Significant Intracranial Response and Long-term Survival after Pembrolizumab in Non-small Cell Lung Cancer Brain Metastases Resistant to Stereotactic Radiotherapy.

Brain metastases from non-small cell lung cancer are typically managed with local therapies, such as surgery and radiotherapy, whereas systemic treatments have historically demonstrated limited efficacy in the intracranial setting. Immune checkpoint inhibitors, particularly programmed cell death-1 inhibitors, have recently demonstrated potential in this context. We report a case of a 48-year-old man with lung adenocarcinoma who developed a radiation-resistant brain metastasis with postoperative recurrence and severe neurological deterioration. Despite multiple courses of stereotactic radiosurgery and surgical resection, the lesion progressed, accompanied by seizures, impaired consciousness, and poor performance status. Pembrolizumab monotherapy was initiated as salvage treatment. Although initial clinical and radiological worsening, rapid tumor regression was observed within 1 month, along with marked neurological recovery. Notably, the patient achieved sustained complete remission without additional systemic therapy and remained alive for more than 7 years after treatment. Histopathological evaluation revealed increased programmed cell death-ligand 1 expression in brain metastasis compared to that in the primary tumor, possibly influenced by prior radiotherapy. This case highlights the potential synergy between radiotherapy and immune checkpoint inhibitors. Even in patients with poor performance status and refractory intracranial disease, programmed cell death-1 blockade may provide durable clinical benefits in selected patients.