記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 75-year-old never-smoker woman presented with dyspnea and loss of appetite. A mass was identified in the left upper lobe of the lung, and the patient was referred to our hospital. Despite the diagnosis of lung adenocarcinoma via bronchoscopy, anaplastic lymphoma kinase (ALK) immunostaining was negative. Rapid weight gain and abdominal distension caused by ascites prompted fluid testing using the AmoyDx® Pan Lung Cancer PCR Panel. EML4-ALK fusion was confirmed, and alectinib therapy was initiated immediately. The tumor size had decreased significantly, and the patient was discharged on day 34. This case highlights the necessity of multiplex genetic testing even when ALK immunostaining is negative.

DOI： 10.2169/internalmedicine.5397-25

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Persister cancer cells, which reversibly adapt to survive EGFR-tyrosine kinase inhibitor (TKI) treatment, contribute to the incurability of EGFR-mutant lung cancer. We previously reported that gefitinib induces CD8+ T cell-related tumor immunity in a genetically engineered mouse model. This study investigates the tolerance of persister cancer cells to EGFR-TKI-induced tumor immunity in this model. EGFR-mutated lung cancer cells (C57BL/6/EgfrdelE748-A752) from the genetically engineered mouse model were transplanted subcutaneously into wild-type C57BL/6J mice. Persistent tissues under osimertinib treatment were analyzed using digital spatial transcriptional profiling, IHC staining, and flow cytometry. The antitumor effect of osimertinib peaked at 14 days, leaving a small population of persister cancer cells. The number of PD-1+ CD8+ cells increased in the tumor microenvironment (TME), and CD8+ cell depletion attenuated the antitumor effect of osimertinib. Digital spatial transcriptional profiling revealed upregulated expression of M2 macrophage-related genes in the TME of persister cancer cells. Consistently, IHC and flow cytometry confirmed an increased number of CD206+ macrophages in the TME. Combining osimertinib with the colony-stimulating factor-1 receptor inhibitor pexidartinib reduced CD206+ macrophages and enhanced the efficacy of osimertinib. Elevated Granzyme B or CD107 expression on CD8+ cells in the TME suggests that macrophages negatively affect osimertinib-induced antitumor immunity. M2-like macrophages may contribute to the immune tolerance of persister cancer cells against EGFR-TKI-induced tumor immunity. A clinical trial evaluating combined osimertinib and colony-stimulating factor-1 receptor inhibitor therapy is warranted for EGFR-mutated lung cancer.

DOI： 10.1158/1535-7163.MCT-25-0002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Endotracheal and endobronchial metastases from peripheral lung adenocarcinoma are rare, and optimal clinical management remains unclear. We herein report a 60-year-old woman with epidermal growth factor receptor (EGFR) exon 19 deletion-positive early-stage lung adenocarcinoma who underwent surgical resection followed by osimertinib treatment for recurrence. She later developed oligoprogressive disease with airway metastases. Bronchoscopic tumor removal was performed, and next-generation sequencing of the resected specimen revealed an acquired EGFR C797S mutation, along with exon 19 deletion. Gefitinib treatment was initiated, which led to a partial response. This case underscores the utility of repeated molecular profiling and local intervention in managing acquired resistance in EGFR-mutant non-small-cell lung cancer.

DOI： 10.2169/internalmedicine.6220-25

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Paclitaxel (PTX) is an essential cytotoxic anticancer agent and a standard treatment regimen component for various malignant tumors, including advanced unresectable non-small cell lung cancer, thymic cancer, and primary unknown cancers. However, chemotherapy-induced peripheral neuropathy (CIPN) caused by PTX is a significant adverse event that may lead to chemotherapy discontinuation and deterioration of the quality of life (QOL). Although treatment modalities such as goshajinkigan (GJG), pregabalin, and duloxetine are empirically utilized for CIPN, there is no established evidence for an agent as a preventive measure. We designed a randomized phase II trial (OLCSG2101) to investigate whether prophylactic GJG administration can prevent the onset of CIPN induced by PTX. METHODS: This study was designed as a two-arm, prospective, randomized, multicenter phase II trial. The patients will be randomly assigned to either the GJG prophylaxis arm (Arm A) or the GJG non-prophylaxis arm (Arm B), using cancer type (lung cancer or not) and age (<70 years or not) as adjustment factors. A total of 66 patients (33 in each arm) will be enrolled. DISCUSSION: The results of this study may contribute to better management of CIPN, which can enable the continuation of chemotherapy and maintenance of the patient's QOL. ETHICS AND DISSEMINATION: Ethical approval was obtained from the certified review board of Okayama University (approval no. CRB21-005) on September 28, 2021. Results will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION: Japan Registry of Clinical Trials (registration number jRCTs061210047).

DOI： 10.1016/j.resinv.2024.07.017

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掲載種別：研究論文（学術雑誌）   出版者・発行元：AME Publishing Company  

DOI： 10.21037/tlcr-23-99

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