Abstract
SMARCA4-deficient undifferentiated tumor is a rare and aggressive malignancy with a poor prognosis, often challenging to diagnose and stage due to its non-specific clinical and imaging features. Herein, we present a case of a 74-year-old male patient initially evaluated for a traumatic knee injury, which serendipitously led to the discovery of a thoracic malignancy. Two FDG PET/CT scans played pivotal roles in initial staging and post-treatment response assessment, guiding multimodal therapy combining chemotherapy, immunotherapy, anti-angiogenesis, and radiotherapy. Sequential PET/CT imaging demonstrated metabolic regression of the primary tumor and metastatic lesions following chemotherapy combined with anti-angiogenic therapy (anlotinib) and PD-L1 inhibition (benmelstobart), followed by consolidative radiotherapy. The treatment achieved complete remission (CR) with sustained disease control at 8 months. This case highlights the potential of a mechanistic-driven, multimodal strategy to overcome therapeutic resistance in SMARCA4-deficient undifferentiated tumor. It underscores the need for further exploration of synergistic regimens in this molecular subset.