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.

Post-Progression Survival Influences Overall Survival among Patients with Advanced Non-Small Cell Lung Cancer Undergoing First-Line Pembrolizumab Monotherapy.

BACKGROUND: Among patients with non-small cell lung cancer (NSCLC), the impact of first-line treatment on overall survival (OS) may be influenced by subsequent therapies. Thus, using patient-level data, we assessed the relationships of progression-free survival (PFS) and post-progression survival (PPS) with OS among patients with high-programmed death-ligand 1 (PD-L1) expression undergoing first-line pembrolizumab monotherapy for NSCLC. METHODS: We reviewed data from 133 patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC at 6 Japanese centers between February 2017 and December 2018. The correlations of PFS and PPS with OS were evaluated at the patient level. RESULTS: Linear regression analyses and Spearman's rank correlation coefficient revealed that PPS was strongly correlated with OS (r = 0.76, p < 0.05, R2 = 0.65), while PFS was only moderately correlated with OS (r = 0.71, p < 0.05, and R2 = 0.4). Furthermore, PPS was significantly associated with performance status at the end of pembrolizumab monotherapy, as well as the use of platinum-based combination chemotherapy after pembrolizumab monotherapy (both p < 0.05). CONCLUSIONS: Among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC, PPS was more strongly correlated with OS, relative to the relationship between PFS and OS. Therefore, subsequent treatment appears to significantly influence OS in patients with disease progression following first-line pembrolizumab monotherapy.

A phase I/II trial of pemetrexed plus radiotherapy in elderly patients with locally advanced non-small cell lung cancer.

Background Radiotherapy (RT) is an effective treatment for elderly patients with locally advanced non-small-cell lung cancer (NSCLC); however, no clinical trials have investigated combination RT with pemetrexed (PEM) in chemotherapy-naive patients ≥71 years old. We conducted a phase I/II study to evaluate the appropriate PEM dose, efficacy, and safety of PEM plus RT in elderly patients. Methods Patients ≥71 years with performance status (PS) scores of 0-2 who had pathologically confirmed stage IIIA/IIIB NSCLC received PEM (500 mg/m2 on day 1 of a 28-day cycle, 4 courses) and RT (a single 2 Gy daily fraction on 5 consecutive days weekly from day 1; 60 Gy total). The primary endpoint was the objective response rate (ORR); the secondary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results Forty-one patients with a median age of 79 years were enrolled; 31 were men. Eighteen patients had squamous cell carcinoma, 27 had stage IIIA disease, and 38 had PS scores 0-1. The ORR was 80.5%, while the median OS and PFS rates were 24.9 and 6.9 months, respectively. Two treatment-related deaths occurred owing to RT-related pneumonitis and severe infection, respectively. Common hematological AEs were leucopenia and neutropenia; common non-hematological AEs were anorexia and constipation. Three patients developed PEM-induced interstitial lung disease; however, most AEs were RT-related. Conclusions Combination PEM and RT shows promising efficacy but relatively severe RT-related toxicities. Therefore, this treatment should be prescribed to elderly patients with caution. Trial registration UMIN 000005036 .

[An Elderly Patient with Non-Small Cell Lung Cancer Who Responded to Salvage S-1 Monotherapy after Gefitinib Therapy].

S-1 is one of the effective chemotherapy regimens for treating non-small cell lung cancer. We report of an elderly patient with non-small cell lung cancer who responded to S-1 monotherapy following gefitinib therapy. An 83-year-old woman was diagnosed with advanced adenocarcinoma of the lungs (cT3N3M1a, Stage IV). Considering her age, monotherapy with vinorelbine was administered as first-line chemotherapy. Despite the completion of four courses, she was diagnosed with progressive disease. Thereafter, after considering her status as a non-smoking woman, gefitinib was introduced as second-line chemotherapy, which resulted in significant tumor size reduction.Tumor regrowth was identified 16 months later, and gefitinib was switched to erlotinib, but the tumor kept increasing in size.S -1 monotherapy was introduced as fourth-line chemotherapy, and the tumor began to decrease in size again. A partial response was obtained after 10 months, without serious adverse effects. Gefitinib following S-1 monotherapy resulted in long-term tumor size control for a total of 27 months in an elderly patient with advanced non-small cell lung cancer.S -1 monotherapy might be one of the options for salvage therapy after gefitinib treatment becomes ineffective.

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.

Pretreatment Glasgow prognostic score predicts survival among patients with high PD-L1 expression administered first-line pembrolizumab monotherapy for non-small cell lung cancer.

BACKGROUND: There are no established biomarkers for predicting the efficacy of first-line pembrolizumab monotherapy in patients with high programmed death-ligand 1 (PD-L1) expression. In this study, we investigated whether the Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) can be used to evaluate the effect of first-line pembrolizumab monotherapy in patients with advanced non-small cell lung cancer (NSCLC) who express high levels of PD-L1. METHODS: We reviewed data from 142 patients with high PD-L1 expression who underwent first-line pembrolizumab monotherapy for NSCLC at six Japanese institutions between February 2017 and June 2019 and assessed the prognostic value of the GPS, NLR, and BMI. The Kaplan-Meier method and Cox proportional hazard models were used to examine differences in progression-free survival (PFS) and overall survival (OS). The GPS, NLR, and BMI were calculated using C-reactive protein and albumin concentrations, neutrophil and lymphocyte counts, and body weight and height, respectively. RESULTS: The GPS independently predicted the first-line pembrolizumab monotherapy efficacy, as a good GPS (GPS 0-1) was associated with a significantly better PFS and OS compared to a poor GPS (GPS 2) (PFS: 11.8 vs. 2.9 months, p < 0.0001; OS: not reached vs. 8.3 months, p < 0.0001). Furthermore, BMI independently predicted efficacy, as patients with high BMI (BMI ≥21.4) exhibited significantly better OS compared to those with low BMI (BMI <21.4) (OS: not reached vs. 14.1 months, p = 0.006). CONCLUSIONS: Among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC, the GPS is significantly correlated with both PFS and OS, and BMI with OS, indicating that they could be used to predict treatment outcome in these patients. To the best of our knowledge, this is the first study to assess the relationship among the GPS, NLR, and BMI and survival among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC.

Retrospective Prognostic Study of Death at Home or Hospice Versus at a Hospital Among Patients With Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Patients with advanced non-small cell lung cancer greatly care about where they will die. Most people in Japan preferred their location of death as their homes. But only 8.2% of patients with cancer spend their last days at home with palliative care in Japan. Many patients with cancer are still going to spend their last days at a hospital (81.7%). OBJECTIVE: We examined the survival times of such patients according to their place of death; that is, whether they died at home, at a hospice, or at a hospital, and investigated patient characteristics. RESULTS: Among the 313 patients recruited, 214 were analyzed in this study: 90, 49, and 75 received hospital-based, home-based, and hospice-based palliative care, respectively. The patients who died at a hospice exhibited significantly longer survival than those who died at hospital (estimated median survival time, 420 days [95% confidence interval [CI]: 325-612 days] versus 252 days [95% CI: 201-316 days]; P < .0001). The characteristics of patients did not differ significantly according to place of death. CONCLUSIONS: Patients who died at a hospice or at home exhibited significantly longer survival than those who died at a hospital for advanced non-small cell lung cancer.

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.

Development of pyogenic granuloma with strong vascular endothelial growth factor receptor-2 expression during ramucirumab treatment.

The angiogenesis inhibitor ramucirumab (IMC-1121B) is a fully humanised IgG1 monoclonal antibody targeting the extracellular domain of vascular endothelial growth factor receptor 2. Ramucirumab has been approved as a second-line treatment for lung cancer. Pyogenic granuloma is an acquired, benign vascular tumour of the skin or mucous membrane. We encountered a patient with pyogenic granuloma who was treated with ramucirumab. The patient was a 48-year-old Japanese woman with advanced lung cancer who had been heavily pretreated using several lines of chemotherapy. Ramucirumab was administered as the fifth-line treatment with docetaxel. After 10 days, a painless rice-coloured or pink papule appeared on her finger. One month later, it increased in size to 20 mm. We examined the pathological condition by immunostaining using the resected specimen diagnosed as pyogenic granuloma. Paradoxically, this vascular tumour arose during the administration of an angiogenesis inhibitor.

Influence of oral care on fractional exhaled nitric oxide.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is an indicator of bronchial inflammation in asthma patients. However, nitric oxide is also produced in the oral cavity, with production depending on the local anaerobic flora and intraoral acidity. OBJECTIVE: To evaluate the influence of oral care on measurement of FeNO, to investigate the influence of sleep when the oral environment changes dramatically, and to assess the impact of oral care on FeNO in the real clinical setting. METHODS: FeNO was measured before and after oral care in 14 subjects on awakening and at bedtime on 2 consecutive days to investigate variation of nitric oxide derived from the oral cavity. It was also measured before and after oral care in 62 outpatients with asthma to assess the clinical relevance of oral cavity nitric oxide. RESULTS: On both days, FeNO was significantly decreased by oral care on awakening (day 1: decrease = 10.6 ± 12.4 ppb, p = 0.0020; day 2: decrease = 11.6 ± 23.7 ppb, p = 0.0009), and the decrease was larger than at bedtime. In addition, FeNO was significantly reduced by oral care in asthma outpatients (decrease = 1.73 ± 0.95 ppb, p = 0.0090), and older age was significantly correlated with the decrease (p = 0.0261). CONCLUSION: Oral care resulted in a decrease of FeNO, especially on awakening. While nitric oxide derived from the oral cavity generally has a limited impact in outpatients with asthma, its influence on measurement of FeNO may need to be considered, especially in elderly patients.

A new method for enhanced expectoration of sputum by vibratory stimulation of the cervical trachea.

BACKGROUND: Expectoration of sputum can be difficult for patients with respiratory conditions such as chronic obstructive pulmonary disease, chronic bronchitis, or bronchiectasis because of the effects of decreased pulmonary function, respiratory muscle fatigue, altered sputum properties, and impaired ciliary function. We developed a new method for the vibratory stimulation of the cervical trachea and this study aimed to compare it with the Acapella (a current oscillation device) method. METHODS: Patients with chronic productive cough and difficulty with expectoration were recruited for the study. The tracheal vibration and Acapella methods were applied for 4 weeks each, according to a crossover design with an intervening 4-week washout period. To perform the tracheal vibration method, an electronic artificial larynx (Yourtone®) was applied to the cervical trachea for up to 5minutes. Patient preference for the two devices was determined from the performance scores recorded for each device and by using a visual analogue scale. RESULTS: Twelve patients were recruited in the study. According to the performance scores assigned by the subjects, the tracheal vibration method was effective in 9 patients, while the Acapella method was effective in 10 patients. Both methods were effective in 8 patients, among whom the tracheal vibration method was more effective in 5 patients. Both methods were found to be ineffective in 1 patient. CONCLUSIONS: The tracheal vibration method may be effective at removing central airway sputum and does not require repeated forced expiratory effort, which can otherwise cause exhaustion in patients with decreased lung function. Further investigation is required to confirm its use as a new oscillation technique.

Orotate phosphoribosyltransferase is overexpressed in malignant pleural mesothelioma: Dramatically responds one case in high OPRT expression.

OBJECTIVE: Malignant pleural mesothelioma (MPM) is a rare and aggressive, treatment-resistant cancer. Pemetrexed, an inhibitor of thymidylate synthase (TS), is used worldwide for MPM as a first-line chemotherapy regimen. However, there is little consensus for a second-line chemotherapy. S-1, a highly effective dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidine, mainly acts via a TS inhibitory mechanism similar to pemetrexed. Orotate phosphoribosyltransferase (OPRT) is a key enzyme related to the first step activation of 5-fluorouracil (5-FU) for inhibiting RNA synthesis. We investigated 5-FU related-metabolism proteins, especially focusing on OPRT expression, in MPM Methods and Patients: Fifteen MPM patients who were diagnosed between July 2004 and December 2013 were enrolled. We examined the protein levels of 5-FU metabolism-related enzymes (TS, DPD, OPRT, and thymidine phosphorylase [TP]) in 14 cases RESULTS: High TS, DPD, OPRT, and TP expressions were seen in 28.6%, 71.4%, 85.7%, and 35.7% of patients, respectively. We found that OPRT expression was extremely high in MPM tissue. We experienced one remarkable case of highly effective S-1 combined therapy for pemetrexed refractory MPM. This case also showed high OPRT protein expression Conclusion: The present study suggests that OPRT expression is high in MPM tumors. Although pemetrexed is mainly used for MPM chemotherapy as a TS inhibitor, S-1 has potential as an anticancer drug not only as a TS inhibitor but also inhibiting RNA synthesis through the OPRT pathway. This is the first report investigating OPRT protein expressions in MPM.

Pseudomesotheliomatous carcinoma due to pleural metastasis from renal pelvic cancer.

A 78-year-old man was referred to our department with a one-week history of dyspnea and coughing. A chest X-ray showed massive left pleural effusion. Computed tomography revealed diffuse irregular thickening of the left pleura similar to malignant mesothelioma and multiple nodules in both lungs. The patient died of respiratory failure nine days after hospitalization. An autopsy revealed metastasis to the pleura and lungs from urothelial carcinoma of the left kidney.

Successful removal of a distally located foreign body using a guide sheath.

This report presents the case of successful removal of a distally located foreign body using a guide sheath (GS). A 78-year-old man was brought for x-ray examination after a dental treatment at a local clinic. A dental instrument, a diamond bur, was missing after the treatment. The chest x-ray revealed a needle-like instrument located in the peripheral right middle lobe. The distally located foreign body was removed with a flexible bronchoscope using a curette and a biopsy forceps placed through a GS. This is the first report of use of a GS to remove a foreign body.

Multiple tuberculous nodules with metachronous changes: a case report.

BACKGROUND: Spontaneous regression of lesions occurs in non-infectious benign diseases, such as sarcoidosis, as well as in infectious diseases, such as tuberculosis. Lung cancer and malignant lymphoma, on the other hand, rarely follow a similar course. We report a rare case of lung tuberculosis that presented with multiple nodules with metachronous changes in size. CASE PRESENTATION: We describe the case of a 50-year-old immunocompetent Japanese man with pulmonary tuberculosis in the form of multifocal nodules. He came to our hospital because of a chest X-ray abnormality. During the course of observation, some nodules reduced while others enlarged in size. Two years after the first visit, fever and pleural effusion appeared. The sputum examination turned out to be positive for tuberculosis. A course of anti-tubercular agents resolved the pleural effusion and multifocal nodules. CONCLUSION: Differences in the manner of granuloma formation suggest that the local immune response can be different even in the same lung field.