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.

Background: The standard therapy for brain metastasis (BM) in non-small cell lung cancer (NSCLC) is radiation therapy (RT), although it is associated with complications such as leukoencephalopathy. In the current report, we retrospectively review data from eight patients who had NSCLC and harbored epidermal growth factor receptor (EGFR) mutations, and who were received erlotinib plus bevacizumab (E+B) as firstline therapy for BM.Methods: Patients were given E+B as first therapy for BM until August 2017 at our institution. Patients receiving local therapy for BM, such as surgery or radiotherapy, were excluded. Patients were administered erlotinib orally (once daily at 150 mg/body) plus bevacizumab by intravenous infusion (15 mg/kg on day 1 of a 21-or 28-day cycle).Results: Eight NSCLC patients who were diagnosed with BM received E+B, including 2 men and 6 women with a median age of 65 years (range, 46-84 years). Four patients had an L858R EGFR mutation, while the other four had an exon 19 deletion. Seven patients had a partial response to E+B treatment, and one had a complete response. The 2-year survival rate was 62.5%. Three patients who were pre-treated with gefitinib had an E+B treatment duration of less than 1 year. At the time of this analysis, four patients had BM-related neurologic symptoms and multiple BMs, and were still receiving E+B with no evidence of treatment failure after more than 1 year.Conclusions: E+B can be used as first-line therapy for BM, even in patients with BM-related neurologic symptoms and multiple BMs.

No abstract

Background: Pulmonary neuroendocrine tumor (NET) occurs with 20% of all lung cancers, and there are a limited number of literatures about the molecular aberrations, treatment and prognosis; especially in resected cases, as the operation indication for large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) is rare due to their aggressive behaviors. We investigated the relationship between postoperative survival and molecular expression patterns of pulmonary NET to establish a more effective treatment strategy.Methods: In the present study, the curative surgical resection of pulmonary NET was reviewed retrospectively. A total of 105 patients with pulmonary NET, who underwent complete resection between 1978 and 2016, were subjected to analysis with respect to histological characterization and clinical behaviors of pulmonary NET using immunohistochemistry (IHC) of neuroendocrine markers and programmed cell death-ligand 1 (PD-L1).Results: The pathological types included 67 SCLC, 18 LCNEC, 14 typical carcinoids (TCs) and 6 atypical carcinoids (ACs). The ACs had significantly worse prognosis than TCs. PD-L1 expression ratio in SCLC/LCNEC/TC/AC was 26.1%/50%/15.4%/20%, respectively. However, it was not significantly correlated with each prognosis. Therefore, the SCLC patients were analyzed, the overall 5-year survival of SCLC patients was found to be 47.3%. In the univariate analysis of the molecular expression of SCLC, neuroendocrine markers such as chromogranin-A (CGA) and synaptophysin (SYN) showed poor prognosis, albeit without significant differences. Conclusions:The neuroendocrine markers such as CGA and SYN might assist the prediction of prognosis and probably influence the decision for adjuvant chemotherapy or follow-up intervals after surgery in SCLC patients; however additional studies are essential.

Shinohara et al. SCC transformation from adenocarcinoma in NSCLC Figure 3 Real time PCR of primary lung adenocarcinoma and pleural squamous cell carcinoma. (A) Real time PCR of the lung tumor represents the activating EGFR mutation (exon 21 L858R point mutation); (B) real time PCR of the pleural recurrence site represents the activating EGFR mutation (exon 21 L858R point mutation). EGFR, epidermal growth factor receptor; PCR, polymerase chain reaction.