***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: OBJECTIVES V and etanib was approved by the U.S. Food and Drug Association for the treatment of advanced medullary thyroid cancer ( MTC ) . Because body weight ( BW ) loss is observed in MTC and because low skeletal muscle mass ( SM ) is associated with drug toxicity , this study assessed effects of v and etanib on SM and adipose tissue ( AT ) and explored the association between SM , toxicity , and serum concentration of v and etanib . METHODS Thirty-three patients with MTC received v and etanib ( n = 23 ) or placebo ( n = 10 ) in the ZETA study .  Visceral AT ( VAT ) , sc AT ( SAT ) , and SM were assessed with computed tomography imaging by measuring tissue cross-sectional areas ( square centimers per square meter ) . Dose-limiting toxicities ( DLTs ) were prospect ively recorded . RESULTS Early at 3 months , compared with placebo group who lost BW , muscle , and SAT , patients treated with v and etanib gained 1.5 kg BW ( P = 0.02 ) , 1.3 cm(2)/m(2 ) ( ∼0.7 kg ) of SM ( P = 0.009 ) , and 4.5 cm(2)/m(2 ) ( ∼0.5 kg ) of SAT ( P = 0.004 ) and gained more VAT , 5.1 cm(2)/m(2 ) ( ∼0.7 kg ) ( P = 0.02 ) . Patients with DLT had lower SM index ( 37.2 vs 44.3 cm(2)/m(2 ) , P = 0.003 ) and a higher v and etanib serum concentration ( 1091 vs 739 ng/mL , P = 0.03 ) . Patients with SM index < 43.1 cm(2)/m(2 ) had a higher probability of DLT ( 73 % vs 14 % , P = 0.004 ) and a higher v and etanib serum concentration ( 1037 vs 745 ng/mL , P = 0.04 ) . Patients with the highest compared with the intermediate and lower levels of v and etanib serum concentration experienced more DLT , respectively , 78 % vs 40 % vs 20 % ( P = 0.04 ) . CONCLUSIONS Muscle and adipose tissues are restored after only 3 months of v and etanib treatment . Patients with low muscle mass had high v and etanib serum concentration and high incidence of toxicities 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 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more 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 PURPOSE Patients with advanced , incurable thyroid cancer not amenable to surgery or radioactive iodine ( (131)I ) therapy have few satisfactory therapeutic options . This multi-institutional study assessed the activity and safety of axitinib , an oral , potent , and selective inhibitor of vascular endothelial growth factor receptors ( VEGFR ) 1 , 2 , and 3 in patients with advanced thyroid cancer . PATIENTS AND METHODS Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I were enrolled onto a single-arm phase II trial to receive axitinib orally ( starting dose , 5 mg twice daily ) . Objective response rate ( ORR ) by Response Evaluation Criteria in Solid Tumors was the primary end point . Secondary end points included duration of response , progression-free survival ( PFS ) , overall survival , safety , and modulation of soluble ( s ) VEGFR . RESULTS Sixty patients were enrolled . Partial responses were observed in 18 patients , yielding an ORR of 30 % ( 95 % CI , 18.9 to 43.2 ) . Stable disease lasting > or = 16 weeks was reported in another 23 patients ( 38 % ) . OBJECTIVE responses were noted in all histologic subtypes . Median PFS was 18.1 months ( 95 % CI , 12.1 to not estimable ) . Axitinib was generally well tolerated , with the most common grade > or = 3 treatment-related adverse event being hypertension ( n = 7 ; 12 % ) . Eight patients ( 13 % ) discontinued treatment because of adverse events . Axitinib selectively decreased sVEGFR-2 and sVEGFR-3 plasma concentrations versus sKIT , demonstrating its targeting of VEGFR . CONCLUSION Axitinib is a selective inhibitor of VEGFR with compelling antitumor activity in all histologic subtypes of advanced thyroid cancer Objectives : Effective management of adverse events ( AEs ) following v and etanib treatment is important to maximize clinical benefits . We examined whether more frequent contact with v and etanib-treated patients reduced AEs of CTCAE grade 2 or higher . Study Design : In this open-label , multicentre , phase III study , patients with locally advanced or metastatic medullary thyroid cancer were r and omized to a patient outreach programme ( outreach ) or a st and ard AE monitoring schedule ( v and etanib control ) for 52 weeks . In addition to st and ard AE monitoring , patients in the outreach arm were contacted every 2 weeks by telephone/during their clinic visit for specific AE question ing related to diarrhoea , nausea , vomiting , fatigue , headache and rash . Patients received v and etanib at 200 or 300 mg/day , depending on the creatinine levels at screening . Results : Altogether , 205 patients were r and omized ( outreach , n = 103 ; v and etanib control , n = 102 ) . This study did not meet its primary objective ; the mean percentage of time patients experienced at least one AE of grade 2 or higher was higher for the outreach group ( 51.65 % ) than for the v and etanib control group ( 45.19 % ) ; the difference was not statistically significant ( t statistic : 1.29 ; 95 % CI -3.44 to 16.37 % ; p = 0.199 ) . The most frequently reported AEs were diarrhoea ( 56.9 % for the outreach group vs. 46.6 % for the v and etanib controls ) , hypertension ( 36.3 vs. 31.1 % ) , rash ( 25.5 vs. 24.3 % ) and nausea ( 25.5 % vs. 18.4 % ) , and the most frequently reported AEs of grade 2 or higher were hypertension ( 33.3 vs. 23.3 % ) , diarrhoea ( 26.5 vs. 24.3 % ) and dermatitis acneiform ( 11.8 vs. 9.7 % ) . Conclusions : Additional outreach to patients treated with v and etanib had no impact on the rate or severity of AEs compared to the st and ard AE monitoring schedule . AEs were consistent with the known safety profile of v and etanib OBJECTIVES Mathematical modeling is used widely in economic evaluations of pharmaceuticals and other health-care technologies . Users of models in government and the private sector need to be able to evaluate the quality of models according to scientific criteria of good practice . This report describes the consensus of a task force convened to provide modelers with guidelines for conducting and reporting modeling studies . METHODS The task force was appointed with the advice and consent of the Board of Directors of ISPOR . Members were experienced developers or users of models , worked in academia and industry , and came from several countries in North America and Europe . The task force met on three occasions , conducted frequent correspondence and exchanges of drafts by electronic mail , and solicited comments on three drafts from a core group of external review ers and more broadly from the membership of ISPOR . RESULTS Criteria for assessing the quality of models fell into three areas : model structure , data used as inputs to models , and model validation . Several major themes cut across these areas . Models and their results should be represented as aids to decision making , not as statements of scientific fact ; therefore , it is inappropriate to dem and that models be vali date d prospect ively before use . However , model assumptions regarding causal structure and parameter estimates should be continually assessed against data , and models should be revised accordingly . Structural assumptions and parameter estimates should be reported clearly and explicitly , and opportunities for users to appreciate the conditional relationship between inputs and outputs should be provided through sensitivity analyses . CONCLUSIONS Model-based evaluations are a valuable re source for health-care decision makers . It is the responsibility of model developers to conduct modeling studies according to the best practicable st and ards of quality and to communicate results with adequate disclosure of assumptions and with the caveat that conclusions are conditional upon the assumptions 
    Output:
    
The costs  of v and etanib in the restricted EU-label population are expected to be lower .
The identified trials suggest that cabozantinib and v and etanib  improve PFS more than the placebo ; however , significant OS benefits were not demonstrated .