***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: PURPOSE To compare conventional fractionation with hypofractionation in patients with a glioblastoma multiforme . Endpoints of the analysis are overall survival and palliative effect . MATERIAL S AND METHODS From 1988 to 1998 , 155 patients with pathologically confirmed glioblastoma multiforme were prospect ively analysed . Patients without irradiation and patients receiving an interstitial boost  were excluded from this analysis . Three different radiation schemes were used in subsequent periods ; 33x2 , 8x5 and 4x7 Gy . In the last 5 years a scheme of 4x7 Gy conformal irradiation was given to poor prognosis patients . The more favourable group received the conventionally fractionated scheme up to 66 Gy . RESULTS Median survival was 7 , 5.6 and 6.6 months for the 33x2 , 8x5 and 4x7 Gy , respectively . In general , patients in the hypofractionation group had far worse prognostic factors compared with patients treated with the conventional scheme . The period of neurological improvement or stabilisation was similar between the 4x7 and 33x2 Gy group . CONCLUSION An extreme hypofractionation scheme of 4x7 Gy conformal irradiation in poor prognostic glioblastoma patients is well tolerated , convenient for the patient and provides equal palliation without negative effects on survival compared with conventional fractionation Background Biological brain tumor imaging using O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET combined with inverse treatment planning for locally restricted dose escalation in patients with glioblastoma multiforme seems to be a promising approach . The aim of this study was to compare inverse with forward treatment planning for an integrated boost dose application in patients suffering from a glioblastoma multiforme , while biological target volumes are based on FET-PET and MRI data sets . Methods In 16 glioblastoma patients an intensity-modulated radiotherapy technique comprising an integrated boost ( IB-IMRT )  and a 3-dimensional conventional radiotherapy ( 3D-CRT ) technique were generated for dosimetric comparison . FET-PET , MRI and treatment planning CT ( P-CT ) were co-registrated . The integrated boost volume ( PTV1 ) was auto-contoured using a cut-off tumor-to-brain ratio ( TBR ) of ≥ 1.6 from FET-PET . PTV2 delineation was MRI-based . The total dose was prescribed to 72 and 60 Gy for PTV1 and PTV2 , using daily fractions of 2.4 and 2 Gy . Results After auto-contouring of PTV1 a marked target shape complexity had an impact on the dosimetric outcome . Patients with 3 - 4 PTV1 subvolumes vs. a single volume revealed a significant decrease in mean dose ( 67.7 vs. 70.6 Gy ) . From convex to complex shaped PTV1 mean doses decreased from 71.3 Gy to 67.7 Gy . The homogeneity and conformity for PTV1 and PTV2 was significantly improved with IB-IMRT . With the use of IB-IMRT the minimum dose within PTV1 ( 61.1 vs. 57.4 Gy ) and PTV2 ( 51.4 vs. 40.9 Gy ) increased significantly , and the mean EUD for PTV2 was improved ( 59.9 vs. 55.3 Gy , p < 0.01 ) . The EUD for PTV1 was only slightly improved ( 68.3 vs. 67.3 Gy ) . The EUD for the brain was equal with both planning techniques . Conclusion In the presented planning study the integrated boost concept based on inversely planned IB-IMRT is feasible . The FET-PET-based automatically contoured PTV1 can lead to very complex geometric configurations , limiting the achievable mean dose in the boost volume . With IB-IMRT a better homogeneity and conformity , compared to 3D-CRT , could be achieved Background Intensity-modulated radiotherapy ( IMRT ) can deliver different doses to two target volumes with high conformity . The purpose of the present study was to compare outcomes provided by two different optimization methods , overlapping structure-based and non-overlapping structure-based methods , for simultaneous integrated boost (SIB)-IMRT for malignant gliomas . Methods Treatment plans for three glioblastomas and one anaplastic astrocytoma were analyzed in the present study . The planning protocol was to deliver 70 Gy/28 fractions ( fr ) to the gross tumor volume ( GTV ) and 56 Gy/28 fr to the surrounding edema . Two different optimization methods were tested for optimizing dose distribution to the GTV and the surrounding edema . One method was the “ including method ” , an overlapping structure-based ( GTV and the clinical target volume [ CTV ] ) optimization method . The other method was the “ annulus method ” , a non-overlapping structure-based ( GTV and the subtracted volume ) optimization method .  Dosimetric indexes derived from dose-volume histograms ( DVHs ) were used for the analysis . Results There was no significant difference between the two methods in the mean doses of the target volumes and the doses delivered to the 5 % or 95 % target volumes ( D05 or D95 ) . The mean dose to the brain by the including method was significantly higher than that delivered by the annulus method ( P = 0.0001 ) . The D05 of the brain showed no significant difference between the two methods . Conclusion The two optimization methods provided comparable dose distributions within the target volumes and normal brain PURPOSE To determine the maximum tolerated dose ( MTD ) of fractionated intensity-modulated radiotherapy ( IMRT ) with temozolomide ( TMZ ) in patients with glioblastoma . METHODS AND MATERIAL S A Phase I clinical trial was performed . Eligible patients had surgically resected or biopsy-proven glioblastoma . Patients started TMZ ( 75 mg/day ) during IMRT and continued for 1 year ( 150 - 200 mg/day , Days 1 - 5 every 28 days ) or until disease progression . Clinical target volume 1 ( CTV1 ) was the tumor bed + /- enhancing lesion with a 10-mm margin ; CTV2 was the area of perifocal edema with a 20-mm margin . Planning target volume 1 ( PTV1 ) and PTV2 were defined as the corresponding CTV plus a 5-mm margin . IMRT was delivered in 25 fractions over 5 weeks . Only the dose for PTV1 was escalated ( planned dose escalation : 60 Gy , 62.5 Gy , 65 Gy ) while maintaining the dose for PTV2 ( 45 Gy , 1.8 Gy/fraction ) . Dose limiting toxicities ( DLT ) were defined as any treatment-related nonhematological adverse effects rated as Grade > or=3 or any hematological toxicity rated as > or=4 by Radiation Therapy Oncology Group ( RTOG ) criteria . RESULTS Nineteen consecutive glioblastoma were treated with step- and -shoot IMRT , planned with the inverse approach ( dose to the PTV1 : 7 patients , 60 Gy ; 6 patients , 62.5 Gy ; 6 patients , 65 Gy ) . Five coplanar beams were used to cover at least 95 % of the target volume with the 95 % isodose line . Median follow-up time was 23 months ( range , 8 - 40 months ) . No patient experienced DLT . Grade 1 - 2 treatment-related neurologic and skin toxicity were common ( 11 and 19 patients , respectively ) . No Grade > 2 late neurologic toxicities were noted . CONCLUSION Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg BACKGROUND In 2004 , a r and omised phase III trial by the European Organisation for Research and Treatment of Cancer ( EORTC ) and National Cancer Institute of Canada Clinical Trials Group ( NCIC ) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy .  We report the final results with a median follow-up of more than 5 years . METHODS Adult patients with newly diagnosed glioblastoma were r and omly assigned to receive either st and ard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide . The methylation status of the methyl-guanine methyl transferase gene , MGMT , was determined retrospectively from the tumour tissue of 206 patients . The primary endpoint was overall survival . Analyses were by intention to treat . This trial is registered with Clinical trials.gov , number NCT00006353 . FINDINGS Between Aug 17 , 2000 , and March 22 , 2002 , 573 patients were assigned to treatment . 278 ( 97 % ) of 286 patients in the radiotherapy alone group and 254 ( 89 % ) of 287 in the combined-treatment group died during 5 years of follow-up . Overall survival was 27.2 % ( 95 % CI 22.2 - 32.5 ) at 2 years , 16.0 % ( 12.0 - 20.6 ) at 3 years , 12.1 % ( 8.5 - 16.4 ) at 4 years , and 9.8 % ( 6.4 - 14.0 ) at 5 years with temozolomide , versus 10.9 % ( 7.6 - 14.8 ) , 4.4 % ( 2.4 - 7.2 ) , 3.0 % ( 1.4 - 5.7 ) , and 1.9 % ( 0.6 - 4.4 ) with radiotherapy alone ( hazard ratio 0.6 , 95 % CI 0.5 - 0.7 ; p<0.0001 ) . A benefit of combined therapy was recorded in all clinical prognostic subgroups , including patients aged 60 - 70 years . Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy . INTERPRETATION Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up . A few patients in favourable prognostic categories survive longer than 5 years . MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide . FUNDING EORTC , NCIC , Nélia and Amadeo Barletta Foundation , Schering-Plough PURPOSE Median survival of patients with glioblastoma multiforme ( GBM ) is only about 4 months with surgery and about 9 months for surgery followed by radiotherapy . Prolonged treatment is futile for many patients and the time of treatment and hospitalization should be minimized . METHODS AND MATERIAL S This was a prospect i ve , nonr and omized study of 30 patients treated with a hypofractionated radiation scheme ( 42 Gy in 14 fractions ) . RESULTS Median survival was 36 weeks . Age , Karnofsky performance status ( KPS ) and extent of surgery were strongly interrelated and all correlated with survival ( p < 0.05 ) . Three prognostic groups were identified . Patients with three favorable prognostic factors ( age < 50 , KPS 80 - 100 , and > or = 75 % of the tumor removed ) had the best prognosis ( median survival 50 weeks ) . Patients with no favorable prognostic factors ( age > or = 50 , KPS < or = 70 , and < 75 % of the tumor removed ) had the worst prognosis ( median survival 25 weeks ) . Median survival of the intermediate group ( with one or two favorable prognostic factors ) was 38 weeks . No severe acute or late toxicity was observed . CONCLUSION The treatment results are comparable to those achieved with conventional radiotherapy schemes . Based on the number of favorable prognostic factors ( age < 50 , KPS 80 - 100 and > or = 75 % of tumor resected ) the radiation schedule should be selected OBJECTIVE The objective of the Brain Tumor Cooperative Group NIH Trial 87 - 01 trial was to investigate the effect of additional implanted radiation therapy in newly diagnosed patients with pathologically confirmed malignant gliomas . METHODS The study involved a r and omized comparison of surgery , external beam radiotherapy , and carmustine ( BCNU ) versus surgery , external beam therapy , interstitial radiotherapy boost , and BCNU in newly diagnosed malignant gliomas . 125I was chosen as best suited for this effort because it allowed preimplantation planning and postimplantation quality assurance review . Two hundred ninety-nine patients met the eligibility criteria and were r and omized into the two arms of the study between December 1987 and April 1994 . Follow-up continued for an additional 3 years . Twenty-nine patients were identified as having committed protocol violations and were excluded , result ing in 270 subjects in the Valid Study Group . One hundred thirty-seven patients received external beam radiation and BCNU , and 133 underwent the 125I implantation plus external beam radiation and BCNU therapy . RESULTS The overall median survival for the Valid Study Group was 64.3 weeks . The median survival for patients receiving additional therapy of 125I was 68.1 weeks , and median survival for those receiving only external beam radiation and BCNU was 58.8 weeks . The cumulative proportion surviving between the two treatment groups was not statistically significantly different ( log-rank test , P = 0.101 ) . As in other studies in the literature , age , Karnofsky score , and pathology 
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From the dosimetrical point of view , conformal radiotherapy and IMRT provide similar results in terms of target coverage , while IMRT is better in terms of dose conformity , in reducing the maximum dose to the organs at risk and in healthy brain sparing .
In clinical reports , a wide variability was recorded concerning dose per fraction , total dose , and chemotherapy administration .
A comprehensive qualitative comparison with literature on similar non-IMRT clinical series showed that in most IMRT series excellent compliance and low rates of toxicity were recorded .
Hypofractionated regimens in association with chemotherapy showed results that are even superior to the st and ard treatment .
According to the available data , the dosimetrical advantages of IMRT translate into the clinical capability of delivering higher dose levels in a shorter time .
This approach in glioblastoma patients with good prognosis suggests the possibility of improving outcomes without an increase in toxicity