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Objectives Immune checkpoint inhibitors (ICIs) have shown antitumor activity against a wide variety of malignancies. ICI-induced immune-related thrombocytopenia is a rare immune-related adverse event (irAE). Little is known about the treatment of refractory immune-related thrombocytopenia in non-small cell lung cancer (NSCLC) patients treated with pembrolizumab. Results We report the case of a patient with advanced NSCLC complicated by pembrolizumab-induced refractory immune-related thrombocytopenia who showed remarkable improvement in the thrombocytopenia in response to eltrombopag olamine treatment. Conclusion Eltrombopag olamine can be a viable treatment option for refractory pembrolizumab-induced immune-related thrombocytopenia in an NSCLC patient.

Background Most patients with non–small-cell lung cancer (NSCLC) are ineligible for clinical trials. However, few studies have reported on the profiles and treatment outcomes for these patients. Therefore, we investigated the characteristics, outcomes, and survival of patients with advanced NSCLC who were ineligible for clinical trials. Materials and Methods We analyzed the data from a retrospective cohort of 786 consecutive patients with a diagnosis of advanced NSCLC. We reviewed the criteria of phase 1 to 3 clinical trials and classified patients according to the common first-line eligibility criteria for lung cancer. Results Of the 786 patients, 469 (60%) were ineligible for clinical trials. The main reasons for ineligibility were brain metastasis (41%), poor performance status (25%), and respiratory disease (24%). For all patients, ineligibility was identified as an independent predictor of overall survival (hazard ratio, 0.78; 95.0% confidence interval, 0.65-0.93; P = .008), even in those with a good performance status who had received chemotherapy (hazard ratio, 0.80; 95.0% confidence interval, 0.65-0.99; P = .037). In the subgroup analysis of ineligible patients, survival varied depending on the reasons for ineligibility. In particular, a history of cancer was not associated with a poor outcome, although this was a common reason for ineligibility. Conclusion Most patients were ineligible for clinical trials and had a shorter overall survival, although this varied depending on the reason for their ineligibility. These results should be considered when applying clinical trial outcomes to real-world patients. Further studies of ineligible patients are needed to improve the treatment decisions in clinical settings.

Introduction Nivolumab has demonstrated efficacy against metastatic NSCLC. Four programmed cell death ligand 1 (PD-L1) immunohistochemistry (IHC) assay systems are available for identification of responders among patients with NSCLC, and these assays show some differing characteristics. Accordingly, in this study, we evaluated the ability of these assays to identify responders to nivolumab therapy. Methods We retrospectively analyzed patients with previously treated advanced NSCLC, who received nivolumab between January 2016 and September 2016. Specimens were stained using four PD-L1 IHC assays (28-8, 22C3, SP142, and SP263). We classified patients as having test results that were strongly positive (tumor proportion score [TPS] ≥50%), weakly positive (TPS 1%–49%), or negative (TPS Results A total of 40 patients with NSCLC and their specimens were analyzed. Analytical comparisons demonstrated good concordance of PD-L1–stained tumor cells among the 28-8, 22C3, and SP263 assays (weighted κ coefficient 0.64–0.71), whereas the SP142 assay showed lower concordance with other assays (weighted κ coefficient 0.39–0.55). Progression-free survival in patients showing strongly positive PD-L1 staining classified by 28-8, 22C3, and SP263 assays was significantly longer than that in patients with a negative result for PD-L1 staining. Predictive performance of response to nivolumab, as assessed by receiver operating characteristic analysis, was also equivalent among the 28-8, 22C3, and SP263 assays (area under the curve 0.75–0.82), whereas the SP142 assay exhibited lower predictive performance (area under the curve 0.68). Conclusions The 28-8, 22C3, and SP263 PD-L1 IHC assays showed equivalent predictive performance, whereas the SP142 assay showed lower predictive performance.

Introduction Nivolumab has demonstrated efficacy against metastatic non-small cell lung cancer (NSCLC). However, immune-related adverse events can occur, among which pneumonitis is relatively common. Lung cancer patients with idiopathic interstitial pneumonia (IIP) have a higher risk of pneumonitis associated with anticancer therapy. We hypothesized that the benefit of nivolumab may outweigh the risks of pneumonitis in patients with NSCLC who have mild IIP. We performed a pilot trial to evaluate the safety of nivolumab in NSCLC patients with mild IIP. Methods Previously treated, inoperable NSCLC patients with mild IIP were enrolled. Mild IIP was defined as having a predicted vital capacity ≥80% and a possible usual interstitial pneumonia (UIP) or inconsistent with UIP pattern on chest high-resolution computed tomography. Patients received nivolumab at a dose of 3 mg/kg biweekly. Results Six patients were enrolled in this trial between April 2016 and December 2016. None experienced drug-related nonhematologic grade 3/4 or hematologic grade 4 adverse events in the 12 weeks following the initiation of nivolumab treatment. Furthermore, none of the patients had pneumonitis of any grade. At the time of analysis, all patients were alive, and 3 had experienced a partial response. Conclusions Nivolumab therapy may be feasible in NSCLC patients with mild IIP. (Trial registration number: UMIN000022037)

Immune checkpoint inhibitors (ICIs) are promising drugs for various cancers. However, immune activation by ICIs can lead to immune-related adverse events (irAEs). Autoimmune encephalitis is a rare irAE, and its clinical features remain unknown. We herein report two patients with ICI-associated autoimmune encephalitis who, saliently, showed elevated adenosine deaminase (ADA) levels in the cerebrospinal fluid (CSF). This is the first report of increased ADA levels in the CSF of patients with ICI-induced autoimmune encephalitis. Although the mechanism of the ADA increase is poorly understood, elevated ADA in the CSF may be informative in the diagnosis of this rare disorder.

371 Background: Though neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil (DCF) showed a promising efficacy in patients (pts) with resectable esophageal squamous cell carcinoma (ESCC), grade 3 anorexia during the course and body weight loss (BWL) were frequently experienced. BWL is considered as a factor for poor survival in operable cancer pts, however, there is rarely reported of the relationship of BWL during neoadjuvant therapy and survival. Methods: We retrospectively evaluated pts of ESCC withclinical stage II or III, excluding T4, who had received neoadjuvant DCF and esophagectomy (R0 resection) at our institution between April 2010 and December 2018. We define the cut-off level at more than 3% weight reduction (BWL3 group) between before and after of first cycle of DCF. Results: Among the 77 pts who were selected for this analysis, 13 patients showed BWL > 3% (BWLS group), and other 64 pts did not (no-BWL group). The median age, proportions of performance status of 0, cT3 stage, cN2-3 stage and serum albumin lower than normal level in no-BWL and BWL3 group were 65 and 67y.o, 59 and 77%, 88 and 54%, 75 and 69%, 34 and 31%, respectively. There was no significant difference inhistological therapeutic effect (grade 2-3) with 50% in no-BWL and 62% in BWL3 group (P = 0. 549). The incidence of postoperative grade 2 or higher pneumoniawas same in both group (23% vs 17%, P = 0. 695). The median overall survival (OS) was not reached in non-BWL group and 39.5 m in BWL3 group (P = 0.048), respectively. The median progression free survival (PFS) was not reached in non-BWL group and 39.5 m in BWL3 group (P = 0.382), respectively. In multivariate analysis, BWL is independent prognostic factor for OS (hazard ratio [HR] = 11.5, 95%CI: 2.45-53.8, P = 0.002). Conclusions: Our exploratory study demonstrated that body weight loss during first course of neoadjuvant DCF therapy for ESCC patients may be a prognostic factor for survival.

Background: Usual gait speed over 4-meter (4mGS) is a simple functional performance measure in older adults. The reliability and validity of the 4mGS has recently been demonstrated in patients with COPD, but there are few data in interstitial pneumonia (IP). Object: To evaluate the correlation between the 4mGS and 6-minute walk test (6MWT) in IP patients. Their underlying physiological factors were also examined. Method: In 52 IP patients, the 4mGS and 6MWT were prospectively performed. Other measurements included the health-related quality of life, modified Medical Research Council (MRC) score, arterial blood gas analyses, pulmonary function tests, muscle strength of skeletal muscle index, and physical activity. Result: 35 patients were male (68.6%) and 34 patients had IPF (66.7%). There was a significant correlation between the 4mGS and 6-minute walk distance (6MWD) (r = 0.57, P Conclusions: The 4mGS was a simple and reliable measure for IP patients.

Concurrent chemoradiation therapy (CCRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD-1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CCRT on programmed cell death ligand-1 (PD-L1) expression on tumor cells is unknown. In this study, we analysed paired NSCLC specimens that had been obtained pre- and post-CCRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. A total of 45 patients with LA-NSCLC were included, among which there were sufficient pre- and post-CCRT specimens in 35 patients. Overall, the percentage of tumor cells with PD-L1 expression significantly decreased between pre- and post-CCRT specimens (P = 0.024). Sixteen, 15, and 4 patients had decreased, unchanged, or increased PD-L1 expression after CCRT, respectively. Median OS of patients with decreased, unchanged, or increased PD-L1 expression was 85.1, 92.8, and 14.6 months, respectively (P

Background Programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have demonstrated antitumor activity, and immunohistochemical analysis of PD-L1 expression has been used to identify the response in patients with non–small-cell lung cancer (NSCLC). Recently, considerable interest has ensued toward extending the benefit of these inhibitors to high-risk patients, such as those with NSCLC and interstitial lung disease (ILD). However, no studies have compared PD-L1 expression in NSCLC patients with and without ILD. Therefore, we conducted a case-control study to evaluate PD-L1 expression and stromal CD8+ lymphocyte density in these patients. Materials and Methods The data from patients with pathologic stage I or II NSCLC who had undergone surgery from January 2007 to January 2016 were analyzed. Results We identified 62 patients with pathologic stage I or II NSCLC and ILD. We compared these patients with 1:1-matched cohort. In both groups with and without ILD, approximately 60% were PD-L1+. Tumor cell PD-L1 expression was similar between the groups (median, 1%; interquartile range, 0%-5%; vs. median, 1%; interquartile range, 0%-5%; P = .49). The proportion of patients with positive (≥ 1%) and strongly positive (≥ 50%) PD-L1 expression was also similar between the 2 groups (P = .46 and P = 1.00, respectively). Additionally, the CD8+ lymphocyte density did not differ between patients with and without ILD. Conclusion PD-L1 expression and stromal CD8+ lymphocyte density were comparable between the NSCLC patients with and without ILD. PD-1 axis inhibitors might be effective for NSCLC patients with ILD.

// Ryobu Mori 1 , Daichi Fujimoto 1 , Munehiro Ito 1 and Keisuke Tomii 1 1 Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Hyogo, Japan Correspondence to: Daichi Fujimoto, email: // Keywords : bevacizumab, malignant pleural effusion, non-small cell lung cancer, ramucirumab, vascular endothelial growth factor Received : February 14, 2017 Accepted : May 01, 2017 Published : May 17, 2017 Abstract Malignant pleural effusion (MPE) is a major problem associated with advanced non-small cell lung cancer for which an optimum treatment strategy has yet to be determined. Notably, vascular endothelial growth factor (VEGF) signaling has been found to influence MPE, and bevacizumab, a VEGF ligand inhibitor, can effectively control MPE. Ramucirumab, a human monoclonal antibody specific for VEGF receptor-2, has recently been approved for advanced non-small cell lung cancer. However, it remains unclear which of these agents more effectively control MPE. We describe a case of a 68-year-old man with advanced non-small cell lung cancer in whom ramucirumab plus docetaxel-refractory MPE was responsive to bevacizumab plus docetaxel combination therapy. The patient’s MPE progressed after two cycles of ramucirumab plus docetaxel second-line chemotherapy. After switching to bevacizumab plus docetaxel, a computed tomography scan revealed a decreased MPE after two cycles of treatment. Bevacizumab may be more effective for treating MPE. However, further investigations are still warranted to determine the optimal VEGF-targeted agent for this condition.

[Background] Despite of evidences showing the benefit of pirfenidone, their use is frequently associated with some adverse effect which could result in discontinuation. We investigated the reason of intolerance and to identify predictors of tolerability to pirfenidone. [Methods] This retrospective study comprised 76 patients with pulmonary fibrosis who were treated with pirfenidone from January 2011 to January 2016. We evaluated the adverse effect affecting patient continuation of a stable maintenance dose. [Result] Nineteen of 76 failed to receive pirfenidone 1200mg/day. Anorexia was reported by eleven patients, which was largest population among the intolerance group. In the comparison to the tolerant group who succeeded in continuing more than 1200mg/day for a month, there was a significant association to prophylactic administration of dopamine receptor antagonists (38% vs 9%, p = 0.04). [Conclusion] This study reveal that anorexia is the most common reason for discontinuation of pirfenidone in the real world. Prophylactic administration of dopamine receptor antagonists provides a significant reduction of anorexia from pirfenione.

We developed a Wide IO DRAM controller chip with Through Silicon Via (TSV) technology. Test circuitry is embedded in the micro-IOs placed between the fine pitch TSVs which can reject TSV connectivity failures prior to stacking process. In order to reduce Vmin degradation induced by 512 DQs simultaneously switching noise, we introduce a package-board impedance optimization method utilizing a full digital noise monitor. We achieved 12.8 GB/s operation, while IO power was reduced by 89 % compared to LPDDR3.