***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 
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    Input: Background The initial quality assurance programme of the EORTC Radiotherapy Cooperative Group in trial 22881/10882 is described . The implication s of its results for quality assurance in future trials are discussed . Methods In the EORTC trial 22881/10882 patients with stage I or II breast cancer are treated with tumor excision , axillary dissection , 50 Gy whole breast irradiation and then r and omized to receive a boost dose of 15 Gy or no boost following complete tumor excision , or between 10 Gy or 25 Gy in case of incomplete excision . To avoid or diminish protocol deviations and to quantify inevitable variations an extensive initial quality assurance programme was conducted . The programme consisted of a dummy run procedure , an individual case review procedure , in vivo dosimetry studies and phantom dosimetry studies . Results This combination of quality assurance procedures allows a good estimation of patient to patient and inter-institutional variations , and early detection of ( potential ) systematic protocol deviations of 3 types : 1 . Deviations due to ambiguities in the protocol prescriptions . 2 . Deviations not known to the institution , such as mistakes in implementation of treatment planning algorithms result ing in a systematic overdosage or underdosage . 3 . Inability of an institution to cope with ( precise ) protocol prescriptions for technical or logistic reasons . Discussion The first 2 types of deviations may be corrected or avoided by direct discussion s and recommendations . With respect to the third type it is up to the trial coordinator to accept participation or not , depending upon the relative importance of the particular deviation(s ) for the trial end points . To be effective , such a quality assurance programme must be implemented as early as possible in the course of a clinical trial . ZusammenfassungHintergrundIm Anfang der EORTC-Studie 22881/10882 wurde ein ausführliches Qualitätssicherungsprogramm durchgeführt . Die Ergebnisse dieses Qualitätssicherungsprogramms werden beschrieben , und die Implikationen für Qualitätssicherungsmaßnahmen zukünftiger Studien werden diskutiert . Method enIn der EORTC-Studie 22881/10882 wurden Patientinnen mit Brustkrebs Stadium I und II wie folgt beh and elt : Exzision des Tumors und Dissektion in der Achsel , gefolgt von Bestrahlung der gesamten Brust mit 50 Gy . Danach wurden die Patientinnen r and omisiert , i m Falle vollständiger Exzision zwischen keinem Boost oder einem Boost von 15 Gy , i m Falle einer unvollständigen Exzision zwischen einem Boost von 10 Gy oder 25 Gy . Um Protokollverstöße zu vermeiden oder zu verringern und um unvermeidliche Variationen zu quantifizieren , wurde am Anfang der Studie ein Qualitätssicherungprogramm durchgeführt . Das Programm best and aus einem Probelauf , einer retrospektiven Analyse von individuellen Fällen und der Auswertung der Dosimetrie an Patientinnen und am Phantom . ErgebnisseDas Qualitätssicherungsprogramm ermöglicht sowohl eine Schätzung der Variation zwischen verschiedenen Patientinnen und Instituten als auch die frühzeitige Erkennung möglicher systematischer Protokollverstöße in drei Kategorien : 1 . Abweichungen wegen Ungenauigkeiten in den Protokollvorschriften , 2 . den Instituten unbekannte Abweichungen , wie zum Beispiel Über- oder Unterdosierung als Folge fehlerhafter Anwendung von Planungsalgorithmen und 3 . Schwierigkeiten in Instituten bei der Ausführung von Protokollvorschriften aus technischen oder logistischen Gründen . DiskussionDie ersten zwei Abweichungskategorien können durch direkte Diskussion und Empfehlungen korrigiert und für zukünftige Patientinnen vermieden werden . Bezogen auf die dritte Kategorie liegt es in der Verantwortlichkeit des Studienkoordinators , die Teilnahme von Instituten zu akzeptieren i m Hinblick auf den Einfluß , den zu erwartende Regelverletzungen auf die Ziele der Studie haben können . Um seine Aufgabe effektiv zu erfüllen , muß ein Qualitätssicherungsprogramm möglichst früh in den Ablauf einer Studie aufgenommen werden 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 ) The EORTC 22881 - 10882 trial in 5178 conservatively treated early breast cancer patients showed that a 16 Gy boost dose significantly improved local control , but increased the risk of breast fibrosis . To investigate predictors for the long-term risk of fibrosis , Cox regression models of the time to moderate or severe fibrosis were developed on a r and om set of 1797 patients with and 1827 patients without a boost , and vali date d in the remaining set . The median follow-up was 10.7 years . The risk of fibrosis significantly increased ( P<0.01 ) with increasing maximum whole breast irradiation ( WBI ) dose and with concomitant chemotherapy , but was independent of age . In the boost arm , the risk further increased ( P<0.01 ) if patients had post-operative breast oedema or haematoma , but it decreased ( P<0.01 ) if WBI was given with > 6 MV photons . The c-index was around 0.62 . Nomograms with these factors are proposed to forecast the long-term risk of moderate or severe fibrosis Two r and omized trials have recently shown a statistically significant improvement in local control when a boost is employed in the conservative treatment of early breast cancer . However , unresolved issues of cost effectiveness , potentially increased toxicity and the inability to automatically generalize these results to Australian and New Zeal and practice remain . In view of these unresolved controversies , the St George and Wollongong hospitals breast boost trial ( SGW trial ) will continue to recruit PURPOSE To determine whether the effect of an additional " boost " radiation after breast conservative therapy ( BCT ) on local control depends on age and evaluate the impact of a treatment policy with a threshold for age . PATIENTS AND METHODS We used data from EORTC 22881 - 10882 trial , with median follow-up of 77.4 months . Patients receiving BCT and 50Gy whole breast irradiation were r and omized to no boost and 16Gy boost ( N=5318 ) . RESULTS In univariate analysis , a boost reduced local failure by a factor of 2 ( P<0.0001 ) . Multivariate analysis showed local control increased with age ( P=0.0003 ) . There was no evidence that the relative effect of a boost on local control depends on age ( P=0.97 ) However in younger patients the 5-year local failure was higher , therefore the absolute reduction was greater . If the threshold-age for boost treatment were set at 40 years , 8.4 % of the study population would receive a boost , result ing in a 5-year local failure of 6.1 % in the study population . Changing the threshold-age to 60 years , 67 % of the study population would receive a boost and the 5-year local failure would be reduced to 4.4 % . CONCLUSIONS In younger patients a boost dose result ed in a greater absolute reduction of local failure . The relative risk reduction was however similar for all ages . Applying a treatment policy with a threshold-age of 60 would result in 0.6 % increase in local failure in the total study population , while sparing the boost to 1/3 of the patients Breast cancer multifocality was studied in mastectomy specimens by correlated specimen radiography and histologic techniques . The patients chosen for study were comparable to those eligible for breast‐conserving surgical therapy . Two study groups , one with 282 invasive cancers ( T1‐2 ) and the other with 32 intraductal cancers , were selected from a group of 399 consecutive cases by omitting patients who were clearly , or very probably , not c and i date s for breast‐conserving surgical therapy according to current trial criteria . Omitted patients included those with clinical ly and /or radiologically multifocal cancers and patients with tumor extension into the chest wall or skin ( 7 % ) . Also excluded were the socalled diffuse invasive cancers ( 8 % ) , the clinical ly and radiologically occult tumors ( 3 % ) , and the invasive cancers larger than 5 cm ( 3 % ) . Of the 282 invasive cancers , 105 ( 37 % ) showed no tumor foci in the mastectomy specimen around the reference mass . In 56 ( 20 % ) tumor foci were present within 2 cm , and in 121 ( 43 % ) tumor was found more than 2 cm from the reference tumor . In 75 ( 27 % ) the tumor foci beyond 2 cm were histologically noninvasive cancers , and in 46 cases ( 16 % ) they contained invasive cancers as well . A comparison between the group with reference tumors less than 2 cm and the group with reference tumors more than 2 cm in size showed no significant difference between the groups in terms of presence or absence of tumor foci or distance of tumor foci from the reference tumor . If the 264 invasive cancers in this series that were 4 cm or less in diameter had been removed with a margin of 3 to 4 cm , 7 % to 9 % of the patients would have had invasive cancer left in the remaining breast tissue , and 4 % to 9 % would have had foci of noninvasive cancer left in the remaining breast tissue . On the basis of the data on the distribution of tumor at different distances from the reference tumor , the current study estimates the expected rates of local recurrences after breast‐conserving surgical procedures relative to the extensiveness of the excision . The possible impact of postoperative local radiation therapy on the rates of expected local recurrence is discussed Background and Aims : To evaluate the effect of electron and high-dose-rate brachytherapy ( HDR BT ) boost on local tumor control ( LTC ) , side effects and cosmesis after breast-conserving surgery ( BCS ) in a prospect i ve r and omized study . Patients and Methods : 207 women with stage I – II breast cancer who underwent BCS were treated by 50 Gy irradiation to the whole breast and then r and omly assigned 
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Subgroup analysis including women older than 40 years of age yielded a HR of 0.65 ( 95 % CI 0.53 to 0.81 ; 2 studies , 5058 women , high- quality evidence ) .We found no data for the outcomes of acute toxicity , quality of life , or costs .
AUTHORS ' CONCLUSIONS It appears that local control rates are increased with the boost to the tumour bed , but we found no evidence of a benefit for other oncological outcomes .
Subgroup analysis including women older than 40 years of age yielded similarly significant results .
Objective percentage of breast retraction assessment appears similar between groups .
It appears that the cosmetic outcome is worse with the boost to the tumour bed , but only when measured by a panel , not when assessed by a physician