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: BACKGROUND AND PURPOSE To determine the feasibility , toxicity , and clinical effectiveness of concurrent weekly cisplatin chemotherapy in conjunction with definitive radiation in the treatment of localised muscle invasive bladder cancer . PATIENTS AND METHODS In January 1997 the Trans Tasman Radiation Oncology Group embarked on a Phase II study ( TROG 97.01 ) of weekly cisplatin ( 35 mg/m(2 ) x 7 doses ) plus radiation to a dose of 63 Gy over 7 weeks . Following an interim toxicity analysis , the dose intensity of cisplatin was reduced to 6 cycles and the radiation schedule changed to 64 Gy over 6.5 weeks leading to the second study ( TROG 99.06 ) . A total of 113 patients were enrolled . RESULTS Acute grade 3 urinary toxicity occurred in 23 % of the patients . Acute grade 4 pelvic toxicity was not seen . Thirty-eight patients ( 33 % ) experienced grade 3 or 4 cisplatin related toxicities with 15 patients ( 12 % ) requiring significant dose modification . The reduced dose intensity in Study 99.06 improved tolerability . Incidence of significant late morbidity was low ( 6 % ) . Seventy-nine patients ( 70 % ) achieved complete remission at the 6 month cystoscopic assessment . Local invasive recurrence was seen in 11 of the 79 patients ( 14 % ) . In 18 patients ( 16 % ) isolated superficial TCC/CIS were detected ( 6 months and beyond ) . The local control rate was 45 % with a functional bladder being retained in 69 of the 113 patients ( 61 % ) . RFS and DSS at 5 years were 33 % and 50 % , respectively . CONCLUSION Our two sequential Phase II studies have shown that concurrent chemoradiation using weekly cisplatin in the management of localised invasive bladder TCC is feasible and reasonably well tolerated . This approach is currently being investigated further in a r and omised study PURPOSE We evaluated the feasibility and efficacy of the organ preserving strategy of intra-arterial cisplatin and concurrent radiotherapy for localized bladder cancer . MATERIAL S AND METHODS Bladder preservation has been pursued over the decades in treatment regimens featuring radiotherapy alone or in conjunction with single or multiagent chemotherapy . The chemotherapy has consisted almost exclusively of intravenously administered drugs . There are theoretical and clinical data demonstrating a higher concentration of cisplatin within tumors following intra-arterial as opposed to intravenous delivery . This study was performed to evaluate whether this increased concentration would enhance radiosensitization and thereby increase the success of bladder preservation . RESULTS We report on our prospect ively collected experience during 15 years of treating 200 patients with localized bladder cancer using this regimen of 3 courses of intra-arterial cisplatin integrated with pelvic radiotherapy  and reserving cystectomy for salvage as required . We report on the efficacy in terms of complete response rate , ultimate tumor-free bladder preservation , overall survival and patterns of failure . We detail the acute and chronic toxicity observed to date . CONCLUSIONS This strategy has result ed in a durable high complete response rate and overall tumor-free bladder preservation rate of 75 % while maintaining a survival comparable to that achieved with cystectomy . These results corroborate the hypothesis that intra-arterial administration of cisplatin enhances radiosensitization during pelvic radiotherapy We conducted a phase I/II study investigating synchronous chemoradiotherapy with mitomycin C and infusional 5-fluorouracil ( 5-FU ) in muscle invasive bladder cancer . Early dose escalation results were previously published . We report the long-term toxicity and efficacy results with the optimised regimen . Patients with muscle invasive bladder cancer with glomerular filtration rate > 25 ml min−1 were eligible .  Mitomycin ( 12 mg m−2 on day 1 only ) and infusional 5-FU ( 500 mg m−2 day−1 ) for 5 days were administered during weeks 1 and 4 of radiotherapy of 55 Gy in 20 fractions . A total of 41 patients were enrolled , median age was 68 years , 33 were male and eight female patients . Out of the 41 patients , 20 ( 49 % ) had hydronephrosis at presentation and 25 ( 62 % ) had T3b or T4 disease . Four patients experienced Grade III thrombocytopenia and three patients had Grade III neutropenia . There were no episodes of febrile neutropenia . Four patients experienced Grade III diarrhoea and 1 Grade III urgency and dysuria . Six patients did not undergo cystoscopic evaluation due to early metastatic spread although there was no clinical suggestion of bladder failure . In all , out of 35 evaluable patients , 25 ( 71 % ) had macroscopic complete response at 3-month cystoscopy , and biopsy confirmed in 24 out of 25 . A total of 16 ( 39 % ) patients remain alive with a median follow-up of 50.7 ( range 23.5–68.8 ) months , 14 with a functioning bladder with no reported long-term treatment-related bladder or bowel toxicity . Five out of 41 patients have undergone salvage cystectomy : two for persistent CIS , two T1 and one muscle invasive recurrence . Four patients have received intravesical chemotherapy , of whom two remain alive with a functioning bladder . Overall 12- , 24- and 60-month ( m ) survival rates were 68 , 49 and 36 % . Local and distant progression free rates were 82 and 86 % at 12-m and 79 and 75 % at 24-m . Organ preservation using multimodality therapy is feasible and safe , even in patients with poor renal reserve , and does not compromise salvage therapies . A national phase III trial BC2001 ( www.bc2001.org.uk ) exploring the effects of synchronous chemoradiotherapy with this regimen is currently recruiting OBJECTIVES To determine the long-term results of a bladder-sparing approach in the treatment of muscle-invasive bladder cancer . METHODS Ninety-four patients with invasive transitional cell carcinoma of the bladder were treated by transurethral resection followed by 2 or 3 cycles of cisplatin-based chemotherapy . Patients were then treated with 6480 cGy of radiation in 49 patients , segmental cystectomy in 8 , or surveillance only in 7 . Patients who failed to respond to chemotherapy or radiation therapy , or who developed recurrent muscle-invasive disease in follow-up , underwent salvage cystectomy . Patients were then carefully followed for a median follow-up of more than 5 years . RESULTS After initial therapy , 53 patients ( 56 % ) were alive with their bladder preserved . Thirty of those 53 ( 57 % ) developed a local recurrence in follow-up . After a median follow-up of more than 5 years , the ultimate relapse-free survival is 49 % ( Stage T2 , 84 % ; T3 , 53 % ; and T4 , 11 % ; P < 0.01 ) . Of all patients enrolled , 53 % had bladder preservation ; however , of the currently surviving patients , 16 of 39 ( 41 % ) have their bladders intact ( T2 , 50 % ; T3 , 37 % ; T4 , 0 % ) . Only 18 % of the initially enrolled population is alive with a preserved bladder . The 5-year survival of patients who had cystectomy at some point during the study , compared with those who have had their bladders preserved , was 65 % versus 40 % , respectively ( P < 0.01 ) . CONCLUSIONS Our long-term results with multimodality therapy with attempted bladder preservation showed no definitive improvement in survival compared with modern series of cystectomy alone , and a disappointingly low rate of disease-free bladder preservation . We found a high rate of locally recurrent disease in the preserved bladders . We also noted a decrease in survival in our patients with bladder preservation compared with those without preservation . Bladder preservation , although possible , should be limited to a very select group of patients 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 tox 
    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: BACKGROUND AND PURPOSE To determine the feasibility , toxicity , and clinical effectiveness of concurrent weekly cisplatin chemotherapy in conjunction with definitive radiation in the treatment of localised muscle invasive bladder cancer . PATIENTS AND METHODS In January 1997 the Trans Tasman Radiation Oncology Group embarked on a Phase II study ( TROG 97.01 ) of weekly cisplatin ( 35 mg/m(2 ) x 7 doses ) plus radiation to a dose of 63 Gy over 7 weeks . Following an interim toxicity analysis , the dose intensity of cisplatin was reduced to 6 cycles and the radiation schedule changed to 64 Gy over 6.5 weeks leading to the second study ( TROG 99.06 ) . A total of 113 patients were enrolled . RESULTS Acute grade 3 urinary toxicity occurred in 23 % of the patients . Acute grade 4 pelvic toxicity was not seen . Thirty-eight patients ( 33 % ) experienced grade 3 or 4 cisplatin related toxicities with 15 patients ( 12 % ) requiring significant dose modification . The reduced dose intensity in Study 99.06 improved tolerability . Incidence of significant late morbidity was low ( 6 % ) . Seventy-nine patients ( 70 % ) achieved complete remission at the 6 month cystoscopic assessment . Local invasive recurrence was seen in 11 of the 79 patients ( 14 % ) . In 18 patients ( 16 % ) isolated superficial TCC/CIS were detected ( 6 months and beyond ) . The local control rate was 45 % with a functional bladder being retained in 69 of the 113 patients ( 61 % ) . RFS and DSS at 5 years were 33 % and 50 % , respectively . CONCLUSION Our two sequential Phase II studies have shown that concurrent chemoradiation using weekly cisplatin in the management of localised invasive bladder TCC is feasible and reasonably well tolerated . This approach is currently being investigated further in a r and omised study PURPOSE We evaluated the feasibility and efficacy of the organ preserving strategy of intra-arterial cisplatin and concurrent radiotherapy for localized bladder cancer . MATERIAL S AND METHODS Bladder preservation has been pursued over the decades in treatment regimens featuring radiotherapy alone or in conjunction with single or multiagent chemotherapy . The chemotherapy has consisted almost exclusively of intravenously administered drugs . There are theoretical and clinical data demonstrating a higher concentration of cisplatin within tumors following intra-arterial as opposed to intravenous delivery . This study was performed to evaluate whether this increased concentration would enhance radiosensitization and thereby increase the success of bladder preservation . RESULTS We report on our prospect ively collected experience during 15 years of treating 200 patients with localized bladder cancer using this regimen of 3 courses of intra-arterial cisplatin integrated with pelvic radiotherapy  and reserving cystectomy for salvage as required . We report on the efficacy in terms of complete response rate , ultimate tumor-free bladder preservation , overall survival and patterns of failure . We detail the acute and chronic toxicity observed to date . CONCLUSIONS This strategy has result ed in a durable high complete response rate and overall tumor-free bladder preservation rate of 75 % while maintaining a survival comparable to that achieved with cystectomy . These results corroborate the hypothesis that intra-arterial administration of cisplatin enhances radiosensitization during pelvic radiotherapy We conducted a phase I/II study investigating synchronous chemoradiotherapy with mitomycin C and infusional 5-fluorouracil ( 5-FU ) in muscle invasive bladder cancer . Early dose escalation results were previously published . We report the long-term toxicity and efficacy results with the optimised regimen . Patients with muscle invasive bladder cancer with glomerular filtration rate > 25 ml min−1 were eligible .  Mitomycin ( 12 mg m−2 on day 1 only ) and infusional 5-FU ( 500 mg m−2 day−1 ) for 5 days were administered during weeks 1 and 4 of radiotherapy of 55 Gy in 20 fractions . A total of 41 patients were enrolled , median age was 68 years , 33 were male and eight female patients . Out of the 41 patients , 20 ( 49 % ) had hydronephrosis at presentation and 25 ( 62 % ) had T3b or T4 disease . Four patients experienced Grade III thrombocytopenia and three patients had Grade III neutropenia . There were no episodes of febrile neutropenia . Four patients experienced Grade III diarrhoea and 1 Grade III urgency and dysuria . Six patients did not undergo cystoscopic evaluation due to early metastatic spread although there was no clinical suggestion of bladder failure . In all , out of 35 evaluable patients , 25 ( 71 % ) had macroscopic complete response at 3-month cystoscopy , and biopsy confirmed in 24 out of 25 . A total of 16 ( 39 % ) patients remain alive with a median follow-up of 50.7 ( range 23.5–68.8 ) months , 14 with a functioning bladder with no reported long-term treatment-related bladder or bowel toxicity . Five out of 41 patients have undergone salvage cystectomy : two for persistent CIS , two T1 and one muscle invasive recurrence . Four patients have received intravesical chemotherapy , of whom two remain alive with a functioning bladder . Overall 12- , 24- and 60-month ( m ) survival rates were 68 , 49 and 36 % . Local and distant progression free rates were 82 and 86 % at 12-m and 79 and 75 % at 24-m . Organ preservation using multimodality therapy is feasible and safe , even in patients with poor renal reserve , and does not compromise salvage therapies . A national phase III trial BC2001 ( www.bc2001.org.uk ) exploring the effects of synchronous chemoradiotherapy with this regimen is currently recruiting OBJECTIVES To determine the long-term results of a bladder-sparing approach in the treatment of muscle-invasive bladder cancer . METHODS Ninety-four patients with invasive transitional cell carcinoma of the bladder were treated by transurethral resection followed by 2 or 3 cycles of cisplatin-based chemotherapy . Patients were then treated with 6480 cGy of radiation in 49 patients , segmental cystectomy in 8 , or surveillance only in 7 . Patients who failed to respond to chemotherapy or radiation therapy , or who developed recurrent muscle-invasive disease in follow-up , underwent salvage cystectomy . Patients were then carefully followed for a median follow-up of more than 5 years . RESULTS After initial therapy , 53 patients ( 56 % ) were alive with their bladder preserved . Thirty of those 53 ( 57 % ) developed a local recurrence in follow-up . After a median follow-up of more than 5 years , the ultimate relapse-free survival is 49 % ( Stage T2 , 84 % ; T3 , 53 % ; and T4 , 11 % ; P < 0.01 ) . Of all patients enrolled , 53 % had bladder preservation ; however , of the currently surviving patients , 16 of 39 ( 41 % ) have their bladders intact ( T2 , 50 % ; T3 , 37 % ; T4 , 0 % ) . Only 18 % of the initially enrolled population is alive with a preserved bladder . The 5-year survival of patients who had cystectomy at some point during the study , compared with those who have had their bladders preserved , was 65 % versus 40 % , respectively ( P < 0.01 ) . CONCLUSIONS Our long-term results with multimodality therapy with attempted bladder preservation showed no definitive improvement in survival compared with modern series of cystectomy alone , and a disappointingly low rate of disease-free bladder preservation . We found a high rate of locally recurrent disease in the preserved bladders . We also noted a decrease in survival in our patients with bladder preservation compared with those without preservation . Bladder preservation , although possible , should be limited to a very select group of patients 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 tox 
    Output:
    