Application of the advanced lung cancer inflammation index for patients with coronavirus disease 2019 pneumonia: Combined risk prediction model with advanced lung cancer inflammation index, computed tomography and chest radiograph.

The purpose of the present study was to evaluate the feasibility of applying the advanced lung cancer inflammation index (ALI) in patients with coronavirus disease 2019 (COVID-19) and to establish a combined ALI and radiologic risk prediction model for disease exacerbation. The present study included patients diagnosed with COVID-19 infection in our single institution from March to October 2020. Patients without clinical information and/or chest computed tomography (CT) upon admission were excluded. A radiologist assessed the CT severity score and abnormality on chest radiograph. The combined ALI and radiologic risk prediction model was developed via random forest classification. Among 79 patients (age, 43±19 years; male/female, 45:34), 72 experienced improvement and seven patients experienced exacerbation after admission. Significant differences were observed between the improved and exacerbated groups in the ALI (median, 47.6 vs. 13.2; P=0.011), frequency of chest radiograph abnormality (24.7 vs. 83.3%; P<0.001), and chest CT score (CCTS; median, 1 vs. 9; P<0.001). For the accuracy of predicting exacerbation, the receiver-operating characteristic curve analysis demonstrated an area under the curve of 0.79 and 0.92 for the ALI and CCTS, respectively. The combined ALI and radiologic risk prediction model had a sensitivity of 1.00 and a specificity of 0.81. Overall, ALI alone and CCTS alone modestly predicted the exacerbation of COVID-19, and the combined ALI and radiologic risk prediction model exhibited decent sensitivity and specificity.

Comparison of semiquantitative chest CT scoring systems to estimate severity in coronavirus disease 2019 (COVID-19) pneumonia.

OBJECTIVES: To compare the clinical usefulness among three different semiquantitative computed tomography (CT) severity scoring systems for coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Two radiologists independently reviewed chest CT images in 108 patients to rate three CT scoring systems (total CT score [TSS], chest CT score [CCTS], and CT severity score [CTSS]). We made a minor modification to CTSS. Quantitative dense area ratio (QDAR: the ratio of lung involvement to lung parenchyma) was calculated using the U-net model. Clinical severity at admission was classified as severe (n = 14) or mild (n = 94). Interobserver agreement, interpretation time, and degree of correlation with clinical severity as well as QDAR were evaluated. RESULTS: Interobserver agreement was excellent (intraclass correlation coefficient: 0.952-0.970, p < 0.001). Mean interpretation time was significantly longer in CTSS (48.9-80.0 s) than in TSS (25.7-41.7 s, p < 0.001) and CCTS (27.7-39.5 s, p < 0.001). Area under the curve for differentiating clinical severity at admission was 0.855-0.842 in TSS, 0.853-0.850 in CCTS, and 0.853-0.836 in CTSS. All scoring systems correlated with QDAR in the order of CCTS (ρ = 0.443-0.448), TSS (ρ = 0.435-0.437), and CTSS (ρ = 0.415-0.426). CONCLUSIONS: All semiquantitative scoring systems demonstrated substantial diagnostic performance for clinical severity at admission with excellent interobserver agreement. Interpretation time was significantly shorter in TSS and CCTS than in CTSS. The correlation between the scoring system and QDAR was highest in CCTS, followed by TSS and CTSS. CCTS appeared to be the most appropriate CT scoring system for clinical practice. KEY POINTS: • Three semiquantitative scoring systems demonstrate substantial accuracy (area under the curve: 0.836-0.855) for diagnosing clinical severity at admission and (area under the curve: 0.786-0.802) for risk of developing critical illness. • Total CT score (TSS) and chest CT score (CCTS) were considered to be more appropriate in terms of clinical usefulness as compared with CT severity score (CTSS), given the shorter interpretation time in TSS and CCTS, and the lowest correlation with quantitative dense area ratio in CTSS. • CCTS is assumed to distinguish subtle from mild lung involvement better than TSS by adopting a 5% threshold in scoring the degree of severity.

Bilateral lung cancer showing various responses to immune checkpoint inhibitors: A case report.

BACKGROUND: Combination immune checkpoint inhibitor (ICI) therapy has become the mainstay in cancer treatment, and the various antitumor effects of ICIs are being observed. Synchronous multiple primary lung cancers (SMPLCs), which simultaneously involve tumors of different histologies, are often encountered in clinical settings. In standard lung cancer treatment, an anticancer drug, usually a platinum-based drug, is administered, and this first treatment provides some antitumor effect. Thus, the initial administration of platinum-based anticancer agent may mask the detection of SMPLCs. The following case represents different antitumor effects on two different primary lung lesions during treatment with ICIs. CASE PRESENTATION: A 72-year-old man was referred to our hospital for an abnormal chest shadow, and computed tomography showed masses in the left lower and right upper lungs. Transbronchial lung biopsy from the left lung tumor revealed an adenocarcinoma. Following the administration of pembrolizumab (200 mg/body over 3 weeks) as monotherapy, the tumor in the left lung rapidly reduced in size. However, the tumor in the right upper lung continued to grow. Finally, his disease was diagnosed as SMPLCs of adenocarcinoma and small cell lung cancer. CONCLUSION: Bilateral lung lesions considered to be intrapulmonary metastases have completely different responses to ICI treatment. It is necessary to consider a diagnosis of SMPLCs if lesions with different responses to antitumor therapy are observed.

Efficacy and safety of immune checkpoint inhibitor monotherapy in pretreated elderly patients with non-small cell lung cancer.

PURPOSE: Immune checkpoint inhibitors (ICIs) are an effective subsequent-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, it remains unclear whether the efficacy and safety of subsequent-line ICI monotherapy in elderly patients (aged ≥ 75 years) are similar to that in non-elderly patients. Therefore, we aimed to investigate the efficacy and safety of ICI monotherapy in pretreated elderly patients with NSCLC. METHODS: Between January 2016 and February 2018, 131 elderly patients with advanced NSCLC who received subsequent-line ICI monotherapy at 13 Japanese institutions were enrolled in this study. Baseline characteristics, the efficacy of ICI treatment, and adverse events were evaluated. RESULTS: Ninety-eight men and 33 women (median age 77 [range 75-87] years) were enrolled. Among those who received subsequent-line ICI monotherapy, the overall response, disease control rates, median progression-free survival (PFS), and overall survival (OS) were 27.4%, 61.8%, 4.5 months, and 16.0 months, respectively. Adverse events such as anorexia, fatigue, pneumonitis, and hypothyroidism were observed. There were two treatment-related deaths due to pneumonitis and thrombocytopenia. Subsequent-line ICI monotherapy in patients with good performance status (PS), receiving steroids for immune-related adverse events (irAEs), and exhibiting partial response (PR) was associated with improved PFS, as well as OS in patients with good PS and PR. CONCLUSIONS: Subsequent-line ICI monotherapy in elderly patients, with previously treated NSCLC, was effective, safe and showed outcomes equivalent to those in non-elderly patients. Immunotherapy provides a survival benefit for elderly patients, who exhibit its efficacy and a favorable general condition.

Efficacy and safety of first-line pembrolizumab monotherapy in elderly patients (aged ≥ 75 years) with non-small cell lung cancer.

PURPOSE: Pembrolizumab is an effective front-line treatment for advanced non-small cell lung cancer (NSCLC) in patients expressing high levels of programmed death-ligand 1 (PD-L1). However, it is unclear whether first-line pembrolizumab has similar efficacy among elderly (aged ≥ 75 years) and younger patients. This study aimed to investigate the safety and efficacy of front-line pembrolizumab monotherapy in older adults with NSCLC expressing high PD-L1. METHODS: A total of 128 patients with advanced NSCLC expressing high PD-L1, including 47 older adults, received first-line pembrolizumab monotherapy at ten institutions in Japan, between February 2017 and February 2018. Data related to patient characteristics, efficacy of pembrolizumab therapy, and the type and severity of adverse events were recorded. RESULTS: Overall, 47 patients [40 men and 7 women; median age 79 (range 75-88) years] were included in our analysis. In patients who received first-line pembrolizumab monotherapy, overall response, disease control rates, median progression-free survival (PFS), and median overall survival (OS) were 53.1%, 74.4%, 7.0 months, and not reached, respectively. Common adverse events included anorexia, fatigue, skin rash, and hypothyroidism. Two treatment-related deaths were noted, due to pneumonitis and infection. First-line pembrolizumab monotherapy was associated with improved PFS in patients with non-progressive disease (PD). In patients with non-PD and good performance status (PS), pembrolizumab monotherapy improved OS. CONCLUSIONS: Elderly patients with NSCLC expressing high PD-L1 tolerated front-line pembrolizumab monotherapy well. Their survival outcomes were equivalent to those of younger patients. In patients with non-PD, first-line pembrolizumab monotherapy may improve PFS; in conjunction with good PS, it additionally improves OS.

Nitrosation of Phenolic Substrates under Mildly Basic Conditions: Selective Preparation of p-Quinone Monooximes and Their Antiviral Activities.

Nitrosation of 3-methoxyphenol and 1-naphthol were examined under both acidic (NaNO(2)-EtCO(2)H-H(2)O) and basic (i-AmNO(2)-K(2)CO(3)-DMF) conditions. Acidic nitrosations afforded ortho-directed products, whereas para-directed nitrosations were observed under basic conditions to yield p-quinone monooximes. The basic para-directed nitrosation was further examined using 15 phenols, two naphthols, and four phenolic heterocyclics. A one-pot operation of the basic nitrosation followed by methylation with dimethyl sulfate gave the corresponding methyl ethers in high yield. Two p-quinone monooximes derived from 3-methoxyphenol and 8-hydroxyquinoline showed a moderate activity against HSV-1, and the latter oxime was also effective against HSV-2. On the other hand, p-quinone monooximes derived from methyl salicylate, 1-naphthol, 7-hydroxy-2-methylbenzo[b]furan, and 8-hydroxycoumarin showed the comparable activity to that of DDI against HIV-1.