Masahide Oki

BACKGROUND: Bronchoscopic limitations in reaching peripheral pulmonary lesions (PPLs) can compromise biopsy sensitivity, especially for small PPLs. Therefore, we developed the balloon dilatation for bronchoscope delivery (BDBD) technique to dilate bronchial pathways and facilitate bronchoscope advancement into the periphery. This study evaluated the diagnostic performance and safety profile of transbronchial biopsy using this technique. METHODS: This multicentre, single-arm, prospective study included patients with bronchus sign-positive PPLs measuring <20 mm. Bronchoscopy was performed using ultrathin or thin bronchoscopes under conscious sedation. When the bronchoscope could not advance further, the BDBD technique was used to approach closer to the target, followed by biopsies. The primary endpoint was the diagnostic sensitivity for malignancy in specimens obtained through the specified procedure, defined as bronchoscope advancement using balloon dilatation, direct biopsy site visualisation and absence of serious adverse events. RESULTS: Eighteen of 22 patients who underwent bronchoscopy with the BDBD technique were ultimately diagnosed with cancer. BDBD enabled bronchoscope advancement in all 18 cases without serious complications, allowed direct biopsy site visualisation in 17 and detected cancer in 14. Thus, the diagnostic sensitivity for malignancy was 77.8% (14/18). Beyond these cases, one patient who met all procedural criteria was diagnosed with cryptococcosis. Another patient was diagnosed with cancer without direct visualisation. On average, BDBD enabled bronchoscope advancement by 2.3 bifurcations. CONCLUSION: In this small observational study, BDBD appeared to be a promising technique for improving the diagnostic sensitivity of bronchoscopy for small PPLs. Further validation is necessary in large cohorts. TRIAL REGISTRATION NUMBER: jRCT2052220174.

INTRODUCTION: PD-L1 inhibitors combined etoposide-platinum (EP) are standard first-line treatments for extensive-stage small-cell lung cancer (ES-SCLC). However, their efficacy remains suboptimal. Irinotecan-cisplatin (IP) is optional regimen for ES-SCLC, and irinotecan has shown potential immunostimulatory activity. This study evaluated the efficacy and safety of IP plus durvalumab in untreated ES-SCLC. METHODS: , day 1) with durvalumab 1500 mg, followed by durvalumab 1500 mg every 4 weeks. Primary endpoint was the 12-month progression-free survival (PFS) rate, assessed by an independent central review (ICR). RESULTS: Between May 2021 and Nov 2022, 42 patients (median age, 66 years; 76.2 % were male; 31.0 % had PS 0) were enrolled. The 12-month PFS rate by ICR was 18.8 % (90 % CI, 9.3-30.8 %), with a median PFS of 5.7 months (95 % CI, 4.9-7.6 months). Median overall survival (OS) was 16.9 months (95 % CI, 11.8-NE), and the 12-month OS rate was 65.8 % (95 % CI, 49.1-78.1). Confirmed overall response rate (ORR) was 65.9 %, and disease control rate (DCR) was 85.4 %. Grade ≥3 adverse events (AEs) occurred in 73.8 %, including two grade 5 (2.4 %; pneumonitis and hepatitis). Pneumonitis occurred in 4.8 % (grade 1 and 5), while diarrhea of grade 3 or more occurred in 7.1 % patients. CONCLUSION: The REBORN study did not demonstrate the expected efficacy of IP plus durvalumab in untreated ES-SCLC, with its efficacy and safety generally comparable to those of EP plus durvalumab.

Immune checkpoint inhibitors (ICIs) have improved prognosis in non-small cell lung cancer (NSCLC). This prospective observational study aimed to validate the clinical impact of nutritional and immunological indices, including neutrophil-to-lymphocyte ratio (NLR), Glasgow prognostic score (GPS), prognostic nutritional index (PNI), controlling nutritional status (CONUT), and skeletal muscle area (SMA) in NSCLC patients treated with first-line ICIs. Three hundred and one patients with programmed cell death-ligand 1 (PD-L1) expression data were enrolled. SMA was measured using computed tomography images at the L3 level. Cut-off values were determined by our previous retrospective reports. The primary endpoint was progression-free survival (PFS). As a translational research, 15 myokines were evaluated from pre-treatment blood samples. The NLR, GPS, PNI, CONUT, and SMA were all significantly associated with PFS (p = .0128, p = .0016, p = .0046, p = .0485, and p = .0161, respectively). Multivariate analysis elucidated that age ≥75 years (p = .0256), male sex (p = .0227), combined chemotherapy (p = .0002), PD-L1 ≥50% (p = .0017), and SMA (p = .0354) were significant predictors of objective response. Multivariate analysis of PFS showed that performance status (p = .0104), PD-L1 (p <.0001), GPS (p = .0042), and SMA (p = .0367) were independent predictors. FSTL-1 was significantly lower in non-responders than in responders (p = .0212). In conclusion, the nutritional and immunological indices were validated to be significant predictors for the efficacy of ICIs. SMA was a predictor of both objective response and PFS, highlighting FSTL-1 as a potential biomarker for response to ICIs.

Idiopathic tracheal stenosis is an extremely rare disease that can constrict the airway, with no established therapeutic strategy. We herein present our experience with a patient with recurrent idiopathic tracheal stenosis treated with sequential endoscopic tracheoplasty using different modalities. A 41-year-old woman presented with dyspnea and wheezing 6 years ago, which gradually worsened over time. Chest computed tomography revealed tracheal stenosis caused by fold-like structures 15 mm below the glottis. Spirometry results indicate central airway stenosis. Bronchoscopy revealed significant tracheal stenosis due to a circumferentially protruding web-like structure. Pathological tissue biopsy revealed nonspecific inflammation and granulation. The patient was diagnosed with idiopathic tracheal stenosis in the absence of any obvious alternative causes. Argon plasma coagulation (APC) therapy was performed because of severe dyspnea and decreased peak flow. Her dyspnea and pulmonary function improved immediately after treatment. Follow-up bronchoscopy after 6 months revealed significant improvement in the stenosis; however, the lesion recurred 10 months after treatment. Therefore, tracheoplasty using a cryoprobe and balloon dilatation was performed as a second treatment, resulting in another successful improvement. Endoscopic tracheoplasty using APC or cryoprobe is effective for idiopathic tracheal stenosis, thereby enabling the selection of treatment strategies at each facility.