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: Faced with the responsibility of treating patients with invasive distal rectal cancer who were medically unacceptable for the indicated radical surgery  , a prospect i ve study was initiated in which high dose preoperative radiation and full-thickness local excision were used . High dose preoperative radiation permitted full-thickness local excision of select cancers , which , by conventional st and ards , otherwise would have required radical surgery and permanent colostomy . Feasibility was measured on the basis of safety of the technique , control of the cancer , and the quality of anal sphincter function expected . Patients were selected initially because of their predicted inability to tolerate radical surgery , but indications were broadened to include those whose tumors had completely disappeared after irradiation . From 1984 to 1988 , 20 patients underwent 21 operative procedures for cancers located between 0 and 7 cm from the anorectal ring . This report is concerned with the 14 patients of this group who were observed for a minimum of 24 months .  High-dose preoperative radiation was administered for a total dose of 4500 cGy . Excision and repair were performed 4 to 6 weeks after completion of radiation therapy . Full-thickness disc or hemicircumferential excision was accomplished by transanal , transsphincteric , and transsacral techniques , which included , in several instances , excision of the sphincter mechanism and perineal body , and /or the vaginal wall . Full-thickness local excision after high-dose radiation therapy for rectal cancers has never been reported . Follow-up observation ranged from 24 to 48 months with a median of 31 months . Rectal reservoir function and sphincter control were good in 13 patients .  Local recurrence developed in three patients ( 21 percent ) , two of whom had postradiation therapy B2 mucinous cancers .  Three-year actuarial rate of local recurrence is 23 percent . One ( 7 percent ) patient died of recurrent disease . Actuarial Kaplan-Meier survival at 3 years is 61 percent . Based on the results of this small , select patient group , high-dose radiation therapy followed by full-thickness local excision appears to be a reasonable option for patients who can not tolerate radical surgery . This bimodal approach also may serve as an option for those who aregoodmedical risks , but for whom sphincter preservation is at stake , and to whom radical surgery offers limited benefits Background The aim of this study was to evaluate the clinical implication s of pathologic complete response ( pCR ) ( i.e. , T0N0M0 ) after neoadjuvant chemoradiation and radical surgery in patients with locally advanced rectal cancer . Material s and Methods A single-center , prospect ively maintained colorectal cancer data base was queried for patients with primary cII and cIII rectal cancer staged by CT and ERUS/MRI undergoing long-course neoadjuvant chemoradiation followed by proctectomy with curative intent between 1997 and 2007 . Patients were stratified into pCR and no-pCR groups and compared with respect to demographics , tumor and treatment characteristics , and oncologic outcomes . Outcomes evaluated were 5-year overall survival , disease-free survival , disease-specific mortality , local recurrence , and distant recurrence . Results The query returned 238 patients ( 73 % male ) , with a median age of 57 years and median follow-up of 54 months . Of these , 58 patients achieved pCR . Patients with pCR vs no-pCR were statistically comparable with respect to demographics , chemoradiation regimens , tumor distance from anal verge , clinical stage , surgical procedures performed , and follow-up time . No patient with pCR had local recurrence . Overall survival and distant recurrence were also significantly improved for patients achieving pCR . Conclusions Achievement of pCR after neoadjuvant chemoradiation is associated with greatly improved cancer outcomes in locally advanced rectal cancer . Future studies should evaluate the relationship between increases in pCR rates and improvements in cancer outcomes in this population 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 This study aim ed to compare the oncologic results for local excision via transanal endoscopic microsurgery ( TEM ) and those for laparoscopic resection ( LR ) via total mesorectal excision in the treatment of T2 N0 , G1 - 2 rectal cancer after neoadjuvant therapy with both treatments , incorporating a 5-year minimum follow-up period . Methods The study enrolled 70 patients whose malignancy was staged at admission as T2 N0 , G1 - 2 rectal cancer located within 6 cm of the anal verge with a tumor diameter less than 3 cm . Of these patients , 35 were r and omized to TEM and 35 to LR . The patients in both groups previously had undergone high-dose radiotherapy ( 5,040 cGy in 28 fractions over 5 weeks ) combined with continuous infusion of 5-flurouracil ( 200 mg/m2/day ) . Results The median follow-up period was 84 months ( range , 72–96 months ) . Two local recurrences ( 5.7 % ) were observed after TEM and 1 ( 2.8 % ) after  LR . Distant metastases ( 2.8 % ) occurred in one case each after TEM and LR .  The probability of survival for rectal cancer was 94 % for TEM and 94 % for LR . Conclusions The study shows similar results between the two treatments in terms of local recurrences , distant metastases , and probability of survival for rectal cancer Purpose Prediction of rectal cancer response to preoperative , neo-adjuvant chemo-radiation therapy ( CRT ) provides the opportunity to identify patients in whom a major response is expected and who may therefore benefit from alternative surgical approaches . Traditional morphological imaging techniques are effective in defining tumour extension in the initial diagnostic and staging work-up , but perform poorly in distinguishing residual neoplastic tissue from scarring post CRT , when restaging the patient before surgery . Fluorine-18 fluorodeoxyglucose positron emission tomography ( FDG-PET ) is a promising tool for monitoring the effect of anti-tumour therapy . The aim of this study was to prospect ively assess the value of sequential FDG-PET scans in predicting the response of locally advanced rectal cancer to neo-adjuvant CRT . Methods Forty-four consecutive patients with locally advanced ( cT3–4 ) primary rectal cancer and four patients with pelvic recurrence of rectal cancer were enrolled in this prospect i ve study . Treatment consisted of external beam intensified radiotherapy ( 50 Gy to the posterior pelvis , 56 Gy to the tumour ) , chemotherapy ( in most cases PVI 5-FU at 300 mg/m2 per day ) and , 8–10 weeks later , surgery with curative intent . All patients underwent FDG-PET/CT both before CRT and 5–6 weeks after completing CRT . One patient died before surgery because of acute myocardial infa rct ion , and was therefore excluded from further analysis . Semi-quantitative measurements of FDG uptake ( SUVmax ) , absolute difference ( ΔSUVmax ) and percent SUVmax difference ( Response Index , RI ) between pre- and post-CRT PET scans were considered . Results were correlated with pathological response , assessed both by histopathological staging of the surgical specimens ( pTNM ) and by the tumour regression grade ( TRG ) according to M and ard ’s criteria ( patients with TRG1–2 being defined as responders and patients with TRG3–5 as non-responders ) . Results Following neo-adjuvant CRT , of the 45 patients su bmi tted to surgery , 23 ( 51.1 % ) were classified as responders according to M and ard ’s criteria ( 8 TRG1 and 15 TRG2 ) , while the remaining 22 ( 48.9 % ) were non-responders ( 9 TRG3 and 13 TRG4–5 ) . Considering all patients , the mean pre-CRT SUVmax was 15.6 , significantly higher than the mean value of 5.4 post CRT ( p < 0.001 ) . Nevertheless , when stratifying patients according to response to CRT ( using M and ard ’s criteria ) , the mean RI was significantly higher in responders than in non-responders ( 75.9 % versus 46.9%,p = 0.0015 ) . Using a 66.2 % SUVmax decrease as the cut-off value ( identified by ROC analysis ) for defining response to therapy , the following parameters were obtained : 79.2 % specificity , 81.2 % sensitivity , 77 % positive predictive value , 89 % negative predictive value and 80 % overall accuracy . Conclusion The results suggest the potential utility of FDG-PET as a complementary diagnostic and prognostic procedure in the assessment of neo-adjuvant CRT response of locally advanced rectal cancer . ΔSUVmax and RI seem the best predictors of CRT response Accurate response assessment after neoadjuvant therapy is essential in patients with rectal cancer . The aim of this study was to assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography ( FDG-PET ) in predicting response of locally advanced rectal cancer to preoperative multimodal treatment . Twenty-two consecutive patients with locally advanced ( uT3/4 ) primary rectal cancer were entered in this prospect i ve pilot study . FDG-PET was performed before and after neoadjuvant radiochemotherapy ( RCT ) with combined regional hyperthermia ( RHT ) . Treatment consisted of external-beam radiotherapy ( 45 Gy ) , chemotherapy ( folinic acid and 5-fluorouracil ) and regional pelvic hyperthermia followed by curative tumour resection 6–8 weeks later . Semi-quantitative measurements ( SUV ) of tumour FDG uptake were made before and 2–4 weeks after completion of neoadjuvant treatment . Two patients who did not receive post-therapeutic restaging by FDG-PET were excluded from the analysis . Results were correlated with findings on endorectal ultrasound ( EUS , n=17 patients ) and histopathology . Histopathological evaluation of the resected tumour revealed complete response in one patient , partial response in 12 and stable disease in seven . SUV reduction in tumours was significantly greater in responders than in non-responders [ 60 % ( ±15 % ) vs 30 % ( ±18 % ) , P=0.003 , CI=95 % ) . Using a minimum post-therapeutic SUV reduction of 36 % to define response , FDG-PET revealed a sensitivity of 100 % ( EUS : 33 % ) and a specificity of 86 % ( EUS : 80 % ) in response prediction ; the corresponding positive and negative predictive values were 93 % ( EUS : 80 % ) and 100 % ( EUS : 33 % ) , respectively . FDG-PET results were statistically significant ( P<0.001 , CI=95 % ) . FDG-PET has great potential in the assessment of tumour response to neoadjuvant RCT in combination with RHT and is superior to EUS for this purpose PURPOSE To develop a positron emission tomography (PET)-based response prediction model to differentiate pathological responders from nonresponders . The predictive strength of the model was vali date d in a second patient group , treated and imaged identical to the patients on which the predictive model was based . METHODS AND MATERIAL S Fifty- 
    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: Faced with the responsibility of treating patients with invasive distal rectal cancer who were medically unacceptable for the indicated radical surgery  , a prospect i ve study was initiated in which high dose preoperative radiation and full-thickness local excision were used . High dose preoperative radiation permitted full-thickness local excision of select cancers , which , by conventional st and ards , otherwise would have required radical surgery and permanent colostomy . Feasibility was measured on the basis of safety of the technique , control of the cancer , and the quality of anal sphincter function expected . Patients were selected initially because of their predicted inability to tolerate radical surgery , but indications were broadened to include those whose tumors had completely disappeared after irradiation . From 1984 to 1988 , 20 patients underwent 21 operative procedures for cancers located between 0 and 7 cm from the anorectal ring . This report is concerned with the 14 patients of this group who were observed for a minimum of 24 months .  High-dose preoperative radiation was administered for a total dose of 4500 cGy . Excision and repair were performed 4 to 6 weeks after completion of radiation therapy . Full-thickness disc or hemicircumferential excision was accomplished by transanal , transsphincteric , and transsacral techniques , which included , in several instances , excision of the sphincter mechanism and perineal body , and /or the vaginal wall . Full-thickness local excision after high-dose radiation therapy for rectal cancers has never been reported . Follow-up observation ranged from 24 to 48 months with a median of 31 months . Rectal reservoir function and sphincter control were good in 13 patients .  Local recurrence developed in three patients ( 21 percent ) , two of whom had postradiation therapy B2 mucinous cancers .  Three-year actuarial rate of local recurrence is 23 percent . One ( 7 percent ) patient died of recurrent disease . Actuarial Kaplan-Meier survival at 3 years is 61 percent . Based on the results of this small , select patient group , high-dose radiation therapy followed by full-thickness local excision appears to be a reasonable option for patients who can not tolerate radical surgery . This bimodal approach also may serve as an option for those who aregoodmedical risks , but for whom sphincter preservation is at stake , and to whom radical surgery offers limited benefits Background The aim of this study was to evaluate the clinical implication s of pathologic complete response ( pCR ) ( i.e. , T0N0M0 ) after neoadjuvant chemoradiation and radical surgery in patients with locally advanced rectal cancer . Material s and Methods A single-center , prospect ively maintained colorectal cancer data base was queried for patients with primary cII and cIII rectal cancer staged by CT and ERUS/MRI undergoing long-course neoadjuvant chemoradiation followed by proctectomy with curative intent between 1997 and 2007 . Patients were stratified into pCR and no-pCR groups and compared with respect to demographics , tumor and treatment characteristics , and oncologic outcomes . Outcomes evaluated were 5-year overall survival , disease-free survival , disease-specific mortality , local recurrence , and distant recurrence . Results The query returned 238 patients ( 73 % male ) , with a median age of 57 years and median follow-up of 54 months . Of these , 58 patients achieved pCR . Patients with pCR vs no-pCR were statistically comparable with respect to demographics , chemoradiation regimens , tumor distance from anal verge , clinical stage , surgical procedures performed , and follow-up time . No patient with pCR had local recurrence . Overall survival and distant recurrence were also significantly improved for patients achieving pCR . Conclusions Achievement of pCR after neoadjuvant chemoradiation is associated with greatly improved cancer outcomes in locally advanced rectal cancer . Future studies should evaluate the relationship between increases in pCR rates and improvements in cancer outcomes in this population 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 This study aim ed to compare the oncologic results for local excision via transanal endoscopic microsurgery ( TEM ) and those for laparoscopic resection ( LR ) via total mesorectal excision in the treatment of T2 N0 , G1 - 2 rectal cancer after neoadjuvant therapy with both treatments , incorporating a 5-year minimum follow-up period . Methods The study enrolled 70 patients whose malignancy was staged at admission as T2 N0 , G1 - 2 rectal cancer located within 6 cm of the anal verge with a tumor diameter less than 3 cm . Of these patients , 35 were r and omized to TEM and 35 to LR . The patients in both groups previously had undergone high-dose radiotherapy ( 5,040 cGy in 28 fractions over 5 weeks ) combined with continuous infusion of 5-flurouracil ( 200 mg/m2/day ) . Results The median follow-up period was 84 months ( range , 72–96 months ) . Two local recurrences ( 5.7 % ) were observed after TEM and 1 ( 2.8 % ) after  LR . Distant metastases ( 2.8 % ) occurred in one case each after TEM and LR .  The probability of survival for rectal cancer was 94 % for TEM and 94 % for LR . Conclusions The study shows similar results between the two treatments in terms of local recurrences , distant metastases , and probability of survival for rectal cancer Purpose Prediction of rectal cancer response to preoperative , neo-adjuvant chemo-radiation therapy ( CRT ) provides the opportunity to identify patients in whom a major response is expected and who may therefore benefit from alternative surgical approaches . Traditional morphological imaging techniques are effective in defining tumour extension in the initial diagnostic and staging work-up , but perform poorly in distinguishing residual neoplastic tissue from scarring post CRT , when restaging the patient before surgery . Fluorine-18 fluorodeoxyglucose positron emission tomography ( FDG-PET ) is a promising tool for monitoring the effect of anti-tumour therapy . The aim of this study was to prospect ively assess the value of sequential FDG-PET scans in predicting the response of locally advanced rectal cancer to neo-adjuvant CRT . Methods Forty-four consecutive patients with locally advanced ( cT3–4 ) primary rectal cancer and four patients with pelvic recurrence of rectal cancer were enrolled in this prospect i ve study . Treatment consisted of external beam intensified radiotherapy ( 50 Gy to the posterior pelvis , 56 Gy to the tumour ) , chemotherapy ( in most cases PVI 5-FU at 300 mg/m2 per day ) and , 8–10 weeks later , surgery with curative intent . All patients underwent FDG-PET/CT both before CRT and 5–6 weeks after completing CRT . One patient died before surgery because of acute myocardial infa rct ion , and was therefore excluded from further analysis . Semi-quantitative measurements of FDG uptake ( SUVmax ) , absolute difference ( ΔSUVmax ) and percent SUVmax difference ( Response Index , RI ) between pre- and post-CRT PET scans were considered . Results were correlated with pathological response , assessed both by histopathological staging of the surgical specimens ( pTNM ) and by the tumour regression grade ( TRG ) according to M and ard ’s criteria ( patients with TRG1–2 being defined as responders and patients with TRG3–5 as non-responders ) . Results Following neo-adjuvant CRT , of the 45 patients su bmi tted to surgery , 23 ( 51.1 % ) were classified as responders according to M and ard ’s criteria ( 8 TRG1 and 15 TRG2 ) , while the remaining 22 ( 48.9 % ) were non-responders ( 9 TRG3 and 13 TRG4–5 ) . Considering all patients , the mean pre-CRT SUVmax was 15.6 , significantly higher than the mean value of 5.4 post CRT ( p < 0.001 ) . Nevertheless , when stratifying patients according to response to CRT ( using M and ard ’s criteria ) , the mean RI was significantly higher in responders than in non-responders ( 75.9 % versus 46.9%,p = 0.0015 ) . Using a 66.2 % SUVmax decrease as the cut-off value ( identified by ROC analysis ) for defining response to therapy , the following parameters were obtained : 79.2 % specificity , 81.2 % sensitivity , 77 % positive predictive value , 89 % negative predictive value and 80 % overall accuracy . Conclusion The results suggest the potential utility of FDG-PET as a complementary diagnostic and prognostic procedure in the assessment of neo-adjuvant CRT response of locally advanced rectal cancer . ΔSUVmax and RI seem the best predictors of CRT response Accurate response assessment after neoadjuvant therapy is essential in patients with rectal cancer . The aim of this study was to assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography ( FDG-PET ) in predicting response of locally advanced rectal cancer to preoperative multimodal treatment . Twenty-two consecutive patients with locally advanced ( uT3/4 ) primary rectal cancer were entered in this prospect i ve pilot study . FDG-PET was performed before and after neoadjuvant radiochemotherapy ( RCT ) with combined regional hyperthermia ( RHT ) . Treatment consisted of external-beam radiotherapy ( 45 Gy ) , chemotherapy ( folinic acid and 5-fluorouracil ) and regional pelvic hyperthermia followed by curative tumour resection 6–8 weeks later . Semi-quantitative measurements ( SUV ) of tumour FDG uptake were made before and 2–4 weeks after completion of neoadjuvant treatment . Two patients who did not receive post-therapeutic restaging by FDG-PET were excluded from the analysis . Results were correlated with findings on endorectal ultrasound ( EUS , n=17 patients ) and histopathology . Histopathological evaluation of the resected tumour revealed complete response in one patient , partial response in 12 and stable disease in seven . SUV reduction in tumours was significantly greater in responders than in non-responders [ 60 % ( ±15 % ) vs 30 % ( ±18 % ) , P=0.003 , CI=95 % ) . Using a minimum post-therapeutic SUV reduction of 36 % to define response , FDG-PET revealed a sensitivity of 100 % ( EUS : 33 % ) and a specificity of 86 % ( EUS : 80 % ) in response prediction ; the corresponding positive and negative predictive values were 93 % ( EUS : 80 % ) and 100 % ( EUS : 33 % ) , respectively . FDG-PET results were statistically significant ( P<0.001 , CI=95 % ) . FDG-PET has great potential in the assessment of tumour response to neoadjuvant RCT in combination with RHT and is superior to EUS for this purpose PURPOSE To develop a positron emission tomography (PET)-based response prediction model to differentiate pathological responders from nonresponders . The predictive strength of the model was vali date d in a second patient group , treated and imaged identical to the patients on which the predictive model was based . METHODS AND MATERIAL S Fifty- 
    Output:
    