Objective:

To describe a case of miliary brain metastases (MBM) from non-small cell lung cancer (NSCLC) with KRAS G12C mutation on targeted therapy. 

Background:

MBM is a rare condition with an incidence of 2.4%-3.8% of patients with metastatic cancer. Patients with MBM may present with diverse neurological symptoms and can have a delayed appearance on imaging. MBM are associated with NSCLC with EGFR mutations, and diagnosis is based on MRI imaging with exclusion of infectious mimics. The prognosis of MBM is poor.

Design/Methods:

Retrospective Chart Review.

Results:

A 70-year-old man, former smoker, with NSCLC with KRAS G12C mutation with bone metastases on sotorasib, who presented to the hospital with one month of confusion and memory loss. Neurological examination was notable for disorientation and deficits in short-term memory. CT Head without contrast and MRI Brain with and without contrast were unremarkable. Systemic imaging revealed no evidence of cancer progression. Lumbar puncture (LP) revealed normal opening pressure, mild lymphocytic pleocytosis with normal CSF protein and glucose; CSF bacterial and fungal cultures, meningitis/encephalitis PCR and paraneoplastic panels, and cytology were negative. Leptomeningeal disease (LMD) or paraneoplastic encephalitis were suspected, and patient was treated with steroids and IVIG empirically. Within 1 week of admission, the patient's neurological exam worsened with lethargy and aphasia. Repeat MRI brain with and without contrast revealed LMD and MBM. Repeat LP revealed similar CSF profile with negative infectious work up (toxoplasma gondii IgG, acid-fast staining, Coccidioides and Lyme antibody titer panels were negative). Sotorasib was discontinued and whole brain radiation was initiated.

Conclusions:

The case report highlights that MBM occurring in a patient with NSCLC with KRAS G12C mutation despite treatment with targeted therapy with intracranial activity. MBM may present in a patient with subacute neurological decline with initial negative radiographic imaging. A high degree of suspicion and interval radiographic imaging is warranted.