human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE This is a prospect i ve , Phase III multicenter r and omized trial to assess the effectiveness of concurrent intravenous mitomycin C , oral 5-fluorouracil ( 5-FU ) , and radiotherapy ( RT ) in locally advanced carcinoma of the cervix . METHODS AND MATERIAL S Between January 1988 and November 1994 , 926 patients with locally advanced carcinoma of the cervix , FIGO Stage IIB-IVA , were entered into this study . The patients were r and omized into four arms , as follows : Arm 1 : conventional RT ; Arm 2 : conventional RT and adjuvant chemotherapy ; Arm 3 : conventional RT plus concurrent chemotherapy ; Arm 4 : conventional RT plus concurrent chemotherapy and adjuvant chemotherapy . Concurrent chemotherapy consisting of intravenous mitomycin C at 10 mg/m(2 ) was given on Days 1 and 29 , and oral 5-FU at 300 mg/day was administered on Days 1 - 14 and 29 - 42 during RT . Adjuvant chemotherapy of 5-FU orally at 200 mg/day was given for three courses of 4 weeks , with a 2-week rest every 6 weeks . Six centers participated in the trial . RESULTS The median follow-up time was 89 months . Acute side effects were generally higher in concurrent arms , but most of the patients tolerated the treatment well . Bone marrow toxicity was also higher in concurrent arms . The 5-year actuarial disease-free survival ( DFS ) was 48.2 % , 54.1 % , 64.5 % , and 59.7 % for arms 1 , 2 , 3 , and 4 , respectively . The pattern of failure revealed a significant increase in locoregional recurrence in the nonconcurrent chemoradiotherapy arm . The local recurrence was 25.5 % , 20.6 % , 14.3 % , and 17.6 % for arms 1 , 2 , 3 , and 4 , respectively . The metastatic rates were not significantly different in all four arms . At the time of analysis , there were no increases in late side effects , especially in gastrointestinal and genitourinary systems . CONCLUSIONS Concurrent chemotherapy , mitomycin C , and 5-FU together with conventional RT showed an improved DFS rate when compared with conventional RT alone in patients with locally advanced carcinoma of the cervix Background : We investigated the feasibility of dose-dense neoadjuvant chemotherapy ( NACT ) with paclitaxel and carboplatin before radical chemoradiation ( CRT ) and assessed the response rate to such a regimen . Methods : CxII is a single-arm phase II trial of 46 patients , with locally advanced cervical cancer ( stage Ib2-IVa ) . Patients received dose-dense carboplatin ( AUC2 ) and paclitaxel ( 80 mg m−2 ) weekly for six cycles followed by CRT ( 40 mg m−2 of weekly cisplatin , 50.4 Gy , 28 fractions plus brachytherapy ) . The primary end point was response rate 12 weeks post-CRT . Results : Baseline characteristics were : median age at diagnosis 43 years ; 72 % squamous , 22 % adenocarcinoma and 7 % adenosquamous histologies ; FIGO stage IB2 ( 11 % ) , II ( 50 % ) , III ( 33 % ) , IV ( 7 % ) . Complete or partial response rate was 70 % ( 95 % CI : 54–82 ) post-NACT and 85 % ( 95 % CI : 71–94 ) post-CRT . The median follow-up was 39.1 months . Overall and progression-free survivals at 3 years were 67 % ( 95 % CI : 51–79 ) and 68 % ( 95 % CI : 51–79 ) , respectively . Grade 3/4 toxicities were 20 % during NACT ( 11 % haematological , 9 % non-haematological ) and 52 % during CRT ( haematological : 41 % , non-haematological : 22 % ) . Conclusion : A good response rate is achieved by dose-dense weekly NACT with carboplatin and paclitaxel followed by radical CRT . This treatment regimen is feasible as evidence d by the acceptable toxicity of NACT and by the high compliance to radiotherapy ( 98 % ) PURPOSE Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation ( CCRT ) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma . METHODS AND MATERIAL S Patients with cervical carcinoma ( FIGO stage IB2-IVA ) were treated with external beam radiation therapy to the whole pelvis ( 50.4 Gy ) and high-dose-rate brachytherapy ( 24 Gy to point A ) . Cisplatin 60 mg/m(2 ) ( Day 1 ) and 5-fluorouracil 1000 mg/m(2 ) ( Days 1 - 5 ) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles . RESULTS Thirty patients ( 94 % ) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation . The most common toxicities of Grade 2 or higher were nausea or vomiting ( 47 % ) and anemia ( 33 % ) . Late complications of the rectum and bladder occurred in 13 % and 6 % of the patients , respectively . The clinical complete response rate was 87 % ( 95 % CI , 75%-99 % ) . During a median follow-up of 27 months ( range , 6 - 58 months ) , 5 patients ( 17 % ) had recurrence ; the sites of failure were 3 ( 10 % ) inside the radiation field and 2 ( 7 % ) outside the radiation field . The estimated 3-year progression-free survival rate was 83 % ( 95 % CI , 67%-99 % ) and overall survival rate was 91 % ( 95 % CI , 79%-100 % ) . CONCLUSIONS Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma . A prospect i ve r and omized trial to compare this treatment strategy with st and ard CCRT seems to be worthwhile BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies PURPOSE To report mature results of a r and omized trial that compared extended-field radiotherapy ( EFRT ) versus pelvic radiotherapy with concomitant fluorouracil and cisplatin ( CTRT ) in women with locoregionally advanced carcinomas of the uterine cervix . PATIENTS AND METHODS Four hundred three women with cervical cancer were r and omly assigned to receive either EFRT or CTRT .  Patients were eligible if they had stage IIB to IVA disease , stage IB to IIA disease with a tumor diameter > or = 5 cm , or positive pelvic lymph nodes . Patients were stratified by stage and by method of lymph node evaluation . RESULTS The median follow-up time for 228 surviving patients was 6.6 years . The overall survival rate for patients treated with CTRT was significantly greater than that for patients treated with EFRT ( 67 % v 41 % at 8 years ; P < .0001 ) . There was an overall reduction in the risk of disease recurrence of 51 % ( 95 % CI , 36 % to 66 % ) for patients who received CTRT . Patients with stage IB to IIB disease who received CTRT had better overall and disease-free survival than those treated with EFRT ( P < .0001 ) ; 116 patients with stage III to IVA disease had better disease-free survival ( P = .05 ) and a trend toward better overall survival ( P = .07 ) if they were r and omly assigned to CTRT . The rate of serious late complications of treatment was similar for the two treatment arms . CONCLUSION Mature analysis confirms that the addition of fluorouracil and cisplatin to radiotherapy significantly improved the survival rate of women with locally advanced cervical cancer without increasing the rate of late treatment-related side effects OBJECTIVES To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose rate brachyradiotherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell carcinoma ( LASCC ) or adeno/adenosquamous carcinoma of the uterine cervix . METHODS Sixty-two patients with primary uterine cervical cancer were enrolled between August 1999 and November 2004 . The patients had to have FIGO-stage IB2 bulky to IVA disease , biopsy-proven squamous cell or adeno/adenosquamous carcinoma of the uterine cervix . The patients were to receive external radiotherapy ( 50 Gy in 25 fractions ) ; ifosfamide 2 g/m2 plus cisplatin 75 mg/m2 was applied concomitantly during two low-dose rate brachyradiotherapy applications ; the planned dose to point A was 85 Gy in total . After the completion of radiotherapy , i.e. external and concomitant chemobrachyradiotherapy , four cycles of consolidation chemotherapy with the same drug combination were to be administered . RESULTS The clinical complete response rate according to WHO-classification ( assessed after the completion of the whole treatment procedures by gynecologic and radiologic evaluation and cervical biopsy ) was 100 % . After a median follow-up of 49 months ( range 11 - 74 months ) , the recurrence-free and overall survival rates were 88.7 % , respectively . The most frequent early toxicities were grade 3 and 4 leukopenias occurring in 25 % and 11 % of the cycles , respectively . Major delayed local complications occurred in 10 patients ( 16.1 % ) . CONCLUSION These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy with the same drug combination is a highly efficacious and very promising treatment protocol for patients with locally advanced LASCC or adeno/adenosquamous carcinoma of the uterine cervix BACKGROUND AND OBJECTIVE Concurrent chemoradiotherapy for cervical carcinoma develops rapidly and has become a common and st and ard therapy in recent years . Both the local control rate and survival rate of patients were increased and the risk of death fell by 30%-50 % . This study aim ed to explore the efficacy of concurrent chemoradiotherapy plus adjuvant chemotherapy on and the treatment compliance of the patients with advanced cervical squamous cell carcinoma . MET 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE This is a prospect i ve , Phase III multicenter r and omized trial to assess the effectiveness of concurrent intravenous mitomycin C , oral 5-fluorouracil ( 5-FU ) , and radiotherapy ( RT ) in locally advanced carcinoma of the cervix . METHODS AND MATERIAL S Between January 1988 and November 1994 , 926 patients with locally advanced carcinoma of the cervix , FIGO Stage IIB-IVA , were entered into this study . The patients were r and omized into four arms , as follows : Arm 1 : conventional RT ; Arm 2 : conventional RT and adjuvant chemotherapy ; Arm 3 : conventional RT plus concurrent chemotherapy ; Arm 4 : conventional RT plus concurrent chemotherapy and adjuvant chemotherapy . Concurrent chemotherapy consisting of intravenous mitomycin C at 10 mg/m(2 ) was given on Days 1 and 29 , and oral 5-FU at 300 mg/day was administered on Days 1 - 14 and 29 - 42 during RT . Adjuvant chemotherapy of 5-FU orally at 200 mg/day was given for three courses of 4 weeks , with a 2-week rest every 6 weeks . Six centers participated in the trial . RESULTS The median follow-up time was 89 months . Acute side effects were generally higher in concurrent arms , but most of the patients tolerated the treatment well . Bone marrow toxicity was also higher in concurrent arms . The 5-year actuarial disease-free survival ( DFS ) was 48.2 % , 54.1 % , 64.5 % , and 59.7 % for arms 1 , 2 , 3 , and 4 , respectively . The pattern of failure revealed a significant increase in locoregional recurrence in the nonconcurrent chemoradiotherapy arm . The local recurrence was 25.5 % , 20.6 % , 14.3 % , and 17.6 % for arms 1 , 2 , 3 , and 4 , respectively . The metastatic rates were not significantly different in all four arms . At the time of analysis , there were no increases in late side effects , especially in gastrointestinal and genitourinary systems . CONCLUSIONS Concurrent chemotherapy , mitomycin C , and 5-FU together with conventional RT showed an improved DFS rate when compared with conventional RT alone in patients with locally advanced carcinoma of the cervix Background : We investigated the feasibility of dose-dense neoadjuvant chemotherapy ( NACT ) with paclitaxel and carboplatin before radical chemoradiation ( CRT ) and assessed the response rate to such a regimen . Methods : CxII is a single-arm phase II trial of 46 patients , with locally advanced cervical cancer ( stage Ib2-IVa ) . Patients received dose-dense carboplatin ( AUC2 ) and paclitaxel ( 80 mg m−2 ) weekly for six cycles followed by CRT ( 40 mg m−2 of weekly cisplatin , 50.4 Gy , 28 fractions plus brachytherapy ) . The primary end point was response rate 12 weeks post-CRT . Results : Baseline characteristics were : median age at diagnosis 43 years ; 72 % squamous , 22 % adenocarcinoma and 7 % adenosquamous histologies ; FIGO stage IB2 ( 11 % ) , II ( 50 % ) , III ( 33 % ) , IV ( 7 % ) . Complete or partial response rate was 70 % ( 95 % CI : 54–82 ) post-NACT and 85 % ( 95 % CI : 71–94 ) post-CRT . The median follow-up was 39.1 months . Overall and progression-free survivals at 3 years were 67 % ( 95 % CI : 51–79 ) and 68 % ( 95 % CI : 51–79 ) , respectively . Grade 3/4 toxicities were 20 % during NACT ( 11 % haematological , 9 % non-haematological ) and 52 % during CRT ( haematological : 41 % , non-haematological : 22 % ) . Conclusion : A good response rate is achieved by dose-dense weekly NACT with carboplatin and paclitaxel followed by radical CRT . This treatment regimen is feasible as evidence d by the acceptable toxicity of NACT and by the high compliance to radiotherapy ( 98 % ) PURPOSE Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation ( CCRT ) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma . METHODS AND MATERIAL S Patients with cervical carcinoma ( FIGO stage IB2-IVA ) were treated with external beam radiation therapy to the whole pelvis ( 50.4 Gy ) and high-dose-rate brachytherapy ( 24 Gy to point A ) . Cisplatin 60 mg/m(2 ) ( Day 1 ) and 5-fluorouracil 1000 mg/m(2 ) ( Days 1 - 5 ) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles . RESULTS Thirty patients ( 94 % ) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation . The most common toxicities of Grade 2 or higher were nausea or vomiting ( 47 % ) and anemia ( 33 % ) . Late complications of the rectum and bladder occurred in 13 % and 6 % of the patients , respectively . The clinical complete response rate was 87 % ( 95 % CI , 75%-99 % ) . During a median follow-up of 27 months ( range , 6 - 58 months ) , 5 patients ( 17 % ) had recurrence ; the sites of failure were 3 ( 10 % ) inside the radiation field and 2 ( 7 % ) outside the radiation field . The estimated 3-year progression-free survival rate was 83 % ( 95 % CI , 67%-99 % ) and overall survival rate was 91 % ( 95 % CI , 79%-100 % ) . CONCLUSIONS Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma . A prospect i ve r and omized trial to compare this treatment strategy with st and ard CCRT seems to be worthwhile BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies PURPOSE To report mature results of a r and omized trial that compared extended-field radiotherapy ( EFRT ) versus pelvic radiotherapy with concomitant fluorouracil and cisplatin ( CTRT ) in women with locoregionally advanced carcinomas of the uterine cervix . PATIENTS AND METHODS Four hundred three women with cervical cancer were r and omly assigned to receive either EFRT or CTRT .  Patients were eligible if they had stage IIB to IVA disease , stage IB to IIA disease with a tumor diameter > or = 5 cm , or positive pelvic lymph nodes . Patients were stratified by stage and by method of lymph node evaluation . RESULTS The median follow-up time for 228 surviving patients was 6.6 years . The overall survival rate for patients treated with CTRT was significantly greater than that for patients treated with EFRT ( 67 % v 41 % at 8 years ; P < .0001 ) . There was an overall reduction in the risk of disease recurrence of 51 % ( 95 % CI , 36 % to 66 % ) for patients who received CTRT . Patients with stage IB to IIB disease who received CTRT had better overall and disease-free survival than those treated with EFRT ( P < .0001 ) ; 116 patients with stage III to IVA disease had better disease-free survival ( P = .05 ) and a trend toward better overall survival ( P = .07 ) if they were r and omly assigned to CTRT . The rate of serious late complications of treatment was similar for the two treatment arms . CONCLUSION Mature analysis confirms that the addition of fluorouracil and cisplatin to radiotherapy significantly improved the survival rate of women with locally advanced cervical cancer without increasing the rate of late treatment-related side effects OBJECTIVES To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose rate brachyradiotherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell carcinoma ( LASCC ) or adeno/adenosquamous carcinoma of the uterine cervix . METHODS Sixty-two patients with primary uterine cervical cancer were enrolled between August 1999 and November 2004 . The patients had to have FIGO-stage IB2 bulky to IVA disease , biopsy-proven squamous cell or adeno/adenosquamous carcinoma of the uterine cervix . The patients were to receive external radiotherapy ( 50 Gy in 25 fractions ) ; ifosfamide 2 g/m2 plus cisplatin 75 mg/m2 was applied concomitantly during two low-dose rate brachyradiotherapy applications ; the planned dose to point A was 85 Gy in total . After the completion of radiotherapy , i.e. external and concomitant chemobrachyradiotherapy , four cycles of consolidation chemotherapy with the same drug combination were to be administered . RESULTS The clinical complete response rate according to WHO-classification ( assessed after the completion of the whole treatment procedures by gynecologic and radiologic evaluation and cervical biopsy ) was 100 % . After a median follow-up of 49 months ( range 11 - 74 months ) , the recurrence-free and overall survival rates were 88.7 % , respectively . The most frequent early toxicities were grade 3 and 4 leukopenias occurring in 25 % and 11 % of the cycles , respectively . Major delayed local complications occurred in 10 patients ( 16.1 % ) . CONCLUSION These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy with the same drug combination is a highly efficacious and very promising treatment protocol for patients with locally advanced LASCC or adeno/adenosquamous carcinoma of the uterine cervix BACKGROUND AND OBJECTIVE Concurrent chemoradiotherapy for cervical carcinoma develops rapidly and has become a common and st and ard therapy in recent years . Both the local control rate and survival rate of patients were increased and the risk of death fell by 30%-50 % . This study aim ed to explore the efficacy of concurrent chemoradiotherapy plus adjuvant chemotherapy on and the treatment compliance of the patients with advanced cervical squamous cell carcinoma . MET 
    Output:
    