Improved survival with combined chemo-radiotherapy in primary central nervous system lymphoma.
BACKGROUND
Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long-term disease control or prolonged survival. We retrospectively analyzed data on the effect of adding high-dose methotrexate (HDMTX) prior to whole brain irradiation (WBI).


METHODS
All patients with PCNSL diagnosed and managed during 1991-2004 were identified and demographic characteristics, prognostic factors, treatment and outcome were reviewed. Of 62 patients, 10 were excluded (4 had WBI<40 Gy and 6 had no treatment). Radiation alone was considered curative with a dose>40 Gy. Combined modality therapy included 3-4 cycles of HDMTX (3 g/m2) followed by WBI.


RESULTS
Of 52 patients analyzed for outcome, 36 had WBI (dose>40 Gy), 16 received 3-4 cycles of HDMTX followed by WBI (combined modality therapy [CMT]). Median age was 48.2 years; 42 years in the CMT group, 51 years in WBI. Patient characteristics were comparable between two groups except for higher multifocal tumor in the CMT group (92% vs. x22%, p=.029). Median follow up was 12.83±6.4 months. The hazard ratio for an event was 0.64 (95% CI, 0.52-0.98) and for death 0.58 (95% CI, 0.48-0.92), both in favor of CMT. Univariate regression analysis using one-way analyses of variance (ANOVA) and multivariate Cox regression analysis for prognostic factors including age (<60 vs. >60 years), ECOG PS (0-2 vs. 3-4), extent of surgery (biopsy vs. debulking), solitary vs multifocal tumor and dose of radiation therapy (<50 Gy vs. >50 Gy) failed to identify any prognostic factor.


CONCLUSIONS
This retrospective comparison supports phase II trial results that indicate that high-dose methotrexate followed by WBI in PCNSL improves outcome.
Abdelsalam
Mahmoud
M
King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. mahmoudabdelsalam@hotmail.com
El-Husseiny
Gamal
G
Akhtar
Saad
S
Khafaga
Yasser
Y
Al-Shabana
Mohamed
M
AlHusaini
Hamed
H
El Weshi
Amr
A
Rahal
Mohamed
M
Maghfoor
Irfan
I
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000473:pathology / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D011379:Prognosis; D011878:Radiotherapy / Q000379:methods*; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate