Identification of a Novel Biomarker in Perilesional CSF During Brain Metastasis Resection

Introduction: Brain metastases occur when cancer cells from a pre-existing tumor “break off” and spread to the brain via the bloodstream. Treatment often consists of surgical excision alongside radiation for a solitary metastasis, while radiation and/or chemotherapy are used for multiple brain metastases. Predicting the risk factors for patients developing this disease has been difficult to attain. In this study, we investigated the potential of perilesional cerebrospinal fluid (CSF) analysis as a biomarker for predicting the development and progression of intracranial metastatic disease. CSF analysis consisted of fluid sampling of the pre-resected perilesional subarachnoid CSF space to detect microscopic tumor cells.

Methods: In this study, thirty-three patients (19 females and 14 males; median age: 65 years; range: 39-82 years) with brain metastases underwent craniotomy for local tumor resection. Patients with known leptomeningeal disease were excluded from this study. Primary cancer origins included breast cancer (n=9), lung cancer - subdivided into small cell lung (n=2) and non-small cell lung (n=8) - renal cell carcinoma (n=4), skin cancer (n=3), esophageal cancer (n-2), and gastroesophageal (n=1).

Results: Before tumor resection results demonstrated the presence of tumor cells (based on histology) in the local CSF and around subarachnoid space in ten patients. Additionally, for these patients, those diagnosed with breast (70%) or non-small cell lung cancer (20%) were more likely to have malignant cells present. Among breast cancer patients (n=9), 77.8% (n=7) were positive for malignant cells in pre-resection washing, followed by the progression of intracranial metastatic disease. Follow-up serial MR imaging did not find any patient with local recurrence at this time.

Conclusion : With these results, perilesional CSF could serve as a novel biomarker for an early detection of distant CNS progression and influence the management of patients with brain metastasis. Further studies will be elucidating the genetic features of these tumor cells.