title: Long-term remission of primary central nervous system lymphoma by intensified methotrexate chemotherapy.
abstract: High-dose (1-3.5 g/m2) methotrexate (MTX) followed by whole-brain radiation therapy (WBRT) has consistently improved length of survival in primary central nervous system lymphoma (PCNSL), but the prognosis remains dismal. To optimize and enhance the dose intensity of MTX, we applied MTX at 8 g/m2 to 20 patients with PCNSL. In an effort to lower the risk of neurotoxic treatment sequelae, the WBRT dose was reduced to 30 Gy in cases of complete remission after MTX therapy. Further, omission of WBRT and administration of stereotactic radiotherapy (SRT) were undertaken in 3 older patients. The overall response rate to the MTX therapy was 83%. The median progression free survival (PFS) was 54 months with a median overall survival (OS) of 57 months. Achieving a complete response after MTX therapy was significantly associated with a longer PFS. Late neurotoxicity was encountered in 4 (50%) of 8 patients who were aged 60 years or older and received WBRT, but in none of 12 patients who were aged less than 60 years or avoided WBRT. All older patients who underwent SRT sustained complete remission without a dementing disease. Intensifying the MTX dosage to 8 g/m2 appears more promising in comparison to results reported with MTX doses of 1-3.5 g/m2. In younger patients, the establishment of complete remission by intensified MTX therapy and subsequent WBRT with a relatively lower dose could promise durable tumor remission with an acceptable neurotoxicity. In older patients, WBRT should be avoided to sustain a meaningful survival, and SRT may provide a valid strategy in terms of enhancing local disease control without undue risk.
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan. takao@med.nihon-u.ac.jp
authors.forename: Takao
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Katayama
authors.forename: Atsuo
authors.initials: A
authors.lastname: Yoshino
authors.forename: Chiaki
authors.initials: C
authors.lastname: Komine
authors.forename: Takakazu
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Takao
authors.initials: T
authors.lastname: Fukushima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D012074:Remission Induction; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate