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: OBJECTIVE To evaluate tumour progression and survival of patients with T1G3 bladder tumours who were followed for 15 years . PATIENTS AND METHODS A subset of 48 patients with T1G3 bladder tumours was entered into a r and omized trial of transurethral resection ( TUR ) or TUR plus bacille Calmette-Guèrin ( BCG ) therapy and followed for a minimum of 15 years . Thirty-nine ( 81 % ) patients received one or more courses of BCG . The endpoints of the study were stage progression ( defined as muscle invasion of metastasis ) and disease-specific survival . RESULTS Of the 48 patients , 25 ( 52 % ) progressed and 15 ( 31 % ) died from the disease ; 33 patients ( 69 % ) survived , including 24 ( 50 % ) with an intact bladder . The median progression-free survival time was 151 months . Tumour progression occurred in 35 % of the patients within the first 5 years , in 16 % after 5 - 10 years and in 12 % of those followed for 10 - 15 years . Deaths from cancer occurred in 25 % of the patients in the first 5 years and in 10 % of patients at risk from 5 to 15 years . CONCLUSIONS Patients with T1G3 bladder tumours who are treated conservatively are at life-long risk of having a muscle-invasive tumour and dying from bladder cancer BACKGROUND Reporting methodology is highly variable and nonst and ardized , yet surgical outcomes are utilized in clinical trial design and evaluation of healthcare provider performance . OBJECTIVE We sought to define the type , incidence , and severity of early postoperative morbidities following  radical cystectomy ( RC )  using a st and ardized reporting methodology . DESIGN , SETTING , AND PARTICIPANTS Between 1995 and 2005 , 1142 consecutive RCs were entered into a prospect i ve complication data base and retrospectively review ed for accuracy . All patients underwent RC/urinary diversion by high-volume fellowship-trained urologic oncologists . MEASUREMENTS All complications within 90 d of surgery were analyzed and grade d according to the Memorial Sloan-Kettering Cancer Center complication grading system . Complications were defined and stratified into 11 specific categories . Univariate and multivariate regression models were used to define predictors of complications . RESULTS AND LIMITATIONS Sixty-four percent ( 735/1142 ) of patients experienced a complication within 90 d of surgery . Among patients experiencing a complication , 67 % experienced a complication during the operative hospital admission and 58 % following discharge . Overall , the highest grade of complication was grade 0 in 36 % ( n=407 ) , grade 1 - 2 in 51 % ( n=582 ) , and grade 3 - 5 in 13 % ( n=153 ) . Gastrointestinal complications were most common ( 29 % ) , followed by infectious complications ( 25 % ) and wound-related complications ( 15 % ) . The 30-d mortality rate was 1.5 % . CONCLUSIONS Surgical morbidity following RC is significant and , when strict reporting guidelines are incorporated , higher than previously published . Accurate reporting of postoperative complications after RC is essential for counseling patients , combined modality treatment planning , clinical trial design , and assessment of surgical success 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 Perioperative cisplatin combination chemotherapy is associated with a survival benefit in patients with invasive bladder cancer ( BCa ) . However , in a recent report from the National Cancer Data base ( NCDB ) , only 11.6 % of stage III BCa patients received perioperative chemotherapy , the majority in the adjuvant setting . OBJECTIVE We explore the impact of postoperative complications on the timing of adjuvant chemotherapy . DESIGN , SETTING , AND PARTICIPANTS An independent review board approved the review of 1142 consecutive radical cystectomies ( RC ) , and data from these cases were entered into a prospect i ve complication data base ( 1995 - 2005 ) which was utilized and retrospectively review ed for accuracy at a single , academic , tertiary cancer center . INTERVENTIONS All patients underwent RC/urinary diversion by high-volume , fellowship-trained , urologic oncologists . MEASUREMENTS All complications within 90 d of surgery were defined and grade d using a five- grade modification of the original Clavien system utilized at Memorial Sloan-Kettering Cancer Center and stratified into 11 categories . Grade 2 - 5 complications typically prohibit starting adjuvant chemotherapy . Univariate and multivariable logistic regression were used to evaluate variables associated with complications . RESULTS AND LIMITATIONS Overall , 64 % ( 735 of 1142 patients ) experienced one or more complications , of which 83 % ( 611 of 735 ) were grade 2 - 5 . Furthermore , 57 % of grade 2 - 5 complications ( 347 of 611 ) occurred between discharge and 90 d , 38 % ( 233 of 611 ) within 6 wk , and 19 % ( 114 of 611 ) between 6 wk and 12 wk , the general time frame for adjuvant chemotherapy . Overall , 26 % ( 298 of 1142 patients ) required readmission . Surgical morbidity at a high-volume tertiary cancer center may not reflect the case mix or surgical experience seen in the community setting . CONCLUSION This series demonstrates that 30 % of patients ( 347 of 1142 ) undergoing RC may not have been able to receive adjuvant chemotherapy due to postoperative complications . This information should be taken into consideration when planning multimodal therapy and further supports the use of perioperative chemotherapy in the neoadjuvant setting 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 Patients with muscle invasive carcinoma of the bladder treated with radical radiation  were prospect ively documented and followed in an attempt to identify prognostic factors predictive of the response to treatment . Data on 121 consecutive patients treated with radical radiation between 1981 and 1985 are presented . Over-all actuarial survival of the patient population ( median age 70 years ) was 31.6 % at 5 years and cause-specific survival was 44.8 % . At analysis 33 of 121 patients ( 27.3 % ) were alive with preserved bladder function . Independent prognostic factors for cause-specific survival and for complete response with radical radiation were tumor configuration , hemoglobin level and clinical stage . The rate free of local relapse was significantly influenced by stage and presence of coexistent carcinoma in situ . The study suggests that factors other than stage and grade influence prognosis in invasive bladder cancer and should be considered in interpreting treatment results PURPOSE A Phase I trial of twice-weekly gemcitabine and concurrent radiation therapy ( RT ) was performed in patients with muscle-invasive bladder cancer . We present the final analysis of bladder-intact survival ( BIS ) , disease-specific survival ( DSS ) , and overall survival ( OS ) . METHODS AND MATERIAL S Eligible patients had muscle-invasive transitional cell carcinoma ( cT2 - 3 ) and were c and i date s for cystectomy . Patients underwent maximal transurethral resection of bladder tumor followed by twice-weekly gemcitabine with concurrent RT to the bladder ( total of 60 Gy over 6 weeks ) . Gemcitabine doses ranged from 10 to 33 mg/m(2 ) . RESULTS Median follow-up was 5.6 years ( range , 0.6 - 9.5 years ) . Twenty-three of 24 patients were evaluable for response . All patients were clinical stage T2 . Locoregional failure occurred in seven patients ( 30 % ) , which were successfully salvaged by radical cystectomy ( n = 5 ) or intravesical therapy ( n = 2 ) . Four local failures occurred > 5 years after therapy . Most local failures were noninvasive tumors ( Ta or Tis , n = 6 ) . Ten patients ( 43 % ) experienced optimal outcome ( no failures and bladder intact ) . The 5-year actuarial estimates of survival are BIS 62 % , OS 76 % , and DSS 82 % . CONCLUSION Twice-weekly gemcitabine with concurrent RT is well tolerated and provides rates of survival and bladder preservation that are comparable to the existing literature . All locoregional failures were successfully salvaged by either radical cystectomy or intravesical therapy . Given the high proportion of late local failures , we recommend long-term monitoring when using this regimen . Future studies comparing the safety and efficacy of gemcitabine- vs. platinum-based bladder preservation protocol s are pending Radical radiotherapy and surgery achieve similar cure rates in muscle-invasive bladder cancer , but the choice of which treatment would be most beneficial can not currently be predicted for individual patients . The primary aim of this study was to assess whether expression of any of a panel of DNA damage signaling proteins in tumor sample s taken before irradiation could be used as a predictive marker of radiotherapy response , or rather was prognostic . Protein expression of MRE11 , RAD50 , NBS1 , ATM , and H2AX was studied by immunohistochemistry in pretreatment tumor specimens from two cohorts of bladder cancer patients ( validation cohort prospect ively acquired ) treated with radical radiotherapy and one cohort of cystectomy patients .  In the radiotherapy test cohort ( n = 86 ) , low tumor MRE11 expression was associated with worse cancer-specific survival compared with high expression [ 43.1 % versus 68.7 % 3-year cause-specific survival ( CSS ) , P = 0.012 ] by Kaplan-Meier analysis . This was confirmed in the radiotherapy validation cohort ( n = 93 ; 43.0 % versus 71.2 % , P = 0.020 ) . However , in the cystectomy cohort ( n = 88 ) , MRE11 expression was not associated with cancer-specific survival , commensurate with MRE11 being a predictive marker . High MRE11 expression in the combined radiotherapy cohort had a significantly better cancer-specific survival compared with the high-expression cystectomy cohort ( 69.9 % versus 53.8 % 3-year CSS , P = 0.021 ) . In this vali date d immunohistochemistry study , MRE11 protein expression was shown and confirmed as a predictive factor associated with survival following bladder cancer radiotherapy , justifying its inclusion in subsequent trial design s. MRE11 expression may ultimately allow patient selection for radiotherapy or cystectomy , thus improving overall cure rates Seventy patients with muscle-invading bladder carcinoma ( clinical stages T2 to T4 ) who were not c and i date s for cystectomy were treated with combined cisplatin and full-dose external-beam radiation on a multi-institutional prospect i ve protocol from 1980 through 1985 . Thirty-six patients 
    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: OBJECTIVE To evaluate tumour progression and survival of patients with T1G3 bladder tumours who were followed for 15 years . PATIENTS AND METHODS A subset of 48 patients with T1G3 bladder tumours was entered into a r and omized trial of transurethral resection ( TUR ) or TUR plus bacille Calmette-Guèrin ( BCG ) therapy and followed for a minimum of 15 years . Thirty-nine ( 81 % ) patients received one or more courses of BCG . The endpoints of the study were stage progression ( defined as muscle invasion of metastasis ) and disease-specific survival . RESULTS Of the 48 patients , 25 ( 52 % ) progressed and 15 ( 31 % ) died from the disease ; 33 patients ( 69 % ) survived , including 24 ( 50 % ) with an intact bladder . The median progression-free survival time was 151 months . Tumour progression occurred in 35 % of the patients within the first 5 years , in 16 % after 5 - 10 years and in 12 % of those followed for 10 - 15 years . Deaths from cancer occurred in 25 % of the patients in the first 5 years and in 10 % of patients at risk from 5 to 15 years . CONCLUSIONS Patients with T1G3 bladder tumours who are treated conservatively are at life-long risk of having a muscle-invasive tumour and dying from bladder cancer BACKGROUND Reporting methodology is highly variable and nonst and ardized , yet surgical outcomes are utilized in clinical trial design and evaluation of healthcare provider performance . OBJECTIVE We sought to define the type , incidence , and severity of early postoperative morbidities following  radical cystectomy ( RC )  using a st and ardized reporting methodology . DESIGN , SETTING , AND PARTICIPANTS Between 1995 and 2005 , 1142 consecutive RCs were entered into a prospect i ve complication data base and retrospectively review ed for accuracy . All patients underwent RC/urinary diversion by high-volume fellowship-trained urologic oncologists . MEASUREMENTS All complications within 90 d of surgery were analyzed and grade d according to the Memorial Sloan-Kettering Cancer Center complication grading system . Complications were defined and stratified into 11 specific categories . Univariate and multivariate regression models were used to define predictors of complications . RESULTS AND LIMITATIONS Sixty-four percent ( 735/1142 ) of patients experienced a complication within 90 d of surgery . Among patients experiencing a complication , 67 % experienced a complication during the operative hospital admission and 58 % following discharge . Overall , the highest grade of complication was grade 0 in 36 % ( n=407 ) , grade 1 - 2 in 51 % ( n=582 ) , and grade 3 - 5 in 13 % ( n=153 ) . Gastrointestinal complications were most common ( 29 % ) , followed by infectious complications ( 25 % ) and wound-related complications ( 15 % ) . The 30-d mortality rate was 1.5 % . CONCLUSIONS Surgical morbidity following RC is significant and , when strict reporting guidelines are incorporated , higher than previously published . Accurate reporting of postoperative complications after RC is essential for counseling patients , combined modality treatment planning , clinical trial design , and assessment of surgical success 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 Perioperative cisplatin combination chemotherapy is associated with a survival benefit in patients with invasive bladder cancer ( BCa ) . However , in a recent report from the National Cancer Data base ( NCDB ) , only 11.6 % of stage III BCa patients received perioperative chemotherapy , the majority in the adjuvant setting . OBJECTIVE We explore the impact of postoperative complications on the timing of adjuvant chemotherapy . DESIGN , SETTING , AND PARTICIPANTS An independent review board approved the review of 1142 consecutive radical cystectomies ( RC ) , and data from these cases were entered into a prospect i ve complication data base ( 1995 - 2005 ) which was utilized and retrospectively review ed for accuracy at a single , academic , tertiary cancer center . INTERVENTIONS All patients underwent RC/urinary diversion by high-volume , fellowship-trained , urologic oncologists . MEASUREMENTS All complications within 90 d of surgery were defined and grade d using a five- grade modification of the original Clavien system utilized at Memorial Sloan-Kettering Cancer Center and stratified into 11 categories . Grade 2 - 5 complications typically prohibit starting adjuvant chemotherapy . Univariate and multivariable logistic regression were used to evaluate variables associated with complications . RESULTS AND LIMITATIONS Overall , 64 % ( 735 of 1142 patients ) experienced one or more complications , of which 83 % ( 611 of 735 ) were grade 2 - 5 . Furthermore , 57 % of grade 2 - 5 complications ( 347 of 611 ) occurred between discharge and 90 d , 38 % ( 233 of 611 ) within 6 wk , and 19 % ( 114 of 611 ) between 6 wk and 12 wk , the general time frame for adjuvant chemotherapy . Overall , 26 % ( 298 of 1142 patients ) required readmission . Surgical morbidity at a high-volume tertiary cancer center may not reflect the case mix or surgical experience seen in the community setting . CONCLUSION This series demonstrates that 30 % of patients ( 347 of 1142 ) undergoing RC may not have been able to receive adjuvant chemotherapy due to postoperative complications . This information should be taken into consideration when planning multimodal therapy and further supports the use of perioperative chemotherapy in the neoadjuvant setting 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 Patients with muscle invasive carcinoma of the bladder treated with radical radiation  were prospect ively documented and followed in an attempt to identify prognostic factors predictive of the response to treatment . Data on 121 consecutive patients treated with radical radiation between 1981 and 1985 are presented . Over-all actuarial survival of the patient population ( median age 70 years ) was 31.6 % at 5 years and cause-specific survival was 44.8 % . At analysis 33 of 121 patients ( 27.3 % ) were alive with preserved bladder function . Independent prognostic factors for cause-specific survival and for complete response with radical radiation were tumor configuration , hemoglobin level and clinical stage . The rate free of local relapse was significantly influenced by stage and presence of coexistent carcinoma in situ . The study suggests that factors other than stage and grade influence prognosis in invasive bladder cancer and should be considered in interpreting treatment results PURPOSE A Phase I trial of twice-weekly gemcitabine and concurrent radiation therapy ( RT ) was performed in patients with muscle-invasive bladder cancer . We present the final analysis of bladder-intact survival ( BIS ) , disease-specific survival ( DSS ) , and overall survival ( OS ) . METHODS AND MATERIAL S Eligible patients had muscle-invasive transitional cell carcinoma ( cT2 - 3 ) and were c and i date s for cystectomy . Patients underwent maximal transurethral resection of bladder tumor followed by twice-weekly gemcitabine with concurrent RT to the bladder ( total of 60 Gy over 6 weeks ) . Gemcitabine doses ranged from 10 to 33 mg/m(2 ) . RESULTS Median follow-up was 5.6 years ( range , 0.6 - 9.5 years ) . Twenty-three of 24 patients were evaluable for response . All patients were clinical stage T2 . Locoregional failure occurred in seven patients ( 30 % ) , which were successfully salvaged by radical cystectomy ( n = 5 ) or intravesical therapy ( n = 2 ) . Four local failures occurred > 5 years after therapy . Most local failures were noninvasive tumors ( Ta or Tis , n = 6 ) . Ten patients ( 43 % ) experienced optimal outcome ( no failures and bladder intact ) . The 5-year actuarial estimates of survival are BIS 62 % , OS 76 % , and DSS 82 % . CONCLUSION Twice-weekly gemcitabine with concurrent RT is well tolerated and provides rates of survival and bladder preservation that are comparable to the existing literature . All locoregional failures were successfully salvaged by either radical cystectomy or intravesical therapy . Given the high proportion of late local failures , we recommend long-term monitoring when using this regimen . Future studies comparing the safety and efficacy of gemcitabine- vs. platinum-based bladder preservation protocol s are pending Radical radiotherapy and surgery achieve similar cure rates in muscle-invasive bladder cancer , but the choice of which treatment would be most beneficial can not currently be predicted for individual patients . The primary aim of this study was to assess whether expression of any of a panel of DNA damage signaling proteins in tumor sample s taken before irradiation could be used as a predictive marker of radiotherapy response , or rather was prognostic . Protein expression of MRE11 , RAD50 , NBS1 , ATM , and H2AX was studied by immunohistochemistry in pretreatment tumor specimens from two cohorts of bladder cancer patients ( validation cohort prospect ively acquired ) treated with radical radiotherapy and one cohort of cystectomy patients .  In the radiotherapy test cohort ( n = 86 ) , low tumor MRE11 expression was associated with worse cancer-specific survival compared with high expression [ 43.1 % versus 68.7 % 3-year cause-specific survival ( CSS ) , P = 0.012 ] by Kaplan-Meier analysis . This was confirmed in the radiotherapy validation cohort ( n = 93 ; 43.0 % versus 71.2 % , P = 0.020 ) . However , in the cystectomy cohort ( n = 88 ) , MRE11 expression was not associated with cancer-specific survival , commensurate with MRE11 being a predictive marker . High MRE11 expression in the combined radiotherapy cohort had a significantly better cancer-specific survival compared with the high-expression cystectomy cohort ( 69.9 % versus 53.8 % 3-year CSS , P = 0.021 ) . In this vali date d immunohistochemistry study , MRE11 protein expression was shown and confirmed as a predictive factor associated with survival following bladder cancer radiotherapy , justifying its inclusion in subsequent trial design s. MRE11 expression may ultimately allow patient selection for radiotherapy or cystectomy , thus improving overall cure rates Seventy patients with muscle-invading bladder carcinoma ( clinical stages T2 to T4 ) who were not c and i date s for cystectomy were treated with combined cisplatin and full-dose external-beam radiation on a multi-institutional prospect i ve protocol from 1980 through 1985 . Thirty-six patients 
    Output:
    