***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: The primary objective of this augmental , prospect i ve , uncontrolled phase II multicentre trial was to assess adverse events ( AE ) associated with malignant glioma resection using 5-aminolevulinic ( 5-ALA ) . During accrual , the st and ard of adjuvant therapy changed to concomitant radiochemotherapy with adjuvant temozolomide ( RT/TMZ ) . Thus , this study also provided a platform for investigating the influence of RT/TMZ on survival in patients with fluorescence-guided resections . Malignant glioma patients , aged 18–75 years and with a Karnofsky performance score ( KPS ) ≥70 % , were eligible . Data were collected on adverse events , KPS , survival and adjuvant therapies . In 243 patients evaluable for safety , 6-week AE incidence was 51.9 % ( nervous system disorders : 30.0 % ) . Three patients experienced four possibly drug-related AEs . Grade III/IV incidence was 18.9 % ( nervous system disorders : 10.7 % ) . About 48 h after surgery , AE incidence was 26.3 % ( 9.9 % grade III/IV ) , which was related to overall survival . A total of 219 patients ( glioblastoma 206 ; anaplastic astrocytoma : 13 ) qualified for efficacy analysis . Median overall survival was 14.1 months ( 95 % CI : 12.0–16.6 ) , but 16.3 ( 13–19.2 ) months in 122 glioblastoma patients receiving RT/TMZ compared to 11.9 ( 9.6–14.1 ) months in the remaining 84 patients ( P = 0.0194 ) . Older patients ( ≥60 years ) had less adjuvant therapies than younger patients . Median survival of older glioblastoma patients with RT/TMZ was also significantly prolonged ( 16.3 ; 12.0–17.2 months vs. 11.2 ; 7.4–14.1 , hazard ratio = 0.55 ; 0.32–0.92 ) . Risks of surgery were similar to past experiences with 5-ALA . Ancillary analyses demonstrated surgical glioblastoma patients , including the elderly , to have derived benefit from RT/TMZ . Thus , older patients should not generally be excluded from accepted therapies ( fluorescence-guided resection plus RT/TMZ ) 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 In high- grade glioma surgery , several techniques are used to achieve the maximum cytoreductive treatment preserving neurological functions . However , the effectiveness of all the methods used alone is reduced by specific limitations of each . We assessed the reliability of a multimodal strategy based on 5-aminolevulinic acid ( 5-ALA ) and neuronavigation . We prospect ively studied 18 patients with suspected , non eloquent-area malignant gliomas amenable for complete resection .  Conventional illumination was used until the excision appeared complete . The cavity was then systematic ally inspected in violet-blue light to identify any residual tumour . Multiple biopsies of both fluorescent and non-fluorescent tissue were performed in all cases . Each specimen was labelled according to the sampling location ( inside or outside the boundary set by the neuronavigator ) . The sample s were analysed by a neuropathologist blinded to the intraoperative classification . We review ed the results of both methods , either singly or in combination . Individual analysis showed higher 5-ALA reliability compared to neuronavigation . However , several false-negative fluorescent specimens were detected . With the combined use of fluorescence and neuroimaging , only 1 sample ( negative for both 5-ALA and navigation ) was tumoral tissue . In our experience , the combined approach showed the best sensitivity and it is recommended in cases of lesions involving non-eloquent areas The extent of resection in high grade glioma is increasingly been shown to positively effect survival . Nevertheless , heterogeneity and migratory behavior of glioma cells make gross total resection very challenging . Several techniques were used in order to improve the detection of residual tumor . Aim of this study was to analyze advantages and limitations of fluorescence and image guided resection . A multicentric prospect i ve study was design ed to evaluate the accuracy of each method . Furthermore , the role of 5-aminolevulinc acid and neuronavigation were review ed . Twenty-three patients harboring suspected high grade glioma , amenable to complete resection , were enrolled .  Fluorescence and image guides were used to perform surgery . Multiple sample s were obtained from the resection cavity of each lesion according to 5-ALA staining positivity and boundaries as delineated by neuronavigation . All sample s were analyzed by a pathologist blinded to the intra-operative labeling . Decision-making based on fluorescence showed a sensitivity of 91.1 % and a specificity of 89.4 % ( p<0.001 ) . On the other h and , the image-guided resection accuracy was low ( sensitivity : 57.8 % ; specificity : 57.4 % ; p=0.346 ) . We observed that the sensitivity of 5-ALA can be improved by the combined use of neuronavigation , but this leads to a significant reduction in specificity . Thus , the use of auxiliary techniques should always be subject to critical skills of the surgeon . We advocate a large-scale study to further improve the assessment of multimodal approaches Purpose The aim of the study was to compare presurgical 18F-fluoroethyl-L-tyrosine ( 18F-FET ) uptake and Gd-diethylenetriaminepentaacetic acid ( DTPA ) enhancement on MRI ( Gd ) with intraoperative 5-aminolevulinic acid ( 5-ALA ) fluorescence in cerebral gliomas . Methods 18F-FET positron emission tomography ( PET ) was performed in 30 patients with brain lesions suggestive of diffuse WHO grade II or III gliomas on MRI .  PET and MRI data were coregistered to guide neuronavigated biopsies before resection . After oral application of 5-ALA , 38 neuronavigated biopsies were taken from predefined tumour areas that were positive or negative for 18F-FET or Gd and checked for 5-ALA fluorescence . 18F-FET uptake with a mean tumour to brain ratio ≥1.6 was rated as positive . Results Of 38 biopsies , 21 corresponded to high- grade glioma tissue ( HGG ) of WHO grade III ( n = 19 ) or IV ( n = 2 ) and 17 biopsies to low- grade glioma tissue ( LGG ) of WHO grade II . In biopsies corresponding to HGG , 18F-FET PET  was positive in 86 % ( 18/21 ) , but 5-ALA and Gd in only 57 % ( 12/21 ) . A mismatch between Gd and 5-ALA was observed in 6 of 21 cases of HGG biopsy sample s ( 3 Gd-positive/5-ALA-negative and 3 Gd-negative/5-ALA-positive ) . In biopsies corresponding to LGG , 18F-FET was positive in 41 % ( 7/17 ) , while 5-ALA and Gd were negative in all but one instance . All tumour areas with 5-ALA fluorescence were positive on 18F-FET PET . Conclusion There are differences between 18F-FET and 5-ALA uptake in cerebral gliomas owing to a limited sensitivity of 5-ALA to detect tumour tissue especially in LGG . 18F-FET PET is more sensitive to detect glioma tissue than 5-ALA fluorescence and should be considered as an additional tool in resection planning 5-Aminolevulenic acid ( ALA ) is a naturally occurring compound in all living mammalian cells.13 ALA is formed within the mitochondria from glycine and metabolized along a pathway in the cytosol and mitochondria into protoporphyrin-IX ( PpIX ) before combining with ferrous to form heme.6,12,14,15 The transformation from PpIX to heme is a rate-limiting step in all tumor cells leading to accumulation of PpIX in the mitochondria of these cells.6,12,14,15 PpIX fluoresces under blue light , and its fluorescence can be observed leading to the application of fluorescence-guided resection ( FGR ) and fluorescence image-guided surgery (FIGS).6,14,15 Stummer et al.14 reported a prospect i ve , uncontrolled series of high- grade gliomas in 2000 and concluded that ALA-induced FGR was very specific and highly sensitive and led to complete resection of enhanced tumor tissue in more than 60 % of patients . The ALA study group reported a r and omized , controlled trial ( RCT ) in which the study population had high- grade gliomas removed using ALA-induced FGR.15  Gross total resection was accomplished in 65 % of the study group compared with 35 % of the controls ( P 0.001 ) , with a tumor-free survival gain of more than 6 weeks ( P 0.001).15 Eljamel et al6 reported an RCT in which ALA Photofrininduced FIGS and repetitive photodynamic therapy ( PDT ) were used and demonstrated that complete surgical resection was achieved in 77 % of the study group , with a tumor-free survival gain of 3.8 months . This study prospect ively explored the use of ALAinduced fluorescence in a wide range of intracranial tumors that may benefit from this technology in terms of intraoperative localization or gross total resection BACKGROUND Oral application of 20 mg/kg body weight of 5-aminolevulinic acid ( ALA ) leads to a highly specific accumulation of fluorescent Protoporphyrin IX ( PPIX ) in malignant glioma tissue . In the past few years , we have participated in several clinical studies design ed to investigate fluorescence guided resection ( FGR ) and photodynamic therapy ( PDT ) . METHODS PPIX selectivity and PPIX bleaching during PDT were assessed with spectroscopic measurements . FGR was performed in 18 clinics in Germany ( ALA-Glioma Study Group , participants see end of paper ) in a phase III trial comprising an ALA group and a white-light group . PDT was performed with microlens fibers or cylindrical diffusers postsurgically to the resection bed . Additionally , a protocol for the interstitial stereotactic placement of cylindrical diffusers was 
    Output:
    
Patients in the 5-ALA group had higher 6-month progression free survival and overall survival than those in the white light group .
Conclusion Based on available literature , there is level 2 evidence that 5-ALA-guided surgery is more effective than conventional neuronavigation-guided surgery in increasing diagnostic accuracy and extent of tumor resection , enhancing quality of life , or prolonging survival in patients with high- grade malignant gliomas