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 The aim of this study was to evaluate whether downstaging impacts prognosis in patients with cII versus cIII rectal cancer . Material s and Methods We identified from our colorectal cancer data base 295 patients with primary cII and cIII rectal cancer staged by CT and ERUS/MRI who received 5-FU-based chemoradiation followed by R0 surgery after a median interval of 7 weeks during 1997–2007 . The median radiotherapy dose was 5040 cGy . We excluded 58 patients with pathologic complete response ( pCR ) and compared among the remaining 162 patients pathologic downstaging ( cII to ypI , cIII to ypII or ypI ) versus no pathologic downstaging ( c stage ≤ yp stage ) . Outcomes evaluated were 5-year overall survival , 3-year cancer-specific survival , disease-free survival , overall recurrence , local recurrence , and distant recurrence . Results The median age was 58 years and median follow-up was 48 months . Patients with downstaging versus no downstaging were statistically comparable with respect to demographics , chemoradiation regimen , interval time between neoadjuvant chemoradiation and surgery , tumor distance from anal verge , surgical procedures performed , and follow-up time . With the exception of local recurrence rates , downstaging result ed in significantly improved cancer outcomes for cIII but not cII . Conclusions Downstaging without pCR is a significant prognostic factor for patients with stage cIII rectal cancer . Tumor response to neoadjuvant chemoradiation should be taken into account when defining the optimal adjuvant chemotherapy regimen for patients with cIII rectal cancer 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 PURPOSE Mutations in KRAS and BRAF genes as well as the loss of expression of phosphatase and tensin homolog ( PTEN ) ( deleted on chromosome 10 ) are associated with impaired activity of antibodies directed against epidermal growth factor receptor in patients with metastatic colorectal cancer . The predictive and prognostic value of the KRAS and BRAF point mutations as well as PTEN expression in patients with locally advanced rectal cancer ( LARC ) treated with cetuximab-based neoadjuvant chemoradiotherapy is unknown . METHODS AND MATERIAL S We have conducted phase I and II trials of the combination of weekly administration of cetuximab and irinotecan and daily doses of capecitabine in conjunction with radiotherapy ( 45 Gy plus 5.4 Gy ) in patients with LARC ( stage uT3/4 or uN+ ) . The status of KRAS and BRAF mutations was determined with direct sequencing , and PTEN expression status was determined with immunohistochemistry testing of diagnostic tumor biopsies . Tumor regression was evaluated by using st and ardized regression grading , and disease-free survival ( DFS ) was calculated according to the Kaplan-Meier method . RESULTS A total of 57 patients were available for analyses . A total of 31.6 % of patients carried mutations in the KRAS genes . No BRAF mutations were found , while the loss of PTEN expression was observed in 9.6 % of patients . Six patients achieved complete remission , and the 3-year DFS rate was 73 % . No correlation was seen between tumor regression or DFS rate and a single marker or a combination of all markers . CONCLUSIONS In the present series , no BRAF mutation was detected . The presence of KRAS mutations and loss of PTEN expression were not associated with impaired response to cetuximab-based chemoradiotherapy and 3-year DFS Purpose The aim of this study was to investigate the efficacy and safety of neoadjuvant cetuximab , capecitabine , and radiotherapy for patients with locally advanced rectal cancer . Methods Sixty-three eligible patients were selectively enrolled in this study . Neoadjuvant treatment consisted of cetuximab and capecitabine for 6 weeks and radiotherapy for 5 weeks . Surgical resection was performed 6–8 weeks after the completion of neoadjuvant treatment . KRAS mutation statuses were analyzed retrospectively after the cetuximab treatment . All the patients underwent a st and ardized postoperative follow-up for at least 3 years . Results A pathological complete response ( pCR ) was achieved in eight patients ( 12.7 % ) . Overall down-staging was found in 49 patients ( 77.8 % ) . The 3-year disease-free survival ( DFS ) rate and overall survival ( OS ) rate was 76.2 % and 81.0 % , respectively . The most common adverse events during neoadjuvant treatment were acneiform skin rash ( 82.5 % ) , radiodermatitis ( 46.0 % ) , and diarrhea ( 36.5 % ) . KRAS mutations were detected in 19 of 63 ( 31.2 % ) tumors . The down-staging rate in patients with KRAS wild-type ( WT ) was significantly higher than patients with KRAS mutation ( P = 0.020 ) . There was no significant difference in the pCR rate , 3-year DFS rate or 3-year OS rate between KRAS WT patients and KRAS-mutated patients . Conclusion Neoadjuvant treatment with cetuximab and capecitabine-based chemoradiotherapy is safe and well tolerated . The pCR rate , 3-year DFS rate and OS rate are not superior to the rate of neoadjuvant chemoradiotherapy using two or more cytotoxic agents . The KRAS WT is highly associated with tumor down-staging to cetuximab plus capecitabine-based CRT in patients with LARC PURPOSE To evaluate the efficacy and safety of preoperative chemoradiation with cetuximab , irinotecan , and capecitabine in patients with rectal cancer . METHODS AND MATERIAL S Forty patients with locally advanced , nonmetastatic , and mid- to lower rectal cancer were enrolled .  Radiotherapy was delivered at a dose of 50.4 Gy/28 fractions . Concurrent chemotherapy consisted of an initial dose of cetuximab of 400 mg/m(2 ) 1 week before radiotherapy , and then cetuximab 250 mg/m(2)/week , irinotecan 40 mg/m(2)/week for 5 consecutive weeks and capecitabine 1,650 mg/m(2)/day for 5 days a week ( weekdays only ) from the first day during radiotherapy . Total mesorectal excision was performed within 6 ± 2 weeks . The pathologic responses and survival outcomes were evaluated as study endpoints , and an additional KRAS mutation analysis was performed . RESULTS In total , 39 patients completed their planned preoperative chemoradiation and underwent R0 resection . The pathologic complete response rate was 23.1 % ( 9/39 ) , and 3 patients ( 7.7 % ) showed near total regression of tumor . The 3-year disease-free and overall survival rates were 80.0 % and 94.7 % , respectively . Grade 3/4 toxicities included leukopenia ( 4 , 10.3 % ) , neutropenia ( 2 , 5.1 % ) , anemia ( 1 , 2.6 % ) , diarrhea ( 2 , 5.1 % ) , fatigue ( 1 , 2.6 % ) , skin rash ( 1 , 2.6 % ) , and ileus ( 1 , 2.6 % ) . KRAS mutations were found in 5 ( 13.2 % ) of 38 patients who had available tissue for testing . Clinical outcomes were not significantly correlated with KRAS mutation status . CONCLUSIONS Preoperative chemoradiation with cetuximab , irinotecan , and capecitabine was active and well tolerated . KRAS mutation status was not a predictive factor for pathologic response in this study PURPOSE To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy ( RT ) followed by surgery and postoperative flurouracil (FU)/leucovorin ( LV ) in patients with rectal cancer . PATIENTS AND METHODS Patients ( n = 94 ) with potentially resectable tumors , ultrasound at stages T2N+ ( n = 4 ) , T3 ( n = 77 ) , T4 ( n = 13 ) were treated with UFT ( 400 mg/m2/d , 5 days a week for 5 weeks ) and concomitant RT to the pelvis ( 45 Gy ; 1.8 Gy/d over 5 weeks ) . Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV . Primary end points included downstaging , pathologic responses , and sphincter-preserving surgery . Secondary end points were recurrence-free survival and overall survival . RESULTS All patients received the full RT dose . Fifteen patients ( 16 % ) needed UFT dose reduction . Preoperative G3 + toxicities included diarrhea ( 14 % ) , leukopenia ( 1 % ) , thrombocytopenia ( 1 % ) , and nausea ( 4 % ) . The downstaging rate was 54 % , pathologic complete response ( pCR ) was 9 % and , in an additional 23 % , there were only residual microscopic foci . When cellular viability criteria were taken into account , the pCR was 15 % . From 43 patients with abdominoperineal resection indication , 11 ( 25 % ) had sphincter-preserving surgery performed . Postoperative scheduled chemotherapy dose was not administered to 24 % of patients because of G3 + toxicity ( diarrhea , 8 % ; mucositis , 9 % ; and leukopenia , 7 % ) . Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without . At 3 years , actuarial patterns of failure were pelvic , 5 % and distant , 11 % . OS was 75 % . CONCLUSION UFT combined with RT is safe and effective . In resectable rectal cancer , if preoperative treatment is considered , this approach can be an option Networks of investigators have begun sharing best practice s , tools and methods for analysis of associations between genetic variation and common diseases . A Network of Investigator Networks has been set up to drive the process , sponsored by the Human Genome Epidemiology Network . A workshop is planned to develop consensus guidelines for reporting results of genetic association studies . Published literature data bases will be integrated , and unpublished data , including ' negative ' studies , will be captured by online journals and through investigator networks . Systematic review s will be exp and ed to include more meta-analyses of individual-level data and prospect i ve meta-analyses . Field synopses will offer regularly up date d overviews BACKGROUND The object of this phase II study was to assess the impact of preoperative external radiation therapy combined with UFT and leucovorin on tumor response , sphincter preservation and tumor control in patients with rectal carcinoma . PATIENTS AND METHODS Forty-one patients with resectable extraperitoneal rectal adenocarcinoma received radiation therapy and two courses of chemotherapy . Chemotherapy consisted of a 2-h infusion of 6S-steroisomer of leucovorin ( 6SLV ) 250 mg/m2 on day 1 , oral 6SLV 7.5 mg every 12 h on days 2 - 14 , and UFT either 350 or 300 mg/m2 on days 1 to 14 every 28 days . Six additional courses of chemotherapy were given after surgery . RESULTS Seven of 16 patients ( 43 % ) who received 350 mg/m2/day of UFT had grade 3 - 4 diarrhea and two other patients ( 12 % ) had grade 3 - 4 dermatitis . The next 25 patients received 300 mg/m2/day of UFT and only 14 % of them had grade 3 - 4 diarrhea . Surgery consisted of low-anterior resection in 26 patients (  
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background The aim of this study was to evaluate whether downstaging impacts prognosis in patients with cII versus cIII rectal cancer . Material s and Methods We identified from our colorectal cancer data base 295 patients with primary cII and cIII rectal cancer staged by CT and ERUS/MRI who received 5-FU-based chemoradiation followed by R0 surgery after a median interval of 7 weeks during 1997–2007 . The median radiotherapy dose was 5040 cGy . We excluded 58 patients with pathologic complete response ( pCR ) and compared among the remaining 162 patients pathologic downstaging ( cII to ypI , cIII to ypII or ypI ) versus no pathologic downstaging ( c stage ≤ yp stage ) . Outcomes evaluated were 5-year overall survival , 3-year cancer-specific survival , disease-free survival , overall recurrence , local recurrence , and distant recurrence . Results The median age was 58 years and median follow-up was 48 months . Patients with downstaging versus no downstaging were statistically comparable with respect to demographics , chemoradiation regimen , interval time between neoadjuvant chemoradiation and surgery , tumor distance from anal verge , surgical procedures performed , and follow-up time . With the exception of local recurrence rates , downstaging result ed in significantly improved cancer outcomes for cIII but not cII . Conclusions Downstaging without pCR is a significant prognostic factor for patients with stage cIII rectal cancer . Tumor response to neoadjuvant chemoradiation should be taken into account when defining the optimal adjuvant chemotherapy regimen for patients with cIII rectal cancer 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 PURPOSE Mutations in KRAS and BRAF genes as well as the loss of expression of phosphatase and tensin homolog ( PTEN ) ( deleted on chromosome 10 ) are associated with impaired activity of antibodies directed against epidermal growth factor receptor in patients with metastatic colorectal cancer . The predictive and prognostic value of the KRAS and BRAF point mutations as well as PTEN expression in patients with locally advanced rectal cancer ( LARC ) treated with cetuximab-based neoadjuvant chemoradiotherapy is unknown . METHODS AND MATERIAL S We have conducted phase I and II trials of the combination of weekly administration of cetuximab and irinotecan and daily doses of capecitabine in conjunction with radiotherapy ( 45 Gy plus 5.4 Gy ) in patients with LARC ( stage uT3/4 or uN+ ) . The status of KRAS and BRAF mutations was determined with direct sequencing , and PTEN expression status was determined with immunohistochemistry testing of diagnostic tumor biopsies . Tumor regression was evaluated by using st and ardized regression grading , and disease-free survival ( DFS ) was calculated according to the Kaplan-Meier method . RESULTS A total of 57 patients were available for analyses . A total of 31.6 % of patients carried mutations in the KRAS genes . No BRAF mutations were found , while the loss of PTEN expression was observed in 9.6 % of patients . Six patients achieved complete remission , and the 3-year DFS rate was 73 % . No correlation was seen between tumor regression or DFS rate and a single marker or a combination of all markers . CONCLUSIONS In the present series , no BRAF mutation was detected . The presence of KRAS mutations and loss of PTEN expression were not associated with impaired response to cetuximab-based chemoradiotherapy and 3-year DFS Purpose The aim of this study was to investigate the efficacy and safety of neoadjuvant cetuximab , capecitabine , and radiotherapy for patients with locally advanced rectal cancer . Methods Sixty-three eligible patients were selectively enrolled in this study . Neoadjuvant treatment consisted of cetuximab and capecitabine for 6 weeks and radiotherapy for 5 weeks . Surgical resection was performed 6–8 weeks after the completion of neoadjuvant treatment . KRAS mutation statuses were analyzed retrospectively after the cetuximab treatment . All the patients underwent a st and ardized postoperative follow-up for at least 3 years . Results A pathological complete response ( pCR ) was achieved in eight patients ( 12.7 % ) . Overall down-staging was found in 49 patients ( 77.8 % ) . The 3-year disease-free survival ( DFS ) rate and overall survival ( OS ) rate was 76.2 % and 81.0 % , respectively . The most common adverse events during neoadjuvant treatment were acneiform skin rash ( 82.5 % ) , radiodermatitis ( 46.0 % ) , and diarrhea ( 36.5 % ) . KRAS mutations were detected in 19 of 63 ( 31.2 % ) tumors . The down-staging rate in patients with KRAS wild-type ( WT ) was significantly higher than patients with KRAS mutation ( P = 0.020 ) . There was no significant difference in the pCR rate , 3-year DFS rate or 3-year OS rate between KRAS WT patients and KRAS-mutated patients . Conclusion Neoadjuvant treatment with cetuximab and capecitabine-based chemoradiotherapy is safe and well tolerated . The pCR rate , 3-year DFS rate and OS rate are not superior to the rate of neoadjuvant chemoradiotherapy using two or more cytotoxic agents . The KRAS WT is highly associated with tumor down-staging to cetuximab plus capecitabine-based CRT in patients with LARC PURPOSE To evaluate the efficacy and safety of preoperative chemoradiation with cetuximab , irinotecan , and capecitabine in patients with rectal cancer . METHODS AND MATERIAL S Forty patients with locally advanced , nonmetastatic , and mid- to lower rectal cancer were enrolled .  Radiotherapy was delivered at a dose of 50.4 Gy/28 fractions . Concurrent chemotherapy consisted of an initial dose of cetuximab of 400 mg/m(2 ) 1 week before radiotherapy , and then cetuximab 250 mg/m(2)/week , irinotecan 40 mg/m(2)/week for 5 consecutive weeks and capecitabine 1,650 mg/m(2)/day for 5 days a week ( weekdays only ) from the first day during radiotherapy . Total mesorectal excision was performed within 6 ± 2 weeks . The pathologic responses and survival outcomes were evaluated as study endpoints , and an additional KRAS mutation analysis was performed . RESULTS In total , 39 patients completed their planned preoperative chemoradiation and underwent R0 resection . The pathologic complete response rate was 23.1 % ( 9/39 ) , and 3 patients ( 7.7 % ) showed near total regression of tumor . The 3-year disease-free and overall survival rates were 80.0 % and 94.7 % , respectively . Grade 3/4 toxicities included leukopenia ( 4 , 10.3 % ) , neutropenia ( 2 , 5.1 % ) , anemia ( 1 , 2.6 % ) , diarrhea ( 2 , 5.1 % ) , fatigue ( 1 , 2.6 % ) , skin rash ( 1 , 2.6 % ) , and ileus ( 1 , 2.6 % ) . KRAS mutations were found in 5 ( 13.2 % ) of 38 patients who had available tissue for testing . Clinical outcomes were not significantly correlated with KRAS mutation status . CONCLUSIONS Preoperative chemoradiation with cetuximab , irinotecan , and capecitabine was active and well tolerated . KRAS mutation status was not a predictive factor for pathologic response in this study PURPOSE To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy ( RT ) followed by surgery and postoperative flurouracil (FU)/leucovorin ( LV ) in patients with rectal cancer . PATIENTS AND METHODS Patients ( n = 94 ) with potentially resectable tumors , ultrasound at stages T2N+ ( n = 4 ) , T3 ( n = 77 ) , T4 ( n = 13 ) were treated with UFT ( 400 mg/m2/d , 5 days a week for 5 weeks ) and concomitant RT to the pelvis ( 45 Gy ; 1.8 Gy/d over 5 weeks ) . Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV . Primary end points included downstaging , pathologic responses , and sphincter-preserving surgery . Secondary end points were recurrence-free survival and overall survival . RESULTS All patients received the full RT dose . Fifteen patients ( 16 % ) needed UFT dose reduction . Preoperative G3 + toxicities included diarrhea ( 14 % ) , leukopenia ( 1 % ) , thrombocytopenia ( 1 % ) , and nausea ( 4 % ) . The downstaging rate was 54 % , pathologic complete response ( pCR ) was 9 % and , in an additional 23 % , there were only residual microscopic foci . When cellular viability criteria were taken into account , the pCR was 15 % . From 43 patients with abdominoperineal resection indication , 11 ( 25 % ) had sphincter-preserving surgery performed . Postoperative scheduled chemotherapy dose was not administered to 24 % of patients because of G3 + toxicity ( diarrhea , 8 % ; mucositis , 9 % ; and leukopenia , 7 % ) . Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without . At 3 years , actuarial patterns of failure were pelvic , 5 % and distant , 11 % . OS was 75 % . CONCLUSION UFT combined with RT is safe and effective . In resectable rectal cancer , if preoperative treatment is considered , this approach can be an option Networks of investigators have begun sharing best practice s , tools and methods for analysis of associations between genetic variation and common diseases . A Network of Investigator Networks has been set up to drive the process , sponsored by the Human Genome Epidemiology Network . A workshop is planned to develop consensus guidelines for reporting results of genetic association studies . Published literature data bases will be integrated , and unpublished data , including ' negative ' studies , will be captured by online journals and through investigator networks . Systematic review s will be exp and ed to include more meta-analyses of individual-level data and prospect i ve meta-analyses . Field synopses will offer regularly up date d overviews BACKGROUND The object of this phase II study was to assess the impact of preoperative external radiation therapy combined with UFT and leucovorin on tumor response , sphincter preservation and tumor control in patients with rectal carcinoma . PATIENTS AND METHODS Forty-one patients with resectable extraperitoneal rectal adenocarcinoma received radiation therapy and two courses of chemotherapy . Chemotherapy consisted of a 2-h infusion of 6S-steroisomer of leucovorin ( 6SLV ) 250 mg/m2 on day 1 , oral 6SLV 7.5 mg every 12 h on days 2 - 14 , and UFT either 350 or 300 mg/m2 on days 1 to 14 every 28 days . Six additional courses of chemotherapy were given after surgery . RESULTS Seven of 16 patients ( 43 % ) who received 350 mg/m2/day of UFT had grade 3 - 4 diarrhea and two other patients ( 12 % ) had grade 3 - 4 dermatitis . The next 25 patients received 300 mg/m2/day of UFT and only 14 % of them had grade 3 - 4 diarrhea . Surgery consisted of low-anterior resection in 26 patients (  
    Output:
    