Case Report: Low-dose radiotherapy as part of multimodal salvage therapy for immunotherapy-resistant SMARCA4-deficient non‐small cell lung cancer

Abstract

SMARCA4-deficient non-small cell lung cancer (SD-NSCLC) is a highly aggressive molecular subtype. This malignancy is often diagnosed at an advanced stage, carrying a dismal prognosis and also demonstrating poor responsiveness to traditional treatment. Beyond its primary site, the disease can exhibit unusual metastatic patterns such as metastasis to oral soft tissues. We report a unique case of a 61-year-old male heavy smoker with molecularly confirmed SD-NSCLC who experienced rapid metastatic progression to the right gingiva and neck lymph nodes shortly after radical surgery and initial chemo-immunotherapy. This clinical scenario exemplifies primary resistance to immune checkpoint inhibitors (ICIs), where pre-existing genetic or microenvironmental barriers hinder initial therapeutic success. To overcome this resistance, a salvage multimodal strategy was implemented, integrating ICIs with etoposide/cisplatin (EP) chemotherapy and low-dose radiotherapy (LDRT). Remarkably, this regimen achieved significant regression of the bulky metastatic lesions and has maintained sustained disease stability for over 15 months, with the patient remaining clinically stable as of the latest follow-up in June 2026. This case may hint the potential role of LDRT as an immunomodulatory component to overcome primary resistance in SD-NSCLC, suggesting a potential therapeutic strategy for patients who experience disease progression following first-line chemo-immunotherapy.