***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 BACKGROUND 5-year results of the UK St and ardisation of Breast Radiotherapy ( START ) trials suggested that lower total doses of radiotherapy delivered in fewer , larger doses ( fractions ) are at least as safe and effective as the historical st and ard regimen ( 50 Gy in 25 fractions ) for women after primary surgery for early breast cancer . In this prespecified analysis , we report the 10-year follow-up of the START trials testing 13 fraction and 15 fraction regimens . METHODS From 1999 to 2002 , women with completely excised invasive breast cancer ( pT1 - 3a , pN0 - 1 , M0 ) were enrolled from 35 UK radiotherapy centres . Patients were r and omly assigned to a treatment regimen after primary surgery followed by chemotherapy and endocrine treatment ( where prescribed ) . R and omisation was computer-generated and stratified by centre , type of primary surgery ( breast-conservation surgery or mastectomy ) , and tumour bed boost radiotherapy . In START-A , a regimen of 50 Gy in 25 fractions over 5 weeks was compared with 41·6 Gy or 39 Gy in 13 fractions over 5 weeks . In START-B , a regimen of 50 Gy in 25 fractions over 5 weeks was compared with 40 Gy in 15 fractions over 3 weeks . Eligibility criteria included age older than 18 years and no immediate surgical reconstruction . Primary endpoints were local-regional tumour relapse and late normal tissue effects . Analysis was by intention to treat . Follow-up data are still being collected . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N59368779 . FINDINGS START-A enrolled 2236 women . Median follow-up was 9·3 years ( IQR 8·0 - 10·0 ) , after which 139 local-regional relapses had occurred . 10-year rates of local-regional relapse did not differ significantly between the 41·6 Gy and 50 Gy regimen groups ( 6·3 % , 95 % CI 4·7 - 8·5 vs 7·4 % , 5·5 - 10·0 ; hazard ratio [ HR ] 0·91 , 95 % CI 0·59 - 1·38 ; p=0·65 ) or the 39 Gy ( 8·8 % , 95 % CI 6·7 - 11·4 ) and 50 Gy regimen groups ( HR 1·18 , 95 % CI 0·79 - 1·76 ; p=0·41 ) . In START-A , moderate or marked breast in duration , telangiectasia , and breast oedema were significantly less common normal tissue effects in the 39 Gy group than in the 50 Gy group . Normal tissue effects did not differ significantly between 41·6 Gy and 50 Gy groups . START-B enrolled 2215 women . Median follow-up was 9·9 years ( IQR 7·5 - 10·1 ) , after which 95 local-regional relapses had occurred . The proportion of patients with local-regional relapse at 10 years did not differ significantly between the 40 Gy group ( 4·3 % , 95 % CI 3·2 - 5·9 ) and the 50 Gy group ( 5·5 % , 95 % CI 4·2 - 7·2 ; HR 0·77 , 95 % CI 0·51 - 1·16 ; p=0·21 ) . In START-B , breast shrinkage , telangiectasia , and breast oedema were significantly less common normal tissue effects in the 40 Gy group than in the 50 Gy group . INTERPRETATION Long-term follow-up confirms that appropriately dosed hypofractionated radiotherapy is safe and effective for patients with early breast cancer . The results support the continued use of 40 Gy in 15 fractions , which has already been adopted by most UK centres as the st and ard of care for women requiring adjuvant radiotherapy for invasive early breast cancer . FUNDING Cancer Research UK , UK Medical Research Council , UK Department of Health OBJECTIVES To assess whether omission of postoperative radiotherapy in women with ' low-risk ' axillary node negative breast cancer ( T0 - 2 ) treated by breast-conserving surgery and endocrine therapy improves quality of life and is more cost-effective . DESIGN A r and omised controlled clinical trial , using a method of minimisation balanced by centre , grade of cancer , age , lymphatic/vascular invasion and preoperative endocrine therapy , was performed . A non-r and omised cohort was also recruited , in order to complete a comprehensive cohort study . SETTING The setting was breast cancer clinics in cancer centres in the UK . PARTICIPANTS Patients aged 65 years or more were eligible provided that their cancers were considered to be at low risk of local recurrence , were suitable for breast-conservation surgery , were receiving endocrine therapy and were able and willing to give informed consent . INTERVENTIONS The st and ard treatment of postoperative breast irradiation or the omission of radiotherapy . MAIN OUTCOME MEASURES Quality of life was the primary outcome measure , together with anxiety and depression and cost-effectiveness . Secondary outcome measures were recurrence rates , functional status , treatment-related morbidity and cosmesis . The principal method of data collection was by question naire , completed at home with a research nurse at four times over 15 months . RESULTS The hypothesised improvement in overall quality of life with the omission of radiotherapy was not seen in the EuroQol assessment or in the functionality and symptoms summary domains of the European Organisation for Research in the Treatment of Cancer ( EORTC ) scales . Some differences were apparent within subscales of the EORTC question naires , and insights into the impact of treatment were also provided by the qualitative data obtained by open-ended questions . Differences were most apparent shortly after the time of completion of radiotherapy . Radiotherapy was then associated with increased breast symptoms and with greater fatigue but with less insomnia and endocrine side-effects . Patients had significant concerns about the delivery of radiotherapy services , such as transport , accommodation and travel costs associated with receiving radiotherapy . By the end of follow-up , patients receiving radiotherapy were expressing less anxiety about recurrence than those who had not received radiotherapy .  Functionality was not greatly affected by treatment . Within the r and omised controlled trial , the Barthel Index demonstrated a small but significant fall in functionality with radiotherapy compared with the no radiotherapy arm of the trial . Results from the non-r and omised patients did not confirm this effect , however . Cosmetic results were better in those not receiving radiotherapy but this did not appear to be an important issue to the patients . The use of home-based assessment s by a research nurse proved to be an effective way of obtaining high- quality data . Costs to the NHS associated with postoperative radiotherapy were calculated to be of the order of 2000 pounds per patient . In the follow-up in this study , there were no recurrences , and the quality of life utilities from EuroQol were almost identical . CONCLUSIONS Although there are no differences in overall quality of life scores between the patients treated with and without radiotherapy , there are several dimensions that exhibit significant advantage to the omission of irradiation . Over the first 15 months , radiotherapy for this population is not a cost-effective treatment . However , the early postoperative outcome does not give a complete answer and the eventual cost-effectiveness will only become clear after long-term follow-up . Extrapolations from these data suggest that radiotherapy may not be a cost-effective treatment unless it results in a recurrence rate that is at least 5 % lower in absolute terms than those treated without radiotherapy . Further research is needed into a number of areas including the long-term aspects of quality of life , clinical outcomes , costs and consequences of omitting radiotherapy 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 invas 
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AUTHORS ' CONCLUSIONS It appeared that local recurrence and ' elsewhere primaries ' ( new primaries in the ipsilateral breast ) are increased with PBI/APBI ( the difference was small ) , but we found no evidence of detriment to other oncological outcomes .
It appeared that cosmetic outcomes and some late effects were worse with PBI/APBI but its use was associated with less acute skin toxicity .