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 After breast-conserving surgery , 90 % of local recurrences occur within the index quadrant despite the presence of multicentric cancers elsewhere in the breast . Thus , restriction of radiation therapy to the tumour bed during surgery might be adequate for selected patients . We compared targeted intraoperative radiotherapy with the conventional policy of whole breast external beam radiotherapy . METHODS Having safely piloted the new technique of single-dose targeted intraoperative radiotherapy with Intrabeam , we launched the TARGIT-A trial on March 24 , 2000 . In this prospect i ve , r and omised , non-inferiority trial , women aged 45 years or older with invasive ductal breast carcinoma undergoing breast-conserving surgery were enrolled from 28 centres in nine countries . Patients were r and omly assigned in a 1:1 ratio to receive targeted intraoperative radiotherapy or whole breast external beam radiotherapy , with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy . Neither patients nor investigators or their teams were masked to treatment assignment . Postoperative discovery of predefined factors ( eg , lobular carcinoma ) could trigger addition of external beam radiotherapy to targeted intraoperative radiotherapy ( in an expected 15 % of patients ) . The primary outcome was local recurrence in the conserved breast . The predefined non-inferiority margin was an absolute difference of 2.5 % in the primary endpoint . All r and omised patients were included in the intention-to-treat analysis . This trial is registered with Clinical Trials.gov , number NCT00983684 . FINDINGS 1113 patients were r and omly allocated to targeted intraoperative radiotherapy  and 1119 were allocated to  external beam radiotherapy .  Of 996 patients who received the allocated treatment in the targeted intraoperative radiotherapy group , 854 ( 86 % ) received targeted intraoperative radiotherapy only and 142 ( 14 % ) received targeted intraoperative radiotherapy plus external beam radiotherapy . 1025 ( 92 % ) patients in the external beam radiotherapy group received the allocated treatment . At 4 years , there were six local recurrences in the intraoperative radiotherapy group and five in the external beam radiotherapy group . The Kaplan-Meier estimate of local recurrence in the conserved breast at 4 years was 1.20 % ( 95 % CI 0.53 - 2.71 ) in the targeted intraoperative radiotherapy and 0.95 % ( 0.39 - 2.31 ) in the external beam radiotherapy group ( difference between groups 0.25 % , -1.04 to 1.54 ; p=0.41 ) . The frequency of any complications and major toxicity was similar in the two groups ( for major toxicity , targeted intraoperative radiotherapy , 37 [ 3.3 % ] of 1113 vs external beam radiotherapy , 44 [ 3.9 % ] of 1119 ; p=0.44 ) . Radiotherapy toxicity ( Radiation Therapy Oncology Group grade 3 ) was lower in the targeted intraoperative radiotherapy group ( six patients [ 0.5 % ] ) than in the external beam radiotherapy group ( 23 patients [ 2.1 % ] ; p=0.002 ) . INTERPRETATION For selected patients with early breast cancer , a single dose of radiotherapy delivered at the time of surgery by use of targeted intraoperative radiotherapy should be considered as an alternative to external beam radiotherapy delivered over several weeks . FUNDING University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre , UCLH Charities , National Institute for Health Research Health Technology Assessment programme , Ninewells Cancer Campaign , National Health and Medical Research Council , and German Federal Ministry of Education and Research ( BMBF ) BACKGROUND In women 70 years of age or older who have early breast cancer , it is unclear whether lumpectomy plus tamoxifen is as effective as lumpectomy followed by tamoxifen plus radiation therapy . METHODS Between July 1994 and February 1999 , we r and omly assigned 636 women who were 70 years of age or older and who had clinical stage I ( T1N0M0 according to the tumor-node-metastasis classification ) , estrogen-receptor-positive breast carcinoma treated by lumpectomy to receive tamoxifen plus radiation therapy ( 317 women ) or tamoxifen alone ( 319 women ) . Primary end points were the time to local or regional recurrence , the frequency of mastectomy for recurrence , breast-cancer-specific survival , the time to distant metastasis , and overall survival . RESULTS The only significant difference between the two groups was in the rate of local or regional recurrence at five years ( 1 percent in the group given tamoxifen plus irradiation and 4 percent in the group given tamoxifen alone , P<0.001 ) . There were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence , distant metastases , or five-year rates of overall survival ( 87 percent in the group given tamoxifen plus irradiation and 86 percent in the tamoxifen group , P=0.94 ) . Assessment by physicians and patients of cosmetic results and adverse events uniformly rated tamoxifen plus irradiation inferior to tamoxifen alone . CONCLUSIONS Lumpectomy plus adjuvant therapy with tamoxifen alone is a realistic choice for the treatment of women 70 years of age or older who have early , estrogen-receptor-positive breast cancer PURPOSE / OBJECTIVE To evaluate feasibility and early clinical outcomes of a single fraction of multi-catheter interstitial high-dose rate brachytherapy for accelerated partial breast irradiation ( APBI ) in the elderly . MATERIAL / METHODS From November 2012 to September 2014 , 26 patients ( ≥70 ) with early breast cancer were enrolled in a prospect i ve phase II trial ( NCT01727011 ) . After lumpectomy , intra-operative catheter implant was performed for post-operative APBI ( single fraction 16 Gy ) . Surveillance was achieved at 1 , 3 and 6 months after APBI , then twice a year . Acute toxicity was investigated . Early cosmetic outcome was analyzed ( patient , radiation oncologist , 2 observers ) . Local and regional relapse-free survival , cancer specific survival and overall survival were analyzed . RESULTS Median age was 77 years [ 69 - 89 ] . Median CTV was 41 cc [ 22 - 95 ] . Acute toxicity was observed in 18 pts ( 70 % ) with a total of 44 events : G1 : 75.7 % ; G2 : 22.8 % ; G3 : 4.5 % . Breast fibrosis ( 31.8 % ) , puncture site inflammation ( 13.6 % ) and skin hyperpigmentation ( 11.4 % ) were the most frequent side effects . Cosmetic evaluation at 6 months was excellent/good in 88 % , 92 % , 85 % and 88 % for patient , radiation oncologist , observer # 1 and # 2 respectively . With a median follow-up of 37.2 months [ 35.6 - 42.3 ] , side effects were G1 : 4 pts ( 15 % ) and G2 : 1 pt ( 4 % ) . Three-year Local and regional relapse-free survival , cancer specific survival and overall survival rates were 100 % , 100 % , 100 % and 95.2 % respectively . CONCLUSIONS For elderly early breast cancer , a post-operative multi-catheter interstitial high-dose rate brachytherapy single dose ( 16 Gy ) appears feasible . Acute toxicity is acceptable as well as early cosmetic outcome . Oncologic outcome seems encouraging and allows going forward with new clinical trials focusing on single fraction APBI PURPOSE Regarding adjuvant radiation therapy making decision for elderly women , Albert ( 2013 ) published a nomogram predicting the mastectomy-free survival ( MFS ) rate with or without adjuvant irradiation . Based on this approach , we proposed to investigate the use of accelerated partial breast irradiation ( APBI ) vs. whole breast irradiation ( WBI ) or endocrine therapy alone in elderly low-risk breast cancer patients . METHODS AND MATERIAL S For each elderly woman treated by conserving surgery and APBI ( multicatheter interstitial high-dose-rate brachytherapy )  , 5- and 10-year MFS rates were calculated . For each treated patient , using the Albert nomogram , we calculated the estimated MFS rates at 5 and 10 years , with and without WBI . Then , we compared the estimated MFS rates after no irradiation and WBI vs. observed MFS rates after APBI . RESULTS From 2005 to 2016 , 79 patients were treated . Median followup was 96.8 months [ 68.6 - 104.9 ] , median age was 77 years [ 66 - 89 ] . Expected 5- and 10-year mastectomy rates calculated with the Albert nomogram without WBI were 2.95 % and 7.25 % , respectively , leading to a 10-year MFS rate of 92.7 % . Expected 5- and 10-year mastectomy rates after WBI were 1.41 % and 3.66 % , respectively , leading to a 10-year MFS rate of 96.3 % . Regarding observed MFS rate , 1 pt ( 1.3 % ) experienced a salvage mastectomy . The 10-year MFS rate after APBI was 97.4 % vs. 96.3 % after WBI ( p = 1 ) and 92.7 % after no irradiation ( p = 0.27 ) . No toxicity Grade 3 or more was observed . CONCLUSIONS APBI seems to be an attractive compromise between WBI and no irradiation for elderly women with early stage breast cancer as far as local control , quality of life and cost benefit is concerned PURPOSE To report interim cosmetic and toxicity results of a multicenter r and omized trial comparing accelerated partial-breast irradiation ( APBI ) using three-dimensional conformal external beam radiation therapy ( 3D-CRT ) with whole-breast irradiation ( WBI ) . PATIENTS AND METHODS Women age > 40 years with invasive or in situ breast cancer ≤ 3 cm were r and omly assigned after breast-conserving surgery to 3D-CRT APBI  ( 38.5 Gy in 10 fractions twice daily ) or WBI ( 42.5 Gy in 16 or 50 Gy in 25 daily fractions ± boost irradiation ) . The primary outcome was ipsilateral breast tumor recurrence ( IBTR ) . Secondary outcomes were cosmesis and toxicity . Adverse cosmesis was defined as a fair or poor global cosmetic score . After a planned interim cosmetic analysis , the data , safety , and monitoring committee recommended release of results . There have been too few IBTR events to trigger an efficacy analysis . RESULTS Between 2006 and 2011 , 2,135 women were r and omly assigned to 3D-CRT APBI or WBI . Median follow-up was 36 months . Adverse cosmesis at 3 years was increased among those treated with APBI compared with WBI as assessed by trained nurses ( 29 % v 17 % ; P < .001 ) , by patients ( 26 % v 18 % ; P = .0022 ) , and by physicians review ing digital photographs ( 35 % v 17 % ; P < .001 ) . Grade 3 toxicities were rare in both treatment arms ( 1.4 % v 0 % ) , but grade 1 and 2 toxicities were increased among those who received APBI compared with WBI ( P < .001 ) . CONCLUSION 3D-CRT APBI  increased rates of adverse cosmesis and late radiation toxicity compared with st and ard WBI . Clinicians and patients are caution ed against the use of 3D-CRT APBI outside the context of a controlled trial BACKGROUND For most older women with early breast cancer , st and ard treatment after breast-conserving surgery is adjuvant whole-breast radiotherapy and adjuvant endocrine treatment . We aim ed to assess the effect omission of whole-breast radiotherapy would have on local control in older women at low risk of local recurrence at 5 years . METHODS Between April 16 , 2003 , and Dec 22 , 2009 , 1326 women aged 65 years or older with early breast cancer judged low-risk ( ie , hormone receptor-positive , axillary node-negative , T1-T2 up to 3 cm at the longest dimension , and clear margins ; grade 3 tumour histology or lymphovascular invasion , but not both , were permitted ) , who had had breast-conserving surgery and were receiving adjuvant endocrine treatment , were recruited into a phase 3 r and omised controlled trial at 76 centres in four countries . Eligible patients were r and omly assigned to either whole-breast radiotherapy ( 40 - 50 Gy in 15 - 25 fractions ) or no radiotherapy by computer-generated permuted block r and omisation , stratified by centre , with a block size of four . The primary endpoint was ipsilateral breast tumour recurrence . Follow-up continues and will end at the 10-year anniversary of the last r and omised patient . Analyses were done by intention to treat . The trial is registered on IS R 
    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: BACKGROUND After breast-conserving surgery , 90 % of local recurrences occur within the index quadrant despite the presence of multicentric cancers elsewhere in the breast . Thus , restriction of radiation therapy to the tumour bed during surgery might be adequate for selected patients . We compared targeted intraoperative radiotherapy with the conventional policy of whole breast external beam radiotherapy . METHODS Having safely piloted the new technique of single-dose targeted intraoperative radiotherapy with Intrabeam , we launched the TARGIT-A trial on March 24 , 2000 . In this prospect i ve , r and omised , non-inferiority trial , women aged 45 years or older with invasive ductal breast carcinoma undergoing breast-conserving surgery were enrolled from 28 centres in nine countries . Patients were r and omly assigned in a 1:1 ratio to receive targeted intraoperative radiotherapy or whole breast external beam radiotherapy , with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy . Neither patients nor investigators or their teams were masked to treatment assignment . Postoperative discovery of predefined factors ( eg , lobular carcinoma ) could trigger addition of external beam radiotherapy to targeted intraoperative radiotherapy ( in an expected 15 % of patients ) . The primary outcome was local recurrence in the conserved breast . The predefined non-inferiority margin was an absolute difference of 2.5 % in the primary endpoint . All r and omised patients were included in the intention-to-treat analysis . This trial is registered with Clinical Trials.gov , number NCT00983684 . FINDINGS 1113 patients were r and omly allocated to targeted intraoperative radiotherapy  and 1119 were allocated to  external beam radiotherapy .  Of 996 patients who received the allocated treatment in the targeted intraoperative radiotherapy group , 854 ( 86 % ) received targeted intraoperative radiotherapy only and 142 ( 14 % ) received targeted intraoperative radiotherapy plus external beam radiotherapy . 1025 ( 92 % ) patients in the external beam radiotherapy group received the allocated treatment . At 4 years , there were six local recurrences in the intraoperative radiotherapy group and five in the external beam radiotherapy group . The Kaplan-Meier estimate of local recurrence in the conserved breast at 4 years was 1.20 % ( 95 % CI 0.53 - 2.71 ) in the targeted intraoperative radiotherapy and 0.95 % ( 0.39 - 2.31 ) in the external beam radiotherapy group ( difference between groups 0.25 % , -1.04 to 1.54 ; p=0.41 ) . The frequency of any complications and major toxicity was similar in the two groups ( for major toxicity , targeted intraoperative radiotherapy , 37 [ 3.3 % ] of 1113 vs external beam radiotherapy , 44 [ 3.9 % ] of 1119 ; p=0.44 ) . Radiotherapy toxicity ( Radiation Therapy Oncology Group grade 3 ) was lower in the targeted intraoperative radiotherapy group ( six patients [ 0.5 % ] ) than in the external beam radiotherapy group ( 23 patients [ 2.1 % ] ; p=0.002 ) . INTERPRETATION For selected patients with early breast cancer , a single dose of radiotherapy delivered at the time of surgery by use of targeted intraoperative radiotherapy should be considered as an alternative to external beam radiotherapy delivered over several weeks . FUNDING University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre , UCLH Charities , National Institute for Health Research Health Technology Assessment programme , Ninewells Cancer Campaign , National Health and Medical Research Council , and German Federal Ministry of Education and Research ( BMBF ) BACKGROUND In women 70 years of age or older who have early breast cancer , it is unclear whether lumpectomy plus tamoxifen is as effective as lumpectomy followed by tamoxifen plus radiation therapy . METHODS Between July 1994 and February 1999 , we r and omly assigned 636 women who were 70 years of age or older and who had clinical stage I ( T1N0M0 according to the tumor-node-metastasis classification ) , estrogen-receptor-positive breast carcinoma treated by lumpectomy to receive tamoxifen plus radiation therapy ( 317 women ) or tamoxifen alone ( 319 women ) . Primary end points were the time to local or regional recurrence , the frequency of mastectomy for recurrence , breast-cancer-specific survival , the time to distant metastasis , and overall survival . RESULTS The only significant difference between the two groups was in the rate of local or regional recurrence at five years ( 1 percent in the group given tamoxifen plus irradiation and 4 percent in the group given tamoxifen alone , P<0.001 ) . There were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence , distant metastases , or five-year rates of overall survival ( 87 percent in the group given tamoxifen plus irradiation and 86 percent in the tamoxifen group , P=0.94 ) . Assessment by physicians and patients of cosmetic results and adverse events uniformly rated tamoxifen plus irradiation inferior to tamoxifen alone . CONCLUSIONS Lumpectomy plus adjuvant therapy with tamoxifen alone is a realistic choice for the treatment of women 70 years of age or older who have early , estrogen-receptor-positive breast cancer PURPOSE / OBJECTIVE To evaluate feasibility and early clinical outcomes of a single fraction of multi-catheter interstitial high-dose rate brachytherapy for accelerated partial breast irradiation ( APBI ) in the elderly . MATERIAL / METHODS From November 2012 to September 2014 , 26 patients ( ≥70 ) with early breast cancer were enrolled in a prospect i ve phase II trial ( NCT01727011 ) . After lumpectomy , intra-operative catheter implant was performed for post-operative APBI ( single fraction 16 Gy ) . Surveillance was achieved at 1 , 3 and 6 months after APBI , then twice a year . Acute toxicity was investigated . Early cosmetic outcome was analyzed ( patient , radiation oncologist , 2 observers ) . Local and regional relapse-free survival , cancer specific survival and overall survival were analyzed . RESULTS Median age was 77 years [ 69 - 89 ] . Median CTV was 41 cc [ 22 - 95 ] . Acute toxicity was observed in 18 pts ( 70 % ) with a total of 44 events : G1 : 75.7 % ; G2 : 22.8 % ; G3 : 4.5 % . Breast fibrosis ( 31.8 % ) , puncture site inflammation ( 13.6 % ) and skin hyperpigmentation ( 11.4 % ) were the most frequent side effects . Cosmetic evaluation at 6 months was excellent/good in 88 % , 92 % , 85 % and 88 % for patient , radiation oncologist , observer # 1 and # 2 respectively . With a median follow-up of 37.2 months [ 35.6 - 42.3 ] , side effects were G1 : 4 pts ( 15 % ) and G2 : 1 pt ( 4 % ) . Three-year Local and regional relapse-free survival , cancer specific survival and overall survival rates were 100 % , 100 % , 100 % and 95.2 % respectively . CONCLUSIONS For elderly early breast cancer , a post-operative multi-catheter interstitial high-dose rate brachytherapy single dose ( 16 Gy ) appears feasible . Acute toxicity is acceptable as well as early cosmetic outcome . Oncologic outcome seems encouraging and allows going forward with new clinical trials focusing on single fraction APBI PURPOSE Regarding adjuvant radiation therapy making decision for elderly women , Albert ( 2013 ) published a nomogram predicting the mastectomy-free survival ( MFS ) rate with or without adjuvant irradiation . Based on this approach , we proposed to investigate the use of accelerated partial breast irradiation ( APBI ) vs. whole breast irradiation ( WBI ) or endocrine therapy alone in elderly low-risk breast cancer patients . METHODS AND MATERIAL S For each elderly woman treated by conserving surgery and APBI ( multicatheter interstitial high-dose-rate brachytherapy )  , 5- and 10-year MFS rates were calculated . For each treated patient , using the Albert nomogram , we calculated the estimated MFS rates at 5 and 10 years , with and without WBI . Then , we compared the estimated MFS rates after no irradiation and WBI vs. observed MFS rates after APBI . RESULTS From 2005 to 2016 , 79 patients were treated . Median followup was 96.8 months [ 68.6 - 104.9 ] , median age was 77 years [ 66 - 89 ] . Expected 5- and 10-year mastectomy rates calculated with the Albert nomogram without WBI were 2.95 % and 7.25 % , respectively , leading to a 10-year MFS rate of 92.7 % . Expected 5- and 10-year mastectomy rates after WBI were 1.41 % and 3.66 % , respectively , leading to a 10-year MFS rate of 96.3 % . Regarding observed MFS rate , 1 pt ( 1.3 % ) experienced a salvage mastectomy . The 10-year MFS rate after APBI was 97.4 % vs. 96.3 % after WBI ( p = 1 ) and 92.7 % after no irradiation ( p = 0.27 ) . No toxicity Grade 3 or more was observed . CONCLUSIONS APBI seems to be an attractive compromise between WBI and no irradiation for elderly women with early stage breast cancer as far as local control , quality of life and cost benefit is concerned PURPOSE To report interim cosmetic and toxicity results of a multicenter r and omized trial comparing accelerated partial-breast irradiation ( APBI ) using three-dimensional conformal external beam radiation therapy ( 3D-CRT ) with whole-breast irradiation ( WBI ) . PATIENTS AND METHODS Women age > 40 years with invasive or in situ breast cancer ≤ 3 cm were r and omly assigned after breast-conserving surgery to 3D-CRT APBI  ( 38.5 Gy in 10 fractions twice daily ) or WBI ( 42.5 Gy in 16 or 50 Gy in 25 daily fractions ± boost irradiation ) . The primary outcome was ipsilateral breast tumor recurrence ( IBTR ) . Secondary outcomes were cosmesis and toxicity . Adverse cosmesis was defined as a fair or poor global cosmetic score . After a planned interim cosmetic analysis , the data , safety , and monitoring committee recommended release of results . There have been too few IBTR events to trigger an efficacy analysis . RESULTS Between 2006 and 2011 , 2,135 women were r and omly assigned to 3D-CRT APBI or WBI . Median follow-up was 36 months . Adverse cosmesis at 3 years was increased among those treated with APBI compared with WBI as assessed by trained nurses ( 29 % v 17 % ; P < .001 ) , by patients ( 26 % v 18 % ; P = .0022 ) , and by physicians review ing digital photographs ( 35 % v 17 % ; P < .001 ) . Grade 3 toxicities were rare in both treatment arms ( 1.4 % v 0 % ) , but grade 1 and 2 toxicities were increased among those who received APBI compared with WBI ( P < .001 ) . CONCLUSION 3D-CRT APBI  increased rates of adverse cosmesis and late radiation toxicity compared with st and ard WBI . Clinicians and patients are caution ed against the use of 3D-CRT APBI outside the context of a controlled trial BACKGROUND For most older women with early breast cancer , st and ard treatment after breast-conserving surgery is adjuvant whole-breast radiotherapy and adjuvant endocrine treatment . We aim ed to assess the effect omission of whole-breast radiotherapy would have on local control in older women at low risk of local recurrence at 5 years . METHODS Between April 16 , 2003 , and Dec 22 , 2009 , 1326 women aged 65 years or older with early breast cancer judged low-risk ( ie , hormone receptor-positive , axillary node-negative , T1-T2 up to 3 cm at the longest dimension , and clear margins ; grade 3 tumour histology or lymphovascular invasion , but not both , were permitted ) , who had had breast-conserving surgery and were receiving adjuvant endocrine treatment , were recruited into a phase 3 r and omised controlled trial at 76 centres in four countries . Eligible patients were r and omly assigned to either whole-breast radiotherapy ( 40 - 50 Gy in 15 - 25 fractions ) or no radiotherapy by computer-generated permuted block r and omisation , stratified by centre , with a block size of four . The primary endpoint was ipsilateral breast tumour recurrence . Follow-up continues and will end at the 10-year anniversary of the last r and omised patient . Analyses were done by intention to treat . The trial is registered on IS R 
    Output:
    