***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: Between May 1986 and February 1988 , 57 patients were accrued to the second dose level of a Phase I/II Pediatric Oncology Group ( POG ) study exploring the use of hyperfractionated radiation therapy ( HRT ) in children with high‐risk brain stem tumors . Local fields were treated with fraction sizes of 117 cGy given twice daily , with a minimum interfraction interval of 6 hours , to a total dose of 7020 cGy in 60 fractions over 6 weeks . Information regarding clinical status during HRT was available for 55 patients ( 44 [ 80 % ] improved , 6 remained stable , and 5 deteriorated ) . Results of initial and follow‐up computed tomography ( CT ) scan and /or magnetic resonance imaging ( MRI ) were available for review for 52 patients . One patient had a complete response ( CR ) to treatment , 3 had a partial response ( PR ) ( more than 50 % response ) , and 40 remained stable , for a total response rate ( CR + PR + stable ) of 77 % . Median time to disease progression was 6 months . Median survival time was 10 months . Survival rate was 39.6 % ( st and ard error [ SE ] = 6.6 % ) at 1 year and 23 % ( SE = 5.8 % ) at 2 years . Complications of treatment included an enhanced skin reaction in six patients and otitis media and /or externa in nine . One patient bled into tumor shortly after completion of HRT , and three had intralesional necrosis . Five patients continued taking steroids for protracted periods in the face of improved clinical and /or radiologic findings . Complications related to the use of steroids included opportunistic infections , impaired glucose tolerance , hypertension , osteoporosis , and significant mood changes . In no patient was there evidence of any late injury attributable to HRT . When compared with results of treatment with HRT at a lower dose level ( 6600 cGy ) , there appears to be a trend toward improved survival at 7020 cGy despite a less favorable patient population at the higher dose level . A second dose escalation to 7560 cGy in 60 fractions over 6 weeks has been implemented as planned BACKGROUND The pediatric diffuse intrinsic pontine glioma ( DIPG ) outcome remains dismal despite multiple therapeutic attempts . PURPOSE To compare the results of treatment of pediatric diffuse intrinsic pontine glioma ( DIPG ) using hypofractionated versus conventional radiotherapy . PATIENTS AND METHODS Seventy-one newly diagnosed DIPG children were r and omized into hypofractionated ( HF ) ( 39Gy/13 fractions in 2.6weeks ) and conventional ( CF ) arm ( 54Gy/30 fractions in 6weeks ) . RESULTS The median and one-year overall survival ( OS ) was 7.8months and 36.4±8.2 % for the hypofractionated arm , and 9.5 and 26.2±7.4 % for the conventional arm respectively . The 18-month OS difference was 2.2 % . The OS hazard ratio ( HR ) was 1.14 ( 95 % CI : 0.70 - 1.89 ) ( p=0.59 ) . The hypofractionated arm had a median and one-year progression-free survival ( PFS ) of 6.6months and 22.5±7.1 % , compared to 7.3 and 17.9±7.1 % for the conventional arm . The PFS HR was 1.10 ( 95 % CI : 0.67 - 1.90 ) ( p=0.71 ) . The 18-month PFS difference was 1.1 % . These differences exceed the non-inferiority margin . The immediate and delayed side effects were not different in the 2 arms . CONCLUSIONS Hypofractionated radiotherapy offers lesser burden on the patients , their families and the treating departments , with nearly comparable results to conventional fractionation , though not fulfilling the non-inferiority assumption This multicenter phase I study aim ed to establish the recommended dose ( RD ) of the epidermal growth factor receptor ( EGFR ) inhibitor erlotinib , given as monotherapy or with radiotherapy to children with malignant brain tumors . Group 1 included patients with refractory or relapsing brain tumors receiving erlotinib alone , and group 2 included newly diagnosed patients with brainstem gliomas receiving radiotherapy and erlotinib .  A conventional 3 + 3 dose escalation and a continual re assessment method , respectively , were utilized in 4 dose levels : 75 , 100 , 125 , and 150 mg/m² per day . Fifty-one children were enrolled ( 30 and 21 , respectively ) ; 50 received treatment . The RD of erlotinib was 125 mg/m² per day as monotherapy or in combination with radiotherapy . Overall , 230 adverse events in 44 patients were possibly treatment related ( 216 , grade s 1 and 2 ; 9 , grade 3 ; 1 , grade 4 ; 4 , grade 5 ) . Dermatologic and neurologic symptoms were common ; intratumoral hemorrhage was confirmed in 3 patients . In group 1 , 8 of 29 patients ( 28 % ) had stable disease with tumor regression approaching 50 % in a malignant glioma and an anaplastic oligoastrocytoma . In group 2 , overall survival was 12.0 months . EGFR overexpression by immunohistochemistry was found in 17 of 38 ( 45 % ) tumor sample s analyzed , with a partial gain of 7p11.2 in 1 glioblastoma ; phosphate and tensin homolog loss was frequent in brainstem glioma ( 15 of 19 ) . Mean ( 95 % CI ) apparent clearance and volume of distribution  for erlotinib were 4.0 L/h ( 3.4 - 4.5 L/h ) and 98.6 L ( 69.8 - 127.0 L ) , respectively , and were independent of the dose level ; mean half-life was 16.6 hours . Thus , erlotinib 125 mg/m² per day has an acceptable tolerability profile in pediatric patients with brain tumors and can be combined with radiotherapy This phase II study was design ed to assess the safety and efficacy of gefitinib given with and following radiation therapy in children newly diagnosed with a poor prognosis brainstem glioma . Eligible patients were those with a previously untreated nondisseminated diffuse intrinsic brainstem glioma . Histological confirmation was not required , provided patients had a characteristic clinical history and MRI findings . Treatment consisted of gefitinib , administered orally , 250 mg/m(2)/day , during st and ard external beam radiotherapy , continuing for up to 13 monthly courses in the absence of disease progression or unacceptable toxicity . Toxicities , particularly intratumoral hemorrhage , were monitored . Pharmacokinetics and investigational imaging studies were performed in consenting patients . Forty-three eligible patients were included in the study . Therapy was well tolerated ; only 4 patients were withdrawn from the study for dose-limiting toxicity after receiving therapy for 6 , 9 , 17 , and 24 weeks . The 12- and 24-month progression-free survival rates were 20.9 ±5.6 % and 9.3 ±4 % , respectively . Overall survival rates were 56.4 ±7.6 % and 19.6 ±5.9 % , respectively , which appear nominally superior to other contemporaneous Pediatric Brain Tumor Consortium trials . Three patients remain progression-free survivors with ≥36 months follow-up . The observation that a subset of children with this generally fatal tumor experienced long-term progression-free survival , coupled with recent observations regarding the molecular features of brainstem gliomas , raises the possibility that prospect i ve molecular characterization may allow enrichment of treatment responders and improvement in outcome results in future studies of biologically targeted agents The purpose of this study is to evaluate the efficacy and toxicity of radiation therapy ( RT ) with concurrent temozolomide ( TMZ ) chemotherapy followed by adjuvant TMZ in children with diffuse intrinsic pontine glioma ( DIPG ) . Newly diagnosed patients younger than 18 years with histologically proven DIPG were treated with focal radiotherapy to a dose of 54 Gy in 30 fractions along with concurrent daily TMZ ( 75 mg/m2/day ) . Four weeks after completing the initial RT – TMZ schedule , adjuvant TMZ ( 200 mg/m2/day , days 1–5 ) was given every 28 days up to six cycles . Responses/progressions were assessed by clinical and 2-monthly MRI follow-up studies . Between September 2005 and September 2009 , 21 patients with newly diagnosed histologically confirmed DIPG were eligible for this study . Median age at diagnosis was 6.4 years ( range 4–16 years ) . At last up date in August 2010 , 17 children have died , 1 child was alive with progressive disease and 3 with stable disease . Metastatic relapse was documented in the cerebral site in two patients and in spinal cord in two cases . The median time to progression was 7.5 months ( range 28 days–14.5 months ) and the median survival was 11.7 months ( range 26 days–17.5 months ) . The 1-year PFS and the 1-year OS were 33 and 50 % , respectively . Five patients presented radiological findings compatible with pseudoprogression during the treatment . Haematological toxicity ( Grade III/IV thrombocytopenia and leucopenia ) was the most commonly found and led to dose reductions of TMZ in 58 % of the patients . TMZ with radiation therapy has not yielded any significant improvement in outcome of children with DIPG and is associated with higher toxicity compared with radiotherapy alone . Novel treatment modalities are needed to improve the outcome of these patients PURPOSE In September 1984 , the Pediatric Oncology Group began accrual to a Phase I/II study design ed to assess the efficacy and toxicity of sequentially escalated doses of hyperfractionated ( twice daily ) radiotherapy in children with poor-prognosis brain stem tumors . Pediatric Oncology Group Study # 8495 closed in June 1990 with a total of 136 patients on study . We report here the outcome of patients treated at the third and final dose level ( 75.6 Gy ) , and compare the results to those obtained at the 66 and 70.2 Gy dose levels . METHODS AND MATERIAL S Patients eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the midbrain , pons or medulla . Histological confirmation of diagnosis was not m and atory provided that the clinical and radiological findings were typical for brain stem glioma . Treatment consisted of radiotherapy delivered to local fields . At the third dose level , fraction sizes of 1.26 Gy were given twice daily , with a minimum interfraction interval of 6 hr to a dose of 75.6 Gy in 60 fractions over 6 weeks . Between 5/89 and 6/90 , 41 patients were accrued to the study . Two were excluded from analysis leaving 39 evaluable patients , 21 male and 19 female , whose ages ranged from 3 to 15 years ( median 7.5 years ) . RESULTS Following treatment , neurological improvement was reported in 30/39 ( 77 % ) of the patients . On central review of imaging studies in 29 patients , one patient was found to have had a complete response to radiotherapy , five a partial ( > 50 % response ) , and only three had non-responding or progressive disease . The median time to disease progression was 7 months ; median survival time was 10 months ; survival at 1 year was 39.9 % ( SE 8.3 % ) and at 2 years , 7 % ( SE 4.8 % ) . The pattern of failure was local in all patients ; in addition six had evidence of leptomeningeal seeding . Morbidity of treatment included an enhanced skin reaction ( 21 % ) , otitis media and /or externa ( 26 % ) , and steroid use > 3 months ( 62 % ) . Intralesional necrosis was a frequent finding ( 45 % ) on imaging studies performed at a median time of 6 weeks post treatment . CONCLUSION The results of treatment in terms of progression-free survival and overall survival are not significantly different ( at p = .55 and p = .46 , respectively ) from those obtained at the two previous dose levels . There is no evidence that higher doses of hyperfractionated radiotherapy given as in this study improve the outlook of patients with poor-risk brain stem gliomas Background . Fewer than 20 % of children with intrinsic brain stem tumors survive longer than 2 years . Although some improvement has been noted in recent trials using higher doses of hyperfractionated radiation therapy ( HRT ) , the feasibility of pre‐irradiation chemotherapy has not been explored in these patients with poor prognosis Background . Brain stem gliomas remain the childhood brain tumors most resistant to treatment . Treatments with hyperfractionated radiotherapy at doses as high as 7560 cGy have been fairly well tolerated . This study was undertaken to determine the toxicity and possible efficacy of hyperfractionated radiotherapy in children with brain stem gliomas using 100 cGy of radiation twice daily , to a total dose of 7800 c 
    Output:
    
The mainly observed adverse effect was local erythema and dry desquamation especially behind the auricles .
There were some other toxicities , but there was no statistically significant difference between treatment groups .
We judged the quality of evidence to be moderate ( i.e. further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate ) for OS , and low for PFS and toxicities .