Background: Osimertinib monotherapy is currently the standard of care as a first-line treatment for patients harboring epidermal growth factor receptor (EGFR) mutations; however, some EGFR-mutated non-small cell lung cancer (NSCLC) patients exhibit primary resistance and an insufficient response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Elevated programmed death-ligand 1 (PD-L1) expression in tumors was reported as a negative predictive factor for outcomes of first-or second-generation EGFR-TKIs.Methods: We prospectively assessed advanced NSCLC patients with EGFR mutations who were treated with osimertinib at 14 institutions in Japan between September 2019 and December 2020. Relationships between outcomes of osimertinib monotherapy and patients' characteristics were reviewed.Results: Seventy-one patients who underwent the tumor PD-L1 test were enrolled. Multivariate analysis identified tumor PD-L1 expression as an independent predictor for progression-free survival (PFS) with osimertinib treatment (P=0.

Purpose To investigate CT patterns of COVID-19 pneumonia associated with respiratory failure (RF) focused on the distribution of lesions. Materials and methods Eighty-five patients with COVID-19 pneumonia were reviewed. CT findings were classified as follows: Type A; patchy ground glass attenuation (GGA) with/without air-space consolidation, Type B; non-segmental GGA with/without air-space consolidation in both the central and peripheral lung portions especially with subpleural spare, and Type C; non-segmental GGA with/without air-space consolidation predominantly distributed in the peripheral lung portion without subpleural spare. We analyzed CT patterns and clinical factors associated with RF, including age categories. Results The number of patients with Type A, B and C was 31 (37%), 24 (28%) and 30 (35%), respectively. Type C and hypertension were independently associated with RF. On comparing between Types B and C, the frequency of traction bronchiectasis was higher in Type C than in Type B ( P < 0.001). The ratio of Type C in patients ≥ 65 years old (66%) was higher than in patients < 40 years old ( P < 0.001) and 40–49 years old ( P = 0.001). Conclusion The Type C, increasing with age, was associated with RF. Traction bronchiectasis in the lesion was more frequent in Type C than in Type B. Secondary abstract A lesion adjacent to the pleura and hypertension is associated with respiratory failure in patients with COVID-19. The frequency of a lesion adjacent to the pleura increased with age. The distribution of lesions is a useful parameter to predict respiratory failure.

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BackgroundHerpes simplex virus (HSV) has various presentations, depending on the patient’s immune status, age, and the route of transmission. In adults, HSV type 1 is found predominantly in the oral area, and HSV type 2 (HSV-2) is commonly found in the genital area. HSV-2 infection without genital lesions is uncommon. Herein we report a unique case of pharyngotonsillitis as an initial manifestation of disseminated HSV-2 infection without genital involvement.Case presentationA 46-year-old male was admitted to our hospital with a 1-week history of fever and sore throat. His past medical history included hypereosinophilic syndrome diagnosed at age 45 years. Physical examination revealed throat congestion, bilaterally enlarged tonsils with exudates, tender cervical lymphadenopathy in the left posterior triangle, and mild epigastric tenderness. The laboratory data demonstrated bicytopenia, elevated liver enzyme levels, and hyperferritinemia. A bone marrow smear showed hypocellular marrow with histiocytes and hemophagocytosis. The diagnosis of HLH was confirmed, and the patient was treated with methylprednisolone pulse therapy on days 1–3. On day 5, despite initial improvement of the fever and sore throat, multiple, new, small bullae developed on the patient’s face, trunk, and extremities. Additional testing showed that he was positive for HSV-specific immunoglobulin M and immunoglobulin G. Disseminated HSV infection was suspected, and intravenous acyclovir (10 mg/kg every 8 h) was begun. A subsequent direct antigen test of a bulla sample was positive for HSV-2. Moreover, tonsillar and esophageal biopsies revealed viral inclusion bodies. Immunohistochemical staining and a quantitative real-time polymerase chain reaction (PCR) assay confirmed the presence of HSV-2. Disseminated HSV-2 infection with multiple bullae, tonsillitis, esophagitis, and suspected hepatic involvement was diagnosed. After a 2-week course of intravenous acyclovir, his hematological status and liver function normalized, and his cutaneous skin lesions resolved. He was discharged on day 22 in good general health and continued taking oral valacyclovir for viral suppression due to his immunosuppressed status.ConclusionDisseminated HSV-2 infection should be considered as one of the differential diagnoses in patients with pharyngotonsillitis and impaired liver function of unknown etiology even if there are no genital lesions.

For non‐small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, the initial therapeutic interventions will have crucial impacts on their clinical outcomes. Drug tolerant factors reportedly have an impact on EGFR‐tyrosine kinase inhibitor sensitivity. This prospective study investigated the impacts of drug tolerant‐related protein expression in tumors based on the efficacy of osimertinib in the first‐setting of EGFR‐mutated advanced NSCLC patients. A total of 92 patients with EGFR‐mutated advanced or postoperative recurrent NSCLC were analyzed and treated with osimertinib at 14 institutions in Japan. AXL, p53, and programmed death‐ligand 1 (PD‐L1) expression in patient tumors was determined using immunohistochemistry. The AXL signaling pathway was investigated using a cell line‐based assay and AXL‐related gene expression in The Cancer Genome Atlas (TCGA) database. High levels of AXL and positive‐p53 expression were detected in 26.1% and 53.3% of the pretreatment EGFR‐mutated NSCLC tumors, respectively. High AXL expression levels were significantly associated with a shorter progression‐free survival compared with low AXL expression levels, irrespective of the EGFR activating mutation status (p = 0.026). Cell line‐based assays indicated that the overexpression of AXL protein accelerated PD‐L1 expression, which induced insensitivity to osimertinib. In the TCGA database, AXL RNA levels were positively correlated with PD‐L1 expression in the lung adenocarcinoma cohort. The results show that high AXL expression levels in tumors impact clinical predictions when using osimertinib to treat EGFR‐mutated NSCLC patients. Trial Registration: UMIN000043942.

Platinum-based chemotherapy is the de facto standard treatment for metastatic or unresectable thymic carcinoma. The optimal chemotherapy regimen has not yet been determined, including whether this should be combined with a second- or third-generation anti-cancer agent. We retrospectively evaluated the data of patients with metastatic or unresectable thymic carcinoma who were treated with a combination of cisplatin and irinotecan as first-line chemotherapy between 2002 and 2021 (trial registration UMIN000012175). The primary endpoint was response rate according to the RECIST criteria version 1.1. Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), and toxicity (adverse events). Some patients analyzed in this study were also included in the previous trial, which was terminated early. For this analysis, we included 18 patients with a median age of 56 years and an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients had clinical stage IVa or IVb thymic carcinoma according to the Masaoka-Koga staging system. The response rate was 44% and the disease control rate was 89%. The median PFS was 8.4 months (95% confidence interval (CI): 2.7–11.6 months) and the median OS was 45.6 months (95% CI: 15.7–69.1 months). Grade 3 or worse hematological toxicity was observed in 5 patients and grade 3 or worse non-hematological toxicity was observed in 3 patients. None of the patients developed febrile neutropenia, and no treatment-related deaths occurred. Thus, the combination of cisplatin and irinotecan as first-line chemotherapy for metastatic thymic carcinoma showed efficacy and acceptable toxicity.

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The severity and asscociated mortality of coronavirus disease 2019 (COVID-19) are higher in patients with thoracic cancer than in healthy populations and those with other cancer types. Here, we investigated real-world data on the incidence of COVID-19 and false-negative cases using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing in patients with thoracic cancer. We retrospectively reviewed patients with advanced thoracic cancer at the National Cancer Center Hospital between March 2020–May 2021. Blood samples were collected and evaluated for IgM and IgG antibodies specific for nucleocapsid (N) and spike (S) protein SARS-CoV-2 before and after rRT-PCR testing. False-negative cases were assessed based on anti-SARS-CoV-2 antibody levels before and after rRT-PCR testing. A total of 2,107 patients with thoracic cancer were identified between March 2020 and May 2021, 7 (0.3%) of whom developed COVID-19. Among the 218 patients who underwent at least one rRT-PCR test because of suspected COVID-19 symptoms or as a screening test at our institute, the most common diagnosis was non-COVID-19 pneumonia (34.4%), followed by tumor fever (30.7%). Furthermore, of the 218 patients, 120 paired serum samples before and after rRT-PCR testing were available. Seroconversion was identified in all three patients with positive SARS-CoV-2 rRT-PCR results but was only observed in 1 out of the 117 patients who tested negative; the rate of false-negative cases was low (0.9%). COVID-19 incidence among patients with advanced thoracic cancer was low during the early phase of the pandemic in Japan.