Pancreatic Adenocarcinoma and Brain Mets: Literature Review

Brain metastases from pancreatic ductal adenocarcinoma (PDAC) are extremely rare (incidence < 1%) but have serious clinical implications and a dismal prognosis. We present two cases of PDAC with brain metastases and review the literature. The first case was a 62-year-old woman who presented with aphasia and was found to have an ischemic stroke plus a ring-enhancing brain lesion; imaging and biopsy confirmed metastatic PDAC with pancreatic, liver, and brain involvement, and she was managed with corticosteroids and palliative cranial radiotherapy. The second patient was a 60-year-old woman who presented with confusion and a hemorrhagic brain mass; the workup revealed a pancreatic head carcinoma with widespread metastases. Her condition deteriorated rapidly and she died shortly after diagnosis, reflecting the aggressive course of PDAC once the central nervous system was involved. Reported clinical presentations of PDAC brain metastases range from incidental findings to severe neurological deficits (commonly headaches, seizures, focal deficits, or altered mental status). Diagnosis relies on brain MRI and confirmatory pathology when needed, especially if the pancreatic primary is not yet identified. There are no standardized treatment guidelines—management is individualized and multidisciplinary, often combining surgical resection of isolated lesions, radiotherapy (stereotactic or whole-brain), and systemic therapy, along with supportive care (e.g., corticosteroids for edema). Prognosis remains poor: median survival after a PDAC brain metastasis diagnosis is only ~2 - 5 months, and very few patients survive beyond one year. Molecular profiling indicates that PDAC tumors causing brain metastases to harbor common mutations (e.g., KRAS, TP53) like typical PDAC, while rarely actionable alterations (such as ALK or NTRK fusions or BRAF mutations) have enabled targeted therapies with CNS activity in select cases. Emerging treatments, including novel KRAS inhibitors and other targeted agents, are under investigation and offer hope for improved systemic and intracranial disease control.