Stage IVB SMARCA4-deficient NSCLC with brain metastasis: stable disease after surgery, radiation, chemotherapy, immunotherapy, and bevacizumab

What happened, in summary

This 71-year-old man with a 50-year smoking history was admitted in July 2024 after 4 months of declining vision. Head CT showed a right occipital brain mass about 35 × 30 mm. He underwent microscopic resection of the brain lesion in August 2024, and pathology supported metastatic SMARCA4-deficient carcinoma, likely from SMARCA4-deficient non-small cell lung cancer. Chest CT showed multiple solid and ground-glass lung nodules, with the largest in the left lower lobe. CT-guided biopsy of that lesion confirmed non-small cell carcinoma consistent with SMARCA4-DNSCLC. The disease was staged T1cNxM1c, Stage IVB. Molecular testing found SMARCA4 p.G256*, TP53 p.M66Gfs75, ATR, BARD1, NSD1, and CHD8 alterations, BRG-1/SMARCA4 protein loss, retained INI1, high tumor mutational burden, no MSI-H, and PD-L1 TPS below 1% in both brain and lung specimens. On September 9, 2024, he began postoperative brain IMRT, 51 Gy in 17 fractions. During radiation, he received pemetrexed and carboplatin plus bevacizumab to reduce cerebral edema, followed by toripalimab. He developed grade 2 oral mucositis, which improved with supportive care. Four cycles of pemetrexed, carboplatin, bevacizumab, and toripalimab led to stable disease and gradual shrinkage of the lung lesion, with no brain recurrence. He later continued bevacizumab plus pemetrexed maintenance and received lung radiotherapy in March 2025. As of October 2025, disease remained stable. Initial tumor markers were markedly elevated, including CA-724 above 300 U/mL, CA-125 245.33 U/mL, and CEA 688.03 ng/mL. The brain and lung tumors shared key molecular changes, supporting a metastatic relationship. Treatment was manageable: later discussion described only grade 1 chemotherapy-related toxicities such as fatigue and nausea, without grade 2 or higher immune-related adverse events.