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 CARTS study is a multicenter feasibility study , investigating the role of rectum saving surgery for distal rectal cancer . Methods / Design Patients with a clinical T1 - 3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant chemoradiation therapy ( 25 fractions of 2 Gy with concurrent capecitabine ) . Transanal Endoscopic Microsurgery ( TEM ) will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response . Primary objective is to determine the number of patients with a ( near ) complete pathological response after chemoradiation therapy and TEM . Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality . A three-step analysis will be performed after 20 , 33 and 55 patients to ensure the feasibility of this treatment protocol . Discussion The CARTS- study is one of the first prospect i ve multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision . The CARTS study is registered at clinical trials.gov ( NCT01273051 Background and aim The aim of this study was to investigate the possible effect of a COX-2 inhibitor in addition to chemoradiation of locally advanced rectal cancer . Material s and methods The study included 35 patients with rectal adenocarcinoma . All patients had a tumor localised ≤10 cm from the anal verge and a circumferential margin ≤5 mm on a magnetic resonance scan . The patients were scheduled to receive external radiation with a tumor dose of 60 Gy supplemented with an endorectal boost of 5 Gy . Concurrent with radiation , the patients received uracil-tegafur 300 mg/m2 daily . Celexocib was scheduled throughout the radiation period in a dose of 400 mg × 2 daily . Results A macular papular rash was seen in 17 ( 49 % ) of the patients leading to stop of medication with celecoxib . Thirty-three patients were operated , and all patients responded to treatment . Complete pathological remission was found in 21 % of the patients and further 24 % had only microscopic residual tumor cells . The results did not suggest any difference according to the accomplishment of the COX-2 medication . Conclusion The addition of a COX-2 inhibitor to chemotherapy-enhanced radiation treatment of rectal cancer was not feasible due to a high incidence of rash in the present study The aim of this study was to investigate the efficacy and safety of chemoradiation using capecitabine and irinotecan as neoadjuvant therapy for patients with rectal cancer .  Conventional radiation was given at daily fractions of 1.8 Gy on 5 days a week for a total dose of 55.8 ( 50.4 + 5.4 ) Gy . Concurrently , irinotecan 40 mg m−2 once weekly and capecitabine continuously at dose levels of 500 , 650 , 750 and 825 mg m−2 twice daily were administered . Surgery was performed 4–6 weeks following completion of chemoradiation . A total of 28 patients ( 3 UICC II , 25 UICC III ) were enrolled and all received treatment . Dose-limiting toxicity was diarrhoea grade IV and h and –foot syndrome at the 825 mg m−2 dose level . The maximum tolerated dose of capecitabine was 750 mg m−2 . Diarrhoea was the most common toxicity : grade III in nine patients . Two patients died , one due to pneumonia and one due to sudden cardiac death . A complete response and only microfocal residual tumour disease was achieved in four and three patients ( 27 % ) . In all , 25 of 28 patients undergoing surgery , 24 ( 96 % ) had R0 resection . Preoperative chemoradiation based on continuous daily capecitabine and weekly irinotecan appears to tolerated and effective in patients with rectal cancer Background Neoadjuvant radiochemotherapy ( RCT ) is now part of the armamentarium of cancer of the lower and middle rectum . It is recommended in current clinical practice prior to surgical excision if the lesion is classified T3/T4 or N+ . Histological complete response , defined by the absence of persistent tumor cell invasion and lymph node ( ypT0N0 ) after pathological examination of surgical specimen has been shown to be an independent prognostic factor of overall survival and disease-free survival . Surgical excision is usually performed between 6 and 8 weeks after completion of CRT and pathological complete response rate ranges around 12 % . In retrospective studies , a lengthening of the interval after RCT beyond 10 weeks was found as an independent factor increasing the rate of pathological complete response ( between 26 % and 31 % ) , with a longer disease-free survival and without increasing the operative morbidity . The aim of the present study is to evaluate in 264 patients the rate of pathological complete response rate of rectal cancer after RCT by lengthening the time between RCT and surgery . Methods / design The current study is a multicenter r and omized trial in two parallel groups comparing 7 and 11 weeks of delay between the end of RCT and cancer surgery of rectal tumors . At the end of the RCT , surgery is planified and r and omization is performed after patient ’s written consent for participation . The histological complete response ( ypT0N0 ) will be determined with analysis of the complete residual tumor and double reading by two pathologists blinded of the group of inclusion . Patients will be followed in clinics for 5 years after surgery . Participation in this trial does not change patient ’s management in terms of treatment , investigations or visits . Secondary endpoints will include overall and disease free survival , rate of sphincter conservation and quality of mesorectal excision .  The number of patients needed is 264.Trial registration Clinical Trial.gov : Background . Preoperative radiochemotherapy is a cornerstone in patients with non- resectable locally advanced rectal cancer ( LARC ) . To improve outcome ( number of R0 resections and survival ) high-dose radiotherapy ( RT ) was combined with oral UFT/l-leucovorin to allow tumour regression before radical intended surgery . Methods . Pelvic RT was delivered with megavoltage photons using a 5 field technique . RT was CT-based , given 5 days a week through one posterior field and two lateral fields ( 48.6 Gy/27 fractions ) to encompass the primary tumour and the regional lymph nodes . In addition , the tumour bed received a concurrent boost ( 5.4 Gy/27 fractions ) and a final boost ( 6 Gy/3 fractions ) ; thus GTV received 60 Gy/30 fractions . Concurrent with RT patients received a daily dose of oral UFT 300 mg/m2 plus l-leucovorin 22.5 mg 5/7days ( divided in three doses ) . Results . From September 2000 to November 2004 , 52 patients ( median age 60 years ( 32–83 ) ; median PS 0 ( 0–2 ) ) with LARC ( 36 primary , 16 recurrent ) were included in this phase II study . All but three patients received the planned 60 Gy , median duration of RT was 42 days ( 25–49 ) . Toxicity was very modest ; only four patients had a dose reduction of UFT . No hematological toxicity of clinical significance was seen . Non-hematological toxicity grade 1 ( GI-toxicity , fatigue and /or dysuria ) was frequently observed but only four patients experienced grade 3 toxicity ( diarrhoea and /or nausea/vomiting ) . Forty patients ( 77 % ) were operated ( 30 R0 , 5 R1 , 5 R2 ) median 55 days ( 27–112 ) after completion of RT . Seven ( 13 % ) patients had a pathological complete response ( pCR ) . Thirty-one patients ( 60 % ) died after median 25.4 months ( 1.6–45.2 months ) . Twenty-one patients ( 40 % ) are still alive June 2007 . Conclusions . Preoperative high-dose RT and concomitant UFT produces major regression in most patients with non-resectable LARC and thus a good chance of cure PURPOSE To vali date tolerance and pathological complete response rate ( pCR ) of a 4-week preoperative course of intensity-modulated radiation therapy ( IMRT ) with concurrent capecitabine and oxaliplatin ( CAPOX ) in patients with locally advanced rectal cancer . METHODS AND MATERIAL S Patients with T3 to T4 and /or N+ rectal cancer received preoperative IMRT ( 47.5 Gy in 19 fractions ) with concurrent capecitabine ( 825 mg/m(2 ) b.i.d . , Monday to Friday ) and oxaliplatin ( 60 mg/m(2 ) on Days 1 , 8 , and 15 ) . Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation . Primary end points were toxicity and pathological response rate . Local control ( LC ) , disease-free survival ( DFS ) , and overall survival ( OS ) were also analyzed . RESULTS A total of 100 patients were evaluated .  Grade 1 to 2 proctitis was observed in 73 patients ( 73 % ) . Grade 3 diarrhea occurred in 9 % of the patients . Grade 3 proctitis in 18 % of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments . The rate of Grade 3 proctitis decreased to 4 % thereafter ( odds ratio , 0.27 ) . A total of 99 patients underwent surgery . A pCR was observed in 13 % of the patients , major response ( 96 - 100 % of histological response ) in 48 % , and pN downstaging in 78 % . An R0 resection was performed in 97 % of the patients . After a median follow-up of 55 months , the LC , DFS , and OS rates were 100 % , 84 % , and 87 % , respectively . CONCLUSIONS Preoperative CAPOX-IMRT therapy ( 47.5 Gy in 20 fractions ) is feasible and safe , and produces major pathological responses in approximately 50 % of patients PURPOSE The aim of this retrospective case-matching study was to compare the treatment outcomes and acute toxicity of preoperative radiotherapy ( RT ) with capecitabine vs. preoperative RT with intermittent 5-fluorouracil ( 5-FU ) infusion , leucovorin , and mitomycin C in rectal cancer . METHODS AND MATERIAL S We matched 34 patients who were treated with preoperative concurrent capecitabine and 50 Gy of RT by their clinical T stage ( T3 or T4 ) and the tumor location ( < or=7 cm or > 7 cm from the anal verge ) with another 68 patients who were treated with preoperative intermittent 5-FU infusion , leucovorin , mitomycin C , and 50 Gy of RT  for a comparison of the pathologic tumor response , local control , distant failure , and survival rates . RESULTS The pathologic complete response rate was 21 % with capecitabine and 18 % with 5-FU and leucovorin ( p = 0.72 ) . The rate of T downstaging after chemoradiation was 59 % for both groups . The rate of sphincter-sparing resection was 38 % after capecitabine plus RT and 43 % after 5-FU plus RT ( p = 0.67 ) . At 3 years , there was no significant difference in the local control rate ( 93 % for capecitabine and 92 % for 5-FU and leucovorin ) , relapse-free rate ( 74 % for capecitabine and 73 % for 5-FU and leucovorin ) , or disease-specific survival rate ( 86 % for capecitabine and 77 % for 5-FU and leucovorin ) . The acute toxicity profile was comparable , with little Grade 3 and 4 toxicity . CONCLUSIONS When administered with concurrent preoperative RT , both capecitabine and intermittent 5-FU infusion with leucovorin modulation provided comparable pathologic tumor response , local control , relapse-free survival , and disease-specific survival rates in rectal cancer We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy ( CapIri-RT ) as neoadjuvant treatment in rectal cancer in a phase-II trial . Patients with rectal cancer clinical stages T3/4 Nx or N+ were recruited to receive irinotecan ( 50 mg m−2 weekly ) and capecitabine ( 500 mg m−2 bid days 1–38 ) with a concurrent RT dose of 50.4 Gy . Surgery was scheduled 4–6 weeks after the completion of chemoradiation . A total of 36 patients ( median age 62 years ; m/f : 27:9 ) including three patients with local recurrence were enclosed onto the trial . The median distance of the tumour from the anal verge was 5 cm . The main toxicity observed was ( NCI-CTC grade s 1/2/3/4 ( n ) ) : Anaemia 23/9/−/− ; leucocytopenia 12/7/7/2 , diarrhoea 13/1 
    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 CARTS study is a multicenter feasibility study , investigating the role of rectum saving surgery for distal rectal cancer . Methods / Design Patients with a clinical T1 - 3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant chemoradiation therapy ( 25 fractions of 2 Gy with concurrent capecitabine ) . Transanal Endoscopic Microsurgery ( TEM ) will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response . Primary objective is to determine the number of patients with a ( near ) complete pathological response after chemoradiation therapy and TEM . Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality . A three-step analysis will be performed after 20 , 33 and 55 patients to ensure the feasibility of this treatment protocol . Discussion The CARTS- study is one of the first prospect i ve multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision . The CARTS study is registered at clinical trials.gov ( NCT01273051 Background and aim The aim of this study was to investigate the possible effect of a COX-2 inhibitor in addition to chemoradiation of locally advanced rectal cancer . Material s and methods The study included 35 patients with rectal adenocarcinoma . All patients had a tumor localised ≤10 cm from the anal verge and a circumferential margin ≤5 mm on a magnetic resonance scan . The patients were scheduled to receive external radiation with a tumor dose of 60 Gy supplemented with an endorectal boost of 5 Gy . Concurrent with radiation , the patients received uracil-tegafur 300 mg/m2 daily . Celexocib was scheduled throughout the radiation period in a dose of 400 mg × 2 daily . Results A macular papular rash was seen in 17 ( 49 % ) of the patients leading to stop of medication with celecoxib . Thirty-three patients were operated , and all patients responded to treatment . Complete pathological remission was found in 21 % of the patients and further 24 % had only microscopic residual tumor cells . The results did not suggest any difference according to the accomplishment of the COX-2 medication . Conclusion The addition of a COX-2 inhibitor to chemotherapy-enhanced radiation treatment of rectal cancer was not feasible due to a high incidence of rash in the present study The aim of this study was to investigate the efficacy and safety of chemoradiation using capecitabine and irinotecan as neoadjuvant therapy for patients with rectal cancer .  Conventional radiation was given at daily fractions of 1.8 Gy on 5 days a week for a total dose of 55.8 ( 50.4 + 5.4 ) Gy . Concurrently , irinotecan 40 mg m−2 once weekly and capecitabine continuously at dose levels of 500 , 650 , 750 and 825 mg m−2 twice daily were administered . Surgery was performed 4–6 weeks following completion of chemoradiation . A total of 28 patients ( 3 UICC II , 25 UICC III ) were enrolled and all received treatment . Dose-limiting toxicity was diarrhoea grade IV and h and –foot syndrome at the 825 mg m−2 dose level . The maximum tolerated dose of capecitabine was 750 mg m−2 . Diarrhoea was the most common toxicity : grade III in nine patients . Two patients died , one due to pneumonia and one due to sudden cardiac death . A complete response and only microfocal residual tumour disease was achieved in four and three patients ( 27 % ) . In all , 25 of 28 patients undergoing surgery , 24 ( 96 % ) had R0 resection . Preoperative chemoradiation based on continuous daily capecitabine and weekly irinotecan appears to tolerated and effective in patients with rectal cancer Background Neoadjuvant radiochemotherapy ( RCT ) is now part of the armamentarium of cancer of the lower and middle rectum . It is recommended in current clinical practice prior to surgical excision if the lesion is classified T3/T4 or N+ . Histological complete response , defined by the absence of persistent tumor cell invasion and lymph node ( ypT0N0 ) after pathological examination of surgical specimen has been shown to be an independent prognostic factor of overall survival and disease-free survival . Surgical excision is usually performed between 6 and 8 weeks after completion of CRT and pathological complete response rate ranges around 12 % . In retrospective studies , a lengthening of the interval after RCT beyond 10 weeks was found as an independent factor increasing the rate of pathological complete response ( between 26 % and 31 % ) , with a longer disease-free survival and without increasing the operative morbidity . The aim of the present study is to evaluate in 264 patients the rate of pathological complete response rate of rectal cancer after RCT by lengthening the time between RCT and surgery . Methods / design The current study is a multicenter r and omized trial in two parallel groups comparing 7 and 11 weeks of delay between the end of RCT and cancer surgery of rectal tumors . At the end of the RCT , surgery is planified and r and omization is performed after patient ’s written consent for participation . The histological complete response ( ypT0N0 ) will be determined with analysis of the complete residual tumor and double reading by two pathologists blinded of the group of inclusion . Patients will be followed in clinics for 5 years after surgery . Participation in this trial does not change patient ’s management in terms of treatment , investigations or visits . Secondary endpoints will include overall and disease free survival , rate of sphincter conservation and quality of mesorectal excision .  The number of patients needed is 264.Trial registration Clinical Trial.gov : Background . Preoperative radiochemotherapy is a cornerstone in patients with non- resectable locally advanced rectal cancer ( LARC ) . To improve outcome ( number of R0 resections and survival ) high-dose radiotherapy ( RT ) was combined with oral UFT/l-leucovorin to allow tumour regression before radical intended surgery . Methods . Pelvic RT was delivered with megavoltage photons using a 5 field technique . RT was CT-based , given 5 days a week through one posterior field and two lateral fields ( 48.6 Gy/27 fractions ) to encompass the primary tumour and the regional lymph nodes . In addition , the tumour bed received a concurrent boost ( 5.4 Gy/27 fractions ) and a final boost ( 6 Gy/3 fractions ) ; thus GTV received 60 Gy/30 fractions . Concurrent with RT patients received a daily dose of oral UFT 300 mg/m2 plus l-leucovorin 22.5 mg 5/7days ( divided in three doses ) . Results . From September 2000 to November 2004 , 52 patients ( median age 60 years ( 32–83 ) ; median PS 0 ( 0–2 ) ) with LARC ( 36 primary , 16 recurrent ) were included in this phase II study . All but three patients received the planned 60 Gy , median duration of RT was 42 days ( 25–49 ) . Toxicity was very modest ; only four patients had a dose reduction of UFT . No hematological toxicity of clinical significance was seen . Non-hematological toxicity grade 1 ( GI-toxicity , fatigue and /or dysuria ) was frequently observed but only four patients experienced grade 3 toxicity ( diarrhoea and /or nausea/vomiting ) . Forty patients ( 77 % ) were operated ( 30 R0 , 5 R1 , 5 R2 ) median 55 days ( 27–112 ) after completion of RT . Seven ( 13 % ) patients had a pathological complete response ( pCR ) . Thirty-one patients ( 60 % ) died after median 25.4 months ( 1.6–45.2 months ) . Twenty-one patients ( 40 % ) are still alive June 2007 . Conclusions . Preoperative high-dose RT and concomitant UFT produces major regression in most patients with non-resectable LARC and thus a good chance of cure PURPOSE To vali date tolerance and pathological complete response rate ( pCR ) of a 4-week preoperative course of intensity-modulated radiation therapy ( IMRT ) with concurrent capecitabine and oxaliplatin ( CAPOX ) in patients with locally advanced rectal cancer . METHODS AND MATERIAL S Patients with T3 to T4 and /or N+ rectal cancer received preoperative IMRT ( 47.5 Gy in 19 fractions ) with concurrent capecitabine ( 825 mg/m(2 ) b.i.d . , Monday to Friday ) and oxaliplatin ( 60 mg/m(2 ) on Days 1 , 8 , and 15 ) . Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation . Primary end points were toxicity and pathological response rate . Local control ( LC ) , disease-free survival ( DFS ) , and overall survival ( OS ) were also analyzed . RESULTS A total of 100 patients were evaluated .  Grade 1 to 2 proctitis was observed in 73 patients ( 73 % ) . Grade 3 diarrhea occurred in 9 % of the patients . Grade 3 proctitis in 18 % of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments . The rate of Grade 3 proctitis decreased to 4 % thereafter ( odds ratio , 0.27 ) . A total of 99 patients underwent surgery . A pCR was observed in 13 % of the patients , major response ( 96 - 100 % of histological response ) in 48 % , and pN downstaging in 78 % . An R0 resection was performed in 97 % of the patients . After a median follow-up of 55 months , the LC , DFS , and OS rates were 100 % , 84 % , and 87 % , respectively . CONCLUSIONS Preoperative CAPOX-IMRT therapy ( 47.5 Gy in 20 fractions ) is feasible and safe , and produces major pathological responses in approximately 50 % of patients PURPOSE The aim of this retrospective case-matching study was to compare the treatment outcomes and acute toxicity of preoperative radiotherapy ( RT ) with capecitabine vs. preoperative RT with intermittent 5-fluorouracil ( 5-FU ) infusion , leucovorin , and mitomycin C in rectal cancer . METHODS AND MATERIAL S We matched 34 patients who were treated with preoperative concurrent capecitabine and 50 Gy of RT by their clinical T stage ( T3 or T4 ) and the tumor location ( < or=7 cm or > 7 cm from the anal verge ) with another 68 patients who were treated with preoperative intermittent 5-FU infusion , leucovorin , mitomycin C , and 50 Gy of RT  for a comparison of the pathologic tumor response , local control , distant failure , and survival rates . RESULTS The pathologic complete response rate was 21 % with capecitabine and 18 % with 5-FU and leucovorin ( p = 0.72 ) . The rate of T downstaging after chemoradiation was 59 % for both groups . The rate of sphincter-sparing resection was 38 % after capecitabine plus RT and 43 % after 5-FU plus RT ( p = 0.67 ) . At 3 years , there was no significant difference in the local control rate ( 93 % for capecitabine and 92 % for 5-FU and leucovorin ) , relapse-free rate ( 74 % for capecitabine and 73 % for 5-FU and leucovorin ) , or disease-specific survival rate ( 86 % for capecitabine and 77 % for 5-FU and leucovorin ) . The acute toxicity profile was comparable , with little Grade 3 and 4 toxicity . CONCLUSIONS When administered with concurrent preoperative RT , both capecitabine and intermittent 5-FU infusion with leucovorin modulation provided comparable pathologic tumor response , local control , relapse-free survival , and disease-specific survival rates in rectal cancer We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy ( CapIri-RT ) as neoadjuvant treatment in rectal cancer in a phase-II trial . Patients with rectal cancer clinical stages T3/4 Nx or N+ were recruited to receive irinotecan ( 50 mg m−2 weekly ) and capecitabine ( 500 mg m−2 bid days 1–38 ) with a concurrent RT dose of 50.4 Gy . Surgery was scheduled 4–6 weeks after the completion of chemoradiation . A total of 36 patients ( median age 62 years ; m/f : 27:9 ) including three patients with local recurrence were enclosed onto the trial . The median distance of the tumour from the anal verge was 5 cm . The main toxicity observed was ( NCI-CTC grade s 1/2/3/4 ( n ) ) : Anaemia 23/9/−/− ; leucocytopenia 12/7/7/2 , diarrhoea 13/1 
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