***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 A phase II study of bevacizumab ( BVZ ) plus irinotecan ( CPT-11 ) was conducted in children with recurrent malignant glioma ( MG ) and intrinsic brainstem glioma ( BSG ) . PATIENTS AND METHODS Eligible patients received two doses of BVZ intravenously ( 10 mg/kg ) 2 weeks apart and then BVZ plus CPT-11 every 2 weeks until progressive disease , unacceptable toxicity , or a maximum of 2 years of therapy . Correlative studies included diffusion weighted and T1 dynamic contrast-enhanced permeability imaging , BVZ pharmacokinetics , and estimation of vascular endothelial growth factor receptor 2 ( VEGFR-2 ) phosphorylation in peripheral blood mononuclear cells ( P BMC ) after single-agent BVZ . RESULTS Thirty-one evaluable patients received a median of two courses of BVZ plus CPT-11 ( range , 1 to 19 ) . No sustained responses were observed in either stratum . Median time to progression for all 34 eligible patients enrolled was 127 days for MG and 71 days for BSG . Progression-free survival rates at 6 months were 41.8 % and 9.7 % for MG and BSG , respectively . Toxicities related to BVZ included grade 1 to 3 fatigue in seven patients , grade 1 to 2 hypertension in seven patients , grade 1 CNS hemorrhage in four patients , and grade 4 CNS ischemia in two patients . The mean diffusion ratio decreased after two doses of BVZ in patients with MG only . Vascular permeability parameters did not change significantly after therapy in either stratum . Inhibition of VEGFR-2 phosphorylation in P BMC was detected in eight of 11 patients after BVZ exposure . CONCLUSION BVZ plus CPT-11 was well-tolerated but had minimal efficacy in children with recurrent malignant glioma and brainstem glioma BACKGROUND The study goal was to determine whether changes in relative cerebral blood volume ( rCBV ) derived from dynamic susceptibility contrast ( DSC ) MRI are predictive of overall survival ( OS ) in patients with recurrent glioblastoma multiforme ( GBM ) when measured 2 , 8 , and 16 weeks after treatment initiation . METHODS Patients with recurrent GBM ( 37/123 ) enrolled in ACRIN 6677/RTOG 0625 , a multicenter , r and omized , phase II trial of bevacizumab with irinotecan or temozolomide , consented to DSC-MRI plus conventional MRI , 21 with DSC-MRI at baseline and at least 1 postbaseline scan . Contrast-enhancing regions of interest were determined semi-automatically using pre- and postcontrast T1-weighted images . Mean tumor rCBV normalized to white matter ( nRCBV ) and st and ardized rCBV ( sRCBV ) were determined for these regions of interest . The OS rates for patients with positive versus negative changes from baseline in nRCBV and sRCBV were compared using Wilcoxon rank-sum and Kaplan-Meier survival estimates with log-rank tests . RESULTS Patients surviving at least 1 year ( OS-1 ) had significantly larger decreases in nRCBV at week 2 ( P = .0451 ) and sRCBV at week 16 ( P = .014 ) . Receiver operating characteristic analysis found the percent changes of nRCBV and sRCBV at week 2 and sRCBV at week 16 , but not rCBV data at week 8 , to be good prognostic markers for OS-1 . Patients with positive change from baseline rCBV had significantly shorter OS than those with negative change at both week 2 and week 16 ( P = .0015 and P = .0067 for nRCBV and P = .0251 and P = .0004 for sRCBV , respectively ) . CONCLUSIONS Early decreases in rCBV are predictive of improved survival in patients with recurrent GBM treated with bevacizumab Bevacizumab , an antibody to vascular endothelial growth factor , is commonly used in the setting of recurrent glioblastoma ( rGB ) . The aim of the present study was to evaluate whether dynamic-contrast-enhanced MRI ( DCE-MRI ) derived microvascular permeability is related to bevacizumab treatment outcome in rGB . Twenty-two patients with rGB underwent DCE-MRI at a median of 2.6 weeks prior initializing bevacizumab therapy .  Follow-up MRI-scans ( DCE-MRI available for 19/22 patients ) were obtained after a median of 9.9 weeks . The volume transfer constant (Ktrans)—an estimate related to microvascular permeability — at baseline and voxel-wise-reduction ( VWR ) in Ktrans at first follow-up were measured from the entire contrast-enhancing tumor ( CET ) and correlated with progression-free and overall survival ( PFS , OS ) using uni- and multivariate cox-regression ( significance -level p < 0.05 ) . Baseline Ktrans ranged from 0.050 to 0.205 min−1 ( median , 0.109 min−1 ) . The VWR in Ktrans ranged from 19.9 to 97.2 % ( median , 89.4 % ) . Patients with lower  baseline Ktrans and higher VWR in Ktrans showed significantly longer PFS and OS . Given the strong correlation of VWR in Ktrans and CET-volume changes ( Spearman ’s ρ = −0.73 , p < 0.01 ) both variables were included in a multivariate model . Thereby , neither VWR in Ktrans nor CET-volume changes retained independent significance for PFS or OS . Pre-treatment Ktrans stratifies PFS and OS in patients with bevacizumab-treated rGB . Although early pharmacodynamics changes in Ktrans were not assessed , the VWR in Ktrans at first follow-up had no additional benefit over assessment of CET-volume changes . Further prospect i ve trials are needed to confirm these findings and to eluci date the potential role of pre-treatment Ktrans as a predictive and /or prognostic biomarker The purpose of this study was to evaluate the activity of single-agent bevacizumab in patients with recurrent anaplastic glioma and assess correlative advanced imaging parameters . Patients with recurrent anaplastic glioma were treated with bevacizumab 10 mg/kg every 2 weeks . Complete patient evaluations were repeated every 4 weeks . Correlative dynamic contrast-enhanced MR and (18)fluorodeoxyglucose PET imaging studies were obtained to evaluate physiologic changes in tumor and tumor vasculature at time points including baseline , 96 h after the first dose , and after the first 4 weeks of therapy . Median overall survival was 12 months ( 95 % confidence interval [ CI ] : 6.08 - 22.8 ) . Median progression-free survival was 2.93 months ( 95 % CI : 2.01 - 4.93 ) , and 6-month progression-free survival was 20.9 % ( 95 % CI : 10.3%-42.5 % ) . Thirteen ( 43 % ) patients achieved a partial response . The most common grade ≥ 3 treatment-related toxicities were hypertension , hypophosphatemia , and thromboembolism . Single-agent bevacizumab produces significant radiographic response in patients with recurrent anaplastic glioma but did not meet the 6-month progression-free survival endpoint . Early change in enhancing tumor volume at 4 days after start of therapy was the most significant prognostic factor for overall and progression-free survival PURPOSE Virtually all patients with malignant glioma ( MG ) eventually recur . This study evaluates the safety of concurrent stereotactic radiosurgery ( SRS ) and bevacizumab ( BVZ ) , an antiangiogenic agent , in treatment of recurrent MG . METHODS AND MATERIAL S Fifteen patients with recurrent MG , treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen  , were enrolled in this prospect i ve trial . Lesions <3 cm in diameter were treated in a single fraction , whereas those 3 to 5 cm in diameter received 5 5-Gy fractions . BVZ was administered immediately before SRS and 2 weeks later . Neurocognitive testing ( Mini-Mental Status Exam , Trail Making Test A/B ) , Functional Assessment of Cancer Therapy-Brain ( FACT-Br ) quality -of-life assessment , physical exam , and dynamic contrast-enhanced magnetic resonance imaging ( DCE-MRI )  were performed immediately before SRS and 1 week and 2 months following completion of SRS . The primary endpoint was central nervous system ( CNS ) toxicity . Secondary endpoints included survival , quality of life , microvascular properties as measured by DCE-MRI , steroid usage , and performance status . RESULTS One grade 3 ( severe headache ) and 2 grade 2 CNS toxicities were observed . No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage . Neurocognition , quality of life , and Karnofsky performance status did not change significantly with treatment . DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months . CONCLUSIONS Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospect i ve trial . A r and omized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach PURPOSE To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain . METHODS AND MATERIAL S A total of 14 patients were entered into a placebo-controlled r and omized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis . All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs . Eligible patients had undergone irradiation for head- and -neck carcinoma , meningioma , or low- to mid- grade glioma . Patients were r and omized to receive intravenous saline or bevacizumab at 3-week intervals . The magnetic resonance imaging findings 3 weeks after the second treatment and clinical signs and symptoms defined the response or progression . RESULTS The volumes of necrosis estimated on T(2)-weighted fluid-attenuated inversion recovery and T(1)-weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded ( 0 of 7 ) , all bevacizumab-treated patients did so ( 5 of 5 r and omized and 7 of 7 crossover ) with decreases in T(2)-weighted fluid-attenuated inversion recovery and T(1)-weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant . All bevacizumab-treated patients - and none of the placebo-treated patients -showed improvement in neurologic symptoms or signs . At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses , only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis ; one patient received a single additional dose of bevacizumab and the other patient received two doses . CONCLUSION The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with radiation necrosis secondary to the treatment of head- and -neck cancer and brain cancer 
    Output:
    
Regarding the pharmacodynamic value of perfusion MRI parameters derived from either DSC-MRI or DCE-MRI , most perfusion MRI parameters ( rCBV , Ktrans , CBVmax , Kpsmax , fpv , Ve and Kep ) demonstrated a consistent decrease on the follow-up MRI after treatment , indicating that perfusion MRI may be helpful for evaluating the anti-angiogenic effect of a bevacizumab-based treatment regimen .
Despite these unsolved issues , the current evidence favoring the use of perfusion MRI as a predictive/prognostic or pharmacodynamic biomarker should be considered in patients with glioma treated using a bevacizumab-based regimen