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The gastrointestinal microbiota was reported as an important factor for the response to cancer immunotherapy. Probiotics associated with gastrointestinal dysbiosis and bacterial richness may affect the efficacy of cancer immunotherapy drugs. However, the clinical impact of probiotics on the efficacy of cancer immunotherapy in patients with nonsmall cell lung cancer (NSCLC) is poorly understood. The outcomes of 294 patients with advanced or recurrent NSCLC who received antiprogrammed cell death-1 (PD-1) therapy (nivolumab or pembrolizumab monotherapy) at three medical centers in Japan were analyzed in our study. We used inverse probability of treatment weighting (IPTW) to minimize the bias arising from the patients' backgrounds. The IPTW-adjusted Kaplan-Meier curves showed that progression-free survival (nonuse vs use: hazard ratio [HR] [95% confidence interval {CI}] = 1.73 [1.42-2.11], log-rank test P = .0229), but not overall survival (nonuse vs use: HR [95%CI] = 1.40 [1.13-1.74], log-rank test P = .1835), was significantly longer in patients who received probiotics. Moreover, the IPTW-adjusted univariate analyses showed that nonuse or use of probiotics was significantly associated with disease control (nonuse vs use: odds ratio [OR] [95%CI] = 0.51 [0.35-0.74], P = .0004) and overall response (nonuse vs use: OR [95%CI] = 0.43 [0.29-0.63], P < .0001). In this multicenter and retrospective study, probiotics use was associated with favorable clinical outcomes in patients with advanced or recurrent NSCLC who received anti-PD-1 monotherapy. The findings should be validated in a future prospective study.

Background/aim Adjuvant platinum-based chemotherapy (APC) has been the standard of care for patients with non-small-cell lung cancer (NSCLC) who have undergone complete pulmonary resection. This study analyzed the clinical and prognostic significance of immunonutritional indices in NSCLC patients receiving APC. Patients and methods We retrospectively reviewed 110 patients from 2008 to 2016. Three immunonutritional indices were calculated: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI). Results The median age was 64 years, and 66 patients were males. Each index showed a significant correlation with primary tumor length. NLR and PLR were significantly correlated with vascular invasion. Prognostic analyses revealed that each index was significantly correlated with postoperative recurrence-free survival (RFS) and overall survival (OS). On multivariate analyses, PNI was an independent predictor of RFS and OS. Conclusion Host immunonutritional status may have a significant effect on the postoperative prognosis of NSCLC in patients receiving APC.

BACKGROUND: Controlling nutritional status (CONUT) and skeletal muscle area (SMA) are both useful prognostic factors in patients with non-small cell lung cancer (NSCLC). We hypothesized that low serum creatine kinase (CK) would be a surrogate of decreased SMA, and defined a novel prognostic factor, CONUT/CK score (CNKS). The aim of this study was to elucidate the clinical significance of CNKS in NSCLC patients. METHODS: One hundred and eighty-nine patients who underwent surgical resection of NSCLC and whose preoperative computed tomography images were available were enrolled. The CNKS was calculated by summing CONUT score and CK score, which was defined as 0 if the CK concentration is within normal range, and 2 if it is under lower limit. The optimal cut-off values of CNKS and CONUT score were 4 and 2, respectively. RESULTS: Low CK was significantly associated with decreased SMA (P=0.012). The high CNKS group was significantly associated with men and smoking history (P=0.006 and P=0.015, respectively). The high CNKS group had significantly shorter overall survival (OS) and disease-free survival (DFS) (P

Programmed death-ligand 1 (PD-L1) expression on lung cancer cells is a prognostic marker and a predictive biomarker for response to immunotherapy. However, previous clinical trials have suggested that other programmed cell death 1 ligands, including programmed death-ligand 2 (PD-L2), might have clinical impacts. This study aimed to analyze the prognostic significance of PD-L2 expression in lung adenocarcinoma patients. The study included 433 patients who underwent surgical resection for lung adenocarcinoma between 2003 and 2012 at Kyushu University Hospital. Both PD-L1 and PD-L2 expression were evaluated by immunohistochemistry. The cutoff value for PD-L2 positivity was set at 1% according to a time-dependent receiver operating characteristic curve for 5-year survival. Of the 433 patients, 306 (70.7%) were positive for PD-L2. No significant association between PD-L1 and PD-L2 expression was observed (P = 0.094). The multivariate analysis showed that the independent predictors of PD-L2 positivity were never-smoker status (P = 0.002), poor differentiation grade (P = 0.008), and advanced stage (P = 0.048). The PD-L2-positive patients had significantly shorter disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016). Both PD-L1 and PD-L2 positivity were independent predictors of OS (P

CD44 isoforms serve as a marker for cancer stem cells. CD44 variant 9 (CD44v9) contributes to the defense against reactive oxygen species, resulting in resistance to chemoradiotherapy. However, the significance of CD44v9 in patients with lung adenocarcinoma is unknown. We used immunohistochemical analysis to retrospectively analyze CD44v9 expression in 268 surgically resected lung adenocarcinomas and investigated the association between CD44v9 expression and patients’ clinicopathological features. The expression of CD44v9 in 193 of 268 (72.0%) patients was significantly associated with early-stage cancer, low-grade tumors, absence of vessel and pleural invasion, and a mutated epidermal growth factor receptor (EGFR) gene. Multivariate logistic analysis revealed that CD44v9 expression was significantly associated with early-stage disease [odds ratio (OR) 0.29, 95% confidence interval (CI) 0.14–0.59; p

Capmatinib is a highly specific, potent and selective MET inhibitor. This was an open‐label, multicenter, dose‐escalation, phase I study conducted in Japanese patients with advanced solid tumors (not selected based on their MET status). The primary objective was to determine the maximum tolerated dose (MTD) and/or highest studied dose being safe. Secondary objectives included safety, pharmacokinetics and preliminary antitumor activity. Dose escalation was guided by a Bayesian Logistic Regression Model dependent on dose‐limiting toxicities (DLT) in cycle 1. Of 44 adult Japanese patients with confirmed advanced solid tumors enrolled, 29 received capmatinib capsules (doses ranging from 100 mg once daily [q.d.] to 600 mg twice daily [b.i.d.]) and 15 received tablets (200 mg b.i.d. and 400 mg b.i.d.). DLT occurred in two patients: grade 2 suicidal ideation (600 mg b.i.d. capsule) and grade 3 depression (400 mg b.i.d. tablet). MTD was not reached. The highest studied dose determined to be safe as tablet was 400 mg b.i.d., whereas it is not yet determined for capsules. Most common adverse events suspected to be drug‐related were increased blood creatinine, nausea, decreased appetite, vomiting and diarrhea. Following repeated daily dosing up to day 15 by q.d. or b.i.d. regimen using capsules, median time to reach maximum plasma drug concentration (T max) was 1.0‐4.0 hours; absorption was more rapid after dosing using tablets, with median T max of 1.0 hour on both days 1 and 15. Eight patients had a best overall response of stable disease. These data support further clinical development of capmatinib.

Immune-related adverse events (irAEs) associated with immune checkpoint inhibitors are becoming more common; however, irAEs involving blood vessels are rare. We report a patient with limb arteriolar vasculitis induced by pembrolizumab plus chemotherapy. He was 60-year-old man who received first-line treatment with pembrolizumab plus chemotherapy for postoperative lung cancer recurrence. Two weeks after the first administration, he experienced Raynaud's phenomenon. We initiated a vasodilator, but his symptoms worsened, and we considered an irAE. We initiated oral prednisolone, and his symptoms gradually improved. A few weeks later, we performed skin biopsies of both of the patient's feet, and pathological examination revealed arteriolar thrombosis with slight perivascular lymphocytic infiltration. Infiltration of neutrophils with karyorrhexis in the subendothelium was also seen. He also developed acute kidney injury, likely owing to thrombosis. Physical examination of bilateral fingers and toes in patients with lung cancer should be performed carefully after administering pembrolizumab therapy.

Background/aim To investigate the role of programmed cell death-ligand 2 (PD-L2) expression as a predictive biomarker for response to anti-programmed cell death-1 (PD-1) drugs in patients with non-small cell lung cancer (NSCLC). Patients and methods Ten patients who had undergone curative lung resection and received the anti-PD-1 drugs for the recurrence were enrolled. The cut-off value for PD-L2 (antibody clone 176611) expression on tumor cells was set at 50%. Tumor response was evaluated according to immune-related response criteria. Results Seven patients (70.0%) were positive for PD-L2. The response rates were 28.6% (2/7) and 33.3% (1/3) in patients with PD-L2-positive and PD-L2-negative NSCLC, respectively. Disease control was obtained in 2 patients despite the programmed cell death-ligand 1 (PD-L1)-negativity (antibody clone 22C3: 0%, antibody clone SP142: 0%), and these tumors expressed PD-L2 (≥1%). Conclusion PD-L2 expression may be a target of immunotherapy in patients with PD-L1-negative NSCLC.

Clinical experience of ceritinib in patients who progressed on alectinib is limited. In this prospective phase II study, we evaluated the activity of ceritinib in alectinib-pretreated patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic (stage IIIB/IV) non-small-cell lung cancer (NSCLC) in Japan. All patients were required to have ≥1 measurable lesion per RECIST, 1.1, and a World Health Organization Performance Status (WHO PS) of 0-1. Prior crizotinib and/or up to 1 chemotherapy regimen was allowed. Primary endpoint was investigator-assessed overall response rate (ORR) per RECIST 1.1. Ceritinib was given at a dose of 750 mg/day fasted. A total of 20 patients were enrolled from August 2015 to March 2017. All patients received prior alectinib (100%), 13 (65.0%) patients received prior platinum-based chemotherapy, and 4 (20%) patients received prior crizotinib. Median duration of exposure and the follow-up time with ceritinib were 3.7 months (range: 0.4-15.1) and 11.6 months (range: 4.8-23.0), respectively. Investigator-assessed ORR was 25% (95% CI: 8.7-49.1). Key secondary endpoints, all investigator assessed, included disease control rate (70.0%; 95% CI: 45.7-88.1), time to response (median, 1.8 months; range: 1.8-2.0), and duration of response (median, 6.3 months; 95% CI: 3.5-9.2). Median progression-free survival was 3.7 months (95% CI: 1.9-5.3). The most common adverse events reported were diarrhea (85.0%), nausea (80.0%), and vomiting (65.0%). Based on our findings, ceritinib could be considered as one of the treatment options for patients with ALK-positive NSCLC who progressed on alectinib. (Trial registration no. NCT02450903).

AIM To investigate the radiological features on computed tomography (CT) of brain metastasis (BM) from epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Thirty-four patients with NSCLC with BMs who underwent surgical resection of the BMs at the Department of Neurosurgery, Kyushu University from 2005 to 2016 were enrolled in the study. The EGFR statuses of the 34 BMs were investigated. Radiological features, including the number, size, and location of the tumor, were delineated by CT. RESULTS Patients with EGFR-mutated BMs had significantly higher frequencies of multiple metastases than those with the non-EGFR-mutated type (p=0.042). BMs harboring mutations in EGFR were more frequently observed in the central area of the brain compared to those without mutations in EGFR (p=0.037). CONCLUSION Careful follow-up of patients with EGFR-mutated NSCLC may be necessary given the high frequencies of multiple BMs and their location in the central area of the brain.

The aim of this study was to elucidate the relationship between family‐associated factors and the postoperative prognosis in patients with nonsmall cell lung cancer (NSCLC). Additionally, we investigated whether having children was associated with the postoperative maintenance of the nutritional status. We selected 438 NSCLC patients who had undergone curative lung resection between 2004 and 2011 at Kyushu University (Fukuoka, Japan), whose family‐associated factors were available. Nutritional indices, including the prognostic nutritional index (PNI), were used to estimate the change in the nutritional status for 1 year after surgery. A propensity score analysis was conducted after adjusting the following variables: sex, age, smoking history, performance status, pathological stage, and histological type. Three hundred patients (68.5%) had both children and partners. Forty‐nine patients (11.2%) only had children, and 56 (12.8%) patients only had a partner. Thirty‐three patients (7.5%) did not have a partner or children. The overall survival (OS) and disease‐free survival (DFS) of the partner‐present and partner‐absent patients did not differ to a statistically significant extent (P = .862 and P = .712, respectively). However, childless patients showed significantly shorter OS and DFS in comparison with patients with children (P = .005 and P = .002, respectively). The postoperative exacerbation of PNI was significantly greater in childless patients than in patients with children (P = .003). These results remained after propensity score matching. Childless patients had a significantly poorer postoperative prognosis than those with children. Surgeons caring for childless NSCLC patients should be aware of the poorer postoperative outcomes in this population.

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have been approved as a standard therapy for metastatic non-small cell lung cancer (NSCLC). Although PD-L1 expression serves as a predictive biomarker for the efficacy of immunotherapy, there are no established biomarkers to predict the expression of PD-L1. The inflammatory markers C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) were recently shown to predict the efficacy of nivolumab for NSCLC patients. Therefore, here we investigated the potential association of PD-L1 expression with systemic inflammatory markers, including CRP, NLR, lymphocyte-monocyte ratio and platelet-lymphocyte ratio.We retrospectively examined tumor PD-L1 expression in 508 surgically resected primary NSCLC cases by immunohistochemical analysis (cut-off value: 1%). The association of PD-L1 expression with preoperative systemic inflammatory markers was assessed by univariate and multivariate analyses. We generated a PD-L1 association score (A-score) from serum CRP level (cut-off value: 0.3 mg/dl) and smoking status to predict PD-L1 expression.Among the total 508 patients, 188 (37.0%) patients were positive for PD-L1 expression at the 1% cut-off value and 90 (17.5%) had elevated serum CRP level. Multivariate logistic regression revealed that PD-L1 positivity was significantly associated with advanced stage, the presence of vascular invasion and high serum CRP level (P = .0336, .0106 and 0.0018, respectively). Though not significant, smoking history tended to be associated with PD-L1 protein expression (P = .0717). There was no correlation with other inflammatory markers. Smoking history with elevated CRP level (A-score: 2) was strongly associated with PD-L1 protein expression (odds ratio: 5.18, P .0001), while it was inversely associated with EGFR mutation (odds ratio: 0.11, P .0001).Our results indicate that among all systemic inflammatory markers examined, serum CRP seems to predict PD-L1 expression in patients with NSCLC however the clinical applicability is limited given the obtained area under the receiver operating characteristic curve values.

Objectives It was reported that programmed cell death-ligand 1 (PD-L1) expression is associated with smoking and wild-type epidermal growth factor receptor (EGFR) in lung adenocarcinoma. However, the association between PD-L1 expression and EGFR mutation site in EGFR mutation-positive lung adenocarcinoma is unclear. Materials and methods We retrospectively examined the relationship between PD-L1 expression and EGFR status in 441 surgically resected primary lung adenocarcinomas. Membrane PD-L1 expression on tumor cells was evaluated by immunohistochemical analysis using a PD-L1 antibody (clone SP142) and defined by tumor proportion scores (TPSs) of 0%, 1–4%, 5–49%, and ≥50%, respectively. Results Two hundred and eighteen (49.4%) patients had wild-type EGFR, and 223 (50.6%) had mutant EGFR—98 (44.0%) with exon 19 deletion, 116 (52.0%) with exon 21 L858R point mutation, and nine (4.0%) with another EGFR mutation. Overall, Fisher’s exact test showed that PD-L1 positivity was associated with wild-type EGFR, and there was only one case with PD-L1 TPS ≥50% among the cases with mutant EGFR. The analysis of cases with mutant EGFR indicated no significant association between EGFR mutation site and PD-L1 expression. However, the prevalence of PD-L1 TPS 5–49% was higher among patients with EGFR exon 19 deletion than with EGFR exon 21 L858R point mutation. Conclusions PD-L1 expression was significantly associated with wild-type EGFR, and PD-L1 TPS ≥50% seldom overlaps with presence of driver oncogene EGFR. There was no significant difference in PD-L1 expression among the EGFR mutation sites

The CXCR4/CXCR7/CXCL12 chemokine axis plays important roles in the migration of tumor cells during cancer development by modulating site‐specific distant metastasis including to regional lymph nodes. We investigated the correlation of these chemokine expressions to prognosis in lymph‐node‐positive non‐small‐cell lung cancer (NSCLC) patients. A total of 140 surgically resected specimens of primary site (PS) and metastatic lymph nodes (MLN) of NSCLC involving hilar and/or mediastinal lymph nodes (N1‐2) were collected. CXCR4, CXCR7 and CXCL12 expressions were evaluated. Cox regression analysis was performed to determine whether these chemokines were independent prognostic factors in N1‐2 NSCLC. High expression of CXCR4 in PS and CXCL12 in MLN was associated with poor overall survival (OS) (P = .025 and .033, respectively). Significant correlations between CXCR4 expression in PS and CXCL12 expression in MLN were observed (P = .040). There was significant difference in OS between 2 groups according to expressions of CXCR4 in PS and CXCL12 in MLN (P = .0033). Expression of CXCL12 in MLN was identified as an independent prognostic factor (HR 1.79, 95% CI 1.08‐3.04, P = .023). CXCL12 in MLN was mainly expressed by tumor cells compared with stromal cells (56% vs 25%, respectively, P < .0001). CXCR4/CXCL12 may play roles in tumor progression in MLN and is associated with poor prognosis of lymph‐node‐positive NSCLC patients.

Liposarcomas are the most common type of mesenchymal neoplasm in soft tissue sarcomas. Although they frequently develop at the lower limbs or retroperitoneum, cases arising from the mediastinum are rare. Furthermore, the incidence of the inflammatory subtype of well-differentiated liposarcoma is known to be low. We experienced a case of a middle mediastinal liposarcoma in a 68-year-old woman. The tumor, which was completely resected, was 92 mm in diameter. The tumor consisted of two different imaging components that showed different growth and which were diagnosed as the lipoma-like subtype and inflammatory subtype of well-differentiated liposarcoma. To the best of our knowledge, this is the first report of a well-differentiated inflammatory liposarcoma arising from the middle mediastinum.

Malignant pleural mesothelioma (MPM) is a devastating neoplasm; however, some patients exhibit a good response to chemotherapy or multidisciplinary therapy, including surgery and chemotherapy. It is therefore important to discover the factors that can be used to select patients who will benefit from such treatment. Although the Controlling Nutritional Status (CONUT) score has been used to predict the prognosis in other types of malignancy, its utility in patients with MPM is unknown. The aim of this study was to clarify the clinical significance of the CONUT in patients with MPM.The data of 83 patients, who were treated with surgery, chemotherapy, or multidisciplinary therapy, were analyzed in the present study. A cut-off CONUT score of 2 was used to classify all of the patients into low or high CONUT groups.Fifty-two of the 83 patients were classified into the low CONUT group. A high CONUT score was significantly correlated with chemotherapy alone (P = .011). The high CONUT group had significantly poorer overall survival (OS) (P .001) and disease- or progression-free survival (DFS/PFS) (P .001). The clinical stage and the CONUT score were found to be independent predictive factors for the OS: clinical stage, I/II and III/IV; P = .001 and CONUT score, ≥ 3 and ≤ 2; P = .011, respectively. The clinical stage and the CONUT score were also independent predictive factors for DFS/PFS: clinical stage, I/II and III/IV; P = .006 and CONUT score, ≥ 3 and ≤ 2; P = .013, respectively.The CONUT score was an independent predictor of a poor prognosis in the patients with MPM. This score provides useful information for selecting patients who will benefit from the treatment.

Erlotinib is one of the treatment choices for patients with advanced non-small cell lung cancer (NSCLC), regardless of the epidermal growth factor receptor (EGFR) mutation status. However, its efficacy for the treatment of patients with NSCLC with EGFR wild type or who are beyond the usage of gefitinib remains controversial. The present study therefore retrospectively assessed the efficacy of erlotinib in patients with wild type EGFR who had previously undergone gefitinib therapy. A total of 222 patients with NSCLC who received chemotherapeutic treatment with erlotinib between July 2007 and February 2013 were evaluated. The background variables, response rates, progression-free survival (PFS) and overall survival rates were retrospectively analyzed. The male/female ratio of patients was 103/119, and patients had a median age of 63 years (range, 33–95 years). A total of 10 of the 222 patients had clinical stages IIIB/IV, 191 had adenocarcinoma, 5 had large cell carcinoma, 10 had squamous cell carcinoma and 6 had NSCLC of a variety not otherwise specified. The EGFR mutation was positive, wild type or unknown in 95, 52 and 75 patients, respectively. In the 52 patients with EGFR wild type, there were 3 partial responders, 25 with stable disease and 24 with progressive disease, for a response rate of 6% [95% confidence interval (CI), 1.3–15%]. The median PFS of EGFR wild type and positive were 1.1 months (95% CI, 1.04–1.16 months) and 5.42 months (95% CI, 5.43–5.68 months), respectively. The results of the study demonstrated that erlotinib is not sufficiently effective for patients with NSCLC who possess the EGFR wild type status.

Background Chemotherapy for non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) has been challenging due to the possibility of the acute exacerbation of ILD as a life-threatening adverse effect. No acceptable regimen for such patients has been established. Therefore, we herein assessed our series of NSCLC patients with ILD who were treated with cisplatin plus etoposide (PE). Patients and methods The unresectable NSCLC patients with ILD detected on chest computed tomography (CT) who received PE at our department between December 2006 and December 2013 were retrospectively reviewed. Cisplatin (80 mg/m2, day 1) and etoposide (100 mg/m2, days 1 to 3) were administered every three weeks. Results Thirty-two consecutive NSCLC patients with ILD were evaluated. Twenty-four received PE as first-line treatment, while the other eight received it as second-line or later treatment. Twenty-three patients exhibited the usual pneumonitis (UIP) pattern, eight possible UIP pattern and one was inconsistent to UIP on CT. Grade 3/4 hematological toxicities were frequently seen, including neutropenia in 23 (74.2%). Febrile neutropenia was seen in six (19.4%) patients. Two patients experienced grade 2 pneumonitis after PE, but successfully recovered. The overall response rate was 31.2%. The median progression-free survival was 3.4 months and the median overall survival for all patients was 8.5 months. Conclusion PE treatment for unresectable NSCLC patients with ILD in our series was considered to be relatively safe, with an acceptable tumor response and survival. Obviously, careful patient selection and management are warranted. A prospective evaluation should also be performed.

e21125 Background: Albumin-bilirubin (ALBI) grade is calculated from albumin and bilirubin values as continuous variables, allowing an accurate evaluation of liver function. Some studies showed that ALBI grade was a prognostic and predictive biomarker for the efficacy of chemotherapy in cancer patients. However, no report has examined the association between ALBI grade and outcome in patients with non-small cell lung cancer (NSCLC) treated with anti-programmed cell death-1 (PD-1)-based therapy. Methods: We retrospectively enrolled 452 patients with advanced or recurrent NSCLC treated with anti-PD-1-based therapy (nivolumab or pembrolizumab monotherapy or pembrolizumab combination therapy) between 2016 and 2019 at three medical centers in Japan. With reference to previous reports, ALBI score was calculated using the formula (log10 (total bilirubin [mg/dL] x 17.1) x 0.66) + (albumin [g/dL] x 10 x −0.085), and the score was stratified as grade 1 (≤ −2.60), grade 2 (more than −2.60 to ≤ −1.39), and grade 3 (more than −1.39). We examined the clinical impact of ALBI grade on outcome in patients with NSCLC receiving anti-PD-1-based therapy using Kaplan–Meier survival analysis with the log-rank test and Cox proportional hazards regression analysis. Results: Of the 452 patients, 158 (35.0%) patients were classified as grade 1, 271 (60.0%) as grade 2, and 23 (5.0%) as grade 3. ALBI grade was strongly correlated with performance status (PS), clinical stage, and body mass index, and mutation status ( P < 0.0001, P = 0.0077, P = 0.0050, and P = 0.0302, respectively). The Kaplan–Meier curves showed that ALBI grade was significantly associated with progression-free survival (PFS) and overall survival (OS) ( P < 0.0001 and P < 0.0001, respectively). Multivariate analyses showed that PS ( P = 0.0044), combination therapy of anti-PD-1 and chemotherapy ( P = 0.0004), programmed cell death-ligand 1 (PD-L1) expression status ( P < 0.0001), and ALBI grade ( P < 0.0001) were independent prognostic factors for PFS. Multivariate analyses also showed that PS ( P = 0.0008), combination therapy of anti-PD-1 and chemotherapy ( P = 0.0066), PD-L1 expression status ( P = 0.0006), and ALBI grade ( P < 0.0001) were independent prognostic factors for OS. In the subgroup analysis, ALBI grade effectively stratified PFS and OS regardless of PD-L1 expression status. Conclusions: We report for the first time that ALBI grade was an independent prognostic factor for PFS and OS in patients with advanced or recurrent NSCLC receiving anti-PD-1-based therapy. These findings should be validated prospectively.

BACKGROUND Jumonji domain-containing 2B, JMJD2B, has been shown to play an important role in the pathogenesis of lung cancer cells. However, the significance of JMJD2B in patients with lung cancer remains to be elucidated. PATIENTS AND METHODS Seventy-eight patients with resected adenocarcinoma, whose data regarding oncogenic drivers in lung cancer were available, were included in the study. Immunohistochemical analysis was performed with a specific antibody for JMJD2B to investigate JMJD2B expression and the significance of JMJD2B expression in survival after surgery was evaluated. RESULTS Among the 78 patients, 50 (64%) exhibited JMJD2B immunopositivity. The overall survival (OS) of the 50 JMJD2B-positive patients after surgery was significantly inferior to that of the JMJD2B-negative patients (five-year survival=56.7% vs. 92.6%; log-rank: p=0.01). Multivariate analysis showed that JMJD2B positivity was an independent prognostic factor. CONCLUSION JMJD2B may be a novel prognostic factor for resected lung adenocarcinoma.

SummaryBackground This phase I study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics, immunogenicity, and antitumor activity of pembrolizumab in Japanese patients with advanced solid tumors. Methods Following an initial dose and a 28-day rest (cycle 1), pembrolizumab was administered as an intravenous infusion at escalating doses (2 or 10 mg/kg) every 2 weeks (Q2W) until disease progression or unacceptable toxicity. Adverse events (AEs) were assessed using CTCAE v4.0, and tumor response was assessed using both RECIST v1.1 and immune-related response criteria (irRC). Full pharmacokinetic sampling was performed during cycle 1. Results Three patients received pembrolizumab at 2.0 mg/kg and seven at 10 mg/kg. No dose-limiting toxicities were observed during cycle 1. Eighty percent of patients experienced drug-related AEs (mostly grade 1 or 2); the most common drug-related AEs were nausea, malaise, pyrexia, and aspartate aminotransferase/alanine transaminase (AST/ALT) elevations (n = 2 each). No drug-related grade 4 or 5 AEs occurred. Immune-related AEs comprised grade 3 ALT elevation (n = 1), grade 3 AST elevation (n = 1), grade 1 pneumonitis (n = 1), and grade 1 thyroid-stimulating hormone elevation (n = 1). The safety and pharmacokinetic profiles of Japanese patients were similar to those previously reported for Caucasian patients. A partial tumor response was observed in one patient with non-small-cell lung cancer (NSCLC) and in one patient with melanoma. Conclusions Pembrolizumab at both 2 and 10 mg/kg Q2W was well tolerated in Japanese patients with advanced solid tumors and showed encouraging anti-tumor activity against melanoma and NSCLC.

Purpose Investigate the safety and tolerability of AZD5363 and define a recommended dose for evaluation in Japanese patients with advanced solid malignancies. Methods AZD5363 was administered orally as a single dose, and then the dose was escalated to twice daily (bid) in separate continuous (every day) and intermittent (4 days on, 3 days off [4/3] or 2 days on, 5 days off [2/5]) dosing schedules to reach recommended doses defined by dose-limiting toxicity (DLT). Doses for continuous, 4/3, and 2/5 intermittent dosing schedules were 80–400, 360–480, and 640 mg, respectively, and were informed by results from an equivalent study in Caucasian patients. Results Forty-one patients received AZD5363. DLTs were only experienced with continuous dosing. 97.6 % of patients reported at least one adverse event (AE); most common were diarrhea (78.0 %), hyperglycemia (68.3 %), nausea (56.1 %), and maculopapular rash (56.1 %). Grade ≥3 AEs were reported by 63.4 % of patients. Exposure of AZD5363 was generally dose proportional for both single and multiple doses. Single-dose pharmacokinetics of AZD5363 was generally predictive of multiple-dose pharmacokinetics. Confirmed partial responses were reported by two patients, both of whom were Akt1 (E17K) mutation positive. One patient in the 480 mg bid 4/3 dosing cohort maintained partial response for >2 years. Conclusions Intermittent dosing of AZD5363 was more tolerable than continuous dosing. 480 mg bid intermittent 4/3 dosing for AZD5363 monotherapy was selected for further investigation. Preliminary evidence of antitumor activity was observed. Akt1 (E17K) is a potent driver mutation that may predict clinical response to AZD5363.

Background/aim Although some previous studies suggested that programmed cell death-ligand 1 (PD-L1) expression was significantly associated with a favorable postoperative prognosis in patients with small-cell lung cancer (SCLC), the prognostic significance of PD-L2 expression remains unknown. The aim of the current study was to investigate the prognostic significance of PD-L2 expression in patients with SCLC. Patients and methods Thirty-eight patients who underwent resection of SCLC were analyzed. A monoclonal anti-human PD-L1 antibody (clone SP142) and a monoclonal anti-human PD-L2 antibody (clone 176611) were used as the primary antibodies. Cut-off value for PD-L1 and PD-L2 expression was set to 1%. Results Among 38 patients, 15 (39.5%) were positive for PD-L2 expression. No significant associations between PD-L2-positivity and clinicopathological factors, including PD-L1 positivity or prognosis were identified. No significant differences in disease-free survival and overall survival were observed between PD-L2-positive patients and PD-L2-negative patients (p=0.367 and p=0.726, respectively). Conclusion PD-L2 expression is not related to clinicopathological factors or postoperative prognosis in patients with SCLC, though this should be further investigated in studies involving larger populations.

Aim: Programmed cell death-ligand 1 and 2 (PD-L1 and PD-L2) are ligands of the programmed cell death-1 (PD1) receptor. PD1/PD-L1 inhibitors have shown clinical efficacy in non-small cell lung cancer (NSCLC). However, relatively little is known about the expression of PD-L2, or its association with the clinicopathological features of NSCLC. Here, the radiological features of PD-L2-positive lung adenocarcinoma were evaluated. Materials and Methods: PD-L1 and PD-L2 expression were evaluated by immuno-histochemical staining of surgically-resected specimens from 393 patients with primary lung adenocarcinoma who underwent preoperative thin-section computed tomography (CT), 222 of whom also underwent (18)F-fluorodeoxyglucose positron-emission tomography/CT ((18)F-FDG-PET/CT). Results: Among the 393 specimens, 132 (33.6%) and 266 (67.7%) were positive for PD-L1 and PD-L2 expression, respectively. Multivariate analysis showed that the absence of surrounding ground glass opacity and the presence of air bronchogram were significantly associated with PD-L2 expression; however, there was no significant association between PD-L2 expression and the consolidation/tumor ratio. In 222 (18)F-FDG-PET/CT, the maximum standardized uptake value was significantly higher in patients with PD-L2-positive compared to those with PD-L2-negative tumors. Conclusion: PD-L2-positive lung adenocarcinomas are less radiologically malignant and invasive than their PD-L1-positive counterparts.

To investigate the radiological features on computed tomography (CT) of brain metastasis (BM) from epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).Thirty-four patients with NSCLC with BMs who underwent surgical resection of the BMs at the Department of Neurosurgery, Kyushu University from 2005 to 2016 were enrolled in the study. The EGFR statuses of the 34 BMs were investigated. Radiological features, including the number, size, and location of the tumor, were delineated by CT.Patients with EGFR-mutated BMs had significantly higher frequencies of multiple metastases than those with the non-EGFR-mutated type (p=0.042). BMs harboring mutations in EGFR were more frequently observed in the central area of the brain compared to those without mutations in EGFR (p=0.037).Careful follow-up of patients with EGFR-mutated NSCLC may be necessary given the high frequencies of multiple BMs and their location in the central area of the brain.

We describe a 77-year-old Japanese woman who presented with three nodule shadows in three different lobes of the right lung, without evidence of lymph node metastasis or distant metastasis. All three tumors were surgically resected. The pathological diagnosis was synchronous multiple primary lung cancer: pT2aN0M0, pStageIB. Based on a differing epidermal growth factor receptor (EGFR) mutation status, no lymph node metastasis, and no distant metastasis, the tumors were characterized as synchronous triple primary rather than intrapulmonary metastases. At eight months after surgery, a new lesion emerged in the right lower lobe. Given that the most advanced tumor had an EGFR del-19 mutation, the patient was orally administered afatinib. Since then, the treatment response of the patient has been assessed as stable disease (SD) for about two years. This is a very rare case of resected triple synchronous primary lung cancer on the same lung side in which the lesions all had a different EGFR mutation status, and this report highlights the clinical utility of surgical resection of multifocal lung nodules without lymph node metastasis or distant metastasis in order to optimize therapy for patients with known driver mutations.

Background/aim Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in cancer pathogenesis. Although clinicopathological significance of EZH2 in non-small cell lung cancer has been gradually elucidated, such significance in small cell lung cancer (SCLC) has yet to be fully investigated. Patients and methods Forty patients with resected SCLC were analyzed for EZH2. EZH2 expression was evaluated using the Allred score (0-8) and was classified into negative (0-6) and positive (7 and 8). We evaluated the association between EZH2 and the clinicopathological characteristics and postoperative survivals. Results Among 40 patients, 15 (37.5%) and 25 (62.5%) were classified as being negative and positive for EZH2, respectively. Fisher's exact test demonstrated no significant associations between the positivity for EZH2 and clinicopathological characteristics. No significant differences were observed in recurrence-free and overall survivals between EZH2-negative/low and EZH2-high patients. Conclusion EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals.

Growing teratoma syndrome (GTS) of the lung is extremely rare, and there are very few reports on this condition. This is a case report of GTS of the lung that was successfully treated by resection. A 19-year-old man, who had been diagnosed with a testicular tumor, lung metastases and left hilar lymph node metastasis, underwent surgical resection for left testicular cancer. After orchiectomy and chemotherapy, the patient was successfully treated with wedge resection of the right upper lobe and left upper lobectomy. In conclusion, the current case suggests that some patients with GTS might be successfully treated by surgical resection.

Takotsubo cardiomyopathy (TC) is a syndrome characterized by transient local systolic dysfunction of the left ventricle with no evidence of coronary artery disease or acute plaque rupture. We present the case of 71-year-old woman who developed TC after two-stage surgery for double primary lung cancer. On computed tomography, lung nodules were identified in the left upper and right middle lobes. Based on the diagnosis of double primary lung cancer, we performed two-stage surgery (left upper lobectomy followed by right middle lobectomy). One day after the second surgery, respiratory failure developed. Electrocardiography showed ST segment elevation, serum troponin levels were elevated, and chest x-ray showed acute pulmonary edema. Cardiac catheterization showed no coronary artery disease and apical akinesia. Based on these findings, we diagnosed TC and the patient recovered with supportive treatment.

Background Spread through air spaces (STAS) is a recently recognized invasive pattern of lung cancer defined by the World Health Organization as micropapillary clusters, solid nests, or single cells spreading within air spaces beyond the edge of the main tumor. Although STAS has been shown to be a significant prognosticator for the postoperative survival in early-stage lung cancer treated with limited resection, its prognostic impact on the survival in completely resected adenocarcinomas with lymph node metastasis remains unclear. Patients and Methods STAS was assessed in a total of 63 adenocarcinomas with lymph node metastasis in patients who underwent complete resection. STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. We evaluated the association between STAS and the clinicopathologic characteristics and the postoperative survival. Results Among 63 patients, 31 (49.2%) and 32 (50.8%) had disease that was pathologically positive for N1 and N2, respectively. STAS was observed in 45 patients (73.0%) and was not significantly associated with any clinicopathologic characteristics. Patients with the STAS had significantly shorter recurrence-free survival (RFS) but not overall survival than those without STAS (P = .04 and P = .35, respectively). The 5-year RFS in patients with and without STAS was 25.1% and 56.7%, respectively. According to a multivariate analysis, positivity for STAS remained an independent prognostic parameter for RFS (hazard ratio = 3.09; 95% confidence interval, 1.47-7.16; P Conclusion STAS was predictive of a poor RFS in completely resected adenocarcinomas with lymph node metastasis.

Background/aim Spread through air spaces (STAS) is a novel invasive pattern of lung cancer, especially adenocarcinoma and squamous cell carcinoma. However, its frequency and significance in patients with resected small cell lung cancer (SCLC) remains unclear. Patients and methods A total of 30 patients with resected SCLC were analyzed for STAS. STAS was classified as either no STAS, low STAS (1-4 single cells or clusters of STAS), or high STAS (≥5 single cells or clusters of STAS). We evaluated the association between STAS and clinicopathological characteristics and postoperative survivals. Results Among 30 patients, 5 (17%), 6 (20%) and 19 (63%) were classified as having no, low and high STAS, respectively. Fisher's exact test demonstrated no significant associations between the positivity for STAS and clinicopathological characteristics. No significant differences were observed in recurrence-free and overall survival between STAS-negative/low and STAS-high patients. Conclusion STAS was frequently observed in patients with resected SCLC.

AIM To investigate the association between positivity for programmed cell death-ligand 1 (PD-L1) in brain metastases (BM) and the prognosis or clinical factors in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Thirty-two patients with surgically resected brain-metastatic NSCLC were enrolled. The PD-L1 expression in BM was analyzed using the antibody against human PD-L1 (clone SP142). The PD-L1 positivity was defined as PD-L1 expression on brain-metastatic tumor cells of ≥5%. RESULTS Seven (21.9%) out of 32 patients showed PD-L1 positivity in BM. The PD-L1-positive BM group had a significantly shorter brain-specific disease-free survival than the PD-L1-negative BM group (p

AIM We investigated the safety of simultaneous bilateral lung resection for lung metastases. PATIENTS AND METHODS We retrospectively analyzed 185 patients with pulmonary metastases who underwent unilateral or bilateral pulmonary resection from August 2009 to December 2016 at a single institution. RESULTS Single-stage bilateral lung resection was undertaken in 19 patients, and the other 166 patients underwent unilateral pulmonary resection, including 20 patients who underwent repeated resections for synchronous or metachronous metastases. Operative time and drainage days in the bilateral group were significantly longer than those in the unilateral group (220±20 vs. 152±6.9 min: p

It has been reported that the tumor microenvironment, including tumor-associated immune cells (ICs) and programmed cell death-ligand 1 (PD-L1) expression, differs between primary and metastatic tumors. This study aimed to elucidate the differences in PD-L1 expression on tumor cells (TCs) and ICs between lung metastases and corresponding primary tumors.We analyzed paired lesions from 44 patients diagnosed with lung metastases between 2005 and 2017 at Kyushu University. The percentages of PD-L1-positive TCs and ICs in lung metastases and the primary tumor were classified into five categories (0:1%; 1: 1%-4%; 2: 5%-9%; 3: 10%-49%; and 4: ≥50%). Lesions in which ≥1% of the TCs and ICs were PD-L1-positive were considered positive.The primary cancers included rectal (n = 19), colon (n = 10), liver (n = 10), bile duct (n = 2), stomach (n = 1), gall bladder (n = 1) and breast (n = 1). Discrepancies in PD-L1 expression on TCs and ICs between lung metastases and primary lesions were observed in 5 (11.4%, κ = 0.23) and 9 (20.5%, κ = 0.11) of the 44 cases, respectively. PD-L1 expression on ICs was higher in lung metastases than paired primary tumors (p = 0.026), although the percentage of PD-L1-positive TCs was not significantly different between lung metastases and primary tumors (p = 0.767).There were significant differences in PD-L1 expression on TCs and ICs between lung metastases and primary tumors. Clinicians should be aware of these differences in the tumor microenvironment when treating patients with immunotherapy.

AIM We evaluated the metabolic characteristics of small-sized lung cancer using 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) with regard to programmed cell death ligand 1 (PD-L1) expression. MATERIALS AND METHODS PD-L1 expression was evaluated by immunohistochemistry with the antibody clone SP142 in 263 patients with surgically resected primary small-sized lung cancer. Specimens with

There have been no previous reports examining how the travel distance affects the outcomes of non-small-cell lung cancer (NSCLC) patients. In this study, we examined the influence of the distance from home to the hospital on patients with NSCLC who underwent surgical resection.From 2006 to 2011, 607 consecutive patients with NSCLC who had undergone pulmonary resection were enrolled. The patients were divided into three groups according to the distance from their home to the hospital: 010, 10-30 and30 km. We analysed the short-term and long-term outcomes according to the group.Two hundred and ninety-six patients lived less than 10 km from the hospital, 111 patients lived 10-30 km and 200 patients lived more than 30 km. There were no differences in the demographics, including age, European Cooperative Oncology Group performance status, histological type, surgical procedure and pathological stage, between the three groups. The mean postoperative hospital stay was as follows: 13.9 days in the10 km group, 13.3 days in the 10-30 km group and 14.3 days in the30 km group (P = 0.04). There were no significant differences in the median length of follow-up (50, 47, 43 months, P = 0.24), disease-free survival (DFS) (5-year DFS, 68.1, 68.2 and 70.1%, P = 0.89) or overall survival (OS) (5-year OS, 80.6, 78.8 and 79.4%, P = 0.99) between the three groups.The distance between home and the hospital was not found to influence the long-term outcomes of the patients with surgically resected NSCLC. Therefore, the travel distance should not represent a contraindication to surgical resection and postoperative therapy for NSCLC.

Introduction: Anaplastic lymphoma kinase (ALK)-rearranged non–small-cell lung cancer (NSCLC) is sensitive to ALK inhibitors, but resistance develops. This study assessed the maximum-tolerated dose, safety, pharmacokinetics (PK), and antitumor activity of ceritinib, a novel ALK inhibitor (ALKi), in Japanese patients with ALK-rearranged malignancies. Methods: This phase I, multicenter, open-label study (NCT01634763) enrolled adult patients with ALK-rearranged (by fluorescence in situ hybridization and/or immunohistochemistry) locally advanced/metastatic malignancy that had progressed despite standard therapy. The study comprised two parts: dose escalation and dose expansion. Ceritinib (single-dose) was administered orally in the 3-day PK run-in period, then once daily, in 21-day cycles. Adaptive dose escalations were guided by a Bayesian model. Results: Twenty patients (80% with ALKi treatment history [ALKi-pretreated]; 19 NSCLC; one inflammatory myofibroblastic tumor) received ceritinib 300 to 750 mg (19 during dose escalation, one in dose expansion). Two dose-limiting toxicities occurred: grade 3 lipase increase (600 mg); grade 3 drug-induced liver injury (750 mg). The most common adverse events were gastrointestinal (nausea: 95%; diarrhea, vomiting: 75%). Ceritinib PK profile was dose proportional across 300 to 750 mg dosages; steady state was reached by day 15. Overall response rate was 55% (11 of 20 patients). Among patients with NSCLC, partial response was observed in two of four ALKi-naive patients, five of nine crizotinib-pretreated patients, two of four alectinib-pretreated patients, and one of two crizotinib and alectinib/ASP3026 pretreated patients. The ASP3026-pretreated inflammatory myofibroblastic tumor patient achieved partial response. Conclusions: Ceritinib maximum-tolerated dose was 750 mg once daily in Japanese patients. Antitumor activity was observed irrespective of prior ALKi treatment history. Dose expansion, examining the activity of ceritinib in alectinib-resistant patients, is ongoing.

Objectives Although chemotherapy and radiotherapy are recommended for patients with limited disease small cell lung cancer (LD-SCLC), several series have reported favorable survival outcomes even in patients with stages II and III disease who underwent surgical resection. The purpose of this study is to compare the outcomes of the use of surgical resection to the other conventional non-surgical treatments in patients with LD-SCLC with respect to each clinical stage. Materials and methods We retrospectively reviewed 277 patients who received treatment for LD-SCLC and compared the outcomes of the use of surgical resection to the other conventional non-surgical treatments. Results The clinical stage was stage I in 50 cases (18%), stage II in 53 cases (19%) and stage III in 174 cases (63%). Eighty-eight patients received surgical resection and 189 patients were treated with non-surgical treatment. Surgery was performed in 44 patients (88%) with stage I, 27 patients (52%) with stage II and 17 patients (10%) with stage III disease. The five-year survival rates of the patients according to clinical stage were 58% in stage I, 29% in stage II and 18% in stage III. The five-year survival rates of the patients with and without surgical resection according to clinical stage were as follows: 62% and 25% in stage I ( p p =0.95), 18% and 18% in stage III ( p =0.35), respectively. In 44 propensity score-matched pairs with stages II and III disease, including matching for variables such as age, gender and the PS, the five-year survival rates was better in patients with surgical resection than in those without surgery ( p =0.04). Conclusion Surgical resection is effective for the patients with stage I LD-SCLC and some cases of stage II or III disease.

This phase I, open-label study evaluated the safety/tolerability and maximum tolerated dose of second-line nintedanib combined with docetaxel in Japanese patients with advanced non-small-cell lung cancer.Eligible patients received docetaxel 60 or 75 mg/m(2) (day 1) plus nintedanib 100, 150, or 200 mg twice daily (bid; days 2-21) in 21-day cycles. Standard 3 + 3 dose escalations were performed separately in patient cohorts with a body surface area (BSA) of less than 1.5 m(2) (BSA1.5) and BSA greater than or equal to 1.5, respectively.Forty-two patients (17 BSA1.5, 25 BSA ≥ 1.5) were treated. The maximum tolerated dose of nintedanib was 150 and 200 mg bid in patients with BSA less than 1.5 and BSA greater than or equal to 1.5 (BSA ≥ 1.5), respectively, in combination with 75 mg/m(2) of docetaxel. Dose-limiting toxicities (all grade 3 hepatic enzyme elevations) occurred in 12 patients (six per cohort). Drug-related adverse events included neutropenia (95%), leukopenia (83%), fatigue (76%), alopecia (71%), decreased appetite (67%), and elevations in alanine aminotransferase (64%) and aspartate aminotransferase (64%). All hepatic enzyme elevations were reversible and manageable with dose reduction or discontinuation. Among 38 evaluable patients, 10 (26%) had a partial response and 18 (47%) had stable disease.Continuous treatment with second-line nintedanib combined with docetaxel was manageable and showed promising signs of efficacy in Japanese patients with advanced non-small-cell lung cancer.

Thymic carcinoma is an exceptionally rare tumor, which has a very poor prognosis, differing from thymoma. Although cytotoxic chemotherapy is commonly used to treat advanced thymic carcinoma, its effectiveness has not been found to be sufficient. There are several reports that thymic carcinoma also harbors an oncogenic driver mutation, similar to lung cancer. A patient with a c-kit mutation-positive thymic carcinoma received imatinib followed by sunitinib consecutively, which are both c-Kit inhibitors. Although the patient had achieved long-term disease control for 21 months, the primary lesion and pulmonary metastases had increased in size by November, 2014. Following failure of imatinib treatment, the patient received sunitinib, a multiple kinase inhibitor, initiated in December, 2014. Following administration of sunitinib, a computed tomography scan revealed a partial response and the disease was effectively controlled with continued sunitinib treatment for 6 months, up to June, 2015. The patient achieved long-term disease control (~27 months) with imatinib followed by sunitinib. The efficacy of consecutive molecular-targeted therapy for thymic carcinoma was demonstrated in this case. Therefore, thymic carcinoma with oncogenic driver mutations should be treated with molecular-targeted agents rather than with cytotoxic drugs, and it may be suitable to treat c-kit mutation-positive thymic carcinoma as a mediastinal gastrointestinal stromal tumor.

Background/aim The aim of this study was to assess the appropriateness of pulmonary metastasectomy (MT), with a focus on the primary organ. Patients and methods The pathological status of the primary organ, outcome of the MT, disease-free interval, and overall survival were assessed. Results The primary organ was the most significant prognostic factor analyzed, with a relative risk of 4.6 (95% confidence interval: 1.69-12.56, p=0.003). Patients with colorectal carcinoma had a better survival than those with another primary organ (p=0.003). The hazard ratios by primary organ in comparison to colorectal carcinoma were 3.2 for head and neck carcinoma, 3.5 for soft tissue sarcoma, 8.3 for hepatocellular carcinoma, and 8.9 for urinary carcinoma. Conclusion Colorectal carcinoma is associated with a greater survival benefit than cancer of other primary organs. Colorectal carcinoma cases should be more aggressively considered for MT than other primary organ cases.

Malignant pleural mesothelioma (MPM), a devastating neoplasm, is traditionally considered to be resistant to antitumor therapy. Identification of clinical prognostic indicators is therefore needed. Although the C-reactive protein/albumin ratio (CAR) has been used to predict the prognosis of many types of malignancy, its utility in patients with MPM is unknown. The data of 100 patients diagnosed as having MPM from 1995 to 2015 at the National Kyushu Cancer Center and Kyushu University were analyzed. The CAR was calculated as serum C-reactive protein concentration divided by albumin concentration. A cutoff for CAR was set at 0.58 according to a receiver operating characteristics curve for 1-year survival. Thirty-five of the 100 (35.0%) patients were classified as having a high CAR. A high CAR was significantly associated with advanced clinical stage (p

Background/aim Women with breast cancer are at increased risk of subsequent primary malignancies, specifically lung cancer. The aim of this study was to report the frequency of lung cancer in patients with breast cancer, and patients' characteristics and surgical outcomes. Patients and methods We investigated 1,066 consecutive female patients undergoing surgical resection for breast cancer and 666 undergoing surgical resection for lung cancer. Results Lung cancer with breast cancer was observed in 14 patients (1.3% of breast cancer and 2.1% of lung cancer cases; mean age=65 years), and 3/14 (21.4%) patients were smokers. Sixteen lung cancer lesions in 14 patients were adenocarcinomas and one was squamous cell carcinoma. All 14 patients were alive at the time of this report; 4/14 (28.6%) patients had recurrent breast cancer and 1/14 (7.1%) had recurrent lung cancer. In synchronous cases, 5/6 (83.3%) patients received concomitant surgery for both breast cancer and lung cancer. Patients' postoperative courses were uneventful. In metachronous cases, eight patients had lung cancer a mean of 33 months after breast cancer surgery. All eight patients received adjuvant therapies and 4/8 (50%) patients received adjuvant therapies for recurrent breast cancer, including chemotherapy, radiotherapy, hormonal therapy, and anti-HER2 therapy. All patients had early-stage lung adenocarcinoma and underwent surgical resection. Conclusion Concomitant surgery for synchronous lung and breast cancer was feasible and safe. In metachronous cases, lung cancers tended to be detected within 3 years after surgery for breast cancer. Careful follow-up for postoperative breast cancer may contribute to the detection of early-stage lung cancer.

We evaluated the metabolic characteristics of small-sized lung cancer usingPD-L1 expression was evaluated by immunohistochemistry with the antibody clone SP142 in 263 patients with surgically resected primary small-sized lung cancer. Specimens with5% tumor membrane staining were considered negative. We examined the association between the frequency of PD-L1 expression and the maximum standardized uptake value (SUVmax) in preoperativeAmong patients with non-small cell lung cancer (NSCLC), the SUVmax was significantly higher in those with PD-L1 expression than in those without (p0.0001). However, there was no correlation between SUVmax and PD-L1 expression in patients with neuroendocrine tumors (p=0.9638). Multivariate analysis revealed that smoking and a high SUVmax were independent predictors of PD-L1 expression.PD-L1 expression was related to high glucose metabolism in small-sized NSCLC.

A relationship between sarcopenia diagnosed by skeletal muscle area (SMA) and poor prognosis in cancer patients has recently been reported. This study aimed to clarify the clinical significance of postoperatively decreased SMA in patients with early non-small cell lung cancer (NSCLC). This study selected 101 patients with pathologic stage 1 NSCLC who had undergone pre- and postoperative (~ 1 year) computed tomography scans and lobectomy between 2005 and 2010 at Kyushu University Hospital. The post/pre ratio was defined as the postoperative normalized SMA (cm2/m2) at the 12th thoracic vertebra level divided by the preoperative normalized SMA. The cutoff value for the post/pre ratio was set at 0.9. The study classified 31 patients (30.7%) as having decreased SMA. Poor performance status (PS) was significantly associated with decreased SMA (p = 0.048). The patients with decreased SMA had a significantly shorter disease-free survival (DFS) (p

We conducted a retrospective analysis to assess the practicality of pneumonectomy, especially after concurrent induction chemoradiotherapy (i-CRT), for locally advanced non-small cell lung cancer (LA-NSCLC). The operative risks vs. the survival benefit of this procedure for such patients is a subject of controversy. The subjects of this retrospective study were 71 consecutive LA-NSCLC patients with cStage IIIA-C NSCLC, who underwent i-CRT followed by curative intent pulmonary resection between February, 2001 and March, 2013. Thirty-two patients underwent pneumonectomy (group P) and 39 patients underwent lobectomy (group L). In group P, 17 (54.8%) patients underwent right pneumonectomy. There was no 30-day postoperative mortality in either group and no significant difference in 90-day postoperative mortality between the groups (3.1% vs. 2.6% in groups P and L, respectively). The 5-year overall survival (OS) rate was 58.7% (95% CI: 41.5–75.9%) in group P and 57.3% (95% CI 41.2–73.4%) in group L, without a significant difference between the groups. Our findings suggest that i-CRT followed by pneumonectomy is feasible, with a similar survival benefit to lobectomy. Thus, pneumonectomy after i-CRT should not be avoided as it is a potentially curative intent strategy for carefully selected patients.