Early irAEs are associated with a better outcome after treatment with immunotherapy. We predicted responses to nivolumab by using early irAEs. Further research is needed to elucidate the mechanisms of these associations.

Serum periostin appears to be a useful biomarker for the development of airflow limitation in asthmatic patients on ICS.

Background: Small airways play important roles in the pathophysiology of asthma. However, relationships between small airway involvement and health status and dyspnea have not been investigated. Objectives: It was the aim of this study to assess the relationships between proximal and peripheral airway functions and health status, dyspnea and disease control in patients with asthma, using impulse oscillometry (IOS). Methods: We performed IOS, spirometry and assessment of health status (Asthma Quality of Life Questionnaire and St. George’s Respiratory Questionnaire), dyspnea (Baseline Dyspnea Index) and disease control (Asthma Control Questionnaire) in 65 asthmatics and evaluated their relationships. Results: Peripheral airway function as evaluated by IOS [R5–R20 (the fall in resistance from 5 to 20 Hz) and X5 (reactance at 5 Hz)], in addition to the proximal airway index (R20), significantly correlated with health status, dyspnea and disease control. Multiple regression analyses revealed that peripheral airway function significantly contributes to these, independently of the proximal airway index. In contrast, forced expiratory volume in 1 s did not significantly contribute to health status or dyspnea. Conclusions: IOS correlated better with clinical symptoms and asthma control than spirometry in patients with asthma. Peripheral and proximal airway functions as assessed separately by IOS independently contribute to health status, dyspnea and disease control, indicating that peripheral airways also represent an important therapeutic target.

HFA-BDP is an effective treatment of small airways in asthma. Prolonged treatment provides a progressive effect over time, which is associated with an attenuation of airway responsiveness.

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 < 0.001). In conclusion, the percentage of PD-L1-positive tumor cells significantly decreased after CCRT. Alteration of PD-L1 expression after neoadjuvant CCRT was associated with prognosis in patients with LA-NSCLC. These data should be considered when developing the optimal approach of integrating PD-1 axis inhibitors with CCRT.

Use of plasma DNA to detect mutations has spread widely as a form of liquid biopsy. EGFR T790M has been observed in half of lung cancer patients who have acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI). Effectiveness of monitoring T790M via plasma DNA during treatment with EGFR-TKI has not been established as an alternative to re-biopsy. This was a prospective multicenter observational study involving non-small cell lung cancer patients carrying EGFR L858R or exon 19 deletions, treated with EGFR-TKI. The primary objective was to determine whether T790M could be detected using plasma DNA in patients with progressive disease (PD). T790M was examined using the mutation-biased PCR and quenching probe (MBP-QP) method, a sensitive, fully-automated system developed in our laboratory. Eighty-nine non-small cell lung cancer patients were enrolled from seven hospitals in Japan. Sequential examinations revealed T790M in plasma DNA among 40% of patients who developed PD. Activating mutations, such as L858R and exon 19 deletions, were detected in 40% of patients using plasma DNA, and either T790M or activating mutations were observed in 62%. Dividing into four periods (before PD, at PD, at discontinuation of EGFR-TKI and subsequently), T790M was detected in 10, 19, 24 and 27% of patients, respectively. Smokers, males, patients having exon 19 deletions and patients who developed new lesions evidenced significantly frequent presence of T790M in plasma DNA. Monitoring T790M with plasma DNA using MBP-QP reflects the clinical course of lung cancer patients treated with EGFR-TKI. Detection of T790M with plasma DNA was correlated with EGFR mutation type, exon 19 deletions and tumor progression. Re-biopsy could be performed only in 14% of PD cases, suggesting difficulty in obtaining re-biopsy specimens in practice. Monitoring T790M with plasma DNA reflects the clinical course, and is potentially useful in designing strategies for subsequent treatment.C ompanion diagnostics has seen growing importance, especially for molecular targeted therapy such as EGFR tyrosine kinase inhibitors (EGFR-TKI) in lung cancer. Recently, a second generation EGFR-TKI, afatinib, evidenced a potent anti-cancer effect against lung cancer cells harboring T790M,(1) but the anti-cancer effect in a phase 2b ⁄ 3 randomized trial was unsatisfactory considering the results of preclinical studies.(2) Because examination of biomarkers related to acquired resistance to EGFR-TKI was not performed in that trial, it is speculated that the patients included those with cancers possessing various mechanisms of acquired resistance to EGFR-TKI. Recently, third generation EGFR-TKI, such as AZD9291 and CO-1686, have shown potent anti-cancer effects in T790M positive non-small cell lung cancer patients. (3,4) Considering this evidence, examination of biomarkers is indispensable for accurate assessment of anti-cancer effects, and timely monitoring of genetic alterations is necessary for determining appropriate treatment.The use of circulating free DNA to detec...

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