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: Neoadjuvant chemotherapy improves the survival of patients with high‐risk urothelial cancer . However , the lack of curative alternatives to cisplatin‐based chemotherapy is limiting for patients with neuropathy or hearing loss  .  Sequential chemotherapy also has not been well studied in the neoadjuvant setting . The authors explored sequential neoadjuvant ifosfamide‐based chemotherapy in a patient cohort at high risk of noncurative cystectomy Urothelial carcinoma of the upper urinary tract ( UUT‐UC ) was a rare , aggressive urologic cancer with a propensity for multifocality , local recurrence , and metastasis . High‐risk patients had poor outcomes . Because of the rarity of these tumors , r and omized clinical trials and data regarding adjuvant chemotherapy in locally advanced tumors are currently unavailable . Our objective was to assess the effect of adjuvant chemotherapy and the impact of potential prognostic factors on survival in high‐risk , postsurgical UUT‐UC patients Purpose To determine through the analysis of our multi-institutional data base whether postoperative adjuvant chemotherapy for upper urinary tract carcinoma with localized invasive upper urinary tract carcinoma ( UUTC ) is beneficial . Methods A study population of 93 patients with pT3N0/xM0 UUTC was eligible for this study . Clinical features evaluated were sex , tumor location ,  adjuvant chemotherapy status , tumor pathology ( histology , grade , infiltrating growth , lymphovascular invasion ( LVI ) ) , and cause of death . Cancer-specific survival ( CSS ) was estimated by Kaplan – Meier method . Prognostic factors related to CSS were analyzed by Cox proportional hazards regression model for multivariate analysis . Results In pT3 patients , overall 5-year CSS rate was 68.4 % and median CSS time was 31 months ( range 3–114 months ) . In the adjuvant chemotherapy group , 5-year CSS rate was 80.8 % , whereas 5-year CSS rate was 64.4 % in the non-adjuvant chemotherapy group . By multivariate analysis , adjuvant chemotherapy status was significantly associated with CSS ( P = 0.008 ) were sex , tumor grade , tumor histology , and LVI presence . Conclusions This study , although it was retrospective study , revealed that adjuvant chemotherapy after RNU may be beneficial in pT3N0/X patients by multivariate analysis . Prospect i ve studies evaluating adjuvant therapy regimens for UTTC are required PURPOSE Radical surgery represents the treatment of choice for carcinoma of the upper urinary tract . Nevertheless , approximately 50 % of patients with stage T > /= 3 or lymph node involvement die from their disease , mainly as a result of the development of distant metastases . Therefore , there is a need for effective adjuvant systemic treatment . We prospect ively studied a cohort of patients who underwent surgery for high-risk carcinoma of the upper urinary tract to assess the feasibility of the combination of paclitaxel and carboplatin as adjuvant treatment . PATIENTS AND METHODS Thirty-six patients with tumor stage > /= 3 or lymph node involvement were treated with four cycles of paclitaxel at 175 mg/m(2 ) and carboplatin ( area under the curve 5 , Calvert Formula ) every 3 weeks following surgery . RESULTS Median follow-up was 40.6 months . Chemotherapy was well tolerated with 32 patients ( 89 % ) receiving full carboplatin and paclitaxel doses without delays . The most frequent grade 3/4 toxicity was neutropenia ( 39 % ) , which was complicated with fever in only one case ( 3 % ) . Nonhematologic grade 3 or 4 toxicities were reported in only one case . Five-year survival was 52 % ( 95 % CI , 35 % to 69 % ) , while 5-year disease-free survival was 40.2 % ( 95 % CI , 15.8 % to 64.6 % ) . Local failure rate was 30 % , as opposed to 17 % of patients who developed distant metastases . No patients with grade 2 tumors relapsed during follow-up , as opposed to 60 % of patients with grade 3 tumors . CONCLUSION Adjuvant chemotherapy with paclitaxel and carboplatin is feasible and may reduce the risk of distant metastases in high-risk upper urinary tract carcinoma PURPOSE Colon cancers exhibiting DNA mismatch repair ( MMR ) defects demonstrate distinct clinical and pathologic features , including better prognosis and reduced response to fluorouracil ( FU ) -based chemotherapy . This prospect i ve study investigated adjuvant chemotherapy containing FU and irinotecan in patients with MMR deficient ( MMR-D ) colon cancers . PATIENTS AND METHODS Cancer and Leukemia Group B 89803 r and omly assigned 1,264 patients with stage III colon cancer to postoperative weekly bolus FU/leucovorin ( LV ) or weekly bolus irinotecan , FU , and LV ( IFL ) .  The primary end point was overall survival ; disease-free survival ( DFS ) was a secondary end point . Tumor expression of the MMR proteins , MLH1 and MSH2 , was determined by immunohistochemistry ( IHC ) . DNA microsatellite instability was also assessed using a panel of mono- and dinucleotide markers . Tumors with MMR defects were those demonstrating loss of MMR protein expression ( MMR-D ) and /or microsatellite instability high ( MSI-H ) genotype . RESULTS Of 723 tumor cases examined by genotyping and IHC , 96 ( 13.3 % ) were MMR-D/MSI-H. Genotyping results were consistent with IHC in 702 cases ( 97.1 % ) . IFL-treated patients with MMR-D/MSI-H tumors showed improved 5-year DFS as compared with those with mismatch repair intact tumors ( 0.76 ; 95 % CI , 0.64 to 0.88 v 0.59 ; 95 % CI , 0.53 to 0.64 ; P = .03 ) . This relationship was not observed among patients treated with FU/LV . A trend toward longer DFS was observed in IFL-treated patients with MMR-D/MSI-H tumors as compared with those receiving FU/LV ( 0.57 ; 95 % CI , 0.42 to 0.71 v 0.76 ; 95 % CI , 0.64 to 0.88 ; P = .07 ; hazard ratio interaction between tumor status and treatment , 0.51 ; likelihood ratio P = .117 ) . CONCLUSION Loss of tumor MMR function may predict improved outcome in patients treated with the IFL regimen  as compared with those receiving FU/LV OBJECTIVES To evaluate the efficacy of adjuvant platinum based chemotherapy in upper urinary tract urothelial cancer following surgical resection in terms of survival benefit and inhibition of bladder cancer recurrence . METHODS Between April 1986 and August 2005 , a total of 132 patients with a diagnosis of upper urinary tract urothelial cancer underwent radical nephroureterectomy with cuff of bladder at our department . A total of 46 patients ( 13 with pT2pN0M0 and 33 with pT3 pN0M0 transitional cell carcinoma without prior bladder cancer ) were enrolled . Patients with locally advanced disease were divided into two groups : the adjuvant chemotherapy group ( 24 patients ) who received adjuvant methotrexate , vinblastine , adriamycin , and cisplatin ( M-VAC ) and the non-adjuvant chemotherapy group who did not receive adjuvant M-VAC ( 22 patients ) . RESULTS There were no statistically significant differences in patient characteristics or 10-year survival between the two groups . The recurrence rate in the non-adjuvant chemotherapy group was significantly higher than in the adjuvant chemotherapy group ( log-rank test , P < 0.0001 ) . Only non-adjuvant chemotherapy was a significant and independent risk factor ( hazard ratio 6.97 ) for the development of intravesical recurrence ( P < 0.01 ) . CONCLUSION Adjuvant M-VAC is an important optional adjuvant therapy and can prevent recurrent bladder tumors following surgery for upper urinary tract transitional cell carcinoma . To determine whether adjuvant chemotherapy has further benefit , a r and omized study would be needed 
    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: Neoadjuvant chemotherapy improves the survival of patients with high‐risk urothelial cancer . However , the lack of curative alternatives to cisplatin‐based chemotherapy is limiting for patients with neuropathy or hearing loss  .  Sequential chemotherapy also has not been well studied in the neoadjuvant setting . The authors explored sequential neoadjuvant ifosfamide‐based chemotherapy in a patient cohort at high risk of noncurative cystectomy Urothelial carcinoma of the upper urinary tract ( UUT‐UC ) was a rare , aggressive urologic cancer with a propensity for multifocality , local recurrence , and metastasis . High‐risk patients had poor outcomes . Because of the rarity of these tumors , r and omized clinical trials and data regarding adjuvant chemotherapy in locally advanced tumors are currently unavailable . Our objective was to assess the effect of adjuvant chemotherapy and the impact of potential prognostic factors on survival in high‐risk , postsurgical UUT‐UC patients Purpose To determine through the analysis of our multi-institutional data base whether postoperative adjuvant chemotherapy for upper urinary tract carcinoma with localized invasive upper urinary tract carcinoma ( UUTC ) is beneficial . Methods A study population of 93 patients with pT3N0/xM0 UUTC was eligible for this study . Clinical features evaluated were sex , tumor location ,  adjuvant chemotherapy status , tumor pathology ( histology , grade , infiltrating growth , lymphovascular invasion ( LVI ) ) , and cause of death . Cancer-specific survival ( CSS ) was estimated by Kaplan – Meier method . Prognostic factors related to CSS were analyzed by Cox proportional hazards regression model for multivariate analysis . Results In pT3 patients , overall 5-year CSS rate was 68.4 % and median CSS time was 31 months ( range 3–114 months ) . In the adjuvant chemotherapy group , 5-year CSS rate was 80.8 % , whereas 5-year CSS rate was 64.4 % in the non-adjuvant chemotherapy group . By multivariate analysis , adjuvant chemotherapy status was significantly associated with CSS ( P = 0.008 ) were sex , tumor grade , tumor histology , and LVI presence . Conclusions This study , although it was retrospective study , revealed that adjuvant chemotherapy after RNU may be beneficial in pT3N0/X patients by multivariate analysis . Prospect i ve studies evaluating adjuvant therapy regimens for UTTC are required PURPOSE Radical surgery represents the treatment of choice for carcinoma of the upper urinary tract . Nevertheless , approximately 50 % of patients with stage T > /= 3 or lymph node involvement die from their disease , mainly as a result of the development of distant metastases . Therefore , there is a need for effective adjuvant systemic treatment . We prospect ively studied a cohort of patients who underwent surgery for high-risk carcinoma of the upper urinary tract to assess the feasibility of the combination of paclitaxel and carboplatin as adjuvant treatment . PATIENTS AND METHODS Thirty-six patients with tumor stage > /= 3 or lymph node involvement were treated with four cycles of paclitaxel at 175 mg/m(2 ) and carboplatin ( area under the curve 5 , Calvert Formula ) every 3 weeks following surgery . RESULTS Median follow-up was 40.6 months . Chemotherapy was well tolerated with 32 patients ( 89 % ) receiving full carboplatin and paclitaxel doses without delays . The most frequent grade 3/4 toxicity was neutropenia ( 39 % ) , which was complicated with fever in only one case ( 3 % ) . Nonhematologic grade 3 or 4 toxicities were reported in only one case . Five-year survival was 52 % ( 95 % CI , 35 % to 69 % ) , while 5-year disease-free survival was 40.2 % ( 95 % CI , 15.8 % to 64.6 % ) . Local failure rate was 30 % , as opposed to 17 % of patients who developed distant metastases . No patients with grade 2 tumors relapsed during follow-up , as opposed to 60 % of patients with grade 3 tumors . CONCLUSION Adjuvant chemotherapy with paclitaxel and carboplatin is feasible and may reduce the risk of distant metastases in high-risk upper urinary tract carcinoma PURPOSE Colon cancers exhibiting DNA mismatch repair ( MMR ) defects demonstrate distinct clinical and pathologic features , including better prognosis and reduced response to fluorouracil ( FU ) -based chemotherapy . This prospect i ve study investigated adjuvant chemotherapy containing FU and irinotecan in patients with MMR deficient ( MMR-D ) colon cancers . PATIENTS AND METHODS Cancer and Leukemia Group B 89803 r and omly assigned 1,264 patients with stage III colon cancer to postoperative weekly bolus FU/leucovorin ( LV ) or weekly bolus irinotecan , FU , and LV ( IFL ) .  The primary end point was overall survival ; disease-free survival ( DFS ) was a secondary end point . Tumor expression of the MMR proteins , MLH1 and MSH2 , was determined by immunohistochemistry ( IHC ) . DNA microsatellite instability was also assessed using a panel of mono- and dinucleotide markers . Tumors with MMR defects were those demonstrating loss of MMR protein expression ( MMR-D ) and /or microsatellite instability high ( MSI-H ) genotype . RESULTS Of 723 tumor cases examined by genotyping and IHC , 96 ( 13.3 % ) were MMR-D/MSI-H. Genotyping results were consistent with IHC in 702 cases ( 97.1 % ) . IFL-treated patients with MMR-D/MSI-H tumors showed improved 5-year DFS as compared with those with mismatch repair intact tumors ( 0.76 ; 95 % CI , 0.64 to 0.88 v 0.59 ; 95 % CI , 0.53 to 0.64 ; P = .03 ) . This relationship was not observed among patients treated with FU/LV . A trend toward longer DFS was observed in IFL-treated patients with MMR-D/MSI-H tumors as compared with those receiving FU/LV ( 0.57 ; 95 % CI , 0.42 to 0.71 v 0.76 ; 95 % CI , 0.64 to 0.88 ; P = .07 ; hazard ratio interaction between tumor status and treatment , 0.51 ; likelihood ratio P = .117 ) . CONCLUSION Loss of tumor MMR function may predict improved outcome in patients treated with the IFL regimen  as compared with those receiving FU/LV OBJECTIVES To evaluate the efficacy of adjuvant platinum based chemotherapy in upper urinary tract urothelial cancer following surgical resection in terms of survival benefit and inhibition of bladder cancer recurrence . METHODS Between April 1986 and August 2005 , a total of 132 patients with a diagnosis of upper urinary tract urothelial cancer underwent radical nephroureterectomy with cuff of bladder at our department . A total of 46 patients ( 13 with pT2pN0M0 and 33 with pT3 pN0M0 transitional cell carcinoma without prior bladder cancer ) were enrolled . Patients with locally advanced disease were divided into two groups : the adjuvant chemotherapy group ( 24 patients ) who received adjuvant methotrexate , vinblastine , adriamycin , and cisplatin ( M-VAC ) and the non-adjuvant chemotherapy group who did not receive adjuvant M-VAC ( 22 patients ) . RESULTS There were no statistically significant differences in patient characteristics or 10-year survival between the two groups . The recurrence rate in the non-adjuvant chemotherapy group was significantly higher than in the adjuvant chemotherapy group ( log-rank test , P < 0.0001 ) . Only non-adjuvant chemotherapy was a significant and independent risk factor ( hazard ratio 6.97 ) for the development of intravesical recurrence ( P < 0.01 ) . CONCLUSION Adjuvant M-VAC is an important optional adjuvant therapy and can prevent recurrent bladder tumors following surgery for upper urinary tract transitional cell carcinoma . To determine whether adjuvant chemotherapy has further benefit , a r and omized study would be needed 
    Output:
    