***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 5-Aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas-a finding that is under investigation for intraoperative identification and resection of these tumours . We aim ed to assess the effect of fluorescence-guided resection with 5-aminolevulinic acid on surgical radicality , progression-free survival , overall survival , and morbidity . METHODS 322 patients aged 23 - 73 years with suspected malignant glioma amenable to complete resection of contrast-enhancing tumour were r and omly assigned to 20 mg/kg bodyweight 5-aminolevulinic acid for fluorescence-guided resection ( n=161 ) or to conventional microsurgery with white light ( n=161 ) . The primary endpoints were the number of patients without contrast-enhancing tumour on early MRI ( ie , that obtained within 72 h after surgery ) and 6-month progression-free survival as assessed by MRI . Secondary endpoints were volume of residual tumour on postoperative MRI , overall survival , neurological deficit , and toxic effects . We report the results of an interim analysis with 270 patients in the full- analysis population ( 139 assigned 5-aminolevulinic acid , 131 assigned white light )  , which excluded patients with ineligible histological and radiological findings as assessed by central review ers who were masked as to treatment allocation ; the interim analysis result ed in termination of the study as defined by the protocol . Primary and secondary endpoints were analysed by intention to treat in the full- analysis population . The study is registered at http://www . clinical trials.gov as NCT00241670 . FINDINGS Median follow-up was 35.4 months ( 95 % CI 1.0 - 56.7 ) . Contrast-enhancing tumour was resected completely in 90 ( 65 % ) of 139 patients assigned 5-aminolevulinic acid compared with 47 ( 36 % ) of 131 assigned white light ( difference between groups 29 % [ 95 % CI 17 - 40 ] , p<0.0001 ) . Patients allocated 5-aminolevulinic acid had higher 6-month progression free survival than did those allocated white light ( 41.0 % [ 32.8 - 49.2 ] vs 21.1 % [ 14.0 - 28.2 ] ; difference between groups 19.9 % [ 9.1 - 30.7 ] , p=0.0003 , Z test ) . Groups did not differ in the frequency of severe adverse events or adverse events in any organ system class reported within 7 days after surgery . INTERPRETATION Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour , leading to improved progression-free survival in patients with malignant glioma Efforts to improve local control and survival by increasing the dose of once‐daily radiation therapy beyond 70 Gray ( Gy ) for patients with malignant gliomas have as yet been unsuccessful . Hyperfractionated radiation therapy ( HF ) should allow for delivery of a higher total dose without increasing normal tissue late effects , whereas accelerated hyperfractionated radiation therapy ( AHF ) may minimize tumor re population by shortening overall treatment time . The Radiation Therapy Oncology Group ( RTOG ) conducted a r and omized Phase I/II study of escalating doses of HF and AHF with carmustine ( bis‐chloroethyl nitrosourea [ BCNU ] ) for adults with supratentorial glioblastoma multiforme ( GBM ) or anaplastic astrocytoma ( AA ) . Primary study endpoints were overall survival and acute and chronic treatment‐related toxicity PURPOSE Alternative dosing schedules of temozolomide may improve survival in patients with newly diagnosed glioblastoma ( GBM ) by increasing the therapeutic index , overcoming common mechanisms of temozolomide resistance , or both . The goal of this r and omized phase II study was to evaluate two different temozolomide regimens in the adjuvant treatment of newly diagnosed GBM . PATIENTS AND METHODS Adult patients with newly diagnosed GBM were r and omly assigned to receive st and ard radiotherapy with concurrent daily temozolomide followed by six adjuvant cycles of either dose-dense ( 150 mg/m(2 ) days 1 to 7 and 15 to 21 ) or metronomic ( 50 mg/m(2 ) continuous daily ) temozolomide . Maintenance doses of 13-cis-retinoic acid were then administered until tumor progression . The primary end point was overall survival ( OS ) at 1 year . Tumor tissue was assayed to determine O(6)-methylguanine-DNA methyltransferase ( MGMT ) promoter methylation status . RESULTS Eighty-five eligible patients were enrolled ; 42 were r and omly assigned to dose-dense and 43 to metronomic temozolomide . The 1-year survival rate was 80 % for the dose-dense arm and 69 % for the metronomic arm ; median OS was 17.1 months ( 95 % CI , 14.0 to 28.1 months ) and 15.1 months ( 95 % CI , 12.3 to 18.9 months ) , respectively . The most common toxicities were myelosuppression ( leukopenia , neutropenia , and thrombocytopenia ) and elevated liver enzymes . Pseudoprogression was observed in 37 % of assessable patients and may have had an impact on estimates of progression-free survival ( 6.6 months in the dose-dense arm and 5.0 months in the metronomic arm ) . CONCLUSION Both dose-dense and metronomic temozolomide regimens were well tolerated with modest toxicity . The dose-dense regimen appears promising , with 1-year survival of 80 % One hundred and three patients with hemispheric supratentorial glioblastoma multiforme were studied . All patients were operated on and a histologic diagnosis of glioblastoma multiforme was made . Patients were r and omly placed in one of three treatment schedules within 3 weeks of surgery : Group A : combined radiation therapy and drug ( CCNU ) therapy ( 26 cases ) ; Group B : CCNU given orally every 6–8 weeks ( 27 cases ) ; Group C : st and ard radiation therapy alone ( 50 cases ) . All patients were periodically controlled by clinical and instrumental ( EEG , scan , EMG , CAT ) evaluations ; laboratory data examinations were also frequently performed . The treatment results have been evaluated according to length of survival , social quality of life , and positive or negative response to chemotherapy . In our opinion the clinical findings are interesting but the statistical results are somewhat negative , especially when the groups of patients are not homogeneous A prospect i ve r and omized controlled multicenter phase III trial was conducted to evaluate the effects of neoadjuvant chemotherapy with nimustine (ACNU)-cisplatin ( CDDP ) when used in conjunction with radiotherapy plus adjuvant temozolomide in patients with newly diagnosed glioblastoma . The study population was r and omly assigned into one treatment and one control group . Both groups received radiotherapy followed by six cycles of adjuvant oral temozolomide ( 150–200 mg/m2 ) for 5 days every 28 days after surgery . Prior to radiotherapy , the treatment group also received two cycles , 6 weeks apart , of neoadjuvant chemotherapy with ACNU ( 40 mg/m2/day ) and CDDP ( 40 mg/m2/day ) infused continuously for 72 h. The primary end-point was median survival time . The study has closed after interim analysis with a total of 82 patients ( 48.8 % of target number ) due to unacceptable high frequency of toxicity profiles in spite of the promising actuarial survival outcome . Median survival time was 28.4 months [ 90 % confidence interval ( CI ) , 21.1 months to not available ] in the treatment group and 18.9 months ( 90 % CI , 17.1–27.4 months ) in the control group ( P = 0.2 ) . The 2-year survival rate and progression-free survival time were 50.9 % and 6.6 months ( 90 % CI , 3.5–9.5 months ) in the treatment group and 27.8 % and 5.1 months ( 90 % CI , 3.8–8.8 months ) in the control group . Grade 3 or 4 toxicity was documented in 26 ( 68.4 % ) patients in the treatment group , including three neutropenic fever and one death from sepsis , while grade 3 or 4 toxicity occurred in 6 patients ( 15.8 % ) in the control group . The high frequency of serious hematological toxicity with ACNU-CDDP neoadjuvant chemotherapy followed by radiotherapy and adjuvant temozolomide limits its usage as primary treatment for glioblastoma . Future studies should aim to identify a sub population at reduced risk for ACNU-CDDP toxicity so that the potential of this protocol can be realized BACKGROUND In this r and omized phase III study , the effectiveness as well as the side-effects of intraarterial [ i.a . ] ( 17 patients ) versus intravenous [ i.v . ] ( 16 patients ) ACNU [ Nimustine ] administration in newly diagnosed glioblastoma , were compared . PATIENTS AND METHODS All patients undenwent extensive surgical resection , and both groups were homogeneous for the other known risk factors . Thirty-three patients with glioblastoma were treated with ACNU at the dose of 80 - 100 mg/m2 . Treatment was repeated every 5 - 8 weeks for a minimum of 2 and maximum of 14 cycles . Total survival time ( TST ) and to time to progression were chosen as outcome variables . RESULTS AND CONCLUSION No significant differences in systemic and hematological toxicity between the i.a . and iv . ACNU administration routes were detected . In both groups , tolerance of the procedure was excellent . Analysis of the main outcome measured showed no significant differences between i.a . and i.v . ACNU administration : time to progression was 6 months for i.a . ACNU and 4 months for i.v . ACNU and total survival time was 17 months for i.a . ACNU and 20 months for i.v . ACNU . In spite of ACNU dose incrementation , obtained through i.a . route administration , and subsequent higher concentration in the tumor bed , no improvement could be achieved in effectiveness The effect of intratumoral recombinant interferon gamma ( rIFN-gamma ) as adjuvant to open cytoreduction and external irradiation of 60 Gy on survival in adults with a newly diagnosed high- grade cerebral glioma was studied . The patients were r and omised during surgery into the rIFN-gamma group ( n = 14 ) or the control group ( n = 17 ) , and the latter received a subcutaneous reservoir of rIFN-gamma injections . Intratumoral rIFN-gamma was given three times a week for 4 weeks until radiotherapy , escalating the dose from 5 micrograms to 50 micrograms . Both groups received external whole-brain irradiation of 40 Gy and a local boost of 20 Gy . After radiotherapy , rIFN-gamma was continued with 50 micrograms twice a week up to 9 weeks . The patients received no chemotherapy . Intratumoral rIFN-gamma was tolerated well with transient fever only . There were 12 glioblastomas ( GBs ) in the control group and nine in the rIFN-gamma group with completed irradiation . The patients were followed clinical ly and by computerised tomography ( CT ) every third month until death . Tumour responses were seen in three interferon-treated ( one still alive 45 months after operation ) and in two conventionally treated patients . The progression of the tumour volumes on CT did not differ between the IFN-treated and control groups . There were no differences in the survival times . Median survival of the  rIFN-gamma-treated patients was 54 weeks ( 95 % CI 35 - 68 ) and of the control patients 55 weeks ( 95 % CI 41 - 77 ) . Intratumoral rIFN-gamma given in the study doses does not seem to inhibit tumour growth or improve the prognosis of patients with high- grade glioma Abstract BACKGROUND : Five-aminolevulinic acid ( 5-ALA ) is used for fluorescence-guided resections of malignant glioma at a dose of 20 mg/kg ; yet , it is unknown whether lower doses may also provide efficacy . OBJECTIVE : To perform a double-blinded r and omized study comparing 3 different doses of 5-ALA . METHODS : Twenty-one patients with suspected malignant glioma were r and omly assigned to 0.2 , 2 , or 20 mg/kg 5-ALA . Investigators were unaware of dose . Intraoperatively , regions of interest were first defined in tumor core , margin , and adjacent white matter under white light . Under violet – blue illumination , the surgeon 's impression of fluorescence was recorded per region , followed by spectrometry and biopsy . Plasma was collected after administration and analyzed for 5-ALA and protoporphyrin IX ( PPIX ) content . RESULTS : The positive predictive value of fluorescence was 100 % . Visual and spectrometric fluorescence assessment 
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Compared with supportive care only , NMA evidence suggested that all treatments apart from BEV_RT prolonged survival to some extent .
When treatments were ranked according to their effects on OS , CRT ranked higher than TMZ , RT and supportive care only , with the latter ranked last .
BEV plus RT was the only treatment for which there was no clear benefit in OS over supportive care only .
Findings from the trial suggest that the intervention probably improves overall survival in this selected patient population .
For elderly people with glioblastoma who are self-caring , evidence suggests that CRT prolongs survival compared with RT and may prolong overall survival compared with TMZ alone .
For those undergoing RT or TMZ therapy , there is probably little difference in QoL overall .
Systemic anti-cancer treatments TMZ and BEV carry a higher risk of severe haematological and thromboembolic events and CRT is probably associated with a higher risk of these events .