Genomic evolutional analysis of surgical resected specimen to assess osimertinib as a first-line therapy in two patients with lung cancer harboring EGFR mutation: Case series.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is crucial for patients with lung cancer harboring EGFR mutations. However, almost all patients experience disease progression, regardless of their response to the targeted therapy, necessitating the development of additional treatment options. Two patients with lung cancer harboring EGFR-L858R mutations in exon 21 were treated by surgical resection during successful osimertinib treatment. Because the pathological diagnosis was suspected to be pleural metastasis, osimertinib treatment was continued until disease progression. We analyzed the evolution of genomic alterations and the levels of AXL using tumor specimens obtained by repeated biopsies during the course of treatment: initial diagnosis, operation, and disease progression. Genetic alterations detected at the three time points were dramatically changed and showed reductions in numbers, while EGFR-L858R mutations were detected in all samples tested in both patients. Immunohistochemical expression of AXL remained positive from the beginning of analysis to disease progression. Clonal evolution under oncogenesis is related to gradual accumulation of genomic alterations during tumor growth. However, our case series revealed that volume reduction procedures may cause this phenomenon. Therefore, identification of intrinsic drug-resistant cells in tumors may be as important as detection of acquired genetic alterations.

Patients with idiopathic pulmonary fibrosis and refractory cough have traction bronchiectasis and distorted airway architecture: a retrospective case review study.

Cough is a common and important sign/symptom in patients with idiopathic pulmonary fibrosis (IPF). However, there have been few reports focusing on cough, and the exact mechanisms for cough in patients with IPF have remained unclear. The objective of this study was to investigate the clinical features of IPF patients with refractory cough and to clarify mechanisms for cough in these patients. We retrospectively reviewed the files of patients with the diagnosis of IPF at Kanazawa University Hospital and compared the clinical features of IPF patients with refractory cough with the clinical features of IPF patients without refractory cough. Among a total of 23 patients with IPF, 10 patients (43.5%) had chronic cough. Of the ten patients, seven patients had concomitant conditions that could lead to cough. Of these seven patients, the cough of four patients was resolved after treatment of their concomitant condition. Finally, among the 23 patients there were 6 (26.1%) with refractory cough associated with IPF. Significant differences were seen between the following clinical features of IPF patients with or without refractory cough, respectively, as follows: lower body mass index (BMI; 18.8±2.5 vs. 22.8±2.5 kg/m2, P<0.01), lower forced vital capacity (FVC; 77.5%±30.4% predicted vs. 99.9%±0.53% predicted, P=0.046), and presence of traction bronchiectasis and distorted airway architecture on high-resolution computed tomography (HRCT; 83.3% vs. 11.8%, P<0.01). The difference between the proportions of patients with or without refractory cough with capsaicin cough sensitivity was not significant. Mechanical stress on the airways due to traction bronchiectasis and distorted airway architecture is a possible mechanism for cough in IPF patients.

Unexpected Diffuse Alveolar Hemorrhage After Bronchoscopy.

CASE PRESENTATION: A 71-year-old woman sought treatment for a nonproductive cough. The patient had experienced no episodes of hemoptysis or shortness of breath. Her illness history included lumbago and dry mouth. The patient did not smoke and had no significant family medical history or medication use. She had no allergies to any food or drugs. Blood test results, including a CBC count, biochemical examination, and coagulation, were unremarkable. Autoantibody screening revealed positive antinuclear antibody findings with a titer of speckled and nucleolar, and anti-Ro/SSA antibodies were elevated at 240 U/mL (normal range, < 7.0 U/mL). Chest CT scan imaging showed a slight infiltrative shadow of the bilateral lower lobes. Because the patient was suspected to have interstitial pneumonia resulting from Sjögren disease, we decided to perform fiber optic bronchoscopy with BAL for evaluation of interstitial lung disease.

Long-Term Survival of Patients With Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitor Monotherapy in Real-World Settings.

BACKGROUND: Immune checkpoint inhibitor (ICI) monotherapy is more effective than cytotoxic chemotherapy in improving overall survival (OS) among patients with advanced-stage non-small cell lung cancer (NSCLC). Recently, chemotherapy combined with ICI has been found to yield good outcomes. However, ICI monotherapy is still considered an important treatment option. Data on long-term progression-free survival (PFS) and OS in real-world settings are limited. PATIENTS AND METHODS: This was a multicenter retrospective observational study. A total of 435 consecutive patients histologically diagnosed with advanced, metastatic, or recurrent NSCLC treated with ICI monotherapy were enrolled in this study from December 2015 to December 2018. Clinical data were collected from electronic medical records and pharmacy databases. RESULTS: The PFS and OS of the patients were 3.4 and 13.0 months, respectively. The objective response and disease control rates were 22.8% and 54.9%, respectively, and the 4-year survival rate was 17.9%. Multivariate analyses revealed that elder patients (>70 years), good Eastern Cooperative Oncology Group Performance Status (ECOG PS) score, programmed death-ligand 1 tumor proportion score (PD-L1 TPS) of ≥ 50%, absence of bone metastasis, and presence of immune-related skin toxicity, which is an immune-related adverse event, were correlated with good PFS. Moreover, good ECOG PS score, PD-L1 TPS of ≥ 50%, absence of bone metastasis, and presence of skin toxicity were correlated with good OS. CONCLUSIONS: The 4-year survival rate was 17.9%. Good ECOG PS score, PD-L1 TPS of ≥ 50%, absence of bone metastasis, and presence of skin toxicity were correlated with good PFS and OS.

Suitability of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration versus Paired Transbronchial Biopsy Specimens for Evaluating Programmed Death Ligand-1 Expression in Stage III and IV Lung Cancer: A Comparative Retrospective Study.

Objectives: Cancer cells usually escape tumor-reactive T-cell responses using immune checkpoint proteins, such as programmed death protein-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1). These proteins can be blocked by immune checkpoint inhibitors (ICIs); the decision on ICI-based first-line treatment for advanced lung cancers depends on the PD-L1 levels in tumor specimens. Determining the PD-L1 expression conventionally requires histological specimens from resected tumors and core biopsy specimens. Non-small cell lung cancer (NSCLC) is usually diagnosed at stage III or IV; therefore, only small biopsy specimens, such as those obtained via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are available. However, the suitability of EBUS-TBNA specimens determining the PD-L1 expression levels in advanced lung cancers remains unclear. Materials and Methods: Here, we investigated the concordance rate of PD-L1 expression between EBUS-TBNA and matched transbronchial biopsy (TBB) specimens. Using the 22C3 anti-PD-L1 antibody (immunohistochemistry), we determined the PD-L1 expression levels in paired specimens obtained from 69 patients (50 with advanced NSCLC and 19 with small cell lung cancer [SCLC]), as well as the efficacy of ICIs in these patients. Results: The concordance rate of PD-L1 expression between the EBUS-TBNA and TBB specimens was 78.3%. The κ values referent to the PD-L1-positive expression rate between EBUS-TBNA and TBB specimens were 0.707 and 0.676 at cutoff limits of ≥1% and ≥50%, respectively. Among the 19 SCLC patients, 16 (84.2%) exhibited no PD-L1 expression in both EBUS-TBNA and TBB specimens. Notably, the progression-free survival of patients with ≥50% PD-L1 expression in the paired specimens who received ICI treatment was 8.3 months. Conclusion: Collectively, our results validate the use of EBUS-TBNA specimens for the determination of the PD-L1 expression levels in the context of NSCLC and SCLC.

Real-World Evidence of Safety and Efficacy of Carboplatin plus Nanoparticle Albumin-Bound Paclitaxel in Patients with Advanced Non-Small-Cell Lung Cancer and Preexisting Interstitial Lung Disease: A Retrospective Study.

Background: Standard chemotherapy for advanced non-small-cell lung cancer (NSCLC) with preexisting interstitial lung disease (ILD) has not yet been established. Although a combination of carboplatin and paclitaxel is most frequently used for patients with advanced NSCLC and ILD, the safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) are yet to be elucidated. Objectives: This study aimed to evaluate the safety and efficacy of carboplatin plus nab-paclitaxel for advanced NSCLC with ILD. Methods: This retrospective study included nine patients with advanced NSCLC and ILD who received carboplatin plus nab-paclitaxel as first-line chemotherapy at the National Hospital Organization Kanazawa Medical Center between April 2013 and December 2017. The ILD-GAP index was used to evaluate mortality risk of baseline ILD. Results: A usual interstitial pneumonia (UIP) pattern of ILD was observed in five (55.6%) patients on their baseline high-resolution computed tomography (HRCT) scans. The median ILD-GAP index was 4 (range, 1-5), and six (66.7%) patients had ILD-GAP index ≥4. We observed no ILD exacerbations or chemotherapy-related deaths. The overall response and disease control rates were 77.8% (95% CI, 40.0-97.2) and 88.9% (95% CI, 51.8-97.2), respectively. The median progression-free survival and overall survival were 5.8 months (95% CI, 2.1-7.7) and 8.0 months (95% CI, 2.6-16.8), respectively. Conclusions: Carboplatin plus nab-paclitaxel showed favorable safety and efficacy in patients who had advanced NSCLC and ILD with a high risk of mortality. Prospective studies are required to further confirm these results.

The prevalence and clinical features of asthma-COPD overlap (ACO) definitively diagnosed according to the Japanese Respiratory Society Guidelines for the Management of ACO 2018.

Background Asthma-COPD overlap (ACO) is a disease that shares clinical features of both asthma and COPD. The purpose of this study is to investigate the prevalence and clinical features of ACO. Methods We retrospectively reviewed data for 170 patients with persistent airflow limitation and diagnosed them according to "The Japanese Respiratory Society Guidelines for the Management of ACO 2018". Results Of the 170 patients, 111 were diagnosed as follows : COPD (74 patients, 66.6%), ACO (34 patients, 30.6%), and asthma (3 patients, 2.8%). There was no significant difference in clinical features between ACO and COPD patients. The following pulmonary function tests were significantly lower in ACO than in COPD patients : forced expiratory volume in 1 second/forced vital capacity, peak expiratory flow, maximal mid-expiratory flow, and the maximum expiratory flow at 50%and75%. The following respiratory impedance parameters were significantly higher in ACO than in COPD patients : respiratory resistance (Rrs) at 5 Hz (R5), Rrsat 20 Hz (R20), R5-R20, and low-frequency reactance area. Conclusions About 30% of patients with persistent airflow limitation were diagnosed with ACO. ACO patients had lower lung function and higher respiratory impedance compared with COPD patients. J. Med. Invest. 66 : 157-164, February, 2019.

IgG4-Related Pleuritis With No Other Organ Involvement.

A 65-year-old man was admitted for productive cough and dyspnea. Bilateral pleural effusions were observed on chest X-ray. Although the bilateral pleural effusions were exudative with an increased number of lymphocytes, bacterial culture and polymerase chain reaction analysis for Mycobacterium tuberculosis were negative. Immunological examinations showed high levels of immunoglobulin G4 (IgG4) in both serum and pleural effusion fluid. Pathologic evaluation of a left pleural biopsy specimen using hematoxylin and eosin staining and immunohistochemical staining showed fibrosis-associated lymphoplasmacytic infiltration, 50 IgG4-positive plasma cells per high-power field, and an IgG4/IgG ratio of 40%. Thus, a diagnosis of IgG4-related pleuritis without other systemic manifestations was established. The bilateral pleural effusion improved following corticosteroid therapy. This is a rare case of IgG4-related pleuritis with no other organ involvement.