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Introduction: Immune checkpoint inhibitors have recently been approved for the treatment of early-stage NSCLC in the perioperative setting on the basis of phase 3 trials. However, the characteristics of such patients who are susceptible to recurrence after adjuvant chemotherapy or who are likely to benefit from postoperative immunotherapy have remained unclear. Methods: This biomarker study (WJOG12219LTR) was designed to evaluate cancer stem cell markers (CD44 and CD133), programmed death-ligand 1 (PD-L1) expression on tumor cells, CD8 expression on tumor-infiltrating lymphocytes, and tumor mutation burden in completely resected stage II to IIIA NSCLC with the use of archived DNA and tissue samples from the prospective WJOG4107 trial. Tumors were classified as inflamed or noninflamed on the basis of the PD-L1 tumor proportion score and CD8+ tumor-infiltrating lymphocyte density. The association between each potential biomarker and relapse-free survival (RFS) during adjuvant chemotherapy was assessed by Kaplan-Meier analysis. Results: A total of 117 patients were included in this study. The median RFS was not reached (95% confidence intervals [CI]: 22.4 mo–not reached; n = 39) and 23.7 months (95% CI: 14.5–43.6; n = 41) in patients with inflamed or noninflamed adenocarcinoma, respectively (log-rank p = 0.02, hazard ratio of 0.52 [95% CI: 0.29–0.93]). Analysis of the combination of tumor inflammation category and TP53 mutation status revealed that inflamed tumors without TP53 mutations were associated with the longest RFS. Conclusions: PD-L1 expression on tumor cells, CD8+ T cell infiltration, and TP53 mutation status may help identify patients with early-stage NSCLC susceptible to recurrence after adjuvant chemotherapy.

Introduction: Perioperative treatment in NSCLC has gained marked attention with the introduction of immune checkpoint inhibitors. Such a paradigm shift has given us additional opportunities to evaluate potential biomarkers in patients with these curable disease stages. Methods: This study (WJOG12319LTR) was designed as a biomarker study to evaluate whether soluble immune markers were prognostic or predictive on relapse-free survival in patients with stage II to IIIA NSCLC who underwent complete resection and adjuvant chemotherapy with cisplatin plus S-1, which is an oral fluoropyrimidine formulation that consists of tegafur, gimeracil, and oteracil, or S-1 alone in the previous WJOG4107 study. Archived plasma samples were assayed for soluble (s) forms of programmed cell death protein 1 (sPD-1), programmed death-ligand 1(sPD-L1), and CTLA-4 (sCTLA-4) with the highly sensitive HISCL system. Using time-dependent receiver operating characteristic curve analysis, the area under the curves were derived and optimal cutoff values were determined. Using the cutoff values, whether the marker was prognostic or predictive was assessed by survival analysis. Results: A total of 150 patients were included in the study. The time-dependent receiver operating characteristics analysis revealed that the area under the curves for sPD-1, sPD-L1, and sCTLA-4 were 0.54, 0.51, and 0.58, respectively. The survival analysis did not reject that hazard ratios were 1 in terms of the soluble immune marker and the treatment-marker interaction for all three markers. Conclusions: There was no proof that circulating concentrations of sPD-1, sPD-L1, and sCTLA-4 were prognostic or predictive factors of the outcome for adjuvant chemotherapy after complete resection in patients with NSCLC.

Abstract Background The clinical and prognostic implications of anaplastic lymphoma kinase (ALK) status in resected lung cancers remain unclear. In this study we analyzed the prognostic and predictive significance of ALK‐positive among patients with completely resected lung adenocarcinoma. Methods We retrospectively reviewed 197 patients with lung adenocarcinoma who underwent complete surgical resection and had been tested for their ALK status. We investigated the impact of an ALK‐positive status on the recurrence‐free survival (RFS) and overall survival (OS) and examined the predictive factors for an ALK‐positive status. Results ALK positivity was noted in 36 (18%) out of 197 patients, and when limited to stage I patients, in 24 (19%) out of 124. In the pathological‐stage I population, while the OS exhibited no significant difference between ALK‐positive and ALK‐negative patients (5‐year OS rate, 81.2% vs. 89.8%, p = 0.226), the RFS of ALK‐positive patients was significantly worse than that of ALK‐negative patients (5‐year RFS rate, 55.9% vs. 78.8%, p = 0.018). A multivariate analysis showed that ALK‐positive status (hazard ratio [HR] 3.431, p = 0.009) was an independent prognostic factor for the RFS. Regarding the relationship between clinicopathological factors and an ALK‐positive status, a high‐grade histological subtype, including solid and micropapillary subtypes (odds ratio [OR] 5.464, p

Background The mammalian Notch family ligands delta‐like 3 (DLL3) is reported to be a potential therapeutic target for large cell neuroendocrine carcinomas (LCNEC). The effect of DLL3 expression on LCNEC prognosis has not yet been elucidated. Methods We reviewed the medical records of 70 LCNEC patients undergoing surgical resection between 2001 and 2015 using a prospectively maintained database. We performed immunohistochemistry for DLL3 and investigated the correlation between the sensitivity of LCNEC to platinum‐based adjuvant chemotherapy. Results DLL3 expression was positive in 26 (37.1%) LCNEC patients. A total of 23 patients (32.9%) received platinum‐based adjuvant chemotherapy. Among patients with DLL3 expression‐positive tumors, no difference was found in the five‐year overall survival (OS) or recurrence‐free survival (RFS) between patients with and without adjuvant chemotherapy (surgery + chemotherapy vs. surgery alone, five‐year OS: 58.3% vs. 35.7% P = 0.36, five‐year RFS: 41.7% vs. 35.7% P = 0.74). In contrast, among patients with DLL3‐negative tumors, significantly greater five‐year OS and RFS rates were observed for patients with adjuvant chemotherapy than for those without it (surgery + chemotherapy vs. surgery alone: five‐year OS: 90.0% vs. 26.9% P

Background Partner of Sld five 3 (Psf3) is a member of the heterotetrameric complex that consists of SLD5, Psf1, Psf2, and Psf3. We have shown in previous studies that high Psf3 expression was a poor prognostic marker for pulmonary adenocarcinoma. Here, we statistically evaluated the relationship between clinicopathologic factors and Psf3 expression in stage I pulmonary adenocarcinoma. Methods A total of 583 patients who had undergone complete resection of stage I pulmonary adenocarcinoma from January 2002 to December 2009 were included in the study. Tissue microarrays were performed, and the resected tumors were divided into groups according to Psf3 expression. Results Of 583 patients, high expression of Psf3 was observed in 211 (36.2%) and low expression of Psf3 observed in 372 (63.8%) patients. Among stage I patients, the five‐year survival rate was 76.7% in the Psf3 high expression group and 90.9% in the Psf3 low expression group (P

A pneumatocele is a cystic change of the lung that is caused by a check valve in the bronchiole due to infection, trauma and positive-pressure ventilation. We herein report a case of pneumatocele triggered by using of continuous positive airway pressure (CPAP) for sleep apnea syndrome (SAS) after pulmonary resection. A 69-year-old man underwent right upper lobectomy for lung cancer and developed interstitial pneumonia (IP) 10th postoperative day (POD). He was treated with steroid pulse therapy (solmedrol 500 mg × 3 days), and thereafter with oral steroid therapy (predonin 30mg/day). Well responded to the steroid therapy, IP was improved. However, he noticed bloody sputum 29th POD, and chest computed tomography showed a giant cystic lesion on the dorsal right lower lobe. We resected the cyst and the pathological findings revealed that the cystic lesion was pneumatocele, and CPAP was strongly suspected of triggering this disease.

Background The aim of this study was to evaluate the efficacy of buttressed stapling using a stapler with an attached polyglycolic acid sheet in reducing the rate of air leak associated with pulmonary lobectomy. Materials and Methods A prospective, randomized, phase III study was conducted to confirm the superiority of a buttressed stapler in a test treatment group to a conventional nonbuttressed stapler in a current international standard of care group among patients undergoing pulmonary lobectomy. The primary end point was the frequency of intraoperative air leaks. Results Although no fatal postoperative bleeding occurred in the present study, this trial closed early with 100 patients because the manufacturer recalled the buttressed stapler based on reports of 13 serious injuries and 3 fatalities following pulmonary resection in routine clinical practice. A total of 76 patients treated with a stapler (35 in the non-B group and 41 in the B group) were included as subjects in the analysis. No statistical differences were observed between the groups in the frequency of intraoperative air leaks (22 [63%] vs. 26 [63%]) or the postoperative duration of air leaks (mean: 3.5 vs. 2.9 days). The frequency of air leak from stapler holes was significantly lower in the B group than in the non-B group (2% [1/41] vs. 20% [7/35]; p = 0.016). Conclusions The efficacy of buttressed stapling in reducing the rate of air leak in patients undergoing pulmonary lobectomy could not be clearly demonstrated. However, air leak from stapler holes can be prevented with buttressed stapling. [ABSTRACT FROM AUTHOR]