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: Only 4 prospect i ve r and omized phase 3 trials have been reported for anal cancer . A prognostic factor analysis for anal cancer from a prospect i ve data base has been published from only 1 study ( N = 110 ) . To confirm and uncover new prognostic factors , we analyzed the prospect i ve data base of intergroup RTOG 98‐11 PURPOSE The long-term up date of US GI Intergroup RTOG 98 - 11 anal cancer trial found that concurrent chemoradiation ( CCRT ) with fluorouracil ( 5-FU ) plus mitomycin had a significant impact on disease-free survival ( DFS ) and overall survival ( OS ) compared with induction plus concurrent 5-FU plus cisplatin . The intent of the current analysis was to determine the impact of tumor node ( TN ) category of disease on survival ( DFS and OS ) , colostomy failure ( CF ) , and relapse ( local-regional failure [ LRF ] and distant metastases [ DM ] ) in this patient group . METHODS AND MATERIAL S DFS and OS were estimated univariately by using the Kaplan-Meier method , and 6 TN categories were compared by the log-rank test ( T2N0 , T3N0 , T4N0 , T2N1 - 3 , T3N1 - 3 , and T4N1 - 3 ) . Time to relapse and colostomy were estimated by the cumulative incidence method , and TN categories were compared using Gray 's test . RESULTS Of 682 patients , 620 were analyzable for outcomes by TN category . All endpoints showed statistically significant differences among the TN categories of disease ( OS , P<.0001 ; DFS , P<.0001 ; LRF , P<.0001 ; DM , P=.0011 ; CF , P=.01 ) . Patients with the poorest OS , DFS , and LRF outcomes were those with T3 - 4N-positive ( + ) disease . CF was lowest for T2N0 and T2N+ ( 11 % , 11 % , respectively ) and worst for the T4N0 , T3N+ , and T4N+ categories ( 26 % , 27 % , 24 % , respectively ) . CONCLUSIONS TN category of disease has a statistically significant impact on OS , DFS , LRF , DM , and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma . Significant challenges remain for patients with T4N0 and T3 - 4N+ categories of disease with regard to survival , relapse , and CF and lesser challenges for T2 - 3N0/T2N+ categories PURPOSE Concomitant radiochemotherapy ( RCT ) is the st and ard for locally advanced anal canal carcinoma ( LAACC ) . Questions regarding the role of induction chemotherapy ( ICT ) and a higher radiation dose in LAACC are pending . Our trial was design ed to determine whether dose escalation of the radiation boost or two cycles of ICT before concomitant RCT lead to an improvement in colostomy-free survival ( CFS ) . PATIENTS AND METHODS Patients with tumors ≥ 40 mm , or < 40 mm and N1 - 3M0 were r and omly assigned to one of four treatment arms : ( A ) two ICT cycles ( fluorouracil 800 mg/m(2)/d intravenous [ IV ] infusion , days 1 through 4 and 29 to 32 ; and cisplatin 80 mg/m(2 ) IV , on days 1 and 29 ) , RCT ( 45 Gy in 25 fractions over 5 weeks , fluorouracil and cisplatin during weeks 1 and 5 ) , and st and ard-dose boost ( SD ; 15 Gy ) ; ( B ) two ICT cycles , RCT , and high-dose boost ( HD ; 20 - 25 Gy ) ; ( C ) : RCT and SD boost ( reference arm ) ; and ( D ) RCT and HD boost . RESULTS Two hundred eighty-three of 307 patients achieved full treatment . With a median follow-up period of 50 months , the 5-year CFS rates were 69.6 % , 82.4 % , 77.1 % , and 72.7 % in arms A , B , C , and D , respectively . Considering the 2 × 2 factorial analysis , the 5-year CFS was 76.5 % versus 75.0 % ( P = .37 ) in groups A and B versus C and D , respectively ( ICT effect ) , and 73.7 % versus 77.8 % in groups A and C versus B and D , respectively ( RT-dose effect ; P = .067 ) . CONCLUSION Using CFS as our main end point , we did not find an advantage for either ICT or HD radiation boost in LAACC . Nevertheless , the results of the most treatment-intense arm B should prompt the design of further intensification studies PURPOSE On initial publication of GI Intergroup Radiation Therapy Oncology Group ( RTOG ) 98 - 11 [ A Phase III R and omized Study of 5-Fluorouracil ( 5-FU ) , Mitomycin , and Radiotherapy Versus 5-Fluorouracil , Cisplatin and Radiotherapy in Carcinoma of the Anal Canal ] , concurrent chemoradiation ( CCR ) with fluorouracil ( FU ) plus mitomycin ( MMC ) decreased colostomy failure ( CF ) when compared with induction plus concurrent FU plus cisplatin ( CDDP ) , but did not significantly impact disease-free survival ( DFS ) or overall survival ( OS ) for anal canal carcinoma . The intent of the up date d analysis was to determine the long-term impact of treatment on survival ( DFS , OS , colostomy-free survival [ CFS ] ) , CF , and relapse ( locoregional failure [ LRF ] , distant metastasis ) in this patient group . PATIENTS AND METHODS Stratification factors included sex , clinical node status , and primary size . DFS and OS were estimated univariately by the Kaplan-Meier method , and treatment arms were compared by log-rank test . Time to relapse and CF were estimated by the cumulative incidence method and treatment arms were compared by using Gray 's test . Multivariate analyses used Cox proportional hazard models to test for treatment differences after adjusting for stratification factors . RESULTS Of 682 patients accrued , 649 were analyzable for outcomes .  DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP ( 5-year DFS , 67.8 % v 57.8 % ; P = .006 ; 5-year OS , 78.3 % v 70.7 % ; P = .026 ) . There was a trend toward statistical significance for CFS ( P = .05 ) , LRF ( P = .087 ) , and CF ( P = .074 ) . Multivariate analysis was statistically significant for treatment and clinical node status for both DFS and OS , for tumor diameter for DFS , and for sex for OS . CONCLUSION CCR with FU/MMC has a statistically significant , clinical ly meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP , and it has borderline significance for CFS , CF , and LRF . Therefore , RT + FU/MMC remains the preferred st and ard of care PURPOSE Radiation Therapy Oncology Group ( RTOG ) 92 - 08 began as a single arm , Phase II trial for patients with anal cancer consisting of radiation ( RT ) + 5-flourouracil + mitomycin-C with a m and atory 2-week break and was amended after completion to evaluate the same treatment regimen without a treatment break . Long-term efficacy and late toxicity reporting are the specific aims of this study . METHODS AND MATERIAL S Survivals were estimated with the Kaplan-Meier method . Overall survival ( OS ) was compared with RTOG 87 - 04 with the log-rank test . Time to local failure , regional failure , locoregional failure ( LRF ) , distant metastases , second primary , and colostomy failure were estimated by the cumulative incidence method . LRF was compared with RTOG 87 - 04 using the Gray 's test . RESULTS Forty-seven patients entered in the m and atory treatment break cohort . The study was reopened in 1995 to the no m and atory treatment break cohort completing accrual with 20 patients in 1996 . Of 67 total patients , 1 patient in the m and atory treatment break portion of the study did not receive any protocol treatment and is excluded from analyses . After adjusting for tumor size , neither cohort showed a statistically significant difference in OS or LRF compared with the RTOG 87 - 04 mitomycin-C arm . No patient in either cohort experienced a Grade 3 or higher late toxicity . CONCLUSIONS No statistically significant differences were seen in OS or LRF when compared to the mitomycin-C arm of RTOG 87 - 04 , but the sample sizes for the m and atory break cohort and the no m and atory break cohort are small . Late toxicity was low and similar for the treatment cohorts Background : The first UKCCCR Anal Cancer Trial ( 1996 ) demonstrated the benefit of chemoradiation over radiotherapy ( RT ) alone for treating epidermoid anal cancer , and it became the st and ard treatment . Patients in this trial have now been followed up for a median of 13 years . Methods : A total of 577 patients were r and omised to receive RT alone or combined modality therapy using 5-fluorouracil and mitomycin C. All patients were scheduled to receive 45 Gy by external beam irradiation . Patients who responded to treatment were recommended to have boost RT , with either an iridium implant or external beam irradiation . Data on relapse and deaths were obtained until October 2007 . Results : Twelve years after treatment , for every 100 patients treated with chemoradiation , there are an expected 25.3 fewer patients with locoregional relapse ( 95 % confidence interval ( CI ) : 17.5–32.0 fewer ) and 12.5 fewer anal cancer deaths ( 95 % CI : 4.3–19.7 fewer ) , compared with 100 patients given RT alone . There was a 9.1 % increase in non-anal cancer deaths in the first 5 years of chemoradiation ( 95 % CI + 3.6 to + 14.6 ) , which disappeared by 10 years . Conclusions : The clear benefit of chemoradiation outweighs an early excess risk of non-anal cancer deaths , and can still be seen 12 years after treatment . Only 11 patients suffered a locoregional relapse as a first event after 5 years , which may influence the choice of end points in future studies PURPOSE The United Kingdom Coordinating Committee on Cancer Research anal cancer trial demonstrated the benefit of combined modality treatment ( CMT ) using radiotherapy ( RT ) , infusional 5-fluorouracil , and mitomycin C over RT alone . The present study retrospectively examines the impact of the recommended 6-week treatment gap and local RT boost on long-term outcome . METHODS AND MATERIAL S A total of 577 patients were r and omly assigned RT alone or CMT .  After a 6-week gap responders received a boost using either additional external beam radiotherapy ( EBRT ) ( 15 Gy ) or iridium-192 implant ( 25 Gy ) . The effect of boost , the gap between initial treatment ( RT alone or CMT ) and boost ( Tgap ) , and overall treatment time ( OTT ) were examined for their impact on outcome . RESULTS Among the 490 good responders , 436 ( 89 % ) patients received a boost after initial treatment . For boosted patients , the risk of anal cancer death decreased by 38 % ( hazard ratio [ HR ] : 0.62 , 99 % CI 0.35 - 1.12 ; p=0.04 ) , but there was no evidence this was mediated via a reduction in locoregional failure ( LRF ) ( HR : 0.90 , 99 % CI 0.48 - 1.68 ; p=0.66 ) . The difference in Tgap was only 1.4 days longer for EBRT boost , compared with implant ( p=0.51 ) . OTT was longer by 6.1 days for EBRT ( p=0.006 ) . Tgap and OTT were not associated with LRF . Radionecrosis was reported in 8 % of boosted , compared with 0 % in unboosted patients ( p=0.03 ) . CONCLUSIONS These results question the benefit of a radiotherapy boost after a 6-week gap . The higher doses of a boost may contribute more to an increased risk of late morbidity , rather than local control Squamous cell carcinoma of the anus ( SCCA ) is a rare cancer but its incidence is increasing throughout the world , and is particularly high in the human immunodeficiency virus positive ( HIV+ ) population . A multidisciplinary approach is m and atory ( involving radiation therapists , medical oncologists , surgeons , radiologists and pathologists ) . SCCA usually spreads in a loco-regional manner within and outside the anal canal . Lymph node involvement at diagnosis is observed in 30 - 40 % of cases while systemic spread is uncommon with distant extrapelvic metastases recorded in 5 - 8 % at onset , and rates of metastatic progression after primary treatment between 10 % and 20 % . SCCA is strongly associated with human papilloma virus ( HPV , types 16 - 18 ) infection . The primary aim of treatment is to achieve cure with loco-regional control 
    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: Only 4 prospect i ve r and omized phase 3 trials have been reported for anal cancer . A prognostic factor analysis for anal cancer from a prospect i ve data base has been published from only 1 study ( N = 110 ) . To confirm and uncover new prognostic factors , we analyzed the prospect i ve data base of intergroup RTOG 98‐11 PURPOSE The long-term up date of US GI Intergroup RTOG 98 - 11 anal cancer trial found that concurrent chemoradiation ( CCRT ) with fluorouracil ( 5-FU ) plus mitomycin had a significant impact on disease-free survival ( DFS ) and overall survival ( OS ) compared with induction plus concurrent 5-FU plus cisplatin . The intent of the current analysis was to determine the impact of tumor node ( TN ) category of disease on survival ( DFS and OS ) , colostomy failure ( CF ) , and relapse ( local-regional failure [ LRF ] and distant metastases [ DM ] ) in this patient group . METHODS AND MATERIAL S DFS and OS were estimated univariately by using the Kaplan-Meier method , and 6 TN categories were compared by the log-rank test ( T2N0 , T3N0 , T4N0 , T2N1 - 3 , T3N1 - 3 , and T4N1 - 3 ) . Time to relapse and colostomy were estimated by the cumulative incidence method , and TN categories were compared using Gray 's test . RESULTS Of 682 patients , 620 were analyzable for outcomes by TN category . All endpoints showed statistically significant differences among the TN categories of disease ( OS , P<.0001 ; DFS , P<.0001 ; LRF , P<.0001 ; DM , P=.0011 ; CF , P=.01 ) . Patients with the poorest OS , DFS , and LRF outcomes were those with T3 - 4N-positive ( + ) disease . CF was lowest for T2N0 and T2N+ ( 11 % , 11 % , respectively ) and worst for the T4N0 , T3N+ , and T4N+ categories ( 26 % , 27 % , 24 % , respectively ) . CONCLUSIONS TN category of disease has a statistically significant impact on OS , DFS , LRF , DM , and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma . Significant challenges remain for patients with T4N0 and T3 - 4N+ categories of disease with regard to survival , relapse , and CF and lesser challenges for T2 - 3N0/T2N+ categories PURPOSE Concomitant radiochemotherapy ( RCT ) is the st and ard for locally advanced anal canal carcinoma ( LAACC ) . Questions regarding the role of induction chemotherapy ( ICT ) and a higher radiation dose in LAACC are pending . Our trial was design ed to determine whether dose escalation of the radiation boost or two cycles of ICT before concomitant RCT lead to an improvement in colostomy-free survival ( CFS ) . PATIENTS AND METHODS Patients with tumors ≥ 40 mm , or < 40 mm and N1 - 3M0 were r and omly assigned to one of four treatment arms : ( A ) two ICT cycles ( fluorouracil 800 mg/m(2)/d intravenous [ IV ] infusion , days 1 through 4 and 29 to 32 ; and cisplatin 80 mg/m(2 ) IV , on days 1 and 29 ) , RCT ( 45 Gy in 25 fractions over 5 weeks , fluorouracil and cisplatin during weeks 1 and 5 ) , and st and ard-dose boost ( SD ; 15 Gy ) ; ( B ) two ICT cycles , RCT , and high-dose boost ( HD ; 20 - 25 Gy ) ; ( C ) : RCT and SD boost ( reference arm ) ; and ( D ) RCT and HD boost . RESULTS Two hundred eighty-three of 307 patients achieved full treatment . With a median follow-up period of 50 months , the 5-year CFS rates were 69.6 % , 82.4 % , 77.1 % , and 72.7 % in arms A , B , C , and D , respectively . Considering the 2 × 2 factorial analysis , the 5-year CFS was 76.5 % versus 75.0 % ( P = .37 ) in groups A and B versus C and D , respectively ( ICT effect ) , and 73.7 % versus 77.8 % in groups A and C versus B and D , respectively ( RT-dose effect ; P = .067 ) . CONCLUSION Using CFS as our main end point , we did not find an advantage for either ICT or HD radiation boost in LAACC . Nevertheless , the results of the most treatment-intense arm B should prompt the design of further intensification studies PURPOSE On initial publication of GI Intergroup Radiation Therapy Oncology Group ( RTOG ) 98 - 11 [ A Phase III R and omized Study of 5-Fluorouracil ( 5-FU ) , Mitomycin , and Radiotherapy Versus 5-Fluorouracil , Cisplatin and Radiotherapy in Carcinoma of the Anal Canal ] , concurrent chemoradiation ( CCR ) with fluorouracil ( FU ) plus mitomycin ( MMC ) decreased colostomy failure ( CF ) when compared with induction plus concurrent FU plus cisplatin ( CDDP ) , but did not significantly impact disease-free survival ( DFS ) or overall survival ( OS ) for anal canal carcinoma . The intent of the up date d analysis was to determine the long-term impact of treatment on survival ( DFS , OS , colostomy-free survival [ CFS ] ) , CF , and relapse ( locoregional failure [ LRF ] , distant metastasis ) in this patient group . PATIENTS AND METHODS Stratification factors included sex , clinical node status , and primary size . DFS and OS were estimated univariately by the Kaplan-Meier method , and treatment arms were compared by log-rank test . Time to relapse and CF were estimated by the cumulative incidence method and treatment arms were compared by using Gray 's test . Multivariate analyses used Cox proportional hazard models to test for treatment differences after adjusting for stratification factors . RESULTS Of 682 patients accrued , 649 were analyzable for outcomes .  DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP ( 5-year DFS , 67.8 % v 57.8 % ; P = .006 ; 5-year OS , 78.3 % v 70.7 % ; P = .026 ) . There was a trend toward statistical significance for CFS ( P = .05 ) , LRF ( P = .087 ) , and CF ( P = .074 ) . Multivariate analysis was statistically significant for treatment and clinical node status for both DFS and OS , for tumor diameter for DFS , and for sex for OS . CONCLUSION CCR with FU/MMC has a statistically significant , clinical ly meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP , and it has borderline significance for CFS , CF , and LRF . Therefore , RT + FU/MMC remains the preferred st and ard of care PURPOSE Radiation Therapy Oncology Group ( RTOG ) 92 - 08 began as a single arm , Phase II trial for patients with anal cancer consisting of radiation ( RT ) + 5-flourouracil + mitomycin-C with a m and atory 2-week break and was amended after completion to evaluate the same treatment regimen without a treatment break . Long-term efficacy and late toxicity reporting are the specific aims of this study . METHODS AND MATERIAL S Survivals were estimated with the Kaplan-Meier method . Overall survival ( OS ) was compared with RTOG 87 - 04 with the log-rank test . Time to local failure , regional failure , locoregional failure ( LRF ) , distant metastases , second primary , and colostomy failure were estimated by the cumulative incidence method . LRF was compared with RTOG 87 - 04 using the Gray 's test . RESULTS Forty-seven patients entered in the m and atory treatment break cohort . The study was reopened in 1995 to the no m and atory treatment break cohort completing accrual with 20 patients in 1996 . Of 67 total patients , 1 patient in the m and atory treatment break portion of the study did not receive any protocol treatment and is excluded from analyses . After adjusting for tumor size , neither cohort showed a statistically significant difference in OS or LRF compared with the RTOG 87 - 04 mitomycin-C arm . No patient in either cohort experienced a Grade 3 or higher late toxicity . CONCLUSIONS No statistically significant differences were seen in OS or LRF when compared to the mitomycin-C arm of RTOG 87 - 04 , but the sample sizes for the m and atory break cohort and the no m and atory break cohort are small . Late toxicity was low and similar for the treatment cohorts Background : The first UKCCCR Anal Cancer Trial ( 1996 ) demonstrated the benefit of chemoradiation over radiotherapy ( RT ) alone for treating epidermoid anal cancer , and it became the st and ard treatment . Patients in this trial have now been followed up for a median of 13 years . Methods : A total of 577 patients were r and omised to receive RT alone or combined modality therapy using 5-fluorouracil and mitomycin C. All patients were scheduled to receive 45 Gy by external beam irradiation . Patients who responded to treatment were recommended to have boost RT , with either an iridium implant or external beam irradiation . Data on relapse and deaths were obtained until October 2007 . Results : Twelve years after treatment , for every 100 patients treated with chemoradiation , there are an expected 25.3 fewer patients with locoregional relapse ( 95 % confidence interval ( CI ) : 17.5–32.0 fewer ) and 12.5 fewer anal cancer deaths ( 95 % CI : 4.3–19.7 fewer ) , compared with 100 patients given RT alone . There was a 9.1 % increase in non-anal cancer deaths in the first 5 years of chemoradiation ( 95 % CI + 3.6 to + 14.6 ) , which disappeared by 10 years . Conclusions : The clear benefit of chemoradiation outweighs an early excess risk of non-anal cancer deaths , and can still be seen 12 years after treatment . Only 11 patients suffered a locoregional relapse as a first event after 5 years , which may influence the choice of end points in future studies PURPOSE The United Kingdom Coordinating Committee on Cancer Research anal cancer trial demonstrated the benefit of combined modality treatment ( CMT ) using radiotherapy ( RT ) , infusional 5-fluorouracil , and mitomycin C over RT alone . The present study retrospectively examines the impact of the recommended 6-week treatment gap and local RT boost on long-term outcome . METHODS AND MATERIAL S A total of 577 patients were r and omly assigned RT alone or CMT .  After a 6-week gap responders received a boost using either additional external beam radiotherapy ( EBRT ) ( 15 Gy ) or iridium-192 implant ( 25 Gy ) . The effect of boost , the gap between initial treatment ( RT alone or CMT ) and boost ( Tgap ) , and overall treatment time ( OTT ) were examined for their impact on outcome . RESULTS Among the 490 good responders , 436 ( 89 % ) patients received a boost after initial treatment . For boosted patients , the risk of anal cancer death decreased by 38 % ( hazard ratio [ HR ] : 0.62 , 99 % CI 0.35 - 1.12 ; p=0.04 ) , but there was no evidence this was mediated via a reduction in locoregional failure ( LRF ) ( HR : 0.90 , 99 % CI 0.48 - 1.68 ; p=0.66 ) . The difference in Tgap was only 1.4 days longer for EBRT boost , compared with implant ( p=0.51 ) . OTT was longer by 6.1 days for EBRT ( p=0.006 ) . Tgap and OTT were not associated with LRF . Radionecrosis was reported in 8 % of boosted , compared with 0 % in unboosted patients ( p=0.03 ) . CONCLUSIONS These results question the benefit of a radiotherapy boost after a 6-week gap . The higher doses of a boost may contribute more to an increased risk of late morbidity , rather than local control Squamous cell carcinoma of the anus ( SCCA ) is a rare cancer but its incidence is increasing throughout the world , and is particularly high in the human immunodeficiency virus positive ( HIV+ ) population . A multidisciplinary approach is m and atory ( involving radiation therapists , medical oncologists , surgeons , radiologists and pathologists ) . SCCA usually spreads in a loco-regional manner within and outside the anal canal . Lymph node involvement at diagnosis is observed in 30 - 40 % of cases while systemic spread is uncommon with distant extrapelvic metastases recorded in 5 - 8 % at onset , and rates of metastatic progression after primary treatment between 10 % and 20 % . SCCA is strongly associated with human papilloma virus ( HPV , types 16 - 18 ) infection . The primary aim of treatment is to achieve cure with loco-regional control 
    Output:
    