Primary central nervous system lymphoma (PCNSL) is a rare cancer accounting for less than 3% of primary brain and central nervous system (CNS) tumors. Tissues involved include the brain parenchyma, leptomeninges, eyes, and spinal cord. High-dose methotrexate (MTX) is the gold standard for newly diagnosed PCNSL. However, Gamma Knife radiosurgery (GKRS) may be efficacious as a co-adjuvant treatment. The purpose of this prospective observational cohort study is to determine the effectiveness of MTX in combination with GKRS in the treatment of PCNSL.

This is a prospective, observational cohort study evaluating the treatment of histologically confirmed PCNSL with MTX as a single agent in a dose of 8 g/m2 (control) and treatment with MTX, plus GKRS. Strict inclusion and exclusion criteria were employed. Primary outcomes were measured by survival rate. Secondary outcomes were assessed by the tumor's responsiveness to treatment and reduction in size as noted on imaging.

Between January 2007 and January 2012, 128 charts were evaluated. Included in this evaluation were 73 chemotherapy (control) and 55 chemotherapy, plus GKRS, patients (variable). The follow-up period was 24 to 49 months (mean: 36.9 months). There were no statistically significant differences in patient demographics or histology diagnosis. Patients were treated with GK doses ranging from 11 Gy to 16 Gy (median: 11 Gy). The median survival rate from initial diagnosis was 26.8 months in the chemotherapy group and 47.6 in the chemotherapy, plus GKRS, group (p-value: 0.0034). All lesions showed a complete response after GKRS when evaluated using magnetic resonance imaging after three to eight weeks (mean range: 6.3 weeks).

The use of GKRS is non-invasive, safe, and shows rapid success, improving the prognosis of the patient. This noninvasive treatment modality should be considered as an option for patients with PCNSL. In our study, GKRS as a co-adjuvant therapy to high-dose methotrexate was statistically significant for greater tumor control, enhanced overall survival period, and a lesser number of complications.