Endobronchial Ultrasound-Guided Transbronchial Biopsy Using Novel Thin Bronchoscope for Diagnosis of Peripheral Pulmonary Lesions

Background:The aim of this study was to evaluate the diagnostic utility of endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) using a novel 3.4-mm thin bronchoscope and a 1.4-mm ultrasonic probe for peripheral pulmonary lesions.Methods:A total of 86 patients with suspected peripheral lesions were included in this prospective study. EBUS-TBBs were performed using a prototype 3.4-mm thin bronchoscope and a 1.4-mm radial ultrasonic probe under fluoroscopic guidance.Results:Twelve patients with endobronchial lesions within the segmental bronchi and three patients who did not return to follow-up were excluded from this analysis. Thus, a total of 71 patients with peripheral pulmonary lesions (mean size, 31.2 ± 12.7 mm) were included in the final analysis. The mean bronchus level reached with the thin bronchoscope was 4.6 generations. Diagnostic histologic specimens were obtained in 49 of 71 patients (69%:80% for malignant lesions and 52% for benign lesions). A definitive diagnosis of malignancy for lesions ≥20 mm and lesions <20 mm was made in 82% (31 of 38) and 67% (four of six), respectively. There were no significant complications.Conclusion:The EBUS-TBB using a 3.4-mm thin bronchoscope and a 1.4-mm radial probe is feasible, accurate, and safe for the diagnosis of peripheral pulmonary lesions

S-1 Plus Cisplatin with Concurrent Radiotherapy for Locally Advanced Non-small Cell Lung Cancer: A Multi-Institutional Phase II Trial (West Japan Thoracic Oncology Group 3706)

Purpose:To evaluate the combination chemotherapy using oral antimetabolite S-1 plus cisplatin (SP) with concurrent thoracic radiotherapy (RT) followed by the consolidation SP for locally advanced non-small cell lung cancer.Patients and Methods:Patients with stage III non-small cell lung cancer, 20 to 74 years of age, and Eastern Cooperative Oncology Group performance status 0 to 1 were eligible. The concurrent phase consisted of full dose S-1 (orally at 40 mg/m2/dose twice daily, on days 1–14) and cisplatin (60 mg/m2 on day 1) repeated every 4 weeks for two cycles with RT delivered beginning on day 1 (60 Gy/30 fractions over 6 weeks). After SP-RT, patients received an additional two cycles of SP as the consolidation phase.Results:Fifty-five patients were registered between November 2006 and December 2007. Of the 50 patients for efficacy analysis, the median age was 64 years; male/female 40/10; Eastern Cooperative Oncology Group performance status 0/1, 21/29; clinical stage IIIA/IIIB 18/32; and adenocarcinoma/others 20/30. There were 42 clinical responses including one complete response with an objective response rate of 84% (95% confidence interval [CI], 71–93%). The 1- and 2-year overall survival rates were 88% (95% CI, 75–94%) and 70% (95% CI, 55–81%), respectively. The median progression-free survival was 20 months. Of the 54 patients for safety analysis, common toxicities in the concurrent phase included grade 3/4 neutropenia (26%), thrombocytopenia (9%), and grade 3 esophagitis (9%) and febrile neutropenia (9%). In one patient, grade 3 pneumonitis was observed in the consolidation phase. There were two treatment-related deaths caused by infection in the concurrent phase.Conclusions:SP-RT showed a promising efficacy against locally advanced NCSLC with acceptable toxicity

Phase II Study of Pleurodesis using Sterile Graded Talc in Patients with Secondary Intractable Pneumothorax: Protocol for a Multicentre, Open-label Single-arm Trial

A pneumothorax can be primary or secondary. A high proportion of patients with secondary spontaneous pneumothorax are the elderly who are in poor general condition due to their impaired cardiac and pulmonary functions as well as due to other complications. Therefore, it may be difficult for these patients to undergo surgical procedures; in addition, the elderly may be at high risk for postoperative pulmonary fistula due to severe adhesions and emphysema complications. These non-operative and high-risk cases may be treated with pleurodesis (a procedure that involves instillation of a chemical or irritant into the thoracic cavity through an injection), bronchoscopic bronchial embolisation, or other procedures. In Japan, no device is currently approved for performing pleurodesis, but an approval of one device is expected soon. This will be an open-label, single-arm multicentre study conducted among 30 patients with secondary intractable pneumothorax who are not indicated to undergo surgery. The primary endpoint will be presence or absence of chest tube removal. The secondary endpoints will be the disappearance/decrease of air leakage, grade of dyspnoea, and duration of drainage. This study will assess the safety and efficacy of sterile graded talc pleurodesis in patients with secondary intractable pneumothorax.This research is (partially) supported by the Project Promoting Clinical Trials for Development of New Drugs and Medical Devices (Japan Medical Association) and Early/Exploratory Clinical Trial Center Development Projects from the Japan Agency for Medical Research and Development (AMED). This study is registered in the Center for Clinical Trials, Japan Medical Association (JMA-IIA00272)

First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset

This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE‐024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a programmed death ligand 1 (PD‐L1) tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum‐based chemotherapy (four to six cycles). The primary end‐point was progression‐free survival; secondary end‐points included overall survival and safety. Of 305 patients randomized in KEYNOTE‐024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). Median progression‐free survival was 41.4 (95% confidence interval [CI], 4.2‐42.5) months with pembrolizumab and 4.1 (95% CI, 2.8‐8.3) months with chemotherapy (hazard ratio [HR], 0.27 [95% CI, 0.11‐0.65]; one‐sided, nominal P = .001). Median overall survival was not reached (NR) (95% CI, 22.9‒NR) and 21.5 (95% CI, 5.2‐35.0) months, respectively (HR, 0.39 [95% CI, 0.17‐0.91]; one‐sided, nominal P = .012). Treatment‐related adverse events occurred in 21/21 (100%) pembrolizumab‐treated and 18/19 (95%) chemotherapy‐treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3‐5 events. Immune‐mediated adverse events and infusion reactions occurred in 11 pembrolizumab‐treated patients (52%) and four chemotherapy‐treated patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3‐5 events. Consistent with results from KEYNOTE‐024 overall, first‐line pembrolizumab improved progression‐free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a PD‐L1 tumor proportion score of 50% or higher. The trial is registered with Clinicaltrials.gov: NCT02142738