***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: AIMS To evaluate the diagnostic and therapeutic procedures which were followed in a European Organization for Research and Treatment of Cancer ( EORTC ) r and omized clinical trial investigating the role of radiotherapy in breast-conserving treatment ( BCT ) for ductal carcinoma in situ ( DCIS ) of the breast . METHODS The medical files of 824 of the 1010 r and omized patients ( 82 % ) were review ed during site visits to 30 participating institutes . RESULTS Large variations occurred , particularly in the surgical procedures and histopathological work-up which were performed . Important risk factors like tumour size and margin status were poorly quantified in the medical files . CONCLUSIONS These findings emphasize the need for establishing uniform guidelines for diagnostic and therapeutic procedures for DCIS , and for clearly defined risk factors for recurrence after BCT for DCIS . Because of its r and omized nature , the main question of the trial , i.e. the effect of  radiotherapy  on the risk of local recurrence , will not be influenced by variation . The risk of local recurrence in itself , and hence the success of BCT for DCIS , may however be influenced by the quality of the initial procedures that were conducted AIM The primary aims were to study risk factors for an ipsilateral breast event ( IBE ) after sector resection for ductal carcinoma in situ of the breast ( DCIS ) in a trial comparing adjuvant radiotherapy to no therapy and to assess predictive factors for response to radiotherapy . Secondary aims were to analyse reproducibility of the histopathological evaluation and to estimate correctness of diagnosis in the trial . SETTING A r and omised trial in Sweden ( the SweDCIS trial ) , including 1046 women with a median of 5.2 years of follow-up in a population , offered routine mammographic screening . METHODS A case-cohort design with a total of 161 cases of IBE ( 42 of those being members of the subcohort ) and 284 sample d for the sub-cohort . Ninety five percent of the participants ' slides could be retrieved and were re-evaluated by three experienced pathologists . RESULTS Low nuclear grade ( NG 1 - 2 ) and absence of necrosis halves the risk of IBE in both irradiated and non-irradiated patients . Lesion size , margins of excision and age at diagnosis did not modify these associations . The presence of necrosis modified the effect of radiotherapy : relative risk was 0.40 with necrosis present and 0.07 with necrosis absent ( p-value for interaction 0.068 ) . In all subsets of prognostic factors , radiotherapy conferred a substantial benefit . The risk factors for in situ and invasive IBE were similar . The agreement between pathologists was moderate ( kappa=0.486 ) . Correctness of diagnosis in the subcohort of SweDCIS was 84.8 % . CONCLUSION Although nuclear grade and necrosis carry prognostic information , we could not define a group with very low risk after sector resection alone . Radiotherapy has a protective effect in all substrata of risk factors studied . The interaction between the presence of necrosis and radiotherapy is a clinical ly and biologically relevant research area PURPOSE Evaluate the effects of radiotherapy after sector resection for ductal carcinoma in situ of the breast ( DCIS ) in patient groups as defined by age , size of the lesion , focality , completeness of excision and mode of detection . PATIENTS AND METHODS A total of 1,067 women in Sweden were r and omly assigned to either postoperative radiotherapy ( RT ) or control from 1987 to 1999 , and 1,046 were followed for a mean of 8 years . The main outcome was new ipsilateral breast cancer events and distant metastasis-free survival analyzed according to intention to treat . RESULTS There were 64 ipsilateral events in the RT arm and 141 in the control group corresponding to a risk reduction of 16.0 percentage points at 10 years ( 95 % CI , 10.3 % to 21.6 % ) and a relative risk of 0.40 ( 95 % CI , 0.30 to 0.54 ) . There was no statistically significant difference in distant metastasis-free survival . There was an effect modification by age , yielding a low effect of RT in women younger than 50 , but substantial protection in women older than 60 years . The age effect was not confounded by focality , lesion size , completeness of excision , or detection mode . There was no group as defined by our stratification variables that had a low risk without radiotherapy . CONCLUSION Our results indicate that younger women have a low protective effect of conventional RT after sector resection . Older women benefit substantially . We caution that the age effect was seen in a subgroup analysis . Further search with conventional clinical variables for a low risk group that does not need RT does not seem fruitful BACKGROUND Inadequate surgical excision with residual involvement of resection margins by tumour after breast conservation results in increased local recurrence rates . To reduce this risk positive margins are , therefore , usually excised . Systemic treatment with tamoxifen or chemotherapy reduces local recurrence , along with radiotherapy . However , no studies to date have examined the correlation between chemoendocrine treatment , together with radiotherapy , and local relapse in patients with unexcised involved resection margins , having had breast conservation treatment . PATIENTS AND METHODS The histopathology reports were review ed of 184 patients who were treated from June 1991 to August 1995 within our r and omised study of neoadjuvant versus adjuvant chemoendocrine therapy with mitozantrone and methotrexate ( 2 M ) + /- mitomycin-C ( 3 M ) and tamoxifen , used concurrently with radiation following conservation surgical treatment . Histological resection margin was considered positive if ductal carcinoma in situ ( DCIS ) or invasive carcinoma was present microscopically less than 1 mm from the excision margin . RESULTS Although 38 % of patients had unexcised microscopically involved margins , local relapse rate as first site of relapse was only 1.9 % after a median follow up of 57 months . There was no difference in distant relapse ( P = 0.2 ) and survival ( P = 0.5 ) between the positive and negative margins groups . CONCLUSIONS The presence of positive unexcised margins does not have a significant effect on outcome in patients who are treated with chemoendocrine therapy together with  radiotherapy . Further clinical trials are required PURPOSE The European Organisation for Research and Treatment of Cancer conducted a r and omized trial investigating the role of radiotherapy ( RT ) after local excision ( LE ) of ductal carcinoma-in-situ ( DCIS ) of the breast . We analyzed the efficacy of RT with 10 years follow-up on both the overall risk of local recurrence ( LR ) and related to clinical , histologic , and treatment factors . PATIENTS AND METHODS After complete LE , women with DCIS were r and omly assigned to no further treatment or RT ( 50 Gy ) . One thous and ten women with mostly ( 71 % ) mammographically detected DCIS were included . The median follow-up was 10.5 years . RESULTS The 10-year LR-free rate was 74 % in the group treated with LE alone compared with 85 % in the women treated by LE plus RT ( log-rank P < .0001 ; hazard ratio [ HR ] = 0.53 ) . The risk of DCIS and invasive LR was reduced by 48 % ( P = .0011 ) and 42 % ( P = .0065 ) respectively . Both groups had similar low risks of metastases and death . At multivariate analysis , factors significantly associated with an increased LR risk were young age ( < or = 40 years ; HR = 1.89 ) , symptomatic detection ( HR = 1.55 ) , intermediately or poorly differentiated DCIS ( as opposed to well-differentiated DCIS ; HR = 1.85 and HR = 1.61 respectively ) , cribriform or solid growth pattern ( as opposed to clinging/micropapillary subtypes ; HR = 2.39 and HR = 2.25 respectively ) , doubtful margins ( HR = 1.84 ) , and treatment by LE alone ( HR = 1.82 ) . The effect of RT was homogeneous across all assessed risk factors . CONCLUSION With long-term follow-up , RT after LE for DCIS continued to reduce the risk of LR , with a 47 % reduction at 10 years . All patient subgroups benefited from RT Selection of patients for r and omised clinical trials may have a large impact on the applicability of the study results to the general population presenting the same disorder . However , clinical characteristics and outcome data on non-entered patients are usually not available . The effects of patient selection for the EORTC 10853 trial investigating the role of radiotherapy in breast conserving therapy for ductal carcinoma in situ have been studied , in an analysis of all patients treated for ductal carcinoma in situ in five participating institutes . The reasons for not entering patients were evaluated and treatment results of the r and omised patients were compared to those not entered . A total of 910 patients were treated for ductal carcinoma in situ . Of these , 477 ( 52 % ) were ineligible , with the size of the lesion being the main reason for in eligibility ( 30 % of all ductal carcinoma in situ ) . Of the 433 eligible patients , 278 ( 64 % ) were r and omised into the trial . The main reasons for non-entry of eligible patients were either physicians ' preference for one of the treatment arms ( 26 % ) or patients ' refusal ( 9 % ) . These percentages showed significant variation among the institutes . At 4 years follow-up , those patients not entered in the trial and treated with local excision and radiotherapy , had higher local recurrence rates than the patients r and omised in the trial and treated with the same approach , ( 17 vs 2 % , P=0.03 ) . The patients treated with local excision alone had equal local recurrence rates ( 11 % in both groups ) . Selection of patients may explain the differences in outcome of the r and omised patients , and those not-entered . Thus , the results of this trial may not be applicable to all patients with ductal carcinoma in situ In EORTC trial 10853 , patients with histologically confirmed surgical clearance of ductal carcinoma in situ ( DCIS ) are being r and omised to observation alone or to receive external radiation to the breast ( 50 Gy ) . So far , 190 patients have been entered from 27 centres . An analysis has been conducted of patients with DCIS presenting to 6 of the participating hospitals . Within these centres there was a total of 216 patients with biopsy confirmed DCIS , without invasion , between 1985 and 1989 . However only 77 ( 36 % ) were entered into the trial . The major reason for non-entry was that DCIS was too extensive ( 76/139 , 55 % ) , so that in situ disease extended to the margins of excision . Other reasons for exclusion included prior breast cancer ( 18 % ) , delay in histological diagnosis ( 6 % ) and a lump measuring more than 3 cm in diameter ( 4 % ) . Only 6 patients ( 4 % ) refused to take part in the trial . Thus the eventual results of the trial may be applicable only to a minority of patients with DCIS The aim of this work is to report the preliminary results of the Hungarian multicentric r and omised DCIS study . Between 2000 and 2007 , 278 patients with ductal carcinoma in situ ( DCIS ) treated by breast-conserving surgery were r and omised according to predetermined risk groups . Low/intermediate-risk patients ( n=29 ) were r and omised to 50 Gy whole-breast irradiation ( WBI ) or observation .  High-risk cases ( n=235 ) were allocated to receive 50 Gy WBI vs. 50 Gy WBI plus 16 Gy tumour bed boost .  Very high-risk patients ( patients with involved surgical margins ; n=14 ) were r and omised to 50 Gy WBI plus 16 Gy tumour bed boost or reoperation ( reexcision plus radiotherapy or mastectomy alone ) . Immunohistochemistry ( IHC ) was performed to detect the expression of potential molecular prognostic markers ( ER , PR , Her2 , p53 , Bcl-2 and Ki-67 ) . At a median follow-up of 36 months no recurrence was observed in the low/intermediate- and very high-risk patient groups . In the high-risk group , 4 ( 1.7 % ) local recurrences and 1 ( 0.4 % ) distant metastasis occurred . No patient died of breast cancer . In the high-risk group of patients , the 3- and 5-year probability of local recurrence was 1.1 % and 3.1 % , respectively . The positive immunostaining for Her2 ( 38 % ) , p53 ( 37 % ) and Ki-67 ( 44 % ) correlated with a high nuclear grade . Significant inverse correlation was found between the expression of ER ( 77 % ) , PR ( 67 % ) , Bcl-2 ( 64 % ) and grade . Preliminary results suggest that breast-conserving surgery followed by radiotherapy yields an annual local recurrence rate of less than 1 % in patients with DCIS . IHC of molecular prognostic markers can assist to gain insight into the biologic heterogeneity of DCIS BACKGROUND As a consequence of mammographic breast screening programmes , ductal carcinoma in situ is diagnosed with increasing frequency . Mastectomy for localised ductal carcinoma in situ is 
    Output:
    
All the subgroups analysed benefited from addition of radiotherapy .
This review confirms the benefit of adding radiotherapy to breast conserving surgery for the treatment of all women diagnosed with DCIS .
No long-term toxicity from use of radiotherapy was identified