Improved Overall Survival in CNS Lymphoma Patients Treated with Concurrent Temozolomide and Radiation

Abstract

CNS lymphoma (CNSL) treatment typically involves high-dose methotrexate-based chemotherapy. Radiation (RT) is often used for chemo-refractory disease or consolidation with whole brain RT (WBRT) with a boost to residual disease. There is no consensus standard of care and intracranial failures remain common. Temozolomide (TMZ) has activity in CNSL, but there is no consensus on concurrent TMZ use with RT. Our goal was to report our institutional experience with treating adult CNSL and to determine whether concurrent TMZ with RT affected patient survival. This IRB-approved retrospective study involved chart review of CNSL patients treated from January 2004 to February 2019. Inclusion criteria were pathologic diagnosis of CNSL, age > 18, receipt of RT, and treatment plan development at our institution. Patients with a history of organ transplant or systemic lymphoma involvement at the time of treatment were excluded. Survival was calculated from the date of RT completion and estimated using the Kaplan Meier method. Univariate comparisons were performed in a commercial scientific 2D graphing and statistics software using log-rank tests. Ninety-nine patients were identified, with a median age of 65 years (range 41 to 85). Seven patients were excluded for palliative RT only (n=4), spinal RT only (n=1), and missing records (n=2). Of the remaining 92 patients, there were 51 males and 41 females. Mean follow-up was 27 months (range 0 days to 12.6 years), and 39 patients remain living. Sixty-nine patients (75%) received WBRT with median dose 23.4Gy (range 12 to 45), while the rest received focal RT. Twenty-six patients (28%) received RT with concurrent TMZ (RT+TMZ), and 18 patients received WBRT+TMZ, with median RT dose 23.4Gy (range 23.4 to 45). Four patients (4.3%) received TMZ with focal RT. In the overall cohort, the median survival was 2.01 years, and the 3-year overall survival was 26%. Receipt of temozolomide concurrently with RT was associated with significantly improved survival (HR 0.38, p=0.01, see table). Additional survival results are shown in the table. The 3-year overall survival in our cohort of patients treated with RT is similar to contemporaneous clinical trial cohorts. Because RT is typically reserved for patients not having a complete response to chemotherapy at our institution, these survival results are encouraging. The receipt of concurrent TMZ with RT for CNSL was associated with significantly improved overall survival. The causality of this relationship and the toxicities of this regimen remain to be determined.Abstract 1278; Table 1Survival Metrics for CNS Lymphoma Patients Treated with Radiation +/- TemozolomideCohortRT with TMZ (n=26)RT without TMZ (n=64)WBRT with TMZ (n=18)WBRT without TMZ (n=47)WBRT with boost (n=22)WBRT without boost (n=25)Median survival (years)4.821.546.821.964.433.03Hazard Ratio0.380.580.6395% CI0.21 to 0.700.27 to 1.220.28 to 1.4p-value0.010.210.25 Open table in a new tab