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: From April 1986 to May 1989 , 112 patients seen at a single institution with previously untreated squamous cell oropharynx carcinoma , Stages III and IV , were r and omly assigned to 66 Gy in 33 fractions of 2 Gy each ( conventional RT ) versus 70.4 Gy in 64 fractions of 1.1 Gy given twice a day with a minimal interfraction interval of 6 hours ( hyperfractionated RT ) . The overall time for both arms was 6 1/2 weeks . Patients were stratified by site ( base of the tongue vs others ) , T stage ( T1/T2 vs T3 vs T4 ) , N stage ( N0/N1 vs N2 vs N3 ) , and lymphnode size ( less than 6 cm vs greater than 6 cm ) . As of January 1990 , an analysis was performed in 98 patients ( 8 patients in the conventional arm and 6 in the hyperfractionation not included ) . The groups were balanced by age , performance status , stage , and site of the primary disease . The median follow-up time was 25 months . The probability of complete loco-regional response was 62 % in the hyperfractionation arm and 52 % for the conventional fractionation ( p = 0.28 ) . There was no difference in the control of lymphnodal disease ( hyperfractionated = 55 % , conventional = 57 % ; p = 0.92 ) , but the disease control in the oropharynx only was significantly improved in the hyperfractionation arm ( 84 % vs 64 % , p = 0.02 ) . Overall survival rate at 42 months was 27 % for the hyperfractionation arm and 8 % for the conventional ( p = 0.03 ) . Survival rates for hyperfractionated versus conventional RT were 40 % versus 18 % ( p = 0.06 ) , respectively , for Stage III patients and 16 % versus 0 % ( p = 0.15 ) , respectively , for Stage IV . There was significant improvement in survival in favor of the hyperfractionation arm in patients with lesions outside the base of the tongue ( 31 % vs 15 % , p = 0.02 ) , for those with a 50 - 70 % Karnofsky status ( 19 % vs 0 % , p = 0.006 ) and for patients with N0/N1 disease ( 38 % vs 15 % , p = 0.03 ) . Acute toxicities were of similar magnitude , although both skin and mucosal reactions appeared earlier on the hyperfractionation scheme . To date , no differences in late toxicity have been observed . We conclude that in a subset group of patients with locally advanced carcinoma of the oropharynx , hyperfractionated radiotherapy appears to provide improved survival without adding to increased toxicity The European Organization for Research on Treatment of Cancer ( EORTC ) Cooperative Group of Radiotherapy started phase II and III trials on modified fractionation schemes in 1980 . As of June 1 , 1992 , 2006 patients have entered eight trials . This short overview will only concentrate on two phase III trials of hyperfractionation ( EORTC trial 22791 ) and accelerated fractionation ( trial 22851 ) Summary The r and omized multicentre trial of continuous hyperfractionated accelerated radiotherapy ( CHART ) versus conventional radiotherapy in patients with advanced head and neck cancer showed no good evidence of a difference in any of the major clinical outcomes of survival , freedom from metastases , loco-regional control and disease-free survival . Therefore an assessment of the effect of treatment on physical and psychological symptoms is vital to balance the costs and benefits of the two treatments . A total of 615 patients were asked to complete a Rotterdam Symptom Checklist and the Hospital Anxiety and Depression Scale , which cover a variety of physical and psychological symptoms , at a total of ten time points . The data consisted of short-term data ( the initial 3 months ) and long-term data ( 1 and 2 years ) . The short-term data was split into an exploratory data set and a confirmatory data set , and analysed using subject-specific and group-based methods . Differences were only cl aim ed if hypotheses generated in the exploratory data set were confirmed in the confirmatory data set . The long-term data was not split into two data sets and was analysed using a group-based approach . There was evidence of significantly worse symptoms of pain at day 21 in those treated with CHART and significantly worse symptoms of cough and hoarseness at 6 weeks in those treated conventionally . There was also evidence to suggest a higher degree of decreased sexual interest at 1 year and sore muscles at 2 years in those treated with conventional radiotherapy . There is no clear indication that one regimen is superior to the other in terms of ‘ quality of life ’ , generally the initially more severe reaction in the CHART group being offset by the longer duration of symptoms in the conventionally treated group PURPOSE To evaluate tumour and normal tissues 3-year response to 7-day-a-week continuous accelerated irradiation ( CAIR ) compared to a conventional treatment ( 5 days per week ) in a r and omized trial . MATERIAL S AND METHODS One hundred patients with squamous cell carcinoma of the head and neck in stage T(2 - 4)N(0 - 1)M(0 ) were entered into the trial between December 1 , 1993 and June 30 , 1996 . Dose per fraction of 2.0 Gy ( to the end of 1994 ) , and 1.8 Gy ( since January 1 , 1995 ) was the same in both arms and delivered once a day at regular 24-h intervals to total dose in the range of 66 - 72 Gy ( depending on tumour stage ) . The only difference was overall treatment time being 5 weeks in the CAIR and 7 weeks in control arm . RESULTS Actuarial 3-year local tumour control was 82 % in the CAIR and 37 % in the control group ( P<0.0001 ) with reduction in local recurrence rate of 83 % . Actuarial 3-year overall survival was 78 and 32 % ( P<0.0001 ) , respectively . Confluent mucositis was significantly more severe and lasted longer in the CAIR than in control arm . After 2.0 Gy fractions five of 23 patients ( 22 % ) in the CAIR developed early necroses over a period of 2 - 4 months of follow-up which can be considered as a consequential to severe protracted acute mucosal reactions ( CLE ) . For this reason dose per fraction was lowered to 1 . 8 Gy and the CLE was not observed again until now . Thus the overall rate of CLE decreased to 10 % . CONCLUSIONS The gain in tumour control is likely the effect of shortening of overall treatment time by 14 days and regular continuous dose delivery during the whole course of radiation therapy including weekends . A 7-day schedule produces more severe acute mucosal reactions lasting longer than in conventional fractionation , however tolerable by patients . Relatively high rate ( 22 % ) of CLE in the 7-day arm observed during the first year of the study was eliminated by decreasing dose per fraction from 2.0 Gy to 1.8 Gy PURPOSE To determine whether , in the postoperative setting , accelerated fractionation ( AF ) radiotherapy ( RT ) yields a superior locoregional control rate compared with conventional fractionation ( CF ) RT in locally advanced squamous cell carcinomas of the oral cavity , oropharynx , larynx , or hypopharynx . METHODS AND MATERIAL S Patients from four institutions with one or more high-risk features ( pT4 , positive resection margins , pN > 1 , perineural/lymphovascular invasion , extracapsular extension , subglottic extension ) after surgery were r and omly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF . Accelerated fractionation consisted of a " biphasic concomitant boost " schedule , with the boost delivered during the first and last weeks of treatment , to deliver 64 Gy in 5 weeks . Informed consent was obtained . The primary endpoint of the study was locoregional control . Analysis was on an intention-to-treat basis . RESULTS From March 1994 to August 2000 , 226 patients were r and omized . At a median follow-up of 30.6 months ( range , 0 - 110 months ) , 2-year locoregional control estimates were 80 % + /- 4 % for CF and 78 % + /- 5 % for AF ( p = 0.52 ) , and 2-year overall survival estimates were 67 % + /- 5 % for CF and 64 % + /- 5 % for AF ( p = 0.84 ) . The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis . However , interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF ( hazard ratio = 0.5 , 95 % confidence interval 0.2 - 1.1 ) . Fifty percent of patients treated with AF developed confluent mucositis , compared with only 27 % of those treated with CF ( p = 0.006 ) . However , mucositis duration was not different between arms . Although preliminary , actuarial Grade 3 + late toxicity estimates at 2 years were 18 % + /- 4 % and 27 % + /- 6 % for CF and AF , respectively ( p = 0.10 ) . CONCLUSION Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection ; however , AF might be an option for patients who delay starting RT One hundred patients with stage II and stage III cancer of the oropharynx and hypopharynx were treated under a protocol in which they were r and omly selected for treatment by surgery alone or by combined preoperative radiotherapy and surgery . The schedule of preoperative radiation therapy chosen was 2,000 rads from a cobalt 60 machine delivered in five days . Eighty-six of the patients were evaluable at three years ; there was no difference in the outcome of the treatment of the two groups . A similar study is urgently needed to determine the value of postoperative radiotherapy in the management of similar cancers From 1971 to 1975 , 100 patients with glottic , supraglottic , and oral cavity lesions were prospect ively r and omized between primary radiation treatment  and primary surgery .  Local control and survival were similar with either treatment for lesions of the oral cavity or supraglottic larynx . Comparison between radiation alone and surgery alone for T1 and T2 glottic laryngeal lesions showed local control rates of 76 % and 100 % ( P=0.32 ) ; after secondary salvage attempts , local control rates were 82 % and 100 % , respectively ( P= 0.52 ) . Neither result approached statistical significance . Successful radiation for early glottic larynx lesions result ed in superior deglutition and equivalent voice function compared to successful primary treatment with conservation laryngectomy . For oral cavity lesions , swallowing was impaired in the same percentage of radiated and operated patients , but fewer primary radiation patients had articulation difficulties . Among the patients with supraglottic larynx lesions , aspiration was not a problem with either radiation or surgery , but successful radiation perhaps maintained a slightly better voice quality EORTC protocol 22791 compared once daily fractionation ( CF ) of 70 Gy in 35 - 40 fractions in 7 - 8 weeks , to pure hyperfractionation ( HF ) of 80.5 Gy in 70 fractions in 7 weeks using 2 fractions of 1.15 Gy per day , in T2-T3 oropharyngeal carcinoma ( excluding base of tongue ) , N0,N1 of less than 3 cm . From 1980 to 1987 , 356 patients were entered . In the final analysis ( June 1990 ) , the local control was significantly higher ( p = 0.02 log-rank ) after HF compared with CF . At 5 years , 59 % of patients are local disease-free in the HF arm compared to 40 % in the CF arm . The superiority of HF was demonstrated in patients staged T3N0,T3N1 but not in T2 . The Cox model confirmed that the treatment regimen was an independent significant prognostic factor for locoregional control ( p = 0.007 log-rank ) . This improvement of locoregional control was responsible for a trend to an improved survival ( p = 0.08 log-rank ) . There was no difference in late normal tissue damage between the two treatment modalities The results are presented of a multi-centre r and omly controlled trial of fast neutron irradiation and mega-voltage X-rays in the treatment of patients with locally advanced squamous cell carcinoma of the head and neck region . No significant difference was observed in local tumour control rates . Salvage  surgery  was performed in a similar number of patients in the two groups . Late morbidity was also similar in the two treatment groups . Patients in a subgroup with cancer of the larynx treated by photons had a significantly better survival than those in the neutron treated group Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after surgery , the possibility that treatment acceleration would offer a therapeutic advantage in postoperative radiotherapy of locally advanced head and neck cancer was investigated . The value of Tpot in predicting the treatment outcome and in selecting patients for accelerated fractionation was tested . Seventy patients with ( T2/N1–N2 ) or ( T3 - 4/any N ) squamous cell carcinoma of the oral cavity , larynx and hypopharynx who underwent radical surgery , were r and omized to either ( a ) accelerated hyperfractionation 
    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: From April 1986 to May 1989 , 112 patients seen at a single institution with previously untreated squamous cell oropharynx carcinoma , Stages III and IV , were r and omly assigned to 66 Gy in 33 fractions of 2 Gy each ( conventional RT ) versus 70.4 Gy in 64 fractions of 1.1 Gy given twice a day with a minimal interfraction interval of 6 hours ( hyperfractionated RT ) . The overall time for both arms was 6 1/2 weeks . Patients were stratified by site ( base of the tongue vs others ) , T stage ( T1/T2 vs T3 vs T4 ) , N stage ( N0/N1 vs N2 vs N3 ) , and lymphnode size ( less than 6 cm vs greater than 6 cm ) . As of January 1990 , an analysis was performed in 98 patients ( 8 patients in the conventional arm and 6 in the hyperfractionation not included ) . The groups were balanced by age , performance status , stage , and site of the primary disease . The median follow-up time was 25 months . The probability of complete loco-regional response was 62 % in the hyperfractionation arm and 52 % for the conventional fractionation ( p = 0.28 ) . There was no difference in the control of lymphnodal disease ( hyperfractionated = 55 % , conventional = 57 % ; p = 0.92 ) , but the disease control in the oropharynx only was significantly improved in the hyperfractionation arm ( 84 % vs 64 % , p = 0.02 ) . Overall survival rate at 42 months was 27 % for the hyperfractionation arm and 8 % for the conventional ( p = 0.03 ) . Survival rates for hyperfractionated versus conventional RT were 40 % versus 18 % ( p = 0.06 ) , respectively , for Stage III patients and 16 % versus 0 % ( p = 0.15 ) , respectively , for Stage IV . There was significant improvement in survival in favor of the hyperfractionation arm in patients with lesions outside the base of the tongue ( 31 % vs 15 % , p = 0.02 ) , for those with a 50 - 70 % Karnofsky status ( 19 % vs 0 % , p = 0.006 ) and for patients with N0/N1 disease ( 38 % vs 15 % , p = 0.03 ) . Acute toxicities were of similar magnitude , although both skin and mucosal reactions appeared earlier on the hyperfractionation scheme . To date , no differences in late toxicity have been observed . We conclude that in a subset group of patients with locally advanced carcinoma of the oropharynx , hyperfractionated radiotherapy appears to provide improved survival without adding to increased toxicity The European Organization for Research on Treatment of Cancer ( EORTC ) Cooperative Group of Radiotherapy started phase II and III trials on modified fractionation schemes in 1980 . As of June 1 , 1992 , 2006 patients have entered eight trials . This short overview will only concentrate on two phase III trials of hyperfractionation ( EORTC trial 22791 ) and accelerated fractionation ( trial 22851 ) Summary The r and omized multicentre trial of continuous hyperfractionated accelerated radiotherapy ( CHART ) versus conventional radiotherapy in patients with advanced head and neck cancer showed no good evidence of a difference in any of the major clinical outcomes of survival , freedom from metastases , loco-regional control and disease-free survival . Therefore an assessment of the effect of treatment on physical and psychological symptoms is vital to balance the costs and benefits of the two treatments . A total of 615 patients were asked to complete a Rotterdam Symptom Checklist and the Hospital Anxiety and Depression Scale , which cover a variety of physical and psychological symptoms , at a total of ten time points . The data consisted of short-term data ( the initial 3 months ) and long-term data ( 1 and 2 years ) . The short-term data was split into an exploratory data set and a confirmatory data set , and analysed using subject-specific and group-based methods . Differences were only cl aim ed if hypotheses generated in the exploratory data set were confirmed in the confirmatory data set . The long-term data was not split into two data sets and was analysed using a group-based approach . There was evidence of significantly worse symptoms of pain at day 21 in those treated with CHART and significantly worse symptoms of cough and hoarseness at 6 weeks in those treated conventionally . There was also evidence to suggest a higher degree of decreased sexual interest at 1 year and sore muscles at 2 years in those treated with conventional radiotherapy . There is no clear indication that one regimen is superior to the other in terms of ‘ quality of life ’ , generally the initially more severe reaction in the CHART group being offset by the longer duration of symptoms in the conventionally treated group PURPOSE To evaluate tumour and normal tissues 3-year response to 7-day-a-week continuous accelerated irradiation ( CAIR ) compared to a conventional treatment ( 5 days per week ) in a r and omized trial . MATERIAL S AND METHODS One hundred patients with squamous cell carcinoma of the head and neck in stage T(2 - 4)N(0 - 1)M(0 ) were entered into the trial between December 1 , 1993 and June 30 , 1996 . Dose per fraction of 2.0 Gy ( to the end of 1994 ) , and 1.8 Gy ( since January 1 , 1995 ) was the same in both arms and delivered once a day at regular 24-h intervals to total dose in the range of 66 - 72 Gy ( depending on tumour stage ) . The only difference was overall treatment time being 5 weeks in the CAIR and 7 weeks in control arm . RESULTS Actuarial 3-year local tumour control was 82 % in the CAIR and 37 % in the control group ( P<0.0001 ) with reduction in local recurrence rate of 83 % . Actuarial 3-year overall survival was 78 and 32 % ( P<0.0001 ) , respectively . Confluent mucositis was significantly more severe and lasted longer in the CAIR than in control arm . After 2.0 Gy fractions five of 23 patients ( 22 % ) in the CAIR developed early necroses over a period of 2 - 4 months of follow-up which can be considered as a consequential to severe protracted acute mucosal reactions ( CLE ) . For this reason dose per fraction was lowered to 1 . 8 Gy and the CLE was not observed again until now . Thus the overall rate of CLE decreased to 10 % . CONCLUSIONS The gain in tumour control is likely the effect of shortening of overall treatment time by 14 days and regular continuous dose delivery during the whole course of radiation therapy including weekends . A 7-day schedule produces more severe acute mucosal reactions lasting longer than in conventional fractionation , however tolerable by patients . Relatively high rate ( 22 % ) of CLE in the 7-day arm observed during the first year of the study was eliminated by decreasing dose per fraction from 2.0 Gy to 1.8 Gy PURPOSE To determine whether , in the postoperative setting , accelerated fractionation ( AF ) radiotherapy ( RT ) yields a superior locoregional control rate compared with conventional fractionation ( CF ) RT in locally advanced squamous cell carcinomas of the oral cavity , oropharynx , larynx , or hypopharynx . METHODS AND MATERIAL S Patients from four institutions with one or more high-risk features ( pT4 , positive resection margins , pN > 1 , perineural/lymphovascular invasion , extracapsular extension , subglottic extension ) after surgery were r and omly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF . Accelerated fractionation consisted of a " biphasic concomitant boost " schedule , with the boost delivered during the first and last weeks of treatment , to deliver 64 Gy in 5 weeks . Informed consent was obtained . The primary endpoint of the study was locoregional control . Analysis was on an intention-to-treat basis . RESULTS From March 1994 to August 2000 , 226 patients were r and omized . At a median follow-up of 30.6 months ( range , 0 - 110 months ) , 2-year locoregional control estimates were 80 % + /- 4 % for CF and 78 % + /- 5 % for AF ( p = 0.52 ) , and 2-year overall survival estimates were 67 % + /- 5 % for CF and 64 % + /- 5 % for AF ( p = 0.84 ) . The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis . However , interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF ( hazard ratio = 0.5 , 95 % confidence interval 0.2 - 1.1 ) . Fifty percent of patients treated with AF developed confluent mucositis , compared with only 27 % of those treated with CF ( p = 0.006 ) . However , mucositis duration was not different between arms . Although preliminary , actuarial Grade 3 + late toxicity estimates at 2 years were 18 % + /- 4 % and 27 % + /- 6 % for CF and AF , respectively ( p = 0.10 ) . CONCLUSION Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection ; however , AF might be an option for patients who delay starting RT One hundred patients with stage II and stage III cancer of the oropharynx and hypopharynx were treated under a protocol in which they were r and omly selected for treatment by surgery alone or by combined preoperative radiotherapy and surgery . The schedule of preoperative radiation therapy chosen was 2,000 rads from a cobalt 60 machine delivered in five days . Eighty-six of the patients were evaluable at three years ; there was no difference in the outcome of the treatment of the two groups . A similar study is urgently needed to determine the value of postoperative radiotherapy in the management of similar cancers From 1971 to 1975 , 100 patients with glottic , supraglottic , and oral cavity lesions were prospect ively r and omized between primary radiation treatment  and primary surgery .  Local control and survival were similar with either treatment for lesions of the oral cavity or supraglottic larynx . Comparison between radiation alone and surgery alone for T1 and T2 glottic laryngeal lesions showed local control rates of 76 % and 100 % ( P=0.32 ) ; after secondary salvage attempts , local control rates were 82 % and 100 % , respectively ( P= 0.52 ) . Neither result approached statistical significance . Successful radiation for early glottic larynx lesions result ed in superior deglutition and equivalent voice function compared to successful primary treatment with conservation laryngectomy . For oral cavity lesions , swallowing was impaired in the same percentage of radiated and operated patients , but fewer primary radiation patients had articulation difficulties . Among the patients with supraglottic larynx lesions , aspiration was not a problem with either radiation or surgery , but successful radiation perhaps maintained a slightly better voice quality EORTC protocol 22791 compared once daily fractionation ( CF ) of 70 Gy in 35 - 40 fractions in 7 - 8 weeks , to pure hyperfractionation ( HF ) of 80.5 Gy in 70 fractions in 7 weeks using 2 fractions of 1.15 Gy per day , in T2-T3 oropharyngeal carcinoma ( excluding base of tongue ) , N0,N1 of less than 3 cm . From 1980 to 1987 , 356 patients were entered . In the final analysis ( June 1990 ) , the local control was significantly higher ( p = 0.02 log-rank ) after HF compared with CF . At 5 years , 59 % of patients are local disease-free in the HF arm compared to 40 % in the CF arm . The superiority of HF was demonstrated in patients staged T3N0,T3N1 but not in T2 . The Cox model confirmed that the treatment regimen was an independent significant prognostic factor for locoregional control ( p = 0.007 log-rank ) . This improvement of locoregional control was responsible for a trend to an improved survival ( p = 0.08 log-rank ) . There was no difference in late normal tissue damage between the two treatment modalities The results are presented of a multi-centre r and omly controlled trial of fast neutron irradiation and mega-voltage X-rays in the treatment of patients with locally advanced squamous cell carcinoma of the head and neck region . No significant difference was observed in local tumour control rates . Salvage  surgery  was performed in a similar number of patients in the two groups . Late morbidity was also similar in the two treatment groups . Patients in a subgroup with cancer of the larynx treated by photons had a significantly better survival than those in the neutron treated group Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after surgery , the possibility that treatment acceleration would offer a therapeutic advantage in postoperative radiotherapy of locally advanced head and neck cancer was investigated . The value of Tpot in predicting the treatment outcome and in selecting patients for accelerated fractionation was tested . Seventy patients with ( T2/N1–N2 ) or ( T3 - 4/any N ) squamous cell carcinoma of the oral cavity , larynx and hypopharynx who underwent radical surgery , were r and omized to either ( a ) accelerated hyperfractionation 
    Output:
    