection of rare tumor cells circulating in the blood (CTCs) presents technical challenges. CellSearch, the only approved system for clinical use, fails to capture epithelial cell adhesion molecule‐negative CTCs such as malignant pleural mesothelioma (MPM). We have developed a novel microfluidic device (CTC‐chip) in which any Ab to capture CTCs is conjugated. The CTC‐chip was coated with an Ab against podoplanin that is abundantly expressed on MPM. Circulating tumor cell‐detection performance was evaluated in experimental models in which MPM cells were spiked in blood sampled from a healthy volunteer and in clinical samples drawn from MPM patients. The CTC‐chip showed superior CTC‐detection performance over CellSearch in experimental models (sensitivity, 63.3%‐64.5% vs 0%‐1.1%; P < .001) and in clinical samples (CTC‐positivity, 68.8% vs 6.3%; P < .001). A receiver operating characteristic (ROC) analysis showed that the CTC test provided a significant diagnostic performance in discrimination of unresectable disease from resectable disease (area under the ROC curve, 0.851; P = .003). The higher CTC count (≥2 cells/mL) was significantly associated with a poor prognosis (P = .030). The novel CTC‐chip enabled sensitive detection of CTCs, which provided significant diagnostic and prognostic information in MPM.

We evaluated the tumour shape as a potential prognostic indicator in lung adenocarcinoma patients. Among 994 patients who underwent curative surgery, 78 cases of adenocarcinoma (N0M0) with tumours ≥ 31 mm in diameter were reviewed. The patients were divided into two groups based on the ratio between the longest and the smallest axis length. The patients who had tumours whose ratios were > 0.5 were defined as the globular shape group (GL) and the others, whose ratio was 0.5 or less, were defined as the ellipse shape group (EL). The 78 patients were divided into two subgroups (57 in the GL and 21 in the EL). The tumour shape was related to the prognosis, and the 5-year overall survival (OS) rate in the GL was 51.5%, and that in the EL was 85.5% (P = 0.018). The 5-year disease-free survival rate of the GL was 46.6% and that of the EL patients was 85.0% (P = 0.04). The multivariate analysis showed that the shape of the tumour and the presence of pleural invasion were the independent and significant factors predicting the OS (P = 0.04 and P < 0.01, respectively). In adenocarcinoma patients, the shape of the tumour is related to the postoperative survival.

The overexpression of Arf6 and GEP100 is responsible for the invasive activity that is crucial for the activation of the epidermal growth factor receptor (EGFR) signaling pathways in human cancer. However, whether or not the expression of the EGFR-GEP100-Arf6 axis can be used as a biomarker for the prognosis of lung cancer has yet to be fully determined. Tumor specimens were collected from 182 patients who underwent a complete resection for lung adenocarcinoma. We analyzed phospho-EGFR (p-EGFR), GEP100, and Arf6 expression levels in the primary tumor by immunohistochemical analysis. The expression of p-EGFR, GEP100, and Arf6 was observed in 65 (35.7%), 95 (52.2%), and 20 (11.0%) patients, respectively. Significant associations between p-EGFR and GEP100 expression and vessel invasion were identified. The expression of these individual molecules was not associated with any statistically significant differences in survival. However, triple positive expression of p-EGFR, GEP100, and Arf6 was significantly associated with an increased risk of death based on the multivariate analysis. The EGFR-GEP100-Arf6 axis affected the prognosis of patients with primary lung adenocarcinoma. The combination of p-EGFR, GEP100, and Arf6 staining can predict the prognosis of patients after surgery.