***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 To define outcome data and prognostic criteria for patients with metastatic renal cell carcinoma ( RCC ) treated with interferon-alfa as initial systemic therapy . The data can be applied to design and interpretation of clinical trials of new agents and treatment programs against this refractory malignancy . PATIENTS AND METHODS Four hundred sixty-three patients with advanced RCC administered interferon-alpha as first-line systemic therapy on six prospect i ve clinical trials were the subjects of this retrospective analysis . Three risk categories for predicting survival were identified on the basis of five pretreatment clinical features by a stratified Cox proportional hazards model . RESULTS The median overall survival time was 13 months . The median time to progression was 4.7 months . Five variables were used as risk factors for short survival : low Karnofsky performance status , high lactate dehydrogenase , low serum hemoglobin , high corrected serum calcium , and time from initial RCC diagnosis to start of interferon-alpha therapy of less than one year . Each patient was assigned to one of three risk groups : those with zero risk factors ( favorable risk ) , those with one or two ( intermediate risk ) , and those with three or more ( poor risk ) . The median time to death of patients deemed favorable risk was 30 months . Median survival time in the intermediate-risk group was 14 months . In contrast , the poor-risk group had a median survival time of 5 months . CONCLUSION Progression-free and overall survival with interferon-alpha treatment can be compared with new therapies in phase II and III clinical investigations . The prognostic model is suitable for risk stratification of phase III trials using interferon-alpha as the comparative treatment arm BACKGROUND The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis . So far , no phase 3 r and omised trials comparing the effectiveness of one targeted agent against another have been reported . We did a r and omised phase 3 study comparing axitinib , a potent and selective second-generation inhibitor of vascular endothelial growth factor ( VEGF ) receptors , with sorafenib , an approved VEGF receptor inhibitor , as second-line therapy in patients with metastatic renal cell cancer . METHODS We included patients coming from 175 sites ( hospitals and outpatient clinics ) in 22 countries aged 18 years or older with confirmed renal clear-cell carcinoma who progressed despite first-line therapy containing sunitinib , bevacizumab plus interferon-alfa , temsirolimus , or cytokines .  Patients were stratified according to Eastern Cooperative Oncology Group performance status and type of previous treatment and then r and omly assigned ( 1:1 ) to either axitinib ( 5 mg twice daily ) or sorafenib ( 400 mg twice daily ) . Axitinib dose increases to 7 mg and then to 10 mg , twice daily , were allowed for those patients without hypertension or adverse reactions above grade 2 . Participants were not masked to study treatment . The primary endpoint was progression-free survival ( PFS ) and was assessed by a masked , independent radiology review and analysed by intention to treat . This trial was registered on Clinical Trials.gov , number NCT00678392 . FINDINGS A total of 723 patients were enrolled and r and omly assigned to receive axitinib ( n=361 ) or sorafenib ( n=362 ) . The median PFS was 6·7 months with axitinib compared to 4·7 months with sorafenib ( hazard ratio 0·665 ; 95 % CI 0·544 - 0·812 ; one-sided p<0·0001 ) . Treatment was discontinued because of toxic effects in 14 ( 4 % ) of 359 patients treated with axitinib and 29 ( 8 % ) of 355 patients treated with sorafenib . The most common adverse events were diarrhoea , hypertension , and fatigue in the axitinib arm , and diarrhoea , palmar-plantar erythrodysaesthesia , and alopecia in the sorafenib arm . INTERPRETATION Axitinib result ed in significantly longer PFS compared with sorafenib . Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma . FUNDING Pfizer Background Kidney and renal pelvis cancers account for 4 % of all new cancer cases in the United States , among which 85 % are renal cell carcinomas ( RCC ) . While cigarette smoking is an established risk factor for RCC , little is known about the contribution of environmental tobacco smoke ( ETS ) to RCC incidence . This study assesses the role of smoking and ETS on RCC incidence using a population -based case-control design in Florida and Georgia . Methods Incident cases ( n = 335 ) were identified from hospital records and the Florida cancer registry , and population controls ( n = 337 ) frequency-matched by age ( + /- 5 years ) , gender , and race were identified through r and om-digit dialing . In-person interviews assessed smoking history and lifetime exposure to ETS at home , work , and public spaces .  Home ETS  was measured in both years and hours of exposure . Odds ratios and 95 % confidence intervals were calculated using logistic regression , controlled for age , gender , race , and BMI . Results Cases were more likely to have smoked 20 or more pack-years , compared with never-smokers ( OR : 1.35 , 95 % CI : 0.93 – 1.95 ) . A protective effect was found for smoking cessation , beginning with 11–20 years of cessation ( OR : 0.39 , 95 % CI : 0.18–0.85 ) and ending with 51 or more years of cessation ( OR : 0.11 , 95 % CI : 0.03–0.39 ) in comparison with those having quit for 1–10 years . Among never-smokers , cases were more likely to report home ETS exposure of greater than 20 years , compared with those never exposed to home ETS ( OR : 2.18 ; 95 % CI : 1.14–4.18 ) . Home ETS associations were comparable when measured in lifetime hours of exposure , with cases more likely to report 30,000 or more hours of home ETS exposure ( OR : 2.37 ; 95 % CI : 1.20–4.69 ) . Highest quartiles of combined home/work ETS exposure among never-smokers , especially with public ETS exposure , increased RCC risk by 2 to 4 times . Conclusion These findings confirm known associations between smoking and RCC and establish a potential etiologic role for ETS , particularly in the home . Differences in methods of retrospective measurement of lifetime smoking and ETS exposure may contribute to discrepancies in measures of associations across studies , and should be addressed in future research Introduction : The Eastern Cooperative Oncology Group ( ECOG ) score is a well known prognostic factor and almost always used to determine eligibility for clinical trials . The  patient-rated performance status score ( Pt-PS ) , section of the patient generated subjective global assessment scale , has identical criteria to the physician-rated ECOG scale ( MD-PS ) . We compared the Pt-PS with MD-PS in patients with advanced non-small cell lung cancer and compared the effect of each rating on eligibility for a hypothetical clinical trial . Methods : Consecutive patients with newly diagnosed advanced non-small cell lung cancer completed a patient generated subjective global assessment self-rated question naire , which was then correlated ( kappa statistic ) with the ECOG PS recorded at the same time . Patients were treated with st and ard chemotherapy .  Survival was determined using Kaplan-Meier statistics . Results : One hundred nine patients ( M : F-54:55 ) were recruited . Pt-PS differed from MD-PS in 59 ( 54 % ) instances ( p = 0.0001 ) . When scores were not congruent , 41/59 ( 69 % ) patients evaluated themselves as having a worse PS than the physician ’s rating . Pt-PS was 0 to 1 in 60 ( 55 % ) patients whereas MD-PS was 0 to 1 in 78 ( 72 % ) patients . The functional status irrespective of evaluator was predictive of survival ( p = 0.001 for MD-PS and p = 0.001 for Pt-PS ) . However , the median survival in those with MD-PS ≥2 was 3.3 ( CI ; 1.7 - 4.9 ) months whereas individuals with Pt-PS ≥2 had a median survival of 6.2 ( CI ; 5.4 - 6.9 ) months . Conclusions : Pt-PS and MD-PS were not congruent in over half of the cases , with Pt-PS scores usually poorer . Almost half the patients would have excluded themselves from a hypothetical clinical trial ( Pt-PS ≥2 ) . This requires prospect i ve evaluation BACKGROUND Response patterns to nivolumab differ from those seen with other approved targeted therapies . OBJECTIVE To investigate the efficacy of nivolumab in previously treated patients with advanced renal cell carcinoma who were treated beyond ( Response Evaluation Criteria In Solid Tumors ) RECIST progression . DESIGN , SETTING , AND PARTICIPANTS This was a subgroup analysis of patients treated with nivolumab in the phase 3 CheckMate 025 study . Patients continuing to tolerate therapy and exhibiting investigator-assessed clinical benefit were eligible to be treated beyond RECIST progression ( TBP ) and received therapy for ≥4 wk after first progression ; patients not treated beyond RECIST progression ( NTBP ) received 0 wk to < 4 wk of therapy after progression . INTERVENTIONS Nivolumab 3mg/kg intravenously every 2 wk . RESULTS AND LIMITATIONS Of 406 nivolumab-treated patients , 316 ( 78 % ) progressed by RECIST criteria . Of those who progressed , 48 % were TBP , 52 % were NTBP . Before being TBP , objective response rate ( 95 % confidence interval ) was 20 % ( 14 - 28 ) and 14 % ( 9 - 21 ) in patients TBP and NTBP , respectively . Differences in clinical characteristics assessed at first progression between patients TBP versus NTBP included better Karnofsky performance status , less deterioration in Karnofsky performance status , shorter time to response , lower incidence of new bone lesions , and improved quality of life . Postprogression , 13 % of all patients TBP ( 20/153 ) had ≥30 % tumor burden reduction including patients with preprogression and postprogression tumor measurements ( n=142 ) and complete/partial response ( 28 % , 8/29 ) , stable disease ( 6 % , 3/47 ) , and progressive disease ( 14 % , 9/66 ) as their best response before being TBP . Incidence of treatment-related adverse events in patients TBP was lower after ( 59 % ) versus before ( 71 % ) progression . Limitations included potential bias from the nonr and omized nature of the analysis . CONCLUSIONS A subset of patients with advanced renal cell carcinoma and RECIST progression experienced tumor reduction postprogression with nivolumab , and had an acceptable safety profile . Clinical judgment remains essential when switching therapy . Clinical Trials.gov Identifier : NCT01668784 . PATIENT SUMMARY A subset of patients with advanced renal cell carcinoma and disease progression may continue to benefit from nivolumab treatment beyond progression as evidence d by tumor reduction postprogression and an acceptable safety profile 
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Conclusions This study suggests that a poor PS is significantly associated with poor prognosis in mRCC patients receiving TKIs