***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: PURPOSE A multicenter , phase II study of single-agent , intravenous methotrexate in newly diagnosed non-AIDS-related primary CNS lymphoma was conducted in the New Approaches to Brain Tumor Therapy ( NABTT ) CNS Consortium . METHODS Methotrexate ( 8 g/m(2 ) ) was initially administered every 2 weeks . The primary end point was radiographic CR or PR , as defined by st and ard radiographic criteria , and secondary end points were survival and drug-related toxicity . RESULTS Twenty-five patients were enrolled with a mean age of 60 years and median Karnofsky Performance Score of 80 . Three of 14 patients who underwent lumbar puncture  had malignant cells on CSF cytopathology , and five of 25 patients had ocular involvement . Two patients could not be evaluated for the primary end point because of the absence of measurable disease in one and death before radiologic imaging in another . All patients have completed the treatment program or progressed . Among 23 patients , there were 12 CR ( 52 % ) , five PR ( 22 % ) , one ( 4 % ) with stable disease , and five progressions ( 22 % ) while on therapy . Seven patients died of tumor progression , and two died of other causes . Median progression-free survival was 12.8 months . Median overall survival for the entire group had not been reached at 22.8 + months . The toxicity of this regimen was modest , with no grade 3 or 4 toxicity in 13 of 25 patients , grade 3 toxicity in eight of 25 patients , and grade 4 toxicity in four of 25 patients after 287 cycles of chemotherapy . CONCLUSION These results indicate that high-dose methotrexate is associated with modest toxicity and a radiographic response proportion ( 74 % ) comparable to more toxic regimens PURPOSE Primary CNS lymphoma ( PCNSL ) is an aggressive primary brain tumor . Cranial irradiation alone rarely results in long-term disease control or prolonged survival . We prospect ively studied the use of combination chemotherapy plus cranial irradiation in newly diagnosed patients with PCNSL . PATIENTS AND METHODS We enrolled 102 newly diagnosed , immunocompetent patients with PCNSL ; 98 were assessable . Patients first received five cycles of methotrexate 2.5 g/m(2 ) , vincristine , procarbazine , and intraventricular methotrexate ( 12 mg ) . Whole-brain radiotherapy ( RT ) was administered to a total dose of 45 Gy and all patients received high-dose cytarabine after RT . RESULTS Fifty-eight percent of patients with measurable disease had a complete response to preirradiation chemotherapy and 36 % had a partial ( > 50 % ) response , for a 94 % response rate . Median progression-free survival was 24.0 months and overall survival was 36.9 months . Age was an important prognostic factor ; median survival was 50.4 months in patients younger than 60 and only 21.8 months in those aged 60 or older ( P < .001 ) . Fifty-three percent of patients had grade 3 or 4 toxicity during induction chemotherapy , half of which was hematologic . However , 12 patients ( 15 % ) experienced severe delayed neurologic toxicity , eight of whom died . CONCLUSION This is the first multicenter trial demonstrating improved survival with the combination of chemotherapy plus RT compared with previous reports of RT alone . A high-dose methotrexate-based regimen produced a high response rate before RT was administered . High-dose methotrexate combined with cranial irradiation is an effective therapeutic approach to PCNSL , but neurotoxicity is a delayed risk of this approach Summary Purpose : To determine whether a lower dose of hyperfractionated whole brain radiation reduces central nervous system morbidity without compromising survival for primary CNS lymphoma ( PCNSL ) patients receiving combined modality treatment . Material s and Methods : One hundred and two patients received a course of pre-radiation chemotherapy , followed by whole brain radiation , followed by cytosine-arabinoside . Initial radiation dose was 45 Gy/25 fractions ( RT ) then the study was amended to reduce this dose for complete responders to induction chemotherapy to 36 Gy/30 fractions/3 weeks ( HFX ) . Eighty-two patients received radiotherapy  and were evaluable for toxicity analysis ( 66 RT patients and 16 HFX patients ) . MMSE scores and survival for the 40 patients who received radiotherapy after complete response to chemotherapy ( 27 RT and 13 HFX ) were compared . There were no notable differences in pre-treatment patient characteristics between the RT and HFX groups . Results : Neurotoxicity : By 4 years , there were 8/82 ( 10 % ) grade 5 neurotoxicities which included 2/16 ( 13 % ) grade 5 encephalopathies and 0/27 in the RT group of complete responders to chemotherapy . Survival : There was no statistically significant difference in overall or progression-free survival ( PFS ) between the chemotherapy-complete responders who received RT and HFX . Cognitive function testing : MMSE scores improved at 8 months across both treatment groups . Analysis of the area under the MMSE curve at 8 months showed no statistically significant difference between RT and HFX groups ( P=0.81 ) . Leukoencephalopathy occurred later in the HFX group than in the RT patients . Conclusion : Although the HFX schedule represented a 25 % reduction in biologically effective tumor dose in comparison , PFS and overall survival were not significantly affected . The HFX regimen delayed but did not eliminate severe neurotoxicity from chemoradiation in PCNSL patients BACKGROUND High-dose methotrexate is the st and ard of care for patients with newly diagnosed primary CNS lymphoma . The role of whole brain radiotherapy is controversial because delayed neurotoxicity limits its acceptance as a st and ard of care . We aim ed to investigate whether first-line chemotherapy based on high-dose methotrexate was non-inferior to the same chemotherapy regimen followed by whole brain radiotherapy for overall survival . METHODS Immunocompetent patients with newly diagnosed primary CNS lymphoma were enrolled from 75 centres and treated between May , 2000 , and May , 2009 . Patients were allocated by computer-generated block r and omisation to receive first-line chemotherapy based on high-dose methotrexate with or without subsequent whole brain radiotherapy , with stratification by age ( < 60 vs ≥60 years ) and institution ( Berlin vs Tübingen vs all other sites ) . The biostatistics centre assigned patients to treatment groups and informed local centres by fax ; physicians and patients were not masked to treatment group after assignment . Patients enrolled between May , 2000 , and August , 2006 , received high-dose methotrexate ( 4 g/m(2 ) ) on day 1 of six 14-day cycles ; thereafter , patients received high-dose methotrexate plus ifosfamide ( 1·5 g/m(2 ) ) on days 3 - 5 of six 14-day cycles . In those assigned to receive first-line chemotherapy followed by radiotherapy , whole brain radiotherapy was given to a total dose of 45 Gy , in 30 fractions of 1·5 Gy given daily on weekdays . Patients allocated to first-line chemotherapy without whole brain radiotherapy who had not achieved complete response were given high-dose cytarabine . The primary endpoint was overall survival , and analysis was per protocol . Our hypothesis was that the omission of whole brain radiotherapy does not compromise overall survival , with a non-inferiority margin of 0·9 . This trial is registered with Clinical Trials.gov , number NCT00153530 . FINDINGS 551 patients ( median age 63 years , IQR 55 - 69 ) were enrolled and r and omised , of whom 318 were treated per protocol . In the per- protocol population , median overall survival was 32·4 months ( 95 % CI 25·8 - 39·0 ) in patients receiving whole brain radiotherapy ( n=154 ) , and 37·1 months ( 27·5 - 46·7 ) in those not receiving whole brain radiotherapy ( n=164 ) , hazard ratio 1·06 ( 95 % CI 0·80 - 1·40 ; p=0·71 ) . Thus our primary hypothesis was not proven . Median progression-free survival was 18·3 months ( 95 % CI 11·6 - 25·0 ) in patients receiving whole brain radiotherapy , and 11·9 months ( 7·3 - 16·5 ; p=0·14 ) in those not receiving whole brain radiotherapy . Treatment-related neurotoxicity in patients with sustained complete response was more common in patients receiving whole brain radiotherapy ( 22/45 , 49 % by clinical assessment ; 35/49 , 71 % by neuroradiology ) than in those who did not ( 9/34 , 26 % ; 16/35 , 46 % ) . INTERPRETATION No significant difference in overall survival was recorded when whole brain radiotherapy was omitted from first-line chemotherapy in patients with newly diagnosed primary CNS lymphoma , but our primary hypothesis was not proven . The progression-free survival benefit afforded by whole brain radiotherapy has to be weighed against the increased risk of neurotoxicity in long-term survivors BACKGROUND We investigated the efficacy and safety of t and em high-dose methotrexate ( HD-MTX ) induction followed by high-dose busulfan/thiotepa ( HD-BuTT ) with autologous peripheral blood stem-cell transplantation ( aPBSCT ) and response-adapted whole-brain radiation therapy ( WBRT ) in patients with newly diagnosed primary central nervous system lymphoma . PATIENTS AND METHODS Twenty-three patients were treated with HD-MTX on days 1 and 10 . In case of at least a partial remission ( PR ) , HD-BuTT followed by aPBSCT was given . Patients without response to induction or without complete remission ( CR ) after HD-BuTT received WBRT . RESULTS Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13 % . CR/PR rates for all patients ( n = 23 ) were 70%/13 % . There were three deaths during therapy . With longer follow-up three neurotoxic deaths occurred in irradiated patients ( n = 9 ) , while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT . At a median follow-up of 15 months ( range 1 - 69 ) median event-free survival ( EFS ) and overall survival ( OS ) for all patients were 17 and 20 months ( Kaplan-Meier ) , after HD-BuTT 27 months and " not reached " , respectively . Estimated 2-year EFS and OS were 45 % and 48 % for all patients versus 56 % and 61 % for the HD-BuTT group , respectively . CONCLUSION MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen . Median survival for patients treated with high-dose chemotherapy is not reached yet . The induction regimen needs optimisation . In this study WBRT was associated with a high incidence of severe neurotoxicity 1522 Background : The role of adjuvant whole-brain irradiation ( WBI ) in PCNSL remains to be defined . Eliminating WBI from the initial treatment could reduce neurotoxicity but also adversly affect disease control and survival . METHODS Fifty-six patients were included in this prospect i ve multicenter trial to evaluate the role of adjuvant WBI in PCNSL : . All received chemotherapy ( CHX ) composed of carmustine , high-dose methotrexate ( HD-MTX ) 1.5 g/m2 , procarbazine , and dexamethasone ( only in course 1 ) . Patients without complete response ( CR ) received salvage chemotherapy with idarubicine and ifosfamide or high-dose cytarabine . Patients with CR after CHX were r and omized to either WBI or one additional CHX course . RESULTS The CR rate after CHX was 61 % ( 34/56 ) , but only 23 patients were r and omized to the two study arms . With a median follow-up of 40 months median overall survival ( OAS ) of all 24 patients without adjuvant WBI was 28.5 months ( 95 % CI 7.7 - 49.2 months ) , that of all 10 responders with adjuvant WBI 12.8 months ( 95 % CI 0 - 40.4 months ; P=0.97 ) . Responders to CHX had significantly longer survival than non-responders ( 18.2 versus 9.9 months , P=0.02 ) . Median OAS was significantly longer at institutions accruing at least 4 patients than at those with fewer patients ( 31.5 versus 9.5 months , P=0.03 ) . Late neurotoxicity developed in 5/24 ( 21 % ) patients younger than 60 years as compared to 6/32 ( 19 % ) older patients ( P=0.84 ) and in 6/28 patients after WBI as compared to 5/22 without WBI treatment ( P=0.9 
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In summary , the currently available evidence ( one RCT ) is not sufficient to conclude that WBR plus chemotherapy and chemotherapy alone have similar effects on overall survival in people with PCNSL .
The findings suggest that the addition of radiotherapy ( WBR ) to chemotherapy may increase progression-free survival , but may also increase the incidence of neurotoxicity compared to chemotherapy only ( methotrexate monotherapy ) .