***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 
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    ***EXAMPLES*** 
    Input: BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies Purpose : Medullary thyroid carcinoma ( MTC ) is a manifestation of multiple endocrine neoplasia type 2 ( MEN2 ) syndromes caused by germline , activating mutations in the RET ( REarranged during Transfection ) proto-oncogene . V and etanib , a VEGF and EGF receptor inhibitor , blocks RET tyrosine kinase activity and is active in adults with hereditary MTC . Experimental Design : We conducted a phase I/II trial of v and etanib for children ( 5–12 years ) and adolescents ( 13–18 years ) with MTC to define a recommended dose and assess antitumor activity . The starting dose was 100 mg/m2 administered orally , once daily , continuously for 28-day treatment cycles . The dose could be escalated to 150 mg/m2/d after two cycles . Radiographic response to  v and etanib  was quantified using RECIST ( v1.0 ) , biomarker response was measured by comparing posttreatment serum calcitonin and carcinoembryonic antigen ( CEA ) levels to baseline , and a patient-reported outcome was used to assess clinical benefit . Results : Sixteen patients with locally advanced or metastatic MTC received v and etanib for a median ( range ) 27 ( 2–52 ) cycles . Eleven patients remain on protocol therapy . Diarrhea was the primary dose-limiting toxicity . In subjects with M918 T RET germline mutations ( n = 15 ) the confirmed objective partial response rate was 47 % ( exact 95 % confidence intervals , 21%–75 % ) . Biomarker partial response was confirmed for calcitonin in 12 subjects and for CEA in 8 subjects . Conclusion : Using an innovative trial design and selecting patients based on target gene expression , we conclude that v and etanib 100 mg/m2/d is a well-tolerated and highly active new treatment for children and adolescents with MEN2B and locally advanced or metastatic MTC . Clin Cancer Res ; 19(15 ) ; 4239–48 . © 2013 AACR BACKGROUND A r and omized phase III trial demonstrated that v and etanib treatment is effective in patients with metastatic medullary thyroid cancer ( MTC ) , leading to regulatory approval , but its use may be associated with toxicities that require specific monitoring and management . The objective of the present study performed in France was to describe the toxicity profile and efficacy of v and etanib treatment when given outside any trial . METHODS Sixty-eight patients were treated with v and etanib in the frame of a temporary use authorization ( ATU ) in France from August 2010 to February 2012 , when the drug was available on request for patients with locally advanced or metastatic MTC . Patients were registered by the French health authorities , and characteristics , treatment parameters , toxicity profile , and efficacy were retrospectively review ed . Eight patients were excluded from the analysis because v and etanib treatment was not administered ( n=3 ) , had been given in a trial before ATU ( n=3 ) , or was given for a non-MTC cancer ( n=2 ) . RESULTS Data from the 60 MTC patients were analyzed . Mean age was 58 years ( range 11 - 83 years ) , 39 patients were male , and six had hereditary MTC . Fifty-six ( 93 % ) had metastatic disease in the mediastinum ( 82 % ) , bones ( 65 % ) , liver ( 53 % ) , or lung ( 53 % ) , and four had only locally advanced disease . At the time of study evaluation , with a median follow-up of 20 months and a median duration of treatment of 9.7 months ( range 0.3 - 36 months ) , 15 patients were continuing v and etanib treatment ( range 18 - 36 months ) . Median progression-free survival was 16.1 months . Twenty-five patients discontinued treatment for disease progression ( range 0.3 - 29 months ) . Best tumor response was a complete response in one patient , a partial response in 12 ( 20 % ) , stable disease in 33 ( 55 % ) , and progression in seven patients ( 12 % ) . All patients had at least one adverse event ( AE ) during treatment . The main AEs were skin toxicity , diarrhea , and asthenia . Sixteen patients ( 27 % ) discontinued treatment for toxicity , and one patient died from v and etanib-induced cardiac toxicity . CONCLUSIONS V and etanib is an effective option for patients with advanced MTC . AEs should be monitored carefully and should be minimized by educating both patients and care providers and by applying symptomatic treatment and dose reduction OBJECTIVE In a phase III trial , Western patients with medullary thyroid cancer ( MTC ) treated with the oral multikinase inhibitor v and etanib showed significantly improved progression-free survival ( PFS ) and objective response rate ( ORR ) compared with placebo . The biology of MTC and pharmacokinetics ( PK ) are similar for Japanese and Western patients ; therefore , similar clinical benefit is anticipated in the Japanese population . This study evaluated the safety and tolerability of v and etanib in Japanese patients with unresectable locally advanced or metastatic MTC . METHODS This was a phase I/II , open-label , nonr and omized study . Patients received v and etanib ( 300 mg daily ) until objective disease progression . The primary endpoints were safety and tolerability . Secondary endpoints included efficacy and PK . Final data analysis was conducted once all patients with measurable baseline disease had been followed to progression , or for 56 weeks . RESULTS Fourteen patients received v and etanib . All patients experienced at least one adverse event ( AE ) , and 7 patients ( 50 % ) experienced grade ≥3 AEs . Common AEs included diarrhea ( 79 % ) , hypertension ( 64 % ) , and rash ( 43 % ) . Four patients reported a total of five serious AEs ( SAEs ) . Eleven patients ( 79 % ) had dose interruptions , and 8 patients ( 57 % ) had dose reductions . One patient discontinued treatment because of an SAE ( interstitial lung disease ) . No patients met the prespecified criterion for QTc prolongation . The ORR was 38 % and PFS at 12 months was 85 % . CONCLUSION Safety and efficacy data were comparable to those previously reported , and AEs were generally manageable by st and ard clinical practice or dose modifications . Overall , v and etanib was considered to be beneficial for Japanese MTC patients . ABBREVIATIONS AE = adverse event CI = confidence interval Css , max = maximum steady-state plasma concentration DCR = disease control rate EGFR = epidermal growth factor receptor ILD = interstitial lung disease MTC = medullary thyroid cancer ORR = objective response rate PFS = progression-free survival PK = pharmacokinetics RECIST = Response Evaluation Criteria in Solid Tumors RET = re-arranged during transfection SAE = serious adverse event VEGFR = vascular endothelial growth factor receptor 
    Output:
    
Conclusion V and etanib should be considered as a promising treatment in advanced MTC .
However , data based on RECIST endpoints do not currently provide high-level evidence on its efficacy