human
***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: Although radical cystectomy ( RC ) is considered as the st and ard therapy for muscle-invasive bladder cancer ( MIBC ) , trimodal therapy ( TMT ) combining transurethral resection of the tumor with radiotherapy and chemotherapy is increasingly recommended as an alternative approach for bladder preservation . In the absence of r and omized trials , we compared the clinical outcomes between RC and TMT using propensity score matching with 50 patients in the RC arm and 29 patients in the TMT arm . With respective median follow-up periods of 23 and 32 months for the RC and TMT groups , 5-year distant metastasis-free survival ( 58 % vs. 67 % ) , overall survival ( 56 % vs. 57 % ) , and cancer-specific survival ( 69 % vs. 63 % ) rates between the RC and TMT groups , respectively , were similar . However , the 5-year local recurrence-free survival was significantly better in the RC group than in the TMT group ( 74 % vs. 35 % ) . Following TMT , acute grade 3 hematological ( n = 2 ) and late grade 3 genitourinary ( n = 1 ) toxicities were reported . These findings demonstrated that oncological outcomes of TMT were comparable with those of RC , except for poorer local control . Large-scale , r and omized trials are warranted to confirm the findings of the present retrospective comparison and to guide toward best treatment options The aim of this study was to define the maximum tolerated doses ( MTDs ) of cisplatin ( CDDP ) and 5‐fluorouracil ( 5‐FU ) administered as protracted intravenous infusion ( PVI ) during hyperfractionated radiotherapy ( HFRT ) administered with organ‐sparing intent to patients with infiltrating transitional cell carcinoma of the bladder ( TCCB ) BACKGROUND We conducted a phase I trial of gemcitabine ( gem ) with concurrent radiotherapy in patients with muscle-invasive bladder cancer ( BC ) ineligible for surgery or cisplatin or refusing organ loss . PATIENTS AND METHODS Patients with urothelial cancer , cT2-T4 , cN0 - 1 , M0 , ineligible for surgery due to local tumor extension , PS , age or co-morbidities or who refused surgery were included . After maximal transurethral resection , the treatment schedule included : twice-weekly i.v . infusion of gem [ dose levels ( DL ) 1 - 6 : 20 , 27 , 30 , 33 , 50 and 40 mg/m(2 ) , respectively ] for 30 min and concurrent radiotherapy ( RT ) to the bladder with 55.5 Gy . The primary end point was to determine the maximum-tolerated dose ( MTD ) and the dose recommended ( RD ) for further studies of this gem schedule . The secondary end point was late toxicity . The MTD was defined by dose-limiting toxicity ( DLT ) in 2 or more of 6 patients , discontinuation of RT and /or gem for > 1 week in 2 or more of 6 patients due to grade ( G ) 3/4 acute and /or late toxicity in more than 2 of 18 patients . RESULTS Thirty-five of 44 patients were assessable for toxicity and thus the primary end point . DLTs occurred in two of five patients at dose level 5 : one G3 alanine aminotransferase elevation and one G3 fatigue . The MTD , therefore , was 50 mg/m(2 ) gem twice weekly . At DL 6 with 40 mg/m(2 ) , the RD was established : only one of six patients developed G3 fatigue and diarrhea . Late toxicity was rare and of low grade ( only G1 - 2 ) . The 2-year locoregional failure rate was 32 % ( 9/28 ) ; 10 of 28 patients ( 38 % ) were alive with an intact bladder and no evidence of recurrent disease , 9 patients developed distant metastases and 6 died of their disease . CONCLUSIONS Gemcitabine in combination with RT is well tolerated in BC patients ineligible for surgery and /or cisplatin . The RD of gemcitabine for subsequent trials is 40 mg/m(2 ) twice weekly with concurrent radiation To test the feasibility of a r and omised trial in muscle‐invasive bladder cancer ( MIBC ) and compare outcomes in patients who receive neoadjuvant chemotherapy followed by radical cystectomy ( RC ) or selective bladder preservation ( SBP )  , where definitive treatment [ RC or radiotherapy ( RT ) ] is determined by response to chemotherapy Given the lack of r and omized evidence comparing trimodal therapy ( TMT ) to radical cystectomy ( RC ) for muscle-invasive urothelial carcinoma of the bladder ( UCB ) , we performed an observational cohort study to examine the comparative effectiveness of these two definitive treatments . Within the National Cancer Data Base (2004 - 2011),we identified 1257 ( 9.8 % ) and 11 586 ( 90.2 % ) patients who received TMT and RC , respectively . Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier analysis showed that median overall survival ( OS ) was similar between the TMT ( 40 mo , 95 % confidence interval [ CI ] 34 - 46 ) and RC groups ( 43 mo 95 % CI 41 - 45 ; p=0.3 ) . In IPTW-adjusted Cox regression analysis with a time-varying covariate , TMT was associated with a significant adverse impact on long-term OS ( hazard ratio 1.37 , 95 % CI 1.16 - 1.59 ; p<0.001 ) . Interaction terms indicated that the adverse treatment effect of TMT versus RC decreased with age ( p=0.004 ) , while there was no significant interaction with gender ( p=0.6 ) , Charlson comorbidity index ( p=0.09 ) or cT stage ( p=0.8 ) . In conclusion , we found that TMT was generally associated with worse long-term OS compared to RC for muscle-invasive UCB . However , the survival benefit of RC should be weighed against the risks of surgery , especially in older patients . These results are preliminary and emphasize the need for a r and omized controlled trial to compare TMT versus RC . PATIENT SUMMARY We examined the comparative effectiveness of trimodal therapy versus radical cystectomy for muscle-invasive urothelial carcinoma of the bladder . We found that trimodal therapy was generally associated with worse long-term overall survival , although there may be no difference with radical cystectomy in older individuals BACKGROUND Whether organ-conserving treatment by combined-modality therapy ( CMT ) achieves comparable long-term survival to radical cystectomy ( RC ) for muscle-invasive bladder cancer ( BCa ) is largely unknown . OBJECTIVE Report long-term outcomes of patients with muscle-invasive BCa treated by CMT .  DESIGN , SETTING , AND PARTICIPANTS We conducted an analysis of successive prospect i ve protocol s at the Massachusetts General Hospital ( MGH ) treating 348 patients with cT2 - 4a disease between 1986 and 2006 . Median follow-up for surviving patients was 7.7 yr . INTERVENTIONS Patients underwent concurrent cisplatin-based chemotherapy and radiation therapy ( RT ) after maximal transurethral resection of bladder tumor ( TURBT ) plus neoadjuvant or adjuvant chemotherapy . Repeat biopsy was performed after 40 Gy , with initial tumor response guiding subsequent therapy . Those patients showing complete response ( CR ) received boost chemotherapy and RT . One hundred two patients ( 29 % ) underwent RC-60 for less than CR and 42 for recurrent invasive tumors . MEASUREMENTS Disease-specific survival ( DSS ) and overall survival ( OS ) were evaluated using the Kaplan-Meier method . RESULTS AND LIMITATIONS Seventy-two percent of patients ( 78 % with stage T2 ) had CR to induction therapy . Five- , 10- , and 15-yr DSS rates were 64 % , 59 % , and 57 % ( T2=74 % , 67 % , and 63 % ; T3 - 4=53 % , 49 % , and 49 % ) , respectively . Five- , 10- , and 15-yr OS rates were 52 % , 35 % , and 22 % ( T2 : 61 % , 43 % , and 28 % ; T3 - 4=41 % , 27 % , and 16 % ) , respectively . Among patients showing CR , 10-yr rates of noninvasive , invasive , pelvic , and distant recurrences were 29 % , 16 % , 11 % , and 32 % , respectively . Among patients undergoing visibly complete TURBT , only 22 % required cystectomy ( vs 42 % with incomplete TURBT ; log-rank p<0.001 ) . In multivariate analyses , clinical T-stage and CR were significantly associated with improved DSS and OS . Use of neoadjuvant chemotherapy did not improve outcomes . No patient required cystectomy for treatment-related toxicity . CONCLUSIONS CMT achieves a CR and preserves the native bladder in > 70 % of patients while offering long-term survival rates comparable to contemporary cystectomy series . These results support modern bladder-sparing therapy as a proven alternative for selected patients To examine combination cisplatin and twice-daily accelerated irradiation ( RT ) after aggressive transurethral resection of bladder tumor ( TURBT ) in an attempt to preserve the bladder and to determine the likelihood that patients who complete this regimen could then complete three cycles of methotrexate , cisplatin , vinblastine ( MCV ) chemotherapy .  Between 1998 and 2000 , 52 patients with Stage T2-T4aN0M0 disease , from 17 institutions , were entered into the trial . Forty-seven patients were deemed eligible ; the planned accrual was 40 . Of the 46 patients , 68 % were > 60 years old , 70 % were men , and 96 % had a Karnofsky score > /=90 . The clinical T stage was T2 in 66 % , T3a in 25 % , and T3b in 9 % . The median follow-up at the time of analysis was 26 months . The protocol required TURBT within 6 weeks of the initiation of induction therapy . Induction treatment involved 13 days of concomitant boost RT , 1.8 Gy to the pelvis in the morning followed by 1.6 Gy to the tumor 4 - 6 h later . For sensitization , cisplatin ( 20 mg/m(2 ) ) was given on the first 3 days of each treatment week . Three to four weeks after induction , patients were evaluated cystoscopically for residual disease . Patients whose biopsies and cytologic evaluations showed no disease completed consolidation chemoirradiation . Patients with residual tumor went on to cystectomy . After either consolidation or cystectomy , patients were to complete three cycles of MCV chemotherapy . Of the 47 patients , 45 % completed all phases of the protocol treatment with minor , or no , deviations . Five patients refused either the postinduction evaluation or cystectomy and 6 refused adjuvant chemotherapy . The CR rate after induction therapy was 74 % . For 2 patients , residual disease after induction was limited to positive cytologic findings , and for 8 patients , biopsy of the primary site revealed persistence . Of the 8 cystectomy patients , 2 had no evidence of disease in the bladder at pathologic review of the surgery specimen . Grade 3 toxicity related to chemotherapy was observed in 11 % of patients during both induction and consolidation , and in 41 % during adjuvant chemotherapy . A total of 8 patients ( 36 % of those receiving adjuvant chemotherapy ) went on to develop Grade 4 neutropenia or thrombocytopenia during additional adjuvant chemotherapy .  Grade 3 toxicity due to RT was seen in 4 % and 0 % of patients during induction and consolidation , respectively . One patient developed Grade 4 hydronephrosis during consolidation . The projected 36-month value for locoregional failure , distant metastasis , overall survival , and bladder-intact survival was 27 % , 29 % , 61 % , and 48 % , respectively . After aggressive TURBT , twice-daily accelerated RT initiated in concomitant-boost format is well tolerated and results in a rate of complete response ( 74 % ) similar to that in previous bladder-sparing trials . The projected 2-year values for locoregional control , bladder-intact survival , and overall survival were also consistent with previously reported trials of bladder-sparing treatment . With only 45 % of patients completing three cycles of MCV , this form of adjuvant chemotherapy appears to be poorly tolerated by most patients BACKGROUND AND PURPOSE To evaluate the efficacy and toxicity of an accelerated fractionation regimen to treat localised muscle invasive bladder cancer . PATIENTS AND METHODS A prospect i ve r and omised trial was undertaken in 229 patients r and omised between 1988 and 1998 comparing accelerated fractionation ( AF ) to a dose of 60.8 Gy in 3 
    Output:
    
agent
***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: Although radical cystectomy ( RC ) is considered as the st and ard therapy for muscle-invasive bladder cancer ( MIBC ) , trimodal therapy ( TMT ) combining transurethral resection of the tumor with radiotherapy and chemotherapy is increasingly recommended as an alternative approach for bladder preservation . In the absence of r and omized trials , we compared the clinical outcomes between RC and TMT using propensity score matching with 50 patients in the RC arm and 29 patients in the TMT arm . With respective median follow-up periods of 23 and 32 months for the RC and TMT groups , 5-year distant metastasis-free survival ( 58 % vs. 67 % ) , overall survival ( 56 % vs. 57 % ) , and cancer-specific survival ( 69 % vs. 63 % ) rates between the RC and TMT groups , respectively , were similar . However , the 5-year local recurrence-free survival was significantly better in the RC group than in the TMT group ( 74 % vs. 35 % ) . Following TMT , acute grade 3 hematological ( n = 2 ) and late grade 3 genitourinary ( n = 1 ) toxicities were reported . These findings demonstrated that oncological outcomes of TMT were comparable with those of RC , except for poorer local control . Large-scale , r and omized trials are warranted to confirm the findings of the present retrospective comparison and to guide toward best treatment options The aim of this study was to define the maximum tolerated doses ( MTDs ) of cisplatin ( CDDP ) and 5‐fluorouracil ( 5‐FU ) administered as protracted intravenous infusion ( PVI ) during hyperfractionated radiotherapy ( HFRT ) administered with organ‐sparing intent to patients with infiltrating transitional cell carcinoma of the bladder ( TCCB ) BACKGROUND We conducted a phase I trial of gemcitabine ( gem ) with concurrent radiotherapy in patients with muscle-invasive bladder cancer ( BC ) ineligible for surgery or cisplatin or refusing organ loss . PATIENTS AND METHODS Patients with urothelial cancer , cT2-T4 , cN0 - 1 , M0 , ineligible for surgery due to local tumor extension , PS , age or co-morbidities or who refused surgery were included . After maximal transurethral resection , the treatment schedule included : twice-weekly i.v . infusion of gem [ dose levels ( DL ) 1 - 6 : 20 , 27 , 30 , 33 , 50 and 40 mg/m(2 ) , respectively ] for 30 min and concurrent radiotherapy ( RT ) to the bladder with 55.5 Gy . The primary end point was to determine the maximum-tolerated dose ( MTD ) and the dose recommended ( RD ) for further studies of this gem schedule . The secondary end point was late toxicity . The MTD was defined by dose-limiting toxicity ( DLT ) in 2 or more of 6 patients , discontinuation of RT and /or gem for > 1 week in 2 or more of 6 patients due to grade ( G ) 3/4 acute and /or late toxicity in more than 2 of 18 patients . RESULTS Thirty-five of 44 patients were assessable for toxicity and thus the primary end point . DLTs occurred in two of five patients at dose level 5 : one G3 alanine aminotransferase elevation and one G3 fatigue . The MTD , therefore , was 50 mg/m(2 ) gem twice weekly . At DL 6 with 40 mg/m(2 ) , the RD was established : only one of six patients developed G3 fatigue and diarrhea . Late toxicity was rare and of low grade ( only G1 - 2 ) . The 2-year locoregional failure rate was 32 % ( 9/28 ) ; 10 of 28 patients ( 38 % ) were alive with an intact bladder and no evidence of recurrent disease , 9 patients developed distant metastases and 6 died of their disease . CONCLUSIONS Gemcitabine in combination with RT is well tolerated in BC patients ineligible for surgery and /or cisplatin . The RD of gemcitabine for subsequent trials is 40 mg/m(2 ) twice weekly with concurrent radiation To test the feasibility of a r and omised trial in muscle‐invasive bladder cancer ( MIBC ) and compare outcomes in patients who receive neoadjuvant chemotherapy followed by radical cystectomy ( RC ) or selective bladder preservation ( SBP )  , where definitive treatment [ RC or radiotherapy ( RT ) ] is determined by response to chemotherapy Given the lack of r and omized evidence comparing trimodal therapy ( TMT ) to radical cystectomy ( RC ) for muscle-invasive urothelial carcinoma of the bladder ( UCB ) , we performed an observational cohort study to examine the comparative effectiveness of these two definitive treatments . Within the National Cancer Data Base (2004 - 2011),we identified 1257 ( 9.8 % ) and 11 586 ( 90.2 % ) patients who received TMT and RC , respectively . Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier analysis showed that median overall survival ( OS ) was similar between the TMT ( 40 mo , 95 % confidence interval [ CI ] 34 - 46 ) and RC groups ( 43 mo 95 % CI 41 - 45 ; p=0.3 ) . In IPTW-adjusted Cox regression analysis with a time-varying covariate , TMT was associated with a significant adverse impact on long-term OS ( hazard ratio 1.37 , 95 % CI 1.16 - 1.59 ; p<0.001 ) . Interaction terms indicated that the adverse treatment effect of TMT versus RC decreased with age ( p=0.004 ) , while there was no significant interaction with gender ( p=0.6 ) , Charlson comorbidity index ( p=0.09 ) or cT stage ( p=0.8 ) . In conclusion , we found that TMT was generally associated with worse long-term OS compared to RC for muscle-invasive UCB . However , the survival benefit of RC should be weighed against the risks of surgery , especially in older patients . These results are preliminary and emphasize the need for a r and omized controlled trial to compare TMT versus RC . PATIENT SUMMARY We examined the comparative effectiveness of trimodal therapy versus radical cystectomy for muscle-invasive urothelial carcinoma of the bladder . We found that trimodal therapy was generally associated with worse long-term overall survival , although there may be no difference with radical cystectomy in older individuals BACKGROUND Whether organ-conserving treatment by combined-modality therapy ( CMT ) achieves comparable long-term survival to radical cystectomy ( RC ) for muscle-invasive bladder cancer ( BCa ) is largely unknown . OBJECTIVE Report long-term outcomes of patients with muscle-invasive BCa treated by CMT .  DESIGN , SETTING , AND PARTICIPANTS We conducted an analysis of successive prospect i ve protocol s at the Massachusetts General Hospital ( MGH ) treating 348 patients with cT2 - 4a disease between 1986 and 2006 . Median follow-up for surviving patients was 7.7 yr . INTERVENTIONS Patients underwent concurrent cisplatin-based chemotherapy and radiation therapy ( RT ) after maximal transurethral resection of bladder tumor ( TURBT ) plus neoadjuvant or adjuvant chemotherapy . Repeat biopsy was performed after 40 Gy , with initial tumor response guiding subsequent therapy . Those patients showing complete response ( CR ) received boost chemotherapy and RT . One hundred two patients ( 29 % ) underwent RC-60 for less than CR and 42 for recurrent invasive tumors . MEASUREMENTS Disease-specific survival ( DSS ) and overall survival ( OS ) were evaluated using the Kaplan-Meier method . RESULTS AND LIMITATIONS Seventy-two percent of patients ( 78 % with stage T2 ) had CR to induction therapy . Five- , 10- , and 15-yr DSS rates were 64 % , 59 % , and 57 % ( T2=74 % , 67 % , and 63 % ; T3 - 4=53 % , 49 % , and 49 % ) , respectively . Five- , 10- , and 15-yr OS rates were 52 % , 35 % , and 22 % ( T2 : 61 % , 43 % , and 28 % ; T3 - 4=41 % , 27 % , and 16 % ) , respectively . Among patients showing CR , 10-yr rates of noninvasive , invasive , pelvic , and distant recurrences were 29 % , 16 % , 11 % , and 32 % , respectively . Among patients undergoing visibly complete TURBT , only 22 % required cystectomy ( vs 42 % with incomplete TURBT ; log-rank p<0.001 ) . In multivariate analyses , clinical T-stage and CR were significantly associated with improved DSS and OS . Use of neoadjuvant chemotherapy did not improve outcomes . No patient required cystectomy for treatment-related toxicity . CONCLUSIONS CMT achieves a CR and preserves the native bladder in > 70 % of patients while offering long-term survival rates comparable to contemporary cystectomy series . These results support modern bladder-sparing therapy as a proven alternative for selected patients To examine combination cisplatin and twice-daily accelerated irradiation ( RT ) after aggressive transurethral resection of bladder tumor ( TURBT ) in an attempt to preserve the bladder and to determine the likelihood that patients who complete this regimen could then complete three cycles of methotrexate , cisplatin , vinblastine ( MCV ) chemotherapy .  Between 1998 and 2000 , 52 patients with Stage T2-T4aN0M0 disease , from 17 institutions , were entered into the trial . Forty-seven patients were deemed eligible ; the planned accrual was 40 . Of the 46 patients , 68 % were > 60 years old , 70 % were men , and 96 % had a Karnofsky score > /=90 . The clinical T stage was T2 in 66 % , T3a in 25 % , and T3b in 9 % . The median follow-up at the time of analysis was 26 months . The protocol required TURBT within 6 weeks of the initiation of induction therapy . Induction treatment involved 13 days of concomitant boost RT , 1.8 Gy to the pelvis in the morning followed by 1.6 Gy to the tumor 4 - 6 h later . For sensitization , cisplatin ( 20 mg/m(2 ) ) was given on the first 3 days of each treatment week . Three to four weeks after induction , patients were evaluated cystoscopically for residual disease . Patients whose biopsies and cytologic evaluations showed no disease completed consolidation chemoirradiation . Patients with residual tumor went on to cystectomy . After either consolidation or cystectomy , patients were to complete three cycles of MCV chemotherapy . Of the 47 patients , 45 % completed all phases of the protocol treatment with minor , or no , deviations . Five patients refused either the postinduction evaluation or cystectomy and 6 refused adjuvant chemotherapy . The CR rate after induction therapy was 74 % . For 2 patients , residual disease after induction was limited to positive cytologic findings , and for 8 patients , biopsy of the primary site revealed persistence . Of the 8 cystectomy patients , 2 had no evidence of disease in the bladder at pathologic review of the surgery specimen . Grade 3 toxicity related to chemotherapy was observed in 11 % of patients during both induction and consolidation , and in 41 % during adjuvant chemotherapy . A total of 8 patients ( 36 % of those receiving adjuvant chemotherapy ) went on to develop Grade 4 neutropenia or thrombocytopenia during additional adjuvant chemotherapy .  Grade 3 toxicity due to RT was seen in 4 % and 0 % of patients during induction and consolidation , respectively . One patient developed Grade 4 hydronephrosis during consolidation . The projected 36-month value for locoregional failure , distant metastasis , overall survival , and bladder-intact survival was 27 % , 29 % , 61 % , and 48 % , respectively . After aggressive TURBT , twice-daily accelerated RT initiated in concomitant-boost format is well tolerated and results in a rate of complete response ( 74 % ) similar to that in previous bladder-sparing trials . The projected 2-year values for locoregional control , bladder-intact survival , and overall survival were also consistent with previously reported trials of bladder-sparing treatment . With only 45 % of patients completing three cycles of MCV , this form of adjuvant chemotherapy appears to be poorly tolerated by most patients BACKGROUND AND PURPOSE To evaluate the efficacy and toxicity of an accelerated fractionation regimen to treat localised muscle invasive bladder cancer . PATIENTS AND METHODS A prospect i ve r and omised trial was undertaken in 229 patients r and omised between 1988 and 1998 comparing accelerated fractionation ( AF ) to a dose of 60.8 Gy in 3 
    Output:
    