***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND To improve survival of elderly patients with primary central nervous system lymphoma ( PCNSL ) , we conducted a phase II study with high-dose methotrexate ( MTX ) combined with procarbazine and CCNU . To reduce neurotoxicity , whole-brain irradiation was reserved for patients not responding to chemotherapy . PATIENTS AND METHODS High-dose MTX was applied on days 1 , 15 , and 30 , procarbazine on days 1 - 10 , and CCNU on day 1 . Study treatment comprised up to three 45-day cycles . There was no lower limit of Karnofsky performance status ( KPS ) . RESULTS Thirty patients with PCNSL ( n = 29 ) or primary ocular lymphoma ( n = 1 ) were included ( median age 70 years , range 57 - 79 years ) . The median initial KPS was 60 % ( range 30%-90 % ) . Best documented response in 27 assessable patients were 12 of 27 ( 44.4 % ) complete remissions , 7 of 27 ( 25.9 % ) partial remissions , and 8 of 27 ( 29.6 % ) disease progressions . Two patients died of probable treatment-related causes . With a median follow-up of 78 months ( range 34 - 105 ) , the 5-year overall survival is 33 % . Eight of 30 patients ( 26.7 % ) are currently alive and well , six without signs of leukoencephalopathy . CONCLUSION The combination of high-dose MTX with procarbazine and CCNU is feasible and effective and results in a low rate of leukoencephalopathy . Comorbidity and toxicity remain of concern when treating PCNSL in elderly patients BACKGROUND Cyclophosphamide , doxorubicin , vincristine , and prednisolone ( CHOP ) is used to treat patients with non-Hodgkin lymphoma . Interval decrease from 3 weeks of treatment ( CHOP-21 ) to 2 weeks ( CHOP-14 ) , and addition of rituximab to CHOP-21 ( R-CHOP-21 ) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma ( DLBCL ) . This r and omised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14 . METHODS 1222 elderly patients ( aged 61 - 80 years ) were r and omly assigned to six or eight cycles of CHOP-14 with or without rituximab . Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement . The primary endpoint was event-free survival ; secondary endpoints were response , progression during treatment , progression-free survival , overall survival , and frequency of toxic effects . Analyses were done by intention to treat . The trial is registered on National Cancer Institute website , number NCT00052936 and as EU-20243 . FINDINGS 3-year event-free survival was 47.2 % after six cycles of CHOP-14 ( 95 % CI 41.2 - 53.3 ) , 53.0 % ( 47.0 - 59.1 ) after eight cycles of CHOP-14 , 66.5 % ( 60.9 - 72.0 ) after six cycles of R-CHOP-14 , and 63.1 % ( 57.4 - 68.8 ) after eight cycles of R-CHOP-14 . Compared with six cycles of CHOP-14 , the improvement in 3-year event-free survival was 5.8 % ( -2.8 - 14.4 ) for eight cycles of CHOP-14 , 19.3 % ( 11.1 - 27.5 ) for six cycles of R-CHOP-14 , and 15.9 % ( 7.6 - 24.2 ) for eight cycles of R-CHOP-14 . 3-year overall survival was 67.7 % ( 62.0 - 73.5 ) for six cycles of CHOP-14 , 66.0 % ( 60.1 - 71.9 ) for eight cycles of CHOP-14 , 78.1 % ( 73.2 - 83.0 ) for six cycles of R-CHOP-14 , and 72.5 % ( 67.1 - 77.9 ) for eight cycles of R-CHOP-14 . Compared with treatment with six cycles of CHOP-14 , overall survival improved by -1.7 % ( -10.0 - 6.6 ) after eight cycles of CHOP-14 , 10.4 % ( 2.8 - 18.0 ) after six cycles of R-CHOP-14 , and 4.8 % ( -3.1 - 12.7 ) after eight cycles of R-CHOP-14 . In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference , and adjusting for known prognostic factors , all three intensified regimens improved 3-year event-free survival ( eight cycles of CHOP-14 : RR [ relative risk ] 0.76 [ 0.60 - 0.95 ] , p=0.0172 ; six cycles of R-CHOP-14 : RR 0.51 [ 0.40 - 0.65 ] , p<0.0001 ; eight cycles of R-CHOP-14 : RR 0.54 [ 0.43 - 0.69 ] , p<0.0001 ) . Progression-free survival improved after six cycles of R-CHOP-14 ( RR 0.50 [ 0.38 - 0.67 ] , p<0.0001 ) , and eight cycles of R-CHOP-14 ( RR 0.59 [ 0.45 - 0.77 ] , p=0.0001 ) . Overall survival improved only after six cycles of R-CHOP-14 ( RR 0.63 [ 0.46 - 0.85 ] , p=0.0031 ) . In patients with a partial response after four cycles of chemotherapy , eight cycles were not better than six cycles . INTERPRETATION Six cycles of R-CHOP-14 significantly improved event-free , progression-free , and overall survival over six cycles of CHOP-14 treatment . Response-adapted addition of chemotherapy beyond six cycles , though widely practice d , is not justified . Of the four regimens assessed in this study , six cycles of R-CHOP-14 is the preferred treatment for elderly patients , with which other approaches should be compared 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 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 The Nordic Lymphoma Group has conducted a phase ll trial in newly diagnosed primary central nervous system lymphoma patients applying an age-adjusted multi-agent immunochemotherapy regimen , which in elderly patients included temozolomide maintenance treatment . Patients aged 18–75 years were eligible . Thirty-nine patients aged 18–65 years and 27 patients aged 66–75 years were enrolled . The median age of the two age groups was 55 and 70 years , respectively .  The overall response rate was 73.8 % for the entire cohort : 69.9 % in the younger and 80.8 % in the elderly subgroup . With a median follow up of 22 months , the 2-year overall survival probability was 60.7 % in patients aged 65 years or under and 55.6 % in patients aged over 65 years ( P=0.40 ) . The estimated progression-free survival at two years was 33.1 % ( 95%CI : 19.1%–47.9 % ) in patients aged under 65 years and 44.4 % ( 95%CI : 25.6%–61.8 % ) in the elderly subgroup ( P=0.74 ) . Median duration 
    Output:
    
Elderly PCNSL patients benefit from HD-MTX-based therapy , especially if combined with oral alkylating agents .
More aggressive HD-MTX protocol s do not seem to improve outcome .
WBRT may improve outcome , but is associated with increased risk for neurological side-effects .