Background: Single-agent amrubicin chemotherapy is a key regimen, especially for small cell lung cancer (SCLC); however, it can cause severe myelosuppression. Purpose: The purpose of this study was to determine the real-world incidence of febrile neutropenia (FN) among patients treated with single-agent amrubicin chemotherapy for thoracic malignancies. Patients and methods: The medical records of consecutive patients with thoracic malignancies, including SCLC and non-small cell lung cancer (NSCLC), who were treated with single-agent amrubicin chemotherapy in cycle 1 between January 2010 and March 2020, were retrospectively analyzed. Results: One hundred and fifty-six patients from four institutions were enrolled. Their characteristics were as follows: median age (range): 68 (32–86); male/female: 126/30; performance status (0/1/2): 9/108/39; SCLC/NSCLC/others: 111/30/15; and prior treatment (0/1/2/3-): 1/96/31/28. One hundred and thirty-four (86%) and 97 (62%) patients experienced grade 3/4 and grade 4 neutropenia, respectively. One hundred and twelve patients (72%) required therapeutic G-CSF treatment, and 47 (30%) developed FN. Prophylactic PEG-G-CSF was not used in cycle 1 in any case. The median overall survival of the patients with FN was significantly shorter than that of the patients without FN (7.2 vs. 10.0 months, p = 0.025). Conclusions: The real-world incidence rate of FN among patients with thoracic malignancies that were treated with single-agent amrubicin chemotherapy was 30%. It is suggested that prophylactic G-CSF should be administered during the practical use of single-agent amrubicin chemotherapy for patients who have already received chemotherapy.

Extraskeletal myxoid chondrosarcoma (EMCS) is an undifferentiated mesenchymal malignancy; however, its immune microenvironment remains to be elucidated. The case of a 34-year-old woman who developed EMCS metastasizing to the pleura is presented here. The pleural EMCS showed hypervascularity, absent PD-L1 expression, and a lack of tumor mutational burden and pathogenic variants. Immunohistological examination of the pleural lesions showed predominant M2 macrophages and sparse CD8 + T cells. EMCS and the tumor stroma were positive for transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF). In contrast, a small number of the stromal vessels were positive for hypoxia inducible factor-1α (HIF-1α). TGF-β1 and VEGF in the tumor stroma and low antigenicity of the tumor cells may help explain how EMCS induced the immunosuppressive microenvironment. These findings may encourage investigators to explore novel combined immunotherapy for EMCS, such as TGF-β1 and VEGF inhibitors, and specific therapy for enhancing tumor antigens. K E Y W O R D S sarcoma, transforming growth factor-β1, tumor-associated macrophages, vascular endothelial growth factor

Introduction Combined treatment using anti-programmed death-ligand 1 antibody (anti-PD-L1) and platinum-etoposide is the current standard first-line treatment for patients with extensive-stage (ES) small cell lung cancer (SCLC). However, the best treatment for relapsed ES-SCLC after the first-line treatment remains unclear. There are some approved chemotherapeutic agents that can be used against ES-SCLC, and treatment with irinotecan is well established as both, a monotherapy and a combined therapy, in combination with platinum. Therefore, we conduct a phase II study with irinotecan in the second- or later-line setting for patients with ES-SCLC who are previously treated with a combination of anti-PD-L1 and platinum-etoposide. Methods Our study will enroll patients who are diagnosed with ES-SCLC and experienced disease progression after treatment of anti-PD-L1 and platinum-etoposide. Patients will receive irinotecan on days 1, 8, and 15, which will be repeated every 4 weeks. Doses of irinotecan (100/80/60 mg/m2) will be determined according to the type of UGT1A1 gene polymorphism, and the treatment will be discontinued following disease progression, intolerance, withdrawal of patient consent, and based on the investigator’s decision. The primary endpoint of the study is the response rate, and the secondary endpoints are overall survival, progression-free survival, and safety. Discussion Since the present first-line treatment has been changed to combined treatment with anti-PD-L1 and platinum-etoposide, the second- or later-line treatment should be re-evaluated for patients with relapsed SCLC. Irinotecan is a major chemotherapeutic agent used for SCLC. This IRICO study demonstrates and re-evaluates the clinical benefits of irinotecan after combined treatment with anti-PD-L1 and platinum-etoposide for patients with ES-SCLC. Registration details This study was registered in the Japan Registry of Clinical Trials (no. jRCT s071210090) on November 4, 2021.

How Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) occasionally occurs following chronic inflammation remains to be elucidated. The case of a 57-year-old man who developed pulmonary EBV-positive DLBCL from underlying silicosis lesions is presented. Immunohistochemical examination of the resected silicosis lesions showed predominant helper T cells and M1/M2 macrophages, with a lack of B cells, regulatory T cells, and resident memory T cells. Two years later, EBVpositive DLBCL emerged unexpectedly from the silicosis. The imbalance of the immune cells in the microenvironment, at least in part, may help explain how chronic inflammation contributes to EBV-positive DLBCL.