***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: BACKGROUND Whether or not toxicity predicts clinical outcomes has long been a question regarding cancer treatments . While prior studies have focused on specific cancers , therapies , and toxicities , no comprehensive evidence exists on whether treatment toxicity predicts favorable outcomes . METHODS We abstract ed treatment toxicity and clinical outcome data from a sample of phase III oncology r and omized clinical trials ( n = 99 trials ) . We investigated whether treatments with relatively greater toxicity compared with their controls had relatively higher , lower , or equivocal rates of clinical efficacy , measured by progression-free survival ( PFS ) and overall survival ( OS ) . Several toxicities were assessed ( all grade s , grade s III/IV , cutaneous rash , gastrointestinal toxicity , and myelosuppression ) . RESULTS Toxicity and efficacy were greater among treatments than controls ( e.g. 3.5 instances of all- grade toxicity per patient in treatment arms versus 2.8 instances in controls , P < 0.001 ; mean PFS of 9.1 months across treatment arms versus 7.1 months across controls , P < 0.001 ; mean OS of 18.6 months across treatment arms versus 16.9 months across controls , P < 0.001 ) . Across trials , greater relative treatment toxicity was strongly associated with greater PFS in treatments versus controls ( P < 0.001 ) , but not OS ( P = 0.44 ) . Although higher relative rates of myelosuppression and cutaneous rash among treatments were not associated with greater treatment efficacy , greater relative gastrointestinal toxicity among treatments was associated with greater relative PFS compared with controls ( P = 0.007 ) . CONCLUSION Across trials , treatments with relatively greater all- grade toxicity compared with controls are associated with relatively greater PFS but not OS 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 This r and omized phase II study examined the use of vinflunine in combination with gemcitabine or carboplatin as first-line chemotherapy in  cisplatin-ineligible patients with advanced urothelial carcinoma . Both doublets were feasible and offered a similar 77 % disease control rate . Response rate ( 44 % ) , overall survival ( 14 months ) and less haematological toxicity favoured vinflunine – gemcitabine BACKGROUND To compare long-term , up date d overall survival ( OS ) of patients with advanced transitional cell carcinoma of the urothelium ( TCCU ) treated with vinflunine plus best supportive care ( BSC ) or BSC alone , after failure of platinum-based chemotherapy . PATIENTS AND METHODS Three hundred and seventy patients were r and omly assigned in a phase III trial and allocated ( 2:1 ) to vinflunine ( 320 or 280 mg/m(2 ) ) plus BSC or BSC alone . The first report ( Bellmunt J , Theodore C , Demkov T et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinumcontaining regimen in patients with advanced transitional cell carcinoma of the urothelial tract . J Clin Oncol 2009 ; 27(27 ) : 4454 - 4461 ) had a median follow-up of 22.1 m and the current report has a follow-up of 45.4 m. RESULTS Three hundred and fifty-two patients had died ( censoring rate 5 % ) . In the intention-to-treat ( ITT ) population , the median OS was 6.9 m and 4.6 m for vinflunine plus BSC versus BSC alone , respectively ( n.s . ) . In multivariate Cox analysis , the addition of vinflunine was independently correlated with improved survival ( HR : 0.719 ; 95 % CI:0.570 - 0.906 , P = 0.0052 ) . In the eligible population , the median OS in both the arms was 6.9 and 4.3 m , respectively ( HR : 0.78 ; 95 % CI:0.61 - 0.96 ; P = 0.0227 ) , indicating an estimated 22 % reduction in the risk of death . CONCLUSIONS The up date d OS data confirm the positive treatment effect of vinflunine on survival that was previously reported . These results are consistent over time and confirm that vinflunine is a valuable option for second-line treatment in patients with advanced TCCU after failure of platinum-based regimens Background : The efficacy of Vinflunine , after failure of platinum-based chemotherapy in patients with metastatic or recurrent Transitional Cell Cancer of the Urothelial Tract , TCCU , has been demonstrated in an international , r and omized , phase III trial comparing Vinflunine plus Best Supportive Care , BSC , with BSC alone . On the basis of that study vinflunine has been approved by the European Medicine Association , EMA , for treatment of TCCU patients after failure of a platinum treatment . However , since data in clinical trials often differ from routine clinical practice due to unselected population and less strict monitoring , “ real life ” experiences are very helpful to verify the efficacy of a new therapy . Methods : This was a spontaneous , observational , retrospective study involving 43 patients with metastatic TCCU treated with vinflunine at our cancer center , data about demographics , disease characteristics , and previous treatments were collected and outcome and toxicities of vinflunine were analyzed . Results : 41 of 43 patients were eligible for RR analysis , the Overall RR was 12 % , the Disease Control Rate was 29 % ; when including only patients treated in II line the DCR rose to 33 % ; the median PFS and the median OS were 2.2 and 6.9 months , respectively . Conclusion : Our findings were consistent with the outcome data emerged in the phase III r and omized trial and in the other observational studies conducted all around Europe in the last 2–3 years . This experience supports the use of vinflunine in patients with advanced TTCU as effective and manageable antineoplastic drug PURPOSE The present study sought to identify pretreatment prognostic factors for overall survival ( OS ) in patients with metastatic transitional cell carcinoma of the urothelial tract ( TCCU ) who experienced treatment failure with the first-line , platinum-based regimen included in the phase III vinflunine trial . PATIENTS AND METHODS In total , 370 patients with platinum-refractory TCCU were included in this analysis . Potential prognostic factors were recorded prospect ively . Univariate analysis was used to identify clinical and laboratory factors that significantly impact survival . Multivariate analysis was used to identify independent prognostic factors , and bootstrap analysis was performed for internal validation , forming a prognostic model . External validation was performed on the phase II vinflunine study CA183001 . RESULTS Multivariate analysis and the internal validation identified Eastern Cooperative Oncology Group performance status ( PS ) more than 0 , hemoglobin level less than 10 g/dL , and the presence of liver metastasis as the main adverse prognostic factors for OS . External validation confirmed these prognostic factors . Four subgroups were formed based on the presence of zero , one , two , or three prognostic factors ; the median OS times for these groups were 14.2 , 7.3 , 3.8 , and 1.7 months ( P < .001 ) , respectively . CONCLUSION We identified and both internally and externally vali date d three adverse risk factors ( PS , hemoglobin level , and liver metastasis ) that predict for OS and developed a scoring system that classifies patients with platinum-refractory disease on second-line chemotherapy into four risk groups with different outcome . Similar to the first-line setting , the presence of visceral metastases and poor PS predict a worse prognosis . These factors , together with low hemoglobin , can be used for prognostication and future patient stratification in clinical trials BACKGROUND Current estimates of the costs of cancer care in the United States are based on data from 2003 and earlier . However , incidence , survival , and practice patterns have been changing for the majority of cancers . METHODS Cancer prevalence was estimated and projected by phase of care ( initial year following diagnosis , continuing , and last year of life ) and tumor site for 13 cancers in men and 16 cancers in women through 2020 . Cancer prevalence was calculated from cancer incidence and survival models estimated from Surveillance , Epidemiology , and End Results ( SEER ) Program data . Annualized net costs were estimated from recent SEER-Medicare linkage data , which included cl aims through 2006 among beneficiaries aged 65 years and older with a cancer diagnosis . Control subjects without cancer were identified from a 5 % r and om sample of all Medicare beneficiaries residing in the SEER areas to adjust for expenditures not related to cancer . All cost estimates were adjusted to 2010 dollars . Different scenarios for assumptions about future trends in incidence , survival , and cost were assessed with sensitivity analysis . RESULTS Assuming constant incidence , survival , and cost , we projected 13.8 and 18.1 million cancer survivors in 2010 and 2020 , respectively , with associated costs of cancer care of 124.57 and 157.77 billion 2010 US dollars . This 27 % increase in medical costs reflects US population changes only . The largest increases were in the continuing phase of care for prostate cancer ( 42 % ) and female breast cancer ( 32 % ) . Projections of current trends in incidence ( declining ) and survival ( increasing ) had small effects on 2020 estimates . However , if costs of care increase annually by 2 % in the initial and last year of life phases of care , the total cost in 2020 is projected to be $ 173 billion , which represents a 39 % increase from 2010 . CONCLUSIONS The national cost of cancer care is substantial and expected to increase because of population changes alone . Our findings have implication s for policy makers in planning and allocation of re sources BACKGROUND Based on the results of phase III trial , vinflunine was approved by European Medicines Agency in 2010 as second line treatment of advanced urothelial cancer in patients with good performance status ( ECOG 0- 1 ) . The objective of this prospect i ve observational study was to assess vinflunine treatment of advanced urothelial cancer patients in terms of progression free survival and overall survival , and to evaluate vinflunine  toxicity . PATIENTS AND METHODS From April 2011 to June 2014 a total of 16 patients ( 100 % ) with advanced urothelial cancer were treated with vinflunine . The median age was 62 years ( range 43- 80 ) and the median Karnofsky index was 90 % ( range 80- 100 % ) . Thirteen patients ( 81.25 % ) had urothelial bladder cancers , two patients ( 12.50 % ) suffered from urothelial cancers of ureter , and one patient (  
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In first-line treatment of UC , either as a maintenance agent after cisplatin or as a primary combination therapy , VIN may be a promising alternative to current treatments .
Second- and third-line VIN monotherapy does provide a proven , although limited , survival benefit in platinum-refractory patients