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 second-line 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.

It was recently reported that a limited pulmonary resection (segmentectomy or wedge resection) was not inferior to a lobectomy in the management of peripheral small-sized adenocarcinoma (tumor ≦ 20 mm) of the lung. We retrospectively analyzed patients undergoing a lobectomy (n = 114) and a limited resection (n = 35) for peripheral small-sized adenocarcinoma of the lung during a 7-year period from April 2001 to March 2008. Our criteria for the limited resection of lung cancer were as follows: (1) adenocarcinoma of 10 mm or less in diameter and (2) adenocarcinoma of 11-20 mm in diameter, in which the ratio of the ground glass opacity is 50% or more, without pleural indentation on computed tomography. Additionally, the frozen sections of the tumors were intraoperatively diagnosed as Noguchi type A or B. The survival and clinical outcomes were analyzed. The 5-year survival rates of the lobectomy group and limited resection groups were 89.2% and 100%, respectively. No recurrence was seen in the limited resection group. Our results suggest that our criteria for limited resection were adequate for the management of small-sized adenocarcinoma of the lung.

The prognostic impact of tumoral programmed death-ligand 1 (PD-L1) expression in correlation with neutrophil-to-lymphocyte ratio (NLR) was retrospectively assessed in 83 patients with completely resected stage I squamous cell carcinoma of the lung, as PD-L1 is a potent regulator of cancer immunity and NLR is a potential surrogate of immune status. Forty-three patients (51.8%) had tumor with positive PD-L1 expression. There was no significant correlation between PD-L1 expression and NLR. PD-L1-positivity failed to provide a significant prognostic impact (overall survival [OS] rate at 5 years, 53.0% in PD-L1-positive patients versus 70.1% in PD-L1-negative patients; P = 0.117). Among NLR-low (<2.2) patients, however, PD-L1-positivity was significantly correlated with a poor prognosis (OS rate at 5 years, 46.1% versus 86.0%; P = 0.020). In contrast, among NLR-high (≥2.2) patients, PD-L1-positivity provided no prognostic impact (P = 0.680). When NLR status and tumoral PD-L1 status were combined, “NLR-low and PD-L1-negative” was a significant and independent factor to predict a favorable recurrence-free survival (hazard ratio, 0.237 [95% confidence interval, 0.083 to 0.674]; P = 0.007) and OS (hazard ratio, 0.260 [0.091 to 0.745]; P = 0.012). These results suggest the prognostic impact of tumoral PD-L1 expression might be influenced by the status of NLR.

Original Article Immune profile analysis of peripheral blood and tumors of lung cancer patients treated with immune checkpoint inhibitors Yoshinobu Ichiki, Takashi Fukuyama, Mari Ueno, Yoshiro Kanasaki, Hidenori Goto, Mai Takahashi, Shuji Mikami, Noritada Kobayashi, Kozo Nakanishi, Shinichi Hayashi, Tsuyoshi Ishida