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: OBJECTIVES Identification of the most influential scientific publications and directions of mainstream reirradiation research . METHODS A systematic search of the data base Scopus ( Elsevier B.V. , www . scopus .com ) was performed , which focused on the time period 1998 - 2010 . Patterns of citation were analysed ( total number of citations accumulated independently of their origin and proportion of highly cited articles , arbitrarily defined as those with ≥50 citations ) . RESULTS Up to 64 articles were published each year . Numbers increased over time , especially after the year 2007 . Among all 76 articles with at least 50 citations , 28 ( 37 % ) focused on head and neck cancer , 27 ( 36 % ) on brain tumours including metastases , and 5 ( 7 % ) on bone metastases . Most articles evaluated external beam approaches while 10 ( 13 % ) focused on brachytherapy . Many of the often quoted publications reported on  stereotactic and /or intensity-modulated radiotherapy  . Two ( 3 % ) reported on r and omised clinical studies and 10 ( 13 % ) on non-r and omised prospect i ve clinical studies ( single institution or cooperative group ) . Only two articles ( 3 % ) reported on experimental animal studies . CONCLUSIONS The number of published reirradiation studies has increased in recent years . Many studies examined highly conformal and precise radiotherapy , in particular of brain and head and neck tumours . Given that few r and omised clinical trials were published , efforts to increase this type of research activity are warranted PURPOSE The combination of irradiation and total mesorectal excision for rectal carcinoma has significantly lowered the incidence of local recurrence . However , a new problem is represented by the patient with locally recurrent cancer who has received previous irradiation to the pelvis . In these patients , local recurrence is very often not easily resectable and reirradiation is expected to be associated with a high risk of late toxicity . The aim of this multicenter phase II study is to evaluate the response rate , resectability rate , local control , and treatment-related toxicity of preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis . METHODS AND MATERIAL S Patients with histologically proven pelvic recurrence of rectal carcinoma , with the absence of extrapelvic disease or bony involvement and previous pelvic irradiation with doses < or = 55 Gy ; age > or = 18 years ; performance status ( PS ) ( Karnofsky ) > or = 60 , and who gave institutional review board-approved written informed consent were treated by preoperative chemoradiation . Radiotherapy was delivered to a planning target volume ( PTV2 ) including the gross tumor volume ( GTV ) plus a 4-cm margin , with a dose of 30 Gy ( 1.2 Gy twice daily with a minimum 6-h interval ) . A boost was delivered , with the same fractionation schedule , to a PTV1 including the GTV plus a 2-cm margin ( 10.8 Gy ) . During the radiation treatment , concurrent chemotherapy was delivered ( 5-fluorouracil , protracted intravenous infusion , 225 mg/m(2)/day , 7 days per week ) . Four to 6 weeks after the end of chemoradiation , patients were evaluated for tumor resectability , and , when feasible , surgical resection of recurrence was performed between 6 - 8 weeks from the end of chemoradiation . Adjuvant chemotherapy was prescribed to all patients , using Raltitrexed , 3 mg/square meter ( sm ) , every 3 weeks , for a total of 5 cycles . Patients were staged using the computed tomography (CT)-based F-classification ( F0 : no side-wall involvement ; F1 , F2 , F3 : 1 , 2 , and 3 - 4 side-walls involved , respectively ) . Toxicity was evaluated on the basis of the Radiation Therapy Oncology Group ( RTOG ) criteria . RESULTS Fifty-nine patients ( 38 male , 21 female ; median age , 62 years ; range , 43 - 77 years ) were enrolled in the study , by 12 different Italian radiotherapy departments . Previous surgery was anterior resection in 45 patients ( 76.3 % ) and abdominal-perineal resection in 14 patients ( 23.7 % ) ; previous radiotherapy dosage ranged between 30 and 55 Gy ( median , 50.4 Gy ) ; the median interval between prior radiation therapy to the onset of reirradiation was 27 months ( range , 9 - 106 months ) ; 44 patients ( 74.6 % ) had received some form of previous chemotherapy ( concurrent and /or adjuvant ) . Fifty-one of 59 patients ( 86.4 % ) completed chemoradiation without treatment interruptions : 6 patients ( 10.2 % ) had temporary treatment interruption due to toxicity or patient compliance , and 2 patients ( 3.4 % ) had definitive treatment interruption . The incidence of Grade 3 lower gastrointestinal acute toxicity was only 5.1 % . No patient developed Grade 4 acute toxicity . After chemoradiation , 5 patients ( 8.5 % ) had complete response ( CR ) , 21 patients ( 35.6 % ) had partial response ( PR ) , 31 patients ( 52.6 % ) had no change ( NC ) and 2 patients ( 3.4 % ) showed progressive disease ( PD ) . Overall , the response rate ( PR + CR ) was 44.1 % ( 95 % confidence interval , 29.0 - 58.9 % ) . Twenty of 24 patients ( 83.3 % ) with pelvic pain before treatment had symptomatic response .  Tumor resection was performed in 30 of 59 patients ( 50.8 % ) including 2 local excisions , 4 anterior resections , 18 abdominoperineal resections , and 6 other . Surgical resection result ed as R0 and R1 in 21 patients ( 35.6 % ) and 3 patients ( 5.1 % ) , respectively . The possibility of radical resection was influenced by tumor response to chemoradiation ( PD/NC : 7/33 ; PR/CR : 14/26 ; p = 0.009 ) . Thirty-three patients received adjuvant chemotherapy , which was completed in 30 ( 50.8 % ) . At a median follow-up of 36 months ( range , 9 - 69 months ) , 28 patients ( 47.5 % ) developed local recurrence or tumor progression in the unresected pelvic disease and 18 patients ( 30.5 % ) developed distant metastasis . Seven patients showed late toxicity , including 2 skin fibrosis , 2 impotence , 2 urinary complications requiring nephrostomy , and 1 small bowel fistula requiring surgical diversion . Overall median survival was 42 months . Five-year actuarial survival was 39.3 % ; 66.8 % in R0 resected patients and 22.3 % in patients treated without surgery or undergoing subtotal tumor removal . Local control and disease-free survival were significantly correlated with the interval between surgical treatment for primary tumor and local recurrence ( p = 0.028 and p = 0.003 , respectively ) . Radical resection significantly influenced local control , disease-free survival , and overall survival ( p = 0.010 , p = 0.010 , and p = 0.050 respectively ) . The multivariate analysis confirmed the impact of surgery-relapse interval on local control ( p = 0.016 ) and disease-free survival ( p = 0.002 ) , and confirmed the correlation between R0 surgery with local control and disease-free survival ( p = 0.016 ) . CONCLUSIONS Use of hyperfractionated chemoradiation was associated with a low rate of acute toxicity and an acceptable incidence of late complications . Pain control was excellent . The overall 5-year survival was 39 % . Despite 87.4 % of patients having F1 - 3 stage disease , approximately one-third ( 35 % ) achieved R0 resection , and two-thirds of patients in this cohort of patients were alive at the 5-year mark . However , further studies using innovative treatment algorithms are warranted to , hopefully , improve the local tumor response and control PURPOSE This study was design ed to identify preoperative and intraoperative features of locally recurrent colorectal cancer that predict R0 resection in patients scheduled for attempted complete resection followed by intraoperative radiation therapy .  METHODS Review of a prospect i ve data base identified 119 patients brought to the intraoperative radiation therapy suite for planned complete resection of locally recurrent rectal ( n = 101 ) and colon ( n = 18 ) cancer between January 1994 and November 2000 . R0 resection was achieved in 61 patients . This group was compared with patients in which an R1 ( n = 38 ) , R2 ( n = 7 ) , or palliative procedure ( n = 13 ) was performed . Variables evaluated included : tumor location , features of the primary tumor , and preoperative findings on computed tomography , magnetic resonance imaging , and history/physical . Tumor location was established by review of operative/pathologic reports and classified as axial ( anastomotic/perineal ) , anterior ( bladder/genitourinary organs ) , posterior ( presacral ) , or lateral ( pelvic sidewall ) . RESULTS When recurrence was confined to the axial location only , or axial and anterior locations , R0 resection was achieved significantly more often than when other locations were involved ( P < 0.001 , P = 0.003 , respectively ) . When a lateral component was present , R0 resection was achieved significantly less often than when there was no lateral component ( P = 0.002 ) . For patients with available preoperative computed tomography and /or magnetic resonance imaging results ( n = 70 ) , the finding of lateral tumor involvement was associated with R0 resection significantly less often than when lateral disease was not identified ( P = 0.004 ) . CONCLUSIONS Pelvic recurrences confined to the axial location , or axial and anterior locations , are more likely to be completely resectable ( R0 ) than those involving the pelvic sidewall . Efforts to enhance preoperative identification and imaging of these patients are clearly justified PURPOSE Local recurrence of rectal cancer following high-dose pelvic radiation presents a difficult management challenge . Conventional wisdom suggests that reirradiation should be avoided and radical pelvic surgery is hazardous after ultra high-dose radiation . METHODS AND MATERIAL S In a unique Phase I/II pilot study , 32 patients with recurrent rectal cancers following previous pelvic radiation underwent planned reirradiation to the pelvis .  Initial radiation doses had ranged from 30 - 64.87 Gy ( median dose 45 Gy ) . Seventeen patients underwent reirradiation followed by radical resection . Fifteen patients were reirradiated for palliative relief of symptoms . Treatment techniques consisted of two lateral fields ( 7 x 7 to 12 x 10 cm ) encompassing the tumor with 2 cm margins . Reirradiation doses ranged from 19.80 - 47.66 Gy , ( median 34.2 Gy ) . Patients also received concurrent low-dose continuous infusion chemotherapy , ( 5-FU 200 - 300 mg/day ) . Total cumulative radiation doses ranged from 70.6 to 111.6 Gy . RESULTS Treatment was well tolerated . Four patients had radiation interrupted/discontinued for diarrhea or leukopenia . Follow-up ranges from 6 months to 36 months . No late sequelae of radiation have been observed to date . Seventeen patients underwent surgical exploration 6 - 8 weeks following reirradiation . Two patients had extensive disease and were not resected . Fifteen patients underwent radical resection of residual tumor ( 4 posterior exenterations , 6 APR , 3 transanal abdominal transanal proctocolectomy with coloanal anastomosis ( TAATA ) , and 2 LAR ) . No patients died postoperatively . No excessive edema , hemorrhage , or adhesions were observed . Two patients developed pelvic abscess and one developed a coloanal stricture . Eleven of 15 resected patients are alive from 6 to 36 months with a 2-year survival of 66 % . Of the patients treated palliatively , symptomatic relief was observed in 13/15 patients . No objective complete response was observed , but 6/15 patients had measurable partial response . Median survival in this group was 14 months . CONCLUSION Based on this experience , we believe that in selected patients radical surgical resection after cumulative ultra high doses ( 70 - 90 Gy ) of radiation can be performed safely . A viable anastomosis is also possible in spite of these high doses . Planned reirradiation for palliative relief of symptoms can be effective without unusual risks of complication . Long-term effects of such ultra high dose radiation and surgery continue to be monitored AIMS When locally advanced or recurrent rectal cancer involves the bladder or prostate , curative treatment often requires pelvic exenteration . The aim was to assess the quality of life ( QoL ) in disease-free patients with urinary diversion after extensive surgery for advanced rectal cancer . METHODS Twelve patients with urinary diversion ( cases ) were compared with 25 r and omly selected patients given the same treatment , but without urinary diversion ( controls ) .  An age- and gender-adjusted general population was identified ( reference ) . QoL was assessed with the EORTC question naires QLQ-C30 , QLQ-CR38 , and parts  of the 
    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: OBJECTIVES Identification of the most influential scientific publications and directions of mainstream reirradiation research . METHODS A systematic search of the data base Scopus ( Elsevier B.V. , www . scopus .com ) was performed , which focused on the time period 1998 - 2010 . Patterns of citation were analysed ( total number of citations accumulated independently of their origin and proportion of highly cited articles , arbitrarily defined as those with ≥50 citations ) . RESULTS Up to 64 articles were published each year . Numbers increased over time , especially after the year 2007 . Among all 76 articles with at least 50 citations , 28 ( 37 % ) focused on head and neck cancer , 27 ( 36 % ) on brain tumours including metastases , and 5 ( 7 % ) on bone metastases . Most articles evaluated external beam approaches while 10 ( 13 % ) focused on brachytherapy . Many of the often quoted publications reported on  stereotactic and /or intensity-modulated radiotherapy  . Two ( 3 % ) reported on r and omised clinical studies and 10 ( 13 % ) on non-r and omised prospect i ve clinical studies ( single institution or cooperative group ) . Only two articles ( 3 % ) reported on experimental animal studies . CONCLUSIONS The number of published reirradiation studies has increased in recent years . Many studies examined highly conformal and precise radiotherapy , in particular of brain and head and neck tumours . Given that few r and omised clinical trials were published , efforts to increase this type of research activity are warranted PURPOSE The combination of irradiation and total mesorectal excision for rectal carcinoma has significantly lowered the incidence of local recurrence . However , a new problem is represented by the patient with locally recurrent cancer who has received previous irradiation to the pelvis . In these patients , local recurrence is very often not easily resectable and reirradiation is expected to be associated with a high risk of late toxicity . The aim of this multicenter phase II study is to evaluate the response rate , resectability rate , local control , and treatment-related toxicity of preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis . METHODS AND MATERIAL S Patients with histologically proven pelvic recurrence of rectal carcinoma , with the absence of extrapelvic disease or bony involvement and previous pelvic irradiation with doses < or = 55 Gy ; age > or = 18 years ; performance status ( PS ) ( Karnofsky ) > or = 60 , and who gave institutional review board-approved written informed consent were treated by preoperative chemoradiation . Radiotherapy was delivered to a planning target volume ( PTV2 ) including the gross tumor volume ( GTV ) plus a 4-cm margin , with a dose of 30 Gy ( 1.2 Gy twice daily with a minimum 6-h interval ) . A boost was delivered , with the same fractionation schedule , to a PTV1 including the GTV plus a 2-cm margin ( 10.8 Gy ) . During the radiation treatment , concurrent chemotherapy was delivered ( 5-fluorouracil , protracted intravenous infusion , 225 mg/m(2)/day , 7 days per week ) . Four to 6 weeks after the end of chemoradiation , patients were evaluated for tumor resectability , and , when feasible , surgical resection of recurrence was performed between 6 - 8 weeks from the end of chemoradiation . Adjuvant chemotherapy was prescribed to all patients , using Raltitrexed , 3 mg/square meter ( sm ) , every 3 weeks , for a total of 5 cycles . Patients were staged using the computed tomography (CT)-based F-classification ( F0 : no side-wall involvement ; F1 , F2 , F3 : 1 , 2 , and 3 - 4 side-walls involved , respectively ) . Toxicity was evaluated on the basis of the Radiation Therapy Oncology Group ( RTOG ) criteria . RESULTS Fifty-nine patients ( 38 male , 21 female ; median age , 62 years ; range , 43 - 77 years ) were enrolled in the study , by 12 different Italian radiotherapy departments . Previous surgery was anterior resection in 45 patients ( 76.3 % ) and abdominal-perineal resection in 14 patients ( 23.7 % ) ; previous radiotherapy dosage ranged between 30 and 55 Gy ( median , 50.4 Gy ) ; the median interval between prior radiation therapy to the onset of reirradiation was 27 months ( range , 9 - 106 months ) ; 44 patients ( 74.6 % ) had received some form of previous chemotherapy ( concurrent and /or adjuvant ) . Fifty-one of 59 patients ( 86.4 % ) completed chemoradiation without treatment interruptions : 6 patients ( 10.2 % ) had temporary treatment interruption due to toxicity or patient compliance , and 2 patients ( 3.4 % ) had definitive treatment interruption . The incidence of Grade 3 lower gastrointestinal acute toxicity was only 5.1 % . No patient developed Grade 4 acute toxicity . After chemoradiation , 5 patients ( 8.5 % ) had complete response ( CR ) , 21 patients ( 35.6 % ) had partial response ( PR ) , 31 patients ( 52.6 % ) had no change ( NC ) and 2 patients ( 3.4 % ) showed progressive disease ( PD ) . Overall , the response rate ( PR + CR ) was 44.1 % ( 95 % confidence interval , 29.0 - 58.9 % ) . Twenty of 24 patients ( 83.3 % ) with pelvic pain before treatment had symptomatic response .  Tumor resection was performed in 30 of 59 patients ( 50.8 % ) including 2 local excisions , 4 anterior resections , 18 abdominoperineal resections , and 6 other . Surgical resection result ed as R0 and R1 in 21 patients ( 35.6 % ) and 3 patients ( 5.1 % ) , respectively . The possibility of radical resection was influenced by tumor response to chemoradiation ( PD/NC : 7/33 ; PR/CR : 14/26 ; p = 0.009 ) . Thirty-three patients received adjuvant chemotherapy , which was completed in 30 ( 50.8 % ) . At a median follow-up of 36 months ( range , 9 - 69 months ) , 28 patients ( 47.5 % ) developed local recurrence or tumor progression in the unresected pelvic disease and 18 patients ( 30.5 % ) developed distant metastasis . Seven patients showed late toxicity , including 2 skin fibrosis , 2 impotence , 2 urinary complications requiring nephrostomy , and 1 small bowel fistula requiring surgical diversion . Overall median survival was 42 months . Five-year actuarial survival was 39.3 % ; 66.8 % in R0 resected patients and 22.3 % in patients treated without surgery or undergoing subtotal tumor removal . Local control and disease-free survival were significantly correlated with the interval between surgical treatment for primary tumor and local recurrence ( p = 0.028 and p = 0.003 , respectively ) . Radical resection significantly influenced local control , disease-free survival , and overall survival ( p = 0.010 , p = 0.010 , and p = 0.050 respectively ) . The multivariate analysis confirmed the impact of surgery-relapse interval on local control ( p = 0.016 ) and disease-free survival ( p = 0.002 ) , and confirmed the correlation between R0 surgery with local control and disease-free survival ( p = 0.016 ) . CONCLUSIONS Use of hyperfractionated chemoradiation was associated with a low rate of acute toxicity and an acceptable incidence of late complications . Pain control was excellent . The overall 5-year survival was 39 % . Despite 87.4 % of patients having F1 - 3 stage disease , approximately one-third ( 35 % ) achieved R0 resection , and two-thirds of patients in this cohort of patients were alive at the 5-year mark . However , further studies using innovative treatment algorithms are warranted to , hopefully , improve the local tumor response and control PURPOSE This study was design ed to identify preoperative and intraoperative features of locally recurrent colorectal cancer that predict R0 resection in patients scheduled for attempted complete resection followed by intraoperative radiation therapy .  METHODS Review of a prospect i ve data base identified 119 patients brought to the intraoperative radiation therapy suite for planned complete resection of locally recurrent rectal ( n = 101 ) and colon ( n = 18 ) cancer between January 1994 and November 2000 . R0 resection was achieved in 61 patients . This group was compared with patients in which an R1 ( n = 38 ) , R2 ( n = 7 ) , or palliative procedure ( n = 13 ) was performed . Variables evaluated included : tumor location , features of the primary tumor , and preoperative findings on computed tomography , magnetic resonance imaging , and history/physical . Tumor location was established by review of operative/pathologic reports and classified as axial ( anastomotic/perineal ) , anterior ( bladder/genitourinary organs ) , posterior ( presacral ) , or lateral ( pelvic sidewall ) . RESULTS When recurrence was confined to the axial location only , or axial and anterior locations , R0 resection was achieved significantly more often than when other locations were involved ( P < 0.001 , P = 0.003 , respectively ) . When a lateral component was present , R0 resection was achieved significantly less often than when there was no lateral component ( P = 0.002 ) . For patients with available preoperative computed tomography and /or magnetic resonance imaging results ( n = 70 ) , the finding of lateral tumor involvement was associated with R0 resection significantly less often than when lateral disease was not identified ( P = 0.004 ) . CONCLUSIONS Pelvic recurrences confined to the axial location , or axial and anterior locations , are more likely to be completely resectable ( R0 ) than those involving the pelvic sidewall . Efforts to enhance preoperative identification and imaging of these patients are clearly justified PURPOSE Local recurrence of rectal cancer following high-dose pelvic radiation presents a difficult management challenge . Conventional wisdom suggests that reirradiation should be avoided and radical pelvic surgery is hazardous after ultra high-dose radiation . METHODS AND MATERIAL S In a unique Phase I/II pilot study , 32 patients with recurrent rectal cancers following previous pelvic radiation underwent planned reirradiation to the pelvis .  Initial radiation doses had ranged from 30 - 64.87 Gy ( median dose 45 Gy ) . Seventeen patients underwent reirradiation followed by radical resection . Fifteen patients were reirradiated for palliative relief of symptoms . Treatment techniques consisted of two lateral fields ( 7 x 7 to 12 x 10 cm ) encompassing the tumor with 2 cm margins . Reirradiation doses ranged from 19.80 - 47.66 Gy , ( median 34.2 Gy ) . Patients also received concurrent low-dose continuous infusion chemotherapy , ( 5-FU 200 - 300 mg/day ) . Total cumulative radiation doses ranged from 70.6 to 111.6 Gy . RESULTS Treatment was well tolerated . Four patients had radiation interrupted/discontinued for diarrhea or leukopenia . Follow-up ranges from 6 months to 36 months . No late sequelae of radiation have been observed to date . Seventeen patients underwent surgical exploration 6 - 8 weeks following reirradiation . Two patients had extensive disease and were not resected . Fifteen patients underwent radical resection of residual tumor ( 4 posterior exenterations , 6 APR , 3 transanal abdominal transanal proctocolectomy with coloanal anastomosis ( TAATA ) , and 2 LAR ) . No patients died postoperatively . No excessive edema , hemorrhage , or adhesions were observed . Two patients developed pelvic abscess and one developed a coloanal stricture . Eleven of 15 resected patients are alive from 6 to 36 months with a 2-year survival of 66 % . Of the patients treated palliatively , symptomatic relief was observed in 13/15 patients . No objective complete response was observed , but 6/15 patients had measurable partial response . Median survival in this group was 14 months . CONCLUSION Based on this experience , we believe that in selected patients radical surgical resection after cumulative ultra high doses ( 70 - 90 Gy ) of radiation can be performed safely . A viable anastomosis is also possible in spite of these high doses . Planned reirradiation for palliative relief of symptoms can be effective without unusual risks of complication . Long-term effects of such ultra high dose radiation and surgery continue to be monitored AIMS When locally advanced or recurrent rectal cancer involves the bladder or prostate , curative treatment often requires pelvic exenteration . The aim was to assess the quality of life ( QoL ) in disease-free patients with urinary diversion after extensive surgery for advanced rectal cancer . METHODS Twelve patients with urinary diversion ( cases ) were compared with 25 r and omly selected patients given the same treatment , but without urinary diversion ( controls ) .  An age- and gender-adjusted general population was identified ( reference ) . QoL was assessed with the EORTC question naires QLQ-C30 , QLQ-CR38 , and parts  of the 
    Output:
    