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: PURPOSE The optimal timing of surgery after preoperative radiotherapy in rectal cancer is unknown . The aim of this trial was to evaluate the role of the interval between preoperative radiotherapy and surgery . PATIENTS AND METHODS Patients with rectal carcinoma accessible to rectal digital examination , staged T2 to T3 , NX , M0 , were r and omized before radiotherapy ( 39 Gy in 13 fractions ) into two groups : in the short interval ( SI ) group , surgery had to be performed within 2 weeks after completion of radiation therapy , compared with 6 to 8 weeks in the long interval ( LI ) group . Between 1991 and 1995 , 201 patients were enrolled onto the study . RESULTS A long interval between preoperative radiotherapy and surgery was associated with a significantly better clinical tumor response ( 53 . 1 % in the SI group v 71.7 % in the LI group , P = .007 ) and pathologic downstaging ( 10.3 % in the SI group v 26 % in the LI group , P = .005 ) . At a median follow-up of 33 months , there were no differences in morbidity , local relapse , and short-term survival between the two groups . Sphincter-preserving surgery was performed in 76 % of cases in the LI group versus 68 % in the SI group ( P = 0.27 ) . CONCLUSION A long interval between preoperative irradiation and surgery provides increased tumor downstaging with no detrimental effect on toxicity and early clinical results . When sphincter preservation is question able , a long interval may increase the chance of a successful sphincter-saving surgery Objective : To determine whether extending the interval between chemoradiation ( CRT ) and surgery , and administering additional chemotherapy during the waiting period has an impact on tumor response , CRT-related toxicity and surgical complications in patients with advanced rectal cancer . Background : Locally advanced rectal cancer is usually treated with preoperative CRT followed by surgery approximately 6 weeks later . The Timing of Rectal Cancer Response to Chemoradiation Consortium design ed a prospect i ve , multicenter , Phase II clinical trial to investigate extending the interval between CRT and surgery , and administering additional chemotherapy during the waiting period . Here , we present preliminary results of this trial , reporting the tumor response , CRT-related toxicity and surgical complications . Methods : Stage II and III rectal cancer patients were treated concurrently with 5-Fluorouracil ( FU ) and radiation for 5 to 6 weeks . Patients in study group ( SG ) 1 underwent total mesorectal excision ( TME ) 6 weeks later . Patients in SG2 with evidence of a clinical response 4 weeks after CRT received 2 cycles of modified FOLFOX-6 ( mFOLFOX-6 ) followed by TME 3 to 5 weeks later . Tumor response , CRT-related toxicity and surgical complications were recorded . Results : One hundred and forty-four patients were accrued . One hundred and thirty-six ( 66 , SG1 ; 70 , SG2 ) were evaluated for CRT-related toxicity . One hundred and twenty-seven ( 60 , SG1 ; 67 , SG2 ) were assessed for tumor response and surgical complications . A similar proportion of patients completed CRT per protocol in both SGs , but the cumulative dose of sensitizing 5-FU and radiation was higher in SG2 . CRT-related toxicity was comparable between SGs . Average time from CRT-to-surgery was 6 ( SG1 ) and 11 weeks ( SG2 ) . Pathologic complete response ( pCR ) was 18 % ( SG1 ) and 25 % ( SG2 ) . Postoperative complications were similar between SGs . Conclusions : Intense neoadjuvant therapy consisting of CRT followed by additional chemotherapy ( mFOLFOX-6 ) , and delaying surgery may result in a modest increase in pCR rate without increasing complications in patients undergoing TME for locally advanced rectal cancer BACKGROUND : In rectal cancer , the st and ard of care after the completion of radiotherapy is surgery at 6 to 8 weeks . However , there is variation regarding the timing of surgery . OBJECTIVE : This investigation aim ed to audit the timing of surgery following radiotherapy and to compare perioperative morbidity and tumor downstaging in patients operated on , before and after the 6- to 8-week window . DESIGN : A retrospective review of rectal cancers treated preoperatively in our cancer network over a 27-month period . The effect of “ time till surgery ” of 6 to 8 weeks , < 6 weeks , and > 8 weeks on T downstaging and nodal downstaging was calculated by univariate and multivariate logistic regression analyses . SETTING : This study was conducted in an oncology tertiary referral center in the Southwest London Cancer Network . PATIENTS : Patients receiving preoperative radiotherapy for primary locally advanced rectal cancer undergoing subsequent surgical resection were eligible . MAIN OUTCOME MEASURES : The primary outcome measurement was time to surgery following the completion of ( chemo ) radiotherapy .  Thirty-day perioperative morbidity and mortality and tumor and nodal downstaging were examined according to the timing of surgery . LIMITATIONS : This study was limited by its nonr and omized retrospective design and the lack of st and ardization of preoperative chemotherapy . RESULTS : Thirty-two ( 34 % ) patients underwent surgery at 6 to 8 weeks , 45 ( 47 % ) at > 8 weeks , and 18 ( 19 % ) at < 6 weeks after radiotherapy . Delay was attributed to scheduling in 87 % of cases and to comorbidities in the remainder . T downstaging occurred in 6 ( 33.3 % ) patients in the < 6 weeks group , in 12 ( 37.5 % ) in the 6 to 8 weeks group , and in 28 ( 62.2 % ) in > 8 weeks group with no significant differences in perioperative morbidity . On multivariate analysis , T downstaging was significantly greater for the > 8 weeks group ( OR , 3.79 ; 95 % CI : 1.11–12.99 ; P = .03 ) . More patients were staged ypT0-T2 , 19 of 45 ( 42 % ) in the > 8 weeks group vs other groups , 14 of 50 ( 28 % , P < .05 ) . CONCLUSIONS : Following radiotherapy , surgery frequently occurs at > 8 weeks and is associated with increased downstaging . The consequences on survival and perioperative morbidity warrant further investigation Summary Background Local recurrence rates in operable rectal cancer are improved by radiotherapy ( with or without chemotherapy ) and surgical techniques such as total mesorectal excision . However , the contributions of surgery and radiotherapy to outcomes are unclear . We assessed the effect of the involvement of the circumferential resection margin and the plane of surgery achieved . Methods In this prospect i ve study , the plane of surgery achieved and the involvement of the circumferential resection margin were assessed by local pathologists , using a st and ard pathological protocol in 1156 patients with operable rectal cancer from the CR07 and NCIC-CTG CO16 trial , which compared short-course ( 5 days ) preoperative radiotherapy and selective postoperative chemoradiotherapy , between March , 1998 , and August , 2005 . All analyses were by intention to treat . This trial is registered , number IS RCT N 28785842 . Findings 128 patients ( 11 % ) had involvement of the circumferential resection margin , and the plane of surgery achieved was classified as good ( mesorectal ) in 604 ( 52 % ) , intermediate ( intramesorectal ) in 398 ( 34 % ) , and poor ( muscularis propria plane ) in 154 ( 13 % ) . We found that both a negative circumferential resection margin and a superior plane of surgery achieved were associated with low local recurrence rates . Hazard ratio ( HR ) was 0·32 ( 95 % CI 0·16–0·63 , p=0·0011 ) with 3-year local recurrence rates of 6 % ( 5–8 % ) and 17 % ( 10–26 % ) for patients who were negative and positive for circumferential resection margin , respectively . For plane of surgery achieved , HRs for mesorectal and intramesorectal groups compared with the muscularis propria group were 0·32 ( 0·16–0·64 ) and 0·48 ( 0·25–0·93 ) , respectively . At 3 years , the estimated local recurrence rates were 4 % ( 3–6 % ) for mesorectal , 7 % ( 5–11 % ) for intramesorectal , and 13 % ( 8–21 % ) for muscularis propria groups . The benefit of short-course preoperative radiotherapy did not differ in the three plane of surgery groups ( p=0·30 for trend ) . Patients in the short-course preoperative radiotherapy group who had a resection in the mesorectal plane had a 3-year local recurrence rate of only 1 % . Interpretation In rectal cancer , the plane of surgery achieved is an important prognostic factor for local recurrence .  Short-course preoperative radiotherapy reduced the rate of local recurrence for all three plane of surgery groups , almost abolishing local recurrence in short-course preoperative radiotherapy patients who had a resection in the mesorectal plane . The plane of surgery achieved should therefore be assessed and reported routinely . Funding Medical Research Council ( UK ) and the National Cancer Institute of Canada Abstract PURPOSE : An interval of six to eight weeks between completion of preoperative chemoradiation therapy and surgical resection of advanced rectal cancer has been described . Our purpose was to determine whether a longer time interval between completion of therapy and resection increases tumor downstaging and affects perioperative morbidity . METHODS : Forty patients with advanced adenocarcinoma of the rectum underwent preoperative chemoradiation on a prospect i ve trial with  irinotecan ( 50 mg/m2 ) , 5-fluorouracil ( 225 mg/m2 ) , and concomitant external-beam radiation ( 45–54 Gy ) followed by complete surgical resection of the tumor with total mesorectal excision . The time interval between completion of chemoradiation and surgical resection ranged from 28 to 97 days . The patients were divided into two groups with 33 eligible patients : Group A ( 4-week to 8-week time interval ; 28–56 days ) and Group B ( 10-week to 14-week interval ; 67–97 days ) . Tumor downstaging was compared between these two groups . The number of patients downstaged by at least one T stage , those downstaged by at least one N stage , those with pathologic complete responses , and those with only residual microscopic tumor foci were compared . Postoperative length of stay , estimated blood loss , perioperative morbidity , and sphincter-sparing procedures were also compared . Chi-squared tests and Student ’s t-test were calculated . RESULTS : Group A had 19 patients , and Group B had 14 patients . Patient demographics were comparable . Mean age was 52 years , and 70 percent of patients were male . There were no deaths . There were no statistical differences in perioperative morbidity , with three anastomotic leaks in Group A. Tumors were downstaged in 58 percent of patients in Group A and 43 percent of those in Group B ( P = 0.61 ) . Nodal downstaging occurred in 78 percent of Group A and 67 percent of Group B ( P = 0.9 ) . The pathologic complete response rate was 21 percent in Group A and 14 percent in Group B ( P = 0.97 ) , and a residual microfocus of tumor was found in 33 percent of patients in Group A and 42 percent of those in Group B ( P = 0.90 ) . These differences were not statistically significant . CONCLUSIONS : Perioperative morbidity is not affected by longer intervals . A longer interval between completion of neoadjuvant chemoradiation and surgical resection may not increase the tumor response rate of advanced rectal cancer in this cohort The aim of this study was to compare CT , MRI and FDG-PET in the prediction of outcome of neoadjuvant radiochemotherapy in patients with locally advanced primary rectal cancer . A total of 23 patients with T3/4 rectal cancer underwent a preoperative radiochemotherapy combined with regional hyperthermia .  Staging was performed using four-slice CT ( n=23 ) , 1.5-T MRI ( n=10 ) , and 18F-FDG-PET ( n=23 ) before and 2–4 weeks after completion of neoadjuvant treatment . Response criteria were a change in T category and tumour volume for CT and MRI and a change in glucose uptake ( st and ard uptake value ) within the tumour for FDG-PET . Imaging results were compared with those of pretherapy endorectal ultrasound and histopathological findings . Histopathology showed a response to neoadjuvant therapy in 13 patients whereas 10 patients were classified as nonresponders . The mean SUV reduction in responders ( 60±14 % ) was significantly higher than in nonresponders ( 37±31 % ; P=0.030 ) . The sensitivity and specificity of FDG-PET in identifying response was 100 % ( CT 54 % , MRI 71 % ) and 60 % ( CT 80 % , MRT 67 % 
    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: PURPOSE The optimal timing of surgery after preoperative radiotherapy in rectal cancer is unknown . The aim of this trial was to evaluate the role of the interval between preoperative radiotherapy and surgery . PATIENTS AND METHODS Patients with rectal carcinoma accessible to rectal digital examination , staged T2 to T3 , NX , M0 , were r and omized before radiotherapy ( 39 Gy in 13 fractions ) into two groups : in the short interval ( SI ) group , surgery had to be performed within 2 weeks after completion of radiation therapy , compared with 6 to 8 weeks in the long interval ( LI ) group . Between 1991 and 1995 , 201 patients were enrolled onto the study . RESULTS A long interval between preoperative radiotherapy and surgery was associated with a significantly better clinical tumor response ( 53 . 1 % in the SI group v 71.7 % in the LI group , P = .007 ) and pathologic downstaging ( 10.3 % in the SI group v 26 % in the LI group , P = .005 ) . At a median follow-up of 33 months , there were no differences in morbidity , local relapse , and short-term survival between the two groups . Sphincter-preserving surgery was performed in 76 % of cases in the LI group versus 68 % in the SI group ( P = 0.27 ) . CONCLUSION A long interval between preoperative irradiation and surgery provides increased tumor downstaging with no detrimental effect on toxicity and early clinical results . When sphincter preservation is question able , a long interval may increase the chance of a successful sphincter-saving surgery Objective : To determine whether extending the interval between chemoradiation ( CRT ) and surgery , and administering additional chemotherapy during the waiting period has an impact on tumor response , CRT-related toxicity and surgical complications in patients with advanced rectal cancer . Background : Locally advanced rectal cancer is usually treated with preoperative CRT followed by surgery approximately 6 weeks later . The Timing of Rectal Cancer Response to Chemoradiation Consortium design ed a prospect i ve , multicenter , Phase II clinical trial to investigate extending the interval between CRT and surgery , and administering additional chemotherapy during the waiting period . Here , we present preliminary results of this trial , reporting the tumor response , CRT-related toxicity and surgical complications . Methods : Stage II and III rectal cancer patients were treated concurrently with 5-Fluorouracil ( FU ) and radiation for 5 to 6 weeks . Patients in study group ( SG ) 1 underwent total mesorectal excision ( TME ) 6 weeks later . Patients in SG2 with evidence of a clinical response 4 weeks after CRT received 2 cycles of modified FOLFOX-6 ( mFOLFOX-6 ) followed by TME 3 to 5 weeks later . Tumor response , CRT-related toxicity and surgical complications were recorded . Results : One hundred and forty-four patients were accrued . One hundred and thirty-six ( 66 , SG1 ; 70 , SG2 ) were evaluated for CRT-related toxicity . One hundred and twenty-seven ( 60 , SG1 ; 67 , SG2 ) were assessed for tumor response and surgical complications . A similar proportion of patients completed CRT per protocol in both SGs , but the cumulative dose of sensitizing 5-FU and radiation was higher in SG2 . CRT-related toxicity was comparable between SGs . Average time from CRT-to-surgery was 6 ( SG1 ) and 11 weeks ( SG2 ) . Pathologic complete response ( pCR ) was 18 % ( SG1 ) and 25 % ( SG2 ) . Postoperative complications were similar between SGs . Conclusions : Intense neoadjuvant therapy consisting of CRT followed by additional chemotherapy ( mFOLFOX-6 ) , and delaying surgery may result in a modest increase in pCR rate without increasing complications in patients undergoing TME for locally advanced rectal cancer BACKGROUND : In rectal cancer , the st and ard of care after the completion of radiotherapy is surgery at 6 to 8 weeks . However , there is variation regarding the timing of surgery . OBJECTIVE : This investigation aim ed to audit the timing of surgery following radiotherapy and to compare perioperative morbidity and tumor downstaging in patients operated on , before and after the 6- to 8-week window . DESIGN : A retrospective review of rectal cancers treated preoperatively in our cancer network over a 27-month period . The effect of “ time till surgery ” of 6 to 8 weeks , < 6 weeks , and > 8 weeks on T downstaging and nodal downstaging was calculated by univariate and multivariate logistic regression analyses . SETTING : This study was conducted in an oncology tertiary referral center in the Southwest London Cancer Network . PATIENTS : Patients receiving preoperative radiotherapy for primary locally advanced rectal cancer undergoing subsequent surgical resection were eligible . MAIN OUTCOME MEASURES : The primary outcome measurement was time to surgery following the completion of ( chemo ) radiotherapy .  Thirty-day perioperative morbidity and mortality and tumor and nodal downstaging were examined according to the timing of surgery . LIMITATIONS : This study was limited by its nonr and omized retrospective design and the lack of st and ardization of preoperative chemotherapy . RESULTS : Thirty-two ( 34 % ) patients underwent surgery at 6 to 8 weeks , 45 ( 47 % ) at > 8 weeks , and 18 ( 19 % ) at < 6 weeks after radiotherapy . Delay was attributed to scheduling in 87 % of cases and to comorbidities in the remainder . T downstaging occurred in 6 ( 33.3 % ) patients in the < 6 weeks group , in 12 ( 37.5 % ) in the 6 to 8 weeks group , and in 28 ( 62.2 % ) in > 8 weeks group with no significant differences in perioperative morbidity . On multivariate analysis , T downstaging was significantly greater for the > 8 weeks group ( OR , 3.79 ; 95 % CI : 1.11–12.99 ; P = .03 ) . More patients were staged ypT0-T2 , 19 of 45 ( 42 % ) in the > 8 weeks group vs other groups , 14 of 50 ( 28 % , P < .05 ) . CONCLUSIONS : Following radiotherapy , surgery frequently occurs at > 8 weeks and is associated with increased downstaging . The consequences on survival and perioperative morbidity warrant further investigation Summary Background Local recurrence rates in operable rectal cancer are improved by radiotherapy ( with or without chemotherapy ) and surgical techniques such as total mesorectal excision . However , the contributions of surgery and radiotherapy to outcomes are unclear . We assessed the effect of the involvement of the circumferential resection margin and the plane of surgery achieved . Methods In this prospect i ve study , the plane of surgery achieved and the involvement of the circumferential resection margin were assessed by local pathologists , using a st and ard pathological protocol in 1156 patients with operable rectal cancer from the CR07 and NCIC-CTG CO16 trial , which compared short-course ( 5 days ) preoperative radiotherapy and selective postoperative chemoradiotherapy , between March , 1998 , and August , 2005 . All analyses were by intention to treat . This trial is registered , number IS RCT N 28785842 . Findings 128 patients ( 11 % ) had involvement of the circumferential resection margin , and the plane of surgery achieved was classified as good ( mesorectal ) in 604 ( 52 % ) , intermediate ( intramesorectal ) in 398 ( 34 % ) , and poor ( muscularis propria plane ) in 154 ( 13 % ) . We found that both a negative circumferential resection margin and a superior plane of surgery achieved were associated with low local recurrence rates . Hazard ratio ( HR ) was 0·32 ( 95 % CI 0·16–0·63 , p=0·0011 ) with 3-year local recurrence rates of 6 % ( 5–8 % ) and 17 % ( 10–26 % ) for patients who were negative and positive for circumferential resection margin , respectively . For plane of surgery achieved , HRs for mesorectal and intramesorectal groups compared with the muscularis propria group were 0·32 ( 0·16–0·64 ) and 0·48 ( 0·25–0·93 ) , respectively . At 3 years , the estimated local recurrence rates were 4 % ( 3–6 % ) for mesorectal , 7 % ( 5–11 % ) for intramesorectal , and 13 % ( 8–21 % ) for muscularis propria groups . The benefit of short-course preoperative radiotherapy did not differ in the three plane of surgery groups ( p=0·30 for trend ) . Patients in the short-course preoperative radiotherapy group who had a resection in the mesorectal plane had a 3-year local recurrence rate of only 1 % . Interpretation In rectal cancer , the plane of surgery achieved is an important prognostic factor for local recurrence .  Short-course preoperative radiotherapy reduced the rate of local recurrence for all three plane of surgery groups , almost abolishing local recurrence in short-course preoperative radiotherapy patients who had a resection in the mesorectal plane . The plane of surgery achieved should therefore be assessed and reported routinely . Funding Medical Research Council ( UK ) and the National Cancer Institute of Canada Abstract PURPOSE : An interval of six to eight weeks between completion of preoperative chemoradiation therapy and surgical resection of advanced rectal cancer has been described . Our purpose was to determine whether a longer time interval between completion of therapy and resection increases tumor downstaging and affects perioperative morbidity . METHODS : Forty patients with advanced adenocarcinoma of the rectum underwent preoperative chemoradiation on a prospect i ve trial with  irinotecan ( 50 mg/m2 ) , 5-fluorouracil ( 225 mg/m2 ) , and concomitant external-beam radiation ( 45–54 Gy ) followed by complete surgical resection of the tumor with total mesorectal excision . The time interval between completion of chemoradiation and surgical resection ranged from 28 to 97 days . The patients were divided into two groups with 33 eligible patients : Group A ( 4-week to 8-week time interval ; 28–56 days ) and Group B ( 10-week to 14-week interval ; 67–97 days ) . Tumor downstaging was compared between these two groups . The number of patients downstaged by at least one T stage , those downstaged by at least one N stage , those with pathologic complete responses , and those with only residual microscopic tumor foci were compared . Postoperative length of stay , estimated blood loss , perioperative morbidity , and sphincter-sparing procedures were also compared . Chi-squared tests and Student ’s t-test were calculated . RESULTS : Group A had 19 patients , and Group B had 14 patients . Patient demographics were comparable . Mean age was 52 years , and 70 percent of patients were male . There were no deaths . There were no statistical differences in perioperative morbidity , with three anastomotic leaks in Group A. Tumors were downstaged in 58 percent of patients in Group A and 43 percent of those in Group B ( P = 0.61 ) . Nodal downstaging occurred in 78 percent of Group A and 67 percent of Group B ( P = 0.9 ) . The pathologic complete response rate was 21 percent in Group A and 14 percent in Group B ( P = 0.97 ) , and a residual microfocus of tumor was found in 33 percent of patients in Group A and 42 percent of those in Group B ( P = 0.90 ) . These differences were not statistically significant . CONCLUSIONS : Perioperative morbidity is not affected by longer intervals . A longer interval between completion of neoadjuvant chemoradiation and surgical resection may not increase the tumor response rate of advanced rectal cancer in this cohort The aim of this study was to compare CT , MRI and FDG-PET in the prediction of outcome of neoadjuvant radiochemotherapy in patients with locally advanced primary rectal cancer . A total of 23 patients with T3/4 rectal cancer underwent a preoperative radiochemotherapy combined with regional hyperthermia .  Staging was performed using four-slice CT ( n=23 ) , 1.5-T MRI ( n=10 ) , and 18F-FDG-PET ( n=23 ) before and 2–4 weeks after completion of neoadjuvant treatment . Response criteria were a change in T category and tumour volume for CT and MRI and a change in glucose uptake ( st and ard uptake value ) within the tumour for FDG-PET . Imaging results were compared with those of pretherapy endorectal ultrasound and histopathological findings . Histopathology showed a response to neoadjuvant therapy in 13 patients whereas 10 patients were classified as nonresponders . The mean SUV reduction in responders ( 60±14 % ) was significantly higher than in nonresponders ( 37±31 % ; P=0.030 ) . The sensitivity and specificity of FDG-PET in identifying response was 100 % ( CT 54 % , MRI 71 % ) and 60 % ( CT 80 % , MRT 67 % 
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