human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : Many men with elevated prostate-specific antigen ( PSA ) levels in serum do not have aggressive prostate cancer and undergo unnecessary biopsy . Retrospective studies using cryopreserved serum suggest that four kallikrein markers can predict biopsy outcome . Methods : Free , intact and total PSA , and kallikrein-related peptidase 2  were measured in cryopreserved blood from 6129 men with elevated PSA ( ≥3.0ng/mL ) participating in the prospect i ve , r and omized trial Prostate Testing for Cancer and Treatment . Marker levels from 4765 men providing anticoagulated plasma  were incorporated into statistical models to predict any- grade and high- grade ( Gleason score ≥7 ) prostate cancer at 10-core biopsy . The models were corrected for optimism by 10-fold cross validation and independently vali date d using markers measured in serum from 1364 men . All statistical tests were two-sided . Results : The four kallikreins enhanced prostate cancer detection compared with PSA and age alone . Area under the curve ( AUC ) for the four kallikreins was 0.719 ( 95 % confidence interval [ CI ] = 0.704 to 0.734 ) vs 0.634 ( 95 % CI = 0.617 to 0.651 , P < .001 ) for PSA and age alone for any- grade cancer , and 0.820 ( 95 % CI = 0.802 to 0.838 ) vs 0.738 ( 95 % CI = 0.716 to 0.761 ) for high- grade cancer . Using a 6 % risk of high- grade cancer as an illustrative cutoff , for 1000 biopsied men with PSA levels of 3.0ng/mL or higher , the model would reduce the need for biopsy in 428 men , detect 119 high- grade cancers , and delay diagnosis of 14 of 133 high- grade cancers . Models exhibited excellent discrimination on independent validation among men with only serum sample s available for analysis . Conclusions : A statistical model based on kallikrein markers was vali date d in a large prospect i ve study and reduces unnecessary biopsies while delaying diagnosis of high- grade cancers in few men PURPOSE To perform a r and omized trial comparing 70 and 80 Gy radiotherapy for prostate cancer . PATIENTS AND METHODS A total of 306 patients with localized prostate cancer were r and omized . No and rogen deprivation was allowed . The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions . Toxicity was grade d using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective , objective , management , analytic scales ( LENT-SOMA ) scales . The patients ' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Question  naire 30-item cancer-specific and 25-item prostate-specific modules . RESULTS The median follow-up was 61 months . According to the 1997-American Society for Therapeutic Radiology and Oncology definition , the 5-year biochemical relapse rate was 39 % and 28 % in the 70- and 80-Gy arms , respectively ( p = .036 ) . Using the Phoenix definition , the 5-year biochemical relapse rate was 32 % and 23.5 % , respectively ( p = .09 ) . The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level > 15 ng/mL. At the last follow-up date , 26 patients had died , 10 of their disease and none of toxicity , with no differences between the two arms . According to the Radiation Therapy Oncology Group scale , the Grade 2 or greater rectal toxicity rate was 14 % and 19.5 % for the 70- and 80-Gy arms ( p = .22 ) , respectively . The Grade 2 or greater urinary toxicity was 10 % at 70 Gy and 17.5 % at 80 Gy ( p = .046 ) . Similar results were observed using the LENT-SOMA scale . Bladder toxicity was more frequent at 80 Gy than at 70 Gy ( p = .039 ) . The quality -of-life question naire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms . CONCLUSION High-dose radiotherapy provided a better 5-year biochemical outcome with slightly greater toxicity BACKGROUND It is not known whether short-term and rogen-deprivation therapy ( ADT ) before and during radiotherapy improves cancer control and overall survival among patients with early , localized prostate adenocarcinoma . METHODS From 1994 through 2001 , we r and omly assigned 1979 eligible patients with stage T1b , T1c , T2a , or T2b prostate adenocarcinoma and a prostate-specific antigen ( PSA ) level of 20 ng per milliliter or less to radiotherapy alone ( 992 patients ) or radiotherapy with 4 months of total and rogen suppression starting 2 months before radiotherapy ( radiotherapy plus short-term ADT , 987 patients ) . The primary end point was overall survival . Secondary end points included disease-specific mortality , distant metastases , biochemical failure ( an increasing level of PSA ) , and the rate of positive findings on repeat prostate biopsy at 2 years . RESULTS The median follow-up period was 9.1 years . The 10-year rate of overall survival was 62 % among patients receiving radiotherapy plus short-term ADT ( the combined-therapy group ) , as compared with 57 % among patients receiving radiotherapy alone ( hazard ratio for death with radiotherapy alone , 1.17 ; P=0.03 ) . The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8 % to 4 % ( hazard ratio for radiotherapy alone , 1.87 ; P=0.001 ) . Biochemical failure , distant metastases , and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT . Acute and late radiation-induced toxic effects were similar in the two groups . The incidence of grade 3 or higher hormone-related toxic effects was less than 5 % . Re analysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients , with no significant reductions among low-risk patients . CONCLUSIONS Among patients with stage T1b , T1c , T2a , or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less , the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival . According to post hoc risk analysis , the benefit was mainly seen in intermediate-risk , but not low-risk , men . ( Funded by the National Cancer Institute ; RTOG 94 - 08 Clinical Trials.gov number , NCT00002597 . ) BACKGROUND The European R and omised study of Screening for Prostate Cancer ( ERSPC ) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up , but screening is controversial because of adverse events such as overdiagnosis . We provide up date d results of mortality from prostate cancer with follow-up to 2010 , with analyses truncated at 9 , 11 , and 13 years . METHODS ERSPC is a multicentre , r and omised trial with a predefined central ised data base , analysis plan , and core age group ( 55 - 69 years ) , which assesses prostate-specific antigen ( PSA ) testing in eight European countries . Eligible men aged 50 - 74 years were identified from population registries and r and omly assigned by computer generated r and om numbers to screening or no intervention ( control ) . Investigators were masked to group allocation . The primary outcome was prostate cancer mortality in the core age group . Analysis was by intention to treat . We did a secondary analysis that corrected for selection bias due to non-participation . Only incidence and no mortality data at 9 years ' follow-up are reported for the French centres . This study is registered with Current Controlled Trials , number IS RCT N49127736 . FINDINGS With data truncated at 13 years of follow-up , 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group .  The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 ( 95 % CI 1·83 - 1·99 ) after 9 years ( 1·64 [ 1·58 - 1·69 ] including France ) , 1·66 ( 1·60 - 1·73 ) after 11 years , and 1·57 ( 1·51 - 1·62 ) after 13 years . The rate ratio of prostate cancer mortality was 0·85 ( 0·70 - 1·03 ) after 9 years , 0·78 ( 0·66 - 0·91 ) after 11 years , and 0·79 ( 0·69 - 0·91 ) at 13 years . The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men r and omised , which is equivalent to one prostate cancer death averted per 781 ( 95 % CI 490 - 1929 ) men invited for screening or one per 27 ( 17 - 66 ) additional prostate cancer detected . After adjustment for non-participation , the rate ratio of prostate cancer mortality in men screened was 0·73 ( 95 % CI 0·61 - 0·88 ) . INTERPRETATION In this up date the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA , with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years . Despite our findings , further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening . FUNDING Each centre had its own funding responsibility Summary Background Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment . We present a pre-planned analysis of the efficacy and side-effects of a r and omised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up . Methods CHHiP is a r and omised , phase 3 , non-inferiority trial that recruited men with localised prostate cancer ( pT1b – T3aN0M0 ) . Patients were r and omly assigned ( 1:1:1 ) to conventional ( 74 Gy delivered in 37 fractions over 7·4 weeks ) or one of two hypofractionated schedules ( 60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks ) all delivered with intensity-modulated techniques . Most patients were given radiotherapy with 3–6 months of neoadjuvant and concurrent and rogen suppression . R and omisation was by computer-generated r and om permuted blocks , stratified by National Comprehensive Cancer Network ( NCCN ) risk group and radiotherapy treatment centre , and treatment allocation was not masked . The primary endpoint was time to biochemical or clinical failure ; the critical hazard ratio ( HR ) for non-inferiority was 1·208 . Analysis was by intention to treat . Long-term follow-up continues . The CHHiP trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N97182923 . Findings Between Oct 18 , 2002 , and June 17 , 2011 , 3216 men were enrolled from 71 centres and r and omly assigned ( 74 Gy group , 1065 patients ; 60 Gy group , 1074 patients ; 57 Gy group , 1077 patients ) . Median follow-up was 62·4 months ( IQR 53·9–77·0 ) . The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3 % ( 95 % CI 86·0–90·2 ) in the 74 Gy group , 90·6 % ( 88·5–92·3 ) in the 60 Gy group , and 85·9 % ( 83·4–88·0 ) in the 57 Gy group . 60 Gy was non-inferior to 74 Gy ( HR 0·84 [ 90 % CI 0·68–1·03 ] , pNI=0·0018 ) but non-inferiority could not be cl aim ed for 57 Gy compared with 74 Gy ( HR 1·20 [ 0·99–1·46 ] , pNI=0·48 ) . Long-term side-effects were similar in the hypofractionated groups compared with the conventional group . There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures . The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group ( RTOG ) grade 2 or worse bowel and 
    Output:
    
agent
Moderate hypofractionation is safe and effective , but longer-term data are still lacking .
Brachytherapy represents an effective way to increase the delivered dose .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : Many men with elevated prostate-specific antigen ( PSA ) levels in serum do not have aggressive prostate cancer and undergo unnecessary biopsy . Retrospective studies using cryopreserved serum suggest that four kallikrein markers can predict biopsy outcome . Methods : Free , intact and total PSA , and kallikrein-related peptidase 2  were measured in cryopreserved blood from 6129 men with elevated PSA ( ≥3.0ng/mL ) participating in the prospect i ve , r and omized trial Prostate Testing for Cancer and Treatment . Marker levels from 4765 men providing anticoagulated plasma  were incorporated into statistical models to predict any- grade and high- grade ( Gleason score ≥7 ) prostate cancer at 10-core biopsy . The models were corrected for optimism by 10-fold cross validation and independently vali date d using markers measured in serum from 1364 men . All statistical tests were two-sided . Results : The four kallikreins enhanced prostate cancer detection compared with PSA and age alone . Area under the curve ( AUC ) for the four kallikreins was 0.719 ( 95 % confidence interval [ CI ] = 0.704 to 0.734 ) vs 0.634 ( 95 % CI = 0.617 to 0.651 , P < .001 ) for PSA and age alone for any- grade cancer , and 0.820 ( 95 % CI = 0.802 to 0.838 ) vs 0.738 ( 95 % CI = 0.716 to 0.761 ) for high- grade cancer . Using a 6 % risk of high- grade cancer as an illustrative cutoff , for 1000 biopsied men with PSA levels of 3.0ng/mL or higher , the model would reduce the need for biopsy in 428 men , detect 119 high- grade cancers , and delay diagnosis of 14 of 133 high- grade cancers . Models exhibited excellent discrimination on independent validation among men with only serum sample s available for analysis . Conclusions : A statistical model based on kallikrein markers was vali date d in a large prospect i ve study and reduces unnecessary biopsies while delaying diagnosis of high- grade cancers in few men PURPOSE To perform a r and omized trial comparing 70 and 80 Gy radiotherapy for prostate cancer . PATIENTS AND METHODS A total of 306 patients with localized prostate cancer were r and omized . No and rogen deprivation was allowed . The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions . Toxicity was grade d using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective , objective , management , analytic scales ( LENT-SOMA ) scales . The patients ' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Question  naire 30-item cancer-specific and 25-item prostate-specific modules . RESULTS The median follow-up was 61 months . According to the 1997-American Society for Therapeutic Radiology and Oncology definition , the 5-year biochemical relapse rate was 39 % and 28 % in the 70- and 80-Gy arms , respectively ( p = .036 ) . Using the Phoenix definition , the 5-year biochemical relapse rate was 32 % and 23.5 % , respectively ( p = .09 ) . The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level > 15 ng/mL. At the last follow-up date , 26 patients had died , 10 of their disease and none of toxicity , with no differences between the two arms . According to the Radiation Therapy Oncology Group scale , the Grade 2 or greater rectal toxicity rate was 14 % and 19.5 % for the 70- and 80-Gy arms ( p = .22 ) , respectively . The Grade 2 or greater urinary toxicity was 10 % at 70 Gy and 17.5 % at 80 Gy ( p = .046 ) . Similar results were observed using the LENT-SOMA scale . Bladder toxicity was more frequent at 80 Gy than at 70 Gy ( p = .039 ) . The quality -of-life question naire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms . CONCLUSION High-dose radiotherapy provided a better 5-year biochemical outcome with slightly greater toxicity BACKGROUND It is not known whether short-term and rogen-deprivation therapy ( ADT ) before and during radiotherapy improves cancer control and overall survival among patients with early , localized prostate adenocarcinoma . METHODS From 1994 through 2001 , we r and omly assigned 1979 eligible patients with stage T1b , T1c , T2a , or T2b prostate adenocarcinoma and a prostate-specific antigen ( PSA ) level of 20 ng per milliliter or less to radiotherapy alone ( 992 patients ) or radiotherapy with 4 months of total and rogen suppression starting 2 months before radiotherapy ( radiotherapy plus short-term ADT , 987 patients ) . The primary end point was overall survival . Secondary end points included disease-specific mortality , distant metastases , biochemical failure ( an increasing level of PSA ) , and the rate of positive findings on repeat prostate biopsy at 2 years . RESULTS The median follow-up period was 9.1 years . The 10-year rate of overall survival was 62 % among patients receiving radiotherapy plus short-term ADT ( the combined-therapy group ) , as compared with 57 % among patients receiving radiotherapy alone ( hazard ratio for death with radiotherapy alone , 1.17 ; P=0.03 ) . The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8 % to 4 % ( hazard ratio for radiotherapy alone , 1.87 ; P=0.001 ) . Biochemical failure , distant metastases , and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT . Acute and late radiation-induced toxic effects were similar in the two groups . The incidence of grade 3 or higher hormone-related toxic effects was less than 5 % . Re analysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients , with no significant reductions among low-risk patients . CONCLUSIONS Among patients with stage T1b , T1c , T2a , or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less , the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival . According to post hoc risk analysis , the benefit was mainly seen in intermediate-risk , but not low-risk , men . ( Funded by the National Cancer Institute ; RTOG 94 - 08 Clinical Trials.gov number , NCT00002597 . ) BACKGROUND The European R and omised study of Screening for Prostate Cancer ( ERSPC ) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up , but screening is controversial because of adverse events such as overdiagnosis . We provide up date d results of mortality from prostate cancer with follow-up to 2010 , with analyses truncated at 9 , 11 , and 13 years . METHODS ERSPC is a multicentre , r and omised trial with a predefined central ised data base , analysis plan , and core age group ( 55 - 69 years ) , which assesses prostate-specific antigen ( PSA ) testing in eight European countries . Eligible men aged 50 - 74 years were identified from population registries and r and omly assigned by computer generated r and om numbers to screening or no intervention ( control ) . Investigators were masked to group allocation . The primary outcome was prostate cancer mortality in the core age group . Analysis was by intention to treat . We did a secondary analysis that corrected for selection bias due to non-participation . Only incidence and no mortality data at 9 years ' follow-up are reported for the French centres . This study is registered with Current Controlled Trials , number IS RCT N49127736 . FINDINGS With data truncated at 13 years of follow-up , 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group .  The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 ( 95 % CI 1·83 - 1·99 ) after 9 years ( 1·64 [ 1·58 - 1·69 ] including France ) , 1·66 ( 1·60 - 1·73 ) after 11 years , and 1·57 ( 1·51 - 1·62 ) after 13 years . The rate ratio of prostate cancer mortality was 0·85 ( 0·70 - 1·03 ) after 9 years , 0·78 ( 0·66 - 0·91 ) after 11 years , and 0·79 ( 0·69 - 0·91 ) at 13 years . The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men r and omised , which is equivalent to one prostate cancer death averted per 781 ( 95 % CI 490 - 1929 ) men invited for screening or one per 27 ( 17 - 66 ) additional prostate cancer detected . After adjustment for non-participation , the rate ratio of prostate cancer mortality in men screened was 0·73 ( 95 % CI 0·61 - 0·88 ) . INTERPRETATION In this up date the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA , with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years . Despite our findings , further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening . FUNDING Each centre had its own funding responsibility Summary Background Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment . We present a pre-planned analysis of the efficacy and side-effects of a r and omised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up . Methods CHHiP is a r and omised , phase 3 , non-inferiority trial that recruited men with localised prostate cancer ( pT1b – T3aN0M0 ) . Patients were r and omly assigned ( 1:1:1 ) to conventional ( 74 Gy delivered in 37 fractions over 7·4 weeks ) or one of two hypofractionated schedules ( 60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks ) all delivered with intensity-modulated techniques . Most patients were given radiotherapy with 3–6 months of neoadjuvant and concurrent and rogen suppression . R and omisation was by computer-generated r and om permuted blocks , stratified by National Comprehensive Cancer Network ( NCCN ) risk group and radiotherapy treatment centre , and treatment allocation was not masked . The primary endpoint was time to biochemical or clinical failure ; the critical hazard ratio ( HR ) for non-inferiority was 1·208 . Analysis was by intention to treat . Long-term follow-up continues . The CHHiP trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N97182923 . Findings Between Oct 18 , 2002 , and June 17 , 2011 , 3216 men were enrolled from 71 centres and r and omly assigned ( 74 Gy group , 1065 patients ; 60 Gy group , 1074 patients ; 57 Gy group , 1077 patients ) . Median follow-up was 62·4 months ( IQR 53·9–77·0 ) . The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3 % ( 95 % CI 86·0–90·2 ) in the 74 Gy group , 90·6 % ( 88·5–92·3 ) in the 60 Gy group , and 85·9 % ( 83·4–88·0 ) in the 57 Gy group . 60 Gy was non-inferior to 74 Gy ( HR 0·84 [ 90 % CI 0·68–1·03 ] , pNI=0·0018 ) but non-inferiority could not be cl aim ed for 57 Gy compared with 74 Gy ( HR 1·20 [ 0·99–1·46 ] , pNI=0·48 ) . Long-term side-effects were similar in the hypofractionated groups compared with the conventional group . There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures . The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group ( RTOG ) grade 2 or worse bowel and 
    Output:
    