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 No multivariate study has assessed the independent prognostic role of  endoscopic ultrasonography ( EUS )  in esophageal cancer , even when considering computed tomography ( CT ) . OBJECTIVE To evaluate the prognostic value of  EUS  in esophageal cancer before exclusive or preoperative radiochemotherapy . METHODS From 1993 to 1999 , the FFCD 9102 study enrolled 444 patients who had cancer of the thoracic esophagus , stages T3 - 4 , N0 - 1 and M0 on CT . The patients received two sessions of chemotherapy in addition to radiotherapy .  The 259 patients with objective response and no contraindications for further treatment were r and omized to undergo surgery or to continue with radiochemotherapy . EUS was performed in 174 patients enrolled in the trial ( mean age : 59 years ) . Tumor characteristics and lymph node status were prospect ively recorded . A Cox statistical model was used to identify any predictive prognostic factors among the clinical , EUS and CT data . RESULTS In the multivariate analysis , three factors were associated with a poor prognosis : inability to ingest solid food ( OR : 1.98 ; P=0.0008 ) ; more than three neoplastic subdiaphragmatic lymph nodes ( LN ) on EUS ( OR : 2.41 ; P<0.0045 ) and age>65 ( OR : 1.53 ; P<0.056 ) . Their prognostic value persisted after adjustment for type of treatment given . Two- and five- year survival rates were 21.5 and 10.5 % , respectively , in the presence of three neoplastic subdiaphragmatic LN , and 43 and 30 % , respectively , in all other cases . CONCLUSION Degree of dysphagia , age and presence of neoplastic subdiaphragmatic LN on EUS were independently predictive of the prognosis for locally advanced esophageal cancer . EUS results should be taken into account in future trials BACKGROUND Two r and omised trials concerning thoracic oesophageal cancer concluded that for squamous cell carcinoma , chemoradiation alone leads to the same overall survival ( OS ) as chemoradiation followed by surgery . One of these trials , FFCD 9102 , r and omised only fit , compliant and operable responders to induction chemoradiation between continuation of chemoradiation and surgery . In the present analysis , the outcome in the patients not eligible for r and omisation was calculated to determine if attempt of surgery should be recommended . METHODS Eligible patients had operable T3-N0/N1-M0 thoracic oesophageal cancer . After initial  chemoradiation  , patients with no clinical response , or with contraindication to follow any attributed treatment , were not r and omised . OS was studied first in the whole population of not r and omised patients , and then specifically in clinical non-responders . The impact of surgery on OS was studied in these two population s. FINDINGS Of the 451 registered patients in the trial , 192 were not r and omised . Among them , 111 were clinical non-responders . Median OS was significantly shorter for non-r and omised patients ( 11.5 months ) than for r and omised patients ( 18.9 months ; p=0.0024 ) . However , for the 112 non-r and omised patients who underwent surgery , median OS was not different from that in r and omised patients : 17.3 versus 18.9 months ( p=0.58 ) . Concerning clinical non-responders , median OS was longer for those who underwent surgery compared to non-operated patients : 17.0 versus 5.5 months ( hazard ratio (HR)=0.39 [ 0.25 - 0.61 ] ; p<0.0001 ) , and again was not different from that in responding , r and omised patients ( p=0.40 ) . INTERPRETATION In patients with locally advanced thoracic oesophageal cancer , overall survival did not differ between responders to induction chemoradiation and patients having surgery after clinical failure of chemoradiation . Surgery should therefore be considered in those patients who are still operable CONTEXT Carcinoma of the esophagus traditionally has been treated by surgery or radiation therapy ( RT ) , but 5-year overall survival rates have been only 5 % to 10 % . We previously reported results of a study conducted from January 1986 to April 1990 of combined chemotherapy and RT vs RT alone when an interim analysis revealed significant benefit for combined therapy . OBJECTIVE To report the long-term outcomes of a previously reported trial design ed to determine if adding chemotherapy during RT improves the survival rate of patients with esophageal carcinoma . DESIGN R and omized controlled trial conducted 1985 to 1990 with follow-up of at least 5 years , followed by a prospect i ve cohort study conducted between May 1990 and April 1991 . SETTING Multi-institution participation , ranging from tertiary academic referral centers to general community practice s. PATIENTS Patients had squamous cell or adenocarcinoma of the esophagus , T1 - 3 N0 - 1 M0 , adequate renal and bone marrow reserve , and a Karnofsky score of at least 50 . Interventions Combined modality therapy ( n = 134 ) : 50 Gy in 25 fractions over 5 weeks , plus cisplatin intravenously on the first day of weeks 1 , 5 , 8 , and 11 , and fluorouracil , 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1 , 5 , 8 , and 11 . In the r and omized study , combined therapy was compared with RT only ( n = 62 ) : 64 Gy in 32 fractions over 6.4 weeks . MAIN OUTCOME MEASURES Overall survival , patterns of failure , and toxic effects . RESULTS Combined therapy significantly increased overall survival compared with RT alone . In the r and omized part of the trial , at 5 years of follow-up the overall survival for combined therapy was 26 % ( 95 % confidence interval [ CI ] , 15%-37 % ) compared with 0 % following RT . In the succeeding nonr and omized part , combined therapy produced a 5-year overall survival of 14 % ( 95 % CI , 6%-23 % ) . Persistence of disease ( despite therapy ) was the most common mode of treatment failure ; however , it was less common in the groups receiving combined therapy ( 34/130 [ 26 % ] ) than in the group treated with RT only ( 23/62 [ 37 % ] ) . Severe acute toxic effects also were greater in the combined therapy groups . There were no significant differences in severe late toxic effects between the groups . However , chemotherapy could be administered as planned in only 89 ( 68 % ) of 130 patients ( 10 % had life-threatening toxic effects with combined therapy vs 2 % in the RT only group ) . CONCLUSION Combined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus , T1 - 3 N0 - 1 M0 , compared with RT alone PURPOSE To compare the local/regional control , survival , and toxicity of combined-modality therapy using high-dose ( 64.8 Gy ) versus st and ard-dose ( 50.4 Gy ) radiation therapy for the treatment of patients with esophageal cancer . PATIENTS AND METHODS A total of 236 patients with clinical stage T1 to T4 , N0/1 , M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach , after stratification by weight loss , primary tumor size , and histology , were r and omized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil ( 5-FU ) ( 1,000 mg/m(2)/24 hours for 4 days ) and cisplatin ( 75 mg/m(2 ) bolus day 1 ) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy . The trial was stopped after an interim analysis . The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive . RESULTS For the 218 eligible patients , there was no significant difference in median survival ( 13.0 v 18.1 months ) , 2-year survival ( 31 % v 40 % ) , or local/regional failure and local/regional persistence of disease ( 56 % v 52 % ) between the high-dose and st and ard-dose arms . Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the st and ard-dose arm , seven of the 11 deaths occurred in patients who had received 50.4 Gy or less . CONCLUSION The higher radiation dose did not increase survival or local/regional control . Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm , it did not seem to be related to the higher radiation dose . The st and ard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy BACKGROUND The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established . We compared chemoradiotherapy followed by surgery with surgery alone in this patient population . METHODS We r and omly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin ( doses titrated to achieve an area under the curve of 2 mg per milliliter per minute ) and paclitaxel ( 50 mg per square meter of body-surface area ) for 5 weeks and concurrent radiotherapy ( 41.4 Gy in 23 fractions , 5 days per week ) , followed by surgery . RESULTS From March 2004 through December 2008 , we enrolled 368 patients , 366 of whom were included in the analysis : 275 ( 75 % ) had adenocarcinoma , 84 ( 23 % ) had squamous-cell carcinoma , and 7 ( 2 % ) had large-cell undifferentiated carcinoma . Of the 366 patients , 178 were r and omly assigned to chemoradiotherapy followed by surgery  , and 188 to surgery alone . The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia ( 6 % ) and neutropenia ( 2 % ) ; the most common major nonhematologic toxic effects were anorexia ( 5 % ) and fatigue ( 3 % ) . Complete resection with no tumor within 1 mm of the resection margins ( R0 ) was achieved in 92 % of patients in the chemoradiotherapy-surgery group versus 69 % in the surgery group ( P<0.001 ) . A pathological complete response was achieved in 47 of 161 patients ( 29 % ) who underwent resection after chemoradiotherapy . Postoperative complications were similar in the two treatment groups , and in-hospital mortality was 4 % in both . Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group . Overall survival was significantly better in the chemoradiotherapy-surgery group ( hazard ratio , 0.657 ; 95 % confidence interval , 0.495 to 0.871 ; P=0.003 ) . CONCLUSIONS Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer . The regimen was associated with acceptable adverse-event rates . ( Funded by the Dutch Cancer Foundation [ KWF Kankerbestrijding ] ; Netherl and s Trial Register number , NTR487 . ) AIM To investigate the role of perioperative chemoradiotherapy ( CRT ) in the treatment of locally advanced thoracic esophageal squamous cell carcinoma ( ESCC ) . METHODS Using preoperative computed tomography (CT)-based staging criteria , 238 patients with ESCC ( stage II-III ) were enrolled in this prospect i ve study between January 1997 and June 2004 . With informed consent , patients were r and omized into 3 groups : preoperative CRT ( 80 cases ) , postoperative CRT ( 78 cases ) and surgery alone ( S ) ( 80 cases ) . The 1- , 3- , 5- and 10-year survival were followed up . Progression-free survival ( PFS ) was chosen as the primary endpoint by treatment arm measured from study entry until documented progression of disease or death from any cause . The secondary endpoint was overall survival ( OS ) determined as the time ( in months ) between the date of therapy and the date of death . Other objectives were surgical and adjuvant therapy complications . RESULTS With median follow-up of 45 mo for all the enrolled patients , significant differences in the 1- , 3- , 5- , 10-year OS ( 91.3 % , 63.5 % , 43.5 % , 24.5 % vs 91 % , 62.8 % , 42.3 % , 24.4 % vs 87.5 % , 51.3 % , 33.8 % , 12.5 % , P = 0.017 
    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 No multivariate study has assessed the independent prognostic role of  endoscopic ultrasonography ( EUS )  in esophageal cancer , even when considering computed tomography ( CT ) . OBJECTIVE To evaluate the prognostic value of  EUS  in esophageal cancer before exclusive or preoperative radiochemotherapy . METHODS From 1993 to 1999 , the FFCD 9102 study enrolled 444 patients who had cancer of the thoracic esophagus , stages T3 - 4 , N0 - 1 and M0 on CT . The patients received two sessions of chemotherapy in addition to radiotherapy .  The 259 patients with objective response and no contraindications for further treatment were r and omized to undergo surgery or to continue with radiochemotherapy . EUS was performed in 174 patients enrolled in the trial ( mean age : 59 years ) . Tumor characteristics and lymph node status were prospect ively recorded . A Cox statistical model was used to identify any predictive prognostic factors among the clinical , EUS and CT data . RESULTS In the multivariate analysis , three factors were associated with a poor prognosis : inability to ingest solid food ( OR : 1.98 ; P=0.0008 ) ; more than three neoplastic subdiaphragmatic lymph nodes ( LN ) on EUS ( OR : 2.41 ; P<0.0045 ) and age>65 ( OR : 1.53 ; P<0.056 ) . Their prognostic value persisted after adjustment for type of treatment given . Two- and five- year survival rates were 21.5 and 10.5 % , respectively , in the presence of three neoplastic subdiaphragmatic LN , and 43 and 30 % , respectively , in all other cases . CONCLUSION Degree of dysphagia , age and presence of neoplastic subdiaphragmatic LN on EUS were independently predictive of the prognosis for locally advanced esophageal cancer . EUS results should be taken into account in future trials BACKGROUND Two r and omised trials concerning thoracic oesophageal cancer concluded that for squamous cell carcinoma , chemoradiation alone leads to the same overall survival ( OS ) as chemoradiation followed by surgery . One of these trials , FFCD 9102 , r and omised only fit , compliant and operable responders to induction chemoradiation between continuation of chemoradiation and surgery . In the present analysis , the outcome in the patients not eligible for r and omisation was calculated to determine if attempt of surgery should be recommended . METHODS Eligible patients had operable T3-N0/N1-M0 thoracic oesophageal cancer . After initial  chemoradiation  , patients with no clinical response , or with contraindication to follow any attributed treatment , were not r and omised . OS was studied first in the whole population of not r and omised patients , and then specifically in clinical non-responders . The impact of surgery on OS was studied in these two population s. FINDINGS Of the 451 registered patients in the trial , 192 were not r and omised . Among them , 111 were clinical non-responders . Median OS was significantly shorter for non-r and omised patients ( 11.5 months ) than for r and omised patients ( 18.9 months ; p=0.0024 ) . However , for the 112 non-r and omised patients who underwent surgery , median OS was not different from that in r and omised patients : 17.3 versus 18.9 months ( p=0.58 ) . Concerning clinical non-responders , median OS was longer for those who underwent surgery compared to non-operated patients : 17.0 versus 5.5 months ( hazard ratio (HR)=0.39 [ 0.25 - 0.61 ] ; p<0.0001 ) , and again was not different from that in responding , r and omised patients ( p=0.40 ) . INTERPRETATION In patients with locally advanced thoracic oesophageal cancer , overall survival did not differ between responders to induction chemoradiation and patients having surgery after clinical failure of chemoradiation . Surgery should therefore be considered in those patients who are still operable CONTEXT Carcinoma of the esophagus traditionally has been treated by surgery or radiation therapy ( RT ) , but 5-year overall survival rates have been only 5 % to 10 % . We previously reported results of a study conducted from January 1986 to April 1990 of combined chemotherapy and RT vs RT alone when an interim analysis revealed significant benefit for combined therapy . OBJECTIVE To report the long-term outcomes of a previously reported trial design ed to determine if adding chemotherapy during RT improves the survival rate of patients with esophageal carcinoma . DESIGN R and omized controlled trial conducted 1985 to 1990 with follow-up of at least 5 years , followed by a prospect i ve cohort study conducted between May 1990 and April 1991 . SETTING Multi-institution participation , ranging from tertiary academic referral centers to general community practice s. PATIENTS Patients had squamous cell or adenocarcinoma of the esophagus , T1 - 3 N0 - 1 M0 , adequate renal and bone marrow reserve , and a Karnofsky score of at least 50 . Interventions Combined modality therapy ( n = 134 ) : 50 Gy in 25 fractions over 5 weeks , plus cisplatin intravenously on the first day of weeks 1 , 5 , 8 , and 11 , and fluorouracil , 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1 , 5 , 8 , and 11 . In the r and omized study , combined therapy was compared with RT only ( n = 62 ) : 64 Gy in 32 fractions over 6.4 weeks . MAIN OUTCOME MEASURES Overall survival , patterns of failure , and toxic effects . RESULTS Combined therapy significantly increased overall survival compared with RT alone . In the r and omized part of the trial , at 5 years of follow-up the overall survival for combined therapy was 26 % ( 95 % confidence interval [ CI ] , 15%-37 % ) compared with 0 % following RT . In the succeeding nonr and omized part , combined therapy produced a 5-year overall survival of 14 % ( 95 % CI , 6%-23 % ) . Persistence of disease ( despite therapy ) was the most common mode of treatment failure ; however , it was less common in the groups receiving combined therapy ( 34/130 [ 26 % ] ) than in the group treated with RT only ( 23/62 [ 37 % ] ) . Severe acute toxic effects also were greater in the combined therapy groups . There were no significant differences in severe late toxic effects between the groups . However , chemotherapy could be administered as planned in only 89 ( 68 % ) of 130 patients ( 10 % had life-threatening toxic effects with combined therapy vs 2 % in the RT only group ) . CONCLUSION Combined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus , T1 - 3 N0 - 1 M0 , compared with RT alone PURPOSE To compare the local/regional control , survival , and toxicity of combined-modality therapy using high-dose ( 64.8 Gy ) versus st and ard-dose ( 50.4 Gy ) radiation therapy for the treatment of patients with esophageal cancer . PATIENTS AND METHODS A total of 236 patients with clinical stage T1 to T4 , N0/1 , M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach , after stratification by weight loss , primary tumor size , and histology , were r and omized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil ( 5-FU ) ( 1,000 mg/m(2)/24 hours for 4 days ) and cisplatin ( 75 mg/m(2 ) bolus day 1 ) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy . The trial was stopped after an interim analysis . The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive . RESULTS For the 218 eligible patients , there was no significant difference in median survival ( 13.0 v 18.1 months ) , 2-year survival ( 31 % v 40 % ) , or local/regional failure and local/regional persistence of disease ( 56 % v 52 % ) between the high-dose and st and ard-dose arms . Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the st and ard-dose arm , seven of the 11 deaths occurred in patients who had received 50.4 Gy or less . CONCLUSION The higher radiation dose did not increase survival or local/regional control . Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm , it did not seem to be related to the higher radiation dose . The st and ard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy BACKGROUND The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established . We compared chemoradiotherapy followed by surgery with surgery alone in this patient population . METHODS We r and omly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin ( doses titrated to achieve an area under the curve of 2 mg per milliliter per minute ) and paclitaxel ( 50 mg per square meter of body-surface area ) for 5 weeks and concurrent radiotherapy ( 41.4 Gy in 23 fractions , 5 days per week ) , followed by surgery . RESULTS From March 2004 through December 2008 , we enrolled 368 patients , 366 of whom were included in the analysis : 275 ( 75 % ) had adenocarcinoma , 84 ( 23 % ) had squamous-cell carcinoma , and 7 ( 2 % ) had large-cell undifferentiated carcinoma . Of the 366 patients , 178 were r and omly assigned to chemoradiotherapy followed by surgery  , and 188 to surgery alone . The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia ( 6 % ) and neutropenia ( 2 % ) ; the most common major nonhematologic toxic effects were anorexia ( 5 % ) and fatigue ( 3 % ) . Complete resection with no tumor within 1 mm of the resection margins ( R0 ) was achieved in 92 % of patients in the chemoradiotherapy-surgery group versus 69 % in the surgery group ( P<0.001 ) . A pathological complete response was achieved in 47 of 161 patients ( 29 % ) who underwent resection after chemoradiotherapy . Postoperative complications were similar in the two treatment groups , and in-hospital mortality was 4 % in both . Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group . Overall survival was significantly better in the chemoradiotherapy-surgery group ( hazard ratio , 0.657 ; 95 % confidence interval , 0.495 to 0.871 ; P=0.003 ) . CONCLUSIONS Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer . The regimen was associated with acceptable adverse-event rates . ( Funded by the Dutch Cancer Foundation [ KWF Kankerbestrijding ] ; Netherl and s Trial Register number , NTR487 . ) AIM To investigate the role of perioperative chemoradiotherapy ( CRT ) in the treatment of locally advanced thoracic esophageal squamous cell carcinoma ( ESCC ) . METHODS Using preoperative computed tomography (CT)-based staging criteria , 238 patients with ESCC ( stage II-III ) were enrolled in this prospect i ve study between January 1997 and June 2004 . With informed consent , patients were r and omized into 3 groups : preoperative CRT ( 80 cases ) , postoperative CRT ( 78 cases ) and surgery alone ( S ) ( 80 cases ) . The 1- , 3- , 5- and 10-year survival were followed up . Progression-free survival ( PFS ) was chosen as the primary endpoint by treatment arm measured from study entry until documented progression of disease or death from any cause . The secondary endpoint was overall survival ( OS ) determined as the time ( in months ) between the date of therapy and the date of death . Other objectives were surgical and adjuvant therapy complications . RESULTS With median follow-up of 45 mo for all the enrolled patients , significant differences in the 1- , 3- , 5- , 10-year OS ( 91.3 % , 63.5 % , 43.5 % , 24.5 % vs 91 % , 62.8 % , 42.3 % , 24.4 % vs 87.5 % , 51.3 % , 33.8 % , 12.5 % , P = 0.017 
    Output:
    