Elevated blood favipiravir levels are inversely associated with ferritin levels and induce the elevation of uric acid levels in COVID-19 treatment: A retrospective single-center study.

INTRODUCTION: Measurement of blood Favipiravir (FPV) levels and accumulation of data in COVID-19 patients are critical for assessing FPV efficacy and safety. We performed a retrospective study based on measurements of blood levels of FPV and related factors in COVID-19 patients admitted to our hospital. Furthermore, we also investigated the association between blood FPV levels and uric acid level alterations before and after FPV administration. METHODS: We enrolled 27 COVID-19 patients who had received FPV treatment at Hokushin General Hospital from April 1 to December 31, 2020. Age, gender, COVID-19 severity, presence of comorbidities, and laboratory data for each subject were investigated to identify factors that correlate with blood FPV levels. Uric acid levels were measured before and after FPV administration and a difference between the levels (i.e., a change of uric acid level) was evaluated. RESULTS: When a significant univariate variable was input by the stepwise method and a combination of variables that maintained statistical superiority was searched, serum ferritin was the only factor that independently affected blood FPV level. Furthermore, in the high-FPV group (20 µg/mL or more), a significant increase in uric acid levels was observed after FPV administration. The increment value was significantly larger than that in the low-FPV group (less than 20 µg/mL). CONCLUSIONS: Ferritin level was an important independent factor inversely affecting blood FPV level. Furthermore, a high blood FPV level induced the elevation of uric acid levels in COVID-19 treatment.

The utility of ground-glass attenuation score for anticancer treatment-related acute exacerbation of interstitial lung disease among lung cancer patients with interstitial lung disease.

BACKGROUND: Acute exacerbation (AE) of interstitial lung disease (ILD) is a fatal adverse event in the treatment of lung cancer patients with ILD. The value of pre-treatment radiological findings obtained by high-resolution computed tomography for the detection of anticancer treatment-related AE of ILD has not been established. METHODS: Two medical record-based retrospective studies were performed. The chemotherapy cohort included 105 lung cancer patients with ILD who received chemotherapy at Tokyo Medical and Dental University between October 2008 and December 2017. The immune checkpoint inhibitor (ICI) cohort included 48 advanced non-small cell lung cancer patients with ILD treated with ICIs at nine institutions between January 2016 and September 2018. Variables were compared between AE-positive and -negative groups. Candidate variables were analyzed by multivariate logistic regression. A P value < 0.05 was considered statistically significant. RESULTS: Anticancer treatment-related AE of ILD occurred in 12 patients (11.4%) in the chemotherapy cohort and seven patients (14.5%) in the ICI cohort. In the multivariate logistic regression analysis, ground-glass attenuation (GGA) score was the only factor significantly associated with the development of AE of ILD in both cohorts (P = 0.037 and 0.01 in the chemotherapy and ICI cohorts, respectively). CONCLUSION: Evaluation of GGA may help predict anticancer treatment-related AE of ILD.

Rechallenge of afatinib for EGFR-mutated non-small cell lung cancer previously treated with osimertinib: a multicenter phase II trial protocol (REAL study).

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC) and contributed to the development of precision medicine. Osimertinib is a standard first-line (1L) treatment for EGFR-mutated NSCLC and has demonstrated superior survival benefits over previous-generation TKIs. However, resistance to osimertinib is nearly inevitable, and subsequent treatment strategies remain unmet medical needs in this setting. Afatinib, a second-generation EGFR-TKI, exhibits activity against certain uncommon EGFR mutation types in the 1L setting. There are a few case reports on the efficacy of afatinib against EGFR-dependent resistance after osimertinib treatment, although these have not been prospectively investigated. Methods: The present phase II, single-arm multicenter trial aims to verify the efficacy and safety of afatinib rechallenge after 1L osimertinib resistance. Patients (aged ≥20 years) with advanced or recurrent non-squamous NSCLC harboring drug-sensitive EGFR mutations (deletion of exon 19 or L858R) who were previously treated with 1L osimertinib and second-line chemotherapy other than TKIs are considered eligible. Undergoing next-generation sequence-based comprehensive genomic profiling is one of the key inclusion criteria. The primary endpoint is the objective response rate; the secondary endpoints are progression-free survival, overall survival, and tolerability. Thirty patients will be recruited in December 2023. Discussion: The results of this study may promote incorporating afatinib rechallenge into the treatment sequence after 1L osimertinib resistance, a setting in which concrete evidence has not been yet established. Registration: UMIN Clinical Trial Registry: UMIN000049225.

Impairment of Social-Related Quality of Life in COVID-19 Pneumonia Survivors: A Prospective Longitudinal Study.

The post-acute sequelae of SARS-CoV-2 (PASC) pose a threat to patients' health-related quality of life (HRQOL). Here, the impact of COVID-19 on HRQOL and the clinical factors associated with impaired HRQOL were examined. Discharged COVID-19 patients were assessed at 3 and 6 months after disease onset. The patients completed a medical examination and the SF-36 questionnaire at these two time points and underwent pulmonary function testing at 6 months after disease onset. All had undergone computed tomography (CT) imaging upon hospital admission. Of the 74 included patients, 38% reported respiratory symptoms at 3 months, and 26% reported respiratory symptoms at 6 months after disease onset. The aggregated SF-36 scores declined in the role/social component summary (RCS), a category related to social activity. Patients with lower RCS tended to have respiratory sequelae or a relatively lower forced vital capacity. The CT score that reflected the extent of COVID-19 pneumonia was inversely correlated with the RCS score (3 months, p = 0.0024; 6 months, p = 0.0464). A high CT score (≥10 points) predicted a low RCS score at 6 months (p = 0.013). This study highlights the impairment of RCS and its associations with respiratory sequelae. The study also emphasizes the importance of radiological findings in predicting long-term HRQOL outcomes after COVID-19.

Non-inferior clinical outcomes of immune checkpoint inhibitors in non-small cell lung cancer patients with interstitial lung disease.

OBJECTIVES: The efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) patients with pre-existing interstitial lung disease (ILD) is unclear. MATERIALS AND METHODS: Retrospective medical data from advanced or recurrent NSCLC patients who were treated with nivolumab or pembrolizumab at ten institutions in Japan between January 2016 and September 2018 were analyzed. Eligible patients were divided into two groups according to the presence of pre-existing ILD. RESULTS: A total of 461 NSCLC patients were enrolled, 412 without ILD (Non-ILD group) and 49 with ILD (ILD group). The response rate (RR) and disease control rate (DCR) of the ILD group were not inferior to those of the Non-ILD group [RR: 49.0 % (24/49) vs. 30.1 % (124/412), P < 0.01 and DCR: 69.4 % (34/49) vs. 51.2 % (211/412), P = 0.016, respectively]. Non-inferior outcomes were also observed with respect to progression-free survival (PFS) and overall survival (OS) (median PFS: 5.9 months vs. 3.5 months, P = 0.14 and median OS: 27.8 months vs. 25.2 months, P = 0.74 in the ILD and Non-ILD groups, respectively). Among immune-related adverse effects (irAEs), checkpoint inhibitor pneumonitis (CIP) was more frequently observed among NSCLC patients in the ILD group [30.6 % (15/49) vs. 9.5 % (39/412), P < 0.01]. The frequency of irAEs other than CIP and infusion reactions was not significantly different between the ILD group and the Non-ILD group. CONCLUSION: These results suggest that the clinical outcomes of ICIs are not significantly affected by pre-existing ILD despite the increased frequency of CIP. NSCLC patients with ILD are therefore probable candidates for ICIs.

[A case of primary pulmonary leiomyosarcoma showing rapid growth and fatal outcome].

An 80-year-old man was admitted to our hospital with a 4.0 x 2.0 cm shadow accompanied by calcification, found on chest CT scans on a health check. The shadow was located in the left lower lobe (S10), and was attached to the pleura. A transbronchial biopsy did not yield a definitive diagnosis. A percutaneous needle biopsy yielded a diagnosis of leiomyosarcoma. A general examination did not show any metastatic lesions in other areas. However, the tumor grew rapidly, with pleural effusion, and therefore he was treated only by palliative therapy. He died from respiratory failure 90 days after onset. The primary site of the tumor was determined to be intrapulmonary area by radiographic and autopsy findings. We report a rare primary pulmonary leiomyosarcoma showing rapid growth and fatal outcome.

Treatment of asthma in smokers: A questionnaire survey in Japanese clinical practice.

BACKGROUND: Cigarette smoking in patients with asthma leads to poor symptom control. As patients who are current smokers have been excluded from enrollment in many clinical trials on asthma, there are few reports on the treatment in current smokers with asthma. In this study, we aimed to assess how respiratory physicians manage asthma in current smokers in Japan. METHODS: Respiratory physicians in 16 Japanese hospitals answered a questionnaire on treatment for patients with asthma between December 2014 and February 2015. Medical records were reviewed for 1756 patients with asthma. RESULTS: The mean patient age was 61.1 years, and 62.9% of the patients were female. A total of 102 patients (5.8%) were current smokers, and 546 patients (31.1%) were former smokers. Long-acting muscarinic antagonists (LAMA) were prescribed more frequently for current smokers with asthma than for former smokers and never smokers with asthma (10.8% vs 4.6%, p = 0.01, 10.8% vs 3.8%, p < 0.01). In contrast, macrolides were prescribed more frequently for former smokers and never smokers with asthma than for current smokers with asthma (7.7% vs 1.0%, p = 0.01, 6.4% vs 1.0%, p = 0.03). Triple therapy, i.e., inhaled corticosteroids, long-acting beta agonists, and LAMA concomitantly, was prescribed for current smokers with asthma more frequently than for former smokers and never smokers with asthma (9.8% vs 4.0%, p = 0.01, 9.8% vs 3.3%, p < 0.01). CONCLUSIONS: According to this survey, current smokers with asthma received more intensive therapy, including LAMA, than did former smokers with asthma.

Plasma hepatocyte growth factor elevation may be associated with early metastatic disease in primary lung cancer patients.

PURPOSE: Hepatocyte growth factor (HGF), a ligand of the c-met proto-oncogene, exhibits activating effects on human lung cancer both in vitro and in vivo. However, few studies have reported the correlations between concentration changes of blood HGF and postsurgical prognosis. METHODS: We evaluated whether surgery-related blood HGF elevation has prognostic significance in patients with surgically resected non-small cell lung cancer. We examined blood HGF concentration, c-met expression, and postoperative prognosis of 25 cases of primary resected, non-small cell lung cancer. RESULTS: We divided the patients into 2 groups according to receiver operating characteristics curve analysis using 7.2 ng/mL as the cut-off value of blood HGF concentration. Survival curve analysis revealed that patients with a high level of HGF (over the cutoff value) exhibited a poor prognosis of metastatic disease, compared to those in the low-level group after curative surgery (log rank test, P = 0.020; Wilcoxon test, P = 0.016). CONCLUSION: Elevation of HGF in plasma may be an important prognostic factor for early metastatic disease in patients with primary lung cancer. Moreover, inhibition of HGF elevation may have therapeutic effects on early distant metastasis of lung cancer.