Treatment of Primary Central Nervous System Lymphoma (PCNSL): Comparison of Whole Brain Radiation Therapy and Partial Brain Radiation Therapy

Abstract

High-dose methotrexate (MTX)-based chemotherapy and whole-brain radiation therapy (WBRT) is considered to be a choice of treatment to cure PCNSL patients younger than 60 years of age. However, unacceptable delayed neurotoxicity is a concern, as the improvement in treatment has increased survival rates. Elimination of WBRT is associated with a higher rate of relapse. Partial-brain irradiation (PBRT) may reduce the risk of neurotoxicity, while maintaining a high rate of tumor control. Since 2005, our group has employed partial-brain irradiation with wide margins in patients with solitary PCNSL. In this study, we analyzed results of treatment for PCNSL, with special reference to WBRT versus PBRT. Between 1993 and 2011, 74 patients (median age, 63; range, 25-90) with histologically-confirmed PCNSL were treated with radiation therapy with or without chemotherapy. Sixty patients were treated with WBRT with or without focal boost, while 14 were treated by PBRT with approximately 4-cm margins from tumor mass generally followed by focal boost. The median patient age was 62 years (range, 25-90) in the WBRT group and 66 years (range, 49-75) in the PBRT group. Multiple tumors were seen in 28 of the 60 patients (47%) of the WBRT group and in 2 of the 14 patients (14%) of the PBRT group. Median maximum tumor diameter was 34.5 mm (range, 3-80) in the WBRT group and 38.5 mm (range, 12-60) in the PBRT group. Daily 2-Gy fractions were used in vast majority of cases. Median total dose was 50 Gy (range, 20-60) in the WBRT group and 50 Gy (range, 30.6-54) in the PBRT group. MTX-based chemotherapy was used in 15 of the 60 patients (25%) of the WBRT group and in 12 of the 14 patients (86%) of the PBRT group. Response rates in WBRT and PBRT groups were 73% and 92%, respectively (P = 0.12). The median survival time was 16 months for the WBRT group and 19 months for the PBRT group. The 3-year overall survival rate was 42% versus 41% (P = 0.17). The 3-year CNS-recurrence rate was 48% and 53%, respectively (P = 0.93); when only patients with a single tumor were analyzed, the rate was 52% versus 40% (P = 0.79). The 3-year extra-CNS-recurrence rate was 20% versus 14% (P = 0.85). In the PBRT group, the 2-year rate for out-of-field CNS recurrence was 15%. Late neurotoxicity of WBRT was encountered in a 65-year-old patient and in 4 patients under 60 years of age. Two patients over 60 years old treated with PBRT developed treatment-related late neurotoxicity, but no patient under 60 years of age treated with PBRT developed this adverse event. PBRT may be considered as a treatment option of solitary PCNSL. Combination with MTX-based chemotherapy may be worthy of further investigation, in place of WBRT.