Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. Accelerated partial breast irradiation for suitable elderly women using a single fraction of multicatheter interstitial high-dose-rate brachytherapy: Early results of the Single-Fraction Elderly Breast Irradiation (SiFEBI) Phase I/II trial. Accelerated partial breast irradiation for elderly women with early breast cancer: A compromise between whole breast irradiation and omission of radiotherapy. Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lumpectomy plus tamoxifen or anastrozole with or without whole breast irradiation in women with favorable early breast cancer. Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial. Impact of partial versus whole breast radiation therapy on fatigue, perceived stress, quality of life and natural killer cell activity in women with breast cancer Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Accelerated partial breast irradiation using intensity-modulated radiotherapy technique compared to whole breast irradiation for patients aged 70 years or older: subgroup analysis from a randomized phase 3 trial EORTC elderly task force position paper: approach to the older cancer patient. Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. Conservative surgery with and without radiotherapy in elderly patients with early-stage breast cancer: a prospective randomised multicentre trial. Partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy. Long-term results of a phase II prospective study. Accelerated partial breast irradiation with IMRT: new technical approach and interim analysis of acute toxicity in a phase III randomized clinical trial. GERICO-03 phase II trial of accelerated and partial breast irradiation in elderly women: feasibility, reproducibility, and impact on functional status. Radiation therapy and tamoxifen after breast-conserving surgery: updated results of a 2 x 2 randomised clinical trial in patients with low risk of recurrence. Single fraction of accelerated partial breast irradiation in the elderly: early clinical outcome Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. Accelerated Partial Breast Irradiation: Executive summary for the update of an ASTRO Evidence-Based Consensus Statement.
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 RCT N.com , number IS RCT N95889329 . FINDINGS 658 women who had undergone breast-conserving surgery and who were receiving adjuvant endocrine treatment were r and omly assigned to receive whole-breast irradiation and 668 were allocated to no further treatment . After median follow-up of 5 years ( IQR 3·84 - 6·05 ) , ipsilateral breast tumour recurrence was 1·3 % ( 95 % CI 0·2 - 2·3 ; n=5 ) in women assigned to whole-breast radiotherapy and 4·1 % ( 2·4 - 5·7 ; n=26 ) in those assigned no radiotherapy ( p=0·0002 ) . Compared with women allocated to whole-breast radiotherapy , the univariate hazard ratio for ipsilateral breast tumour recurrence in women assigned to no radiotherapy was 5·19 ( 95 % CI 1·99 - 13·52 ; p=0·0007 ) . No differences in regional recurrence , distant metastases , contralateral breast cancers , or new breast cancers were noted between groups . 5-year overall survival was 93·9 % ( 95 % CI 91·8 - 96·0 ) in both groups ( p=0·34 ) . 89 women died ; eight of 49 patients allocated to no radiotherapy and four of 40 assigned to radiotherapy died from breast cancer . INTERPRETATION Postoperative whole-breast radiotherapy after breast-conserving surgery and adjuvant endocrine treatment result ed in a significant but modest reduction in local recurrence for women aged 65 years or older with early breast cancer 5 years after r and omisation . However , the 5-year rate of ipsilateral breast tumour recurrence is probably low enough for omission of radiotherapy to be considered for some patients . FUNDING Chief Scientist Office ( Scottish Government ) , Breast Cancer Institute ( Western General Hospital , Edinburgh ) PURPOSE In women with favorable early breast cancer treated by lumpectomy plus tamoxifen or anastrazole  , it remains unclear whether whole breast radiotherapy is beneficial . METHODS AND MATERIAL Between January 1996 and June 2004 , the Austrian Breast and Colorectal Cancer Study Group ( ABCSG ) r and omly assigned 869 women to receive breast radiotherapy + /- boost ( n = 414 ) or not ( n = 417 ) after breast-conserving surgery ( ABCSG Study 8A ) . Favorable early breast cancer was specified as tumor size <3 cm , Grading 1 or 2 , negative lymph nodes , positive estrogen and /or progesterone receptor status , and manageable by breast-conserving surgery .  Breast radiotherapy was performed after lumpectomy with 2 tangential opposed breast fields with mean 50 Gy , plus boost in 71 % of patients with mean 10 Gy , in a median of 6 weeks . The primary endpoint was local relapse-free survival ; further endpoints were contralateral breast cancer , distant metastases , and disease-free and overall survival . The median follow-up was 53.8 months . RESULTS The mean age was 66 years . Overall , there were 21 local relapses , with 2 relapses in the radiotherapy group ( 5-y rate 0.4 % ) vs. 19 in the no-radiotherapy group ( 5.1 % ) , respectively ( p = 0.0001 , hazard ratio 10.2 ) . Overall relapses occurred in 30 patients , with 7 events in the radiotherapy group ( 5-y rate 2.1 % ) vs. 23 events in the no-radiotherapy group ( 6.1 % ) ( p = 0.002 , hazard ratio 3.5 ) . No significant differences were found for distant metastases and overall survival . CONCLUSION Breast radiotherapy + /- boost in women with favorable early breast cancer after lumpectomy combined with tamoxifen/anastrazole leads to a significant reduction in local and overall relapse BACKGROUND Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation ( APBI ) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival . Here , we present 5-year results of patient-reported quality of life . METHODS We did this r and omised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries . Patients aged 40 years or older with 0-IIA breast cancer were r and omly assigned ( 1:1 ) after breast-conserving surgery ( resection margins ≥2 mm ) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy . R and omisation was stratified by study centre , tumour type , and menopausal status , with a block size of ten and an automated dynamic algorithm . There was no masking of patients or investigators . The primary endpoint of the trial was ipsilateral local recurrence . Here , we present 5-year results of quality of life ( a prespecified secondary endpoint ) . Quality -of-life question naires ( European Organisation for Research and Treatment of Cancer QLQ-C30 , breast cancer module QLQ-BR23 ) were completed before radiotherapy ( baseline 1 ) , immediately after radiotherapy ( baseline 2 ) , and during follow-up . We analysed the data according to treatment received ( as-treated population ) . Recruitment was completed in 2009 , and long-term follow-up is continuing . The trial is registered at Clinical Trials.gov , number NCT00402519 . FINDINGS Between April 20 , 2004 , and July 30 , 2009 , 633 patients had accelerated partial breast irradiation and 551 patients had  whole-breast irradiation . Quality -of-life question naires at baseline 1 were available for 334 ( 53 % ) of 663 patients in  the APBI group and 314 ( 57 % ) of 551 patients in the  whole-breast irradiation group ; the response rate was similar during follow-up . Global health status ( range 0 - 100 ) was stable in both groups : at baseline 1 , APBI group mean score 65·5 ( SD 20·6 ) versus whole-breast irradiation group 64·6 ( 19·6 ) , p=0·37 ; at 5 years , APBI group 66·2 ( 22·2 ) versus whole-breast irradiation group 66·0 ( 21·8 ) , p=0·94 . The only moderate , significant difference ( difference of 10 - 20 points ) between the groups was found in the breast symptoms scale . Breast symptom scores were significantly higher ( ie , worse ) after whole-breast irradiation than after APBI at baseline 2 ( difference of means 13·6 , 95 % CI 9·7 - 17·5 ; p<0·0001 ) and at 3-month follow-up ( difference of means 12·7 , 95 % CI 9·8 - 15·6 ; p<0·0001 ) . INTERPRETATION APBI with multicatheter brachytherapy was not associated with worse quality of life compared with whole-breast irradiation . This finding supports APBI as an alternative treatment option after breast-conserving surgery for patients with early breast cancer . FUNDING German Cancer Aid Introduction This pilot study used a prospect i ve longitudinal design to compare the effect of adjuvant whole breast radiation therapy ( WBRT ) versus partial breast radiation therapy ( PBRT ) on fatigue , perceived stress , quality of life and natural killer cell activity ( NKCA ) in women receiving radiation after breast cancer surgery . Methods Women ( N = 30 ) with early-stage breast cancer received either PBRT , Mammosite brachytherapy at dose of 34 Gy 10 fractions/5 days , ( N = 15 ) or WBRT , 3-D conformal techniques at dose of 50 Gy + 10 Gy Boost/30 fractions , ( N = 15 ) . Treatment was determined by the attending oncologist after discussion with the patient and the choice was based on tumor stage and clinical need . Women were assessed prior to initiation of radiation therapy and twice after completion of radiation therapy . At each assessment , blood was obtained for determination of NKCA and the following instruments were administered : Perceived Stress Scale ( PSS ) , Functional Assessment of Cancer Therapy-Fatigue ( FACT-F ) , and Functional Assessment of Cancer Therapy-General ( FACT-G ) . Hierarchical linear modeling ( HLM ) was used to evaluate group differences in initial outcomes and change in outcomes over time . Results Fatigue ( FACT-F ) levels , which were similar prior to radiation therapy , demonstrated a significant difference in trajectory . Women who received PBRT reported progressively lower fatigue ; conversely fatigue worsened over time for women who received WBRT . No difference in perceived stress was observed between women who received PBRT or WBRT . Both groups of women reported similar levels of quality of life ( FACT-G ) prior to initiation of radiation therapy . However , HLM analysis revealed significant group differences in the trajectory of quality of life , such that women receiving PBRT exhibited a linear increase in quality of life over time after completion of radiation therapy ; whereas women receiving WBRT showed a decreasing trajectory . NKCA was also similar between therapy groups but additional post hoc analysis revealed that better quality of life significantly predicted higher NKCA regardless of therapy . Conclusions Compared to WBRT , PBRT results in more rapid recovery from cancer-related fatigue with improved restoration of quality of life after radiation therapy . Additionally , better quality of life predicts higher NKCA against tumor targets , emphasizing the importance of fostering quality of life for women undergoing adjuvant radiation therapy BACKGROUND Intraoperative radiotherapy with electrons allows the substitution of conventional postoperative whole breast irradiation with one session of radiotherapy with the same equivalent dose during surgery . However , its ability to control for recurrence of local disease required confirmation in a r and omised controlled trial . METHODS This study was done at the European Institute of Oncology ( Milan , Italy ) . Women aged 48 - 75 years with early breast cancer , a maximum tumour diameter of up to 2·5 cm , and suitable for breast-conserving surgery were r and omly assigned in a 1:1 ratio ( using a r and om permuted block design , stratified for clinical tumour size [ < 1·0 cm vs 1·0 - 1·4 cm vs ≥1·5 cm ] ) to receive either whole-breast external radiotherapy or intraoperative radiotherapy with electrons . Study coordinators , clinicians , and patients were aware of the assignment . Patients in the intraoperative radiotherapy group received one dose of 21 Gy to the tumour bed during surgery . Those in the external radiotherapy group received 50 Gy in 25 fractions of 2 Gy , followed by a boost of 10 Gy in five fractions . This was an equivalence trial ; the prespecified equivalence margin was local recurrence of 7·5 % in the intraoperative radiotherapy group . The primary endpoint was occurrence of ipsilateral breast tumour recurrences ( IBTR ) ; overall survival was a secondary outcome . The main analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01849133 . FINDINGS 1305 patients were r and omised ( 654 to external radiotherapy and 651 to intraoperative radiotherapy ) between Nov 20 , 2000 , and Dec 27 , 2007 . After a medium follow-up of 5·8 years ( IQR 4·1 - 7·7 ) , 35 patients in the intraoperative radiotherapy group and four patients in the external radiotherapy group had had an IBTR ( p<0·0001 ) . The 5-year event rate for IBRT was 4·4 % ( 95 % CI 2·7 - 6·1 ) in the intraoperative radiotherapy group and 0·4 % ( 0·0 - 1·0 ) in the external radiotherapy group ( hazard ratio 9·3 [ 95 % CI 3·3 - 26·3 ] ) . During the same period , 34 women allocated to intraoperative radiotherapy and 31 to external radiotherapy died ( p=0·59 ) . 5-year overall survival was 96·8 % ( 95 % CI 95·3 - 98·3 ) in the intraoperative radiotherapy group and 96·9 % ( 95·5 - 98·3 ) in the external radiotherapy group . In patients with data available ( n=464 for intraoperative radiotherapy ; n=412 for external radiotherapy ) we noted significantly fewer skin side-effects in women in the intraoperative radiotherapy group than in those in the external radiotherapy group ( p=0·0002 ) . INTERPRETATION Although the rate of IBTR in the intraoperative radiotherapy group was within the prespecified equivalence margin , the rate was significantly greater than with external radiotherapy , and overall survival did not differ between groups . Improved selection of patients could reduce the rate of IBTR  with intraoperative radiotherapy with electrons . FUNDING Italian Association for Cancer Research , Jacqueline Seroussi Memorial Foundation for Cancer Research , and Umberto Veronesi Foundation The purpose of this study was to report the efficacy and the safety profile on the subset of selected early breast cancer ( BC ) patients aged 70 years or older from a single-center phase 3 trial comparing  whole breast irradiation ( WBI ) to accelerated partial breast irradiation ( APBI ) using intensity-modulated radiation therapy technique .  Between 2005 and 2013 , 520 patients aged more than 40 years old were enrolled and r and omly assigned to receive either WBI or APBI in a 1:1 ratio . Eligible patients were women with early BC ( maximum diameter 2.5 cm ) suitable for breast conserving surgery . This study is registered with Clinical Trials.gov , NCT02104895 . A total of 117 patients aged 70 years or more were analyzed ( 58 in the WBI arm , 59 in the APBI arm ) . At a median follow-up of 5-years ( range 3.4–7.0 ) , the ipsilateral breast tumor recurrence ( IBTR ) rate was 1.9 % in both groups . No significant difference between the two groups was identified ( log-rank test p = 0.96 ) . The 5-year disease-free survival ( DFS ) rates in the WBI group and APBI group were 6.1 and 1.9 % , respectively ( p = 0.33 ) . The APBI group presented significantly better results in terms of acute skin toxicity , considering both any grade ( p = 0.0001 ) and grade 2 or higher ( p = 0.0001 ) . Our subgroup analyses showed a very low rate and no significant difference in terms of IBTR , using both WBI and APBI . A significant impact on patients compliance in terms of acute and early late toxicity was shown , which could translate in a consistent improvement of overall quality of life As a result of an increasing life expectancy , the incidence of cancer cases diagnosed in the older population is rising . Indeed , cancer incidence is 11-fold higher in persons over the age of 65 than in younger ones . Despite this high incidence of cancer in older patients , solid data regarding the most appropriate approach and best treatment for older cancer patients are still lacking , mostly due to under-representation of these patients in prospect i ve clinical trials . The clinical behaviour of common malignant diseases , e.g. breast , ovarian and lung cancers , lymphomas and acute leukaemias , may be different in older patients because of intrinsic variation of the neoplastic cells and the ability of the tumour host to support neoplastic growth . The decision to treat or not these patients should be based on patients ' functional age rather than the chronological age . Assessment of patients ' functional age includes the evaluation of health , functional status , nutrition , cognition and the psychosocial and economic context . The purpose of this paper is to focus on the influence of age on cancer presentation and cancer management in older cancer patients and to provide suggestions on clinical trial development and methodology in this population BACKGROUND We determined the effect of breast irradiation plus tamoxifen on disease-free survival and local relapse in women 50 years of age or older who had T1 or T2 node-negative breast cancer . METHODS Between December 1992 and June 2000 , 769 women with early breast cancer ( tumor diameter , 5 cm or less ) were r and omly assigned to receive breast irradiation plus tamoxifen ( 386 women ) or tamoxifen alone ( 383 women ) . The median follow-up was 5.6 years . RESULTS The rate of local relapse at five years was 7.7 percent in the tamoxifen group and 0.6 percent in the group given tamoxifen plus irradiation ( hazard ratio , 8.3 ; 95 percent confidence interval , 3.3 to 21.2 ; P<0.001 ) , with corresponding five-year disease-free survival rates of 84 percent and 91 percent ( P=0.004 ) . A planned subgroup analysis of 611 women with T1 , receptor-positive tumors indicated a benefit from radiotherapy ( five-year rates of local relapse , 0.4 percent with tamoxifen plus radiotherapy and 5.9 percent with tamoxifen alone ; P<0.001 ) . Overall , there was a significant difference in the rate of axillary relapse at five years ( 2.5 percent in the tamoxifen group and 0.5 percent in the group given tamoxifen plus irradiation , P=0.049 ) , but no significant difference in the rates of distant relapse or overall survival . CONCLUSIONS As compared with tamoxifen alone , radiotherapy plus tamoxifen significantly reduces the risk of breast and axillary recurrence after lumpectomy in women with small , node-negative , hormone-receptor-positive breast cancers Breast conserving therapy ( BCT ) including postoperative irradiation of the remaining breast tissue is generally accepted as the best treatment for the majority of patients with early-stage breast cancer . The question is whether there is a necessity for irradiating all patients . Between 2001 and 2005 , 749 women aged 55 - 75 years with infiltrating breast carcinoma were r and omly assigned to breast conservative surgery , with or without radiotherapy ( RT ) , to evaluate the incidence of in-breast recurrence ( IBR ) . After 5 years of median follow-up , the cumulative incidence of IBR was 2.5 % in the surgery-only arm and 0.7 % in the surgery plus RT arm . There are no differences in terms of overall survival and distant disease-free survival . The preliminary evaluation suggests that breast irradiation after conservative surgery can be avoided without exposing these patients to an increased risk of distant-disease recurrence . Prolonged follow-up will further clarify the possible risks and late sequelae potentially induced by breast RT PURPOSE We report the long-term results of phase II prospect i ve study with accelerated partial breast irradiation ( APBI ) using interstitial multi-catheter high-dose-rate brachytherapy . METHODS 240 patients received APBI ( 4Gy , twice daily ; total dose 32Gy ) . RESULTS Median follow-up was 96months . Recurrences in the treated breast developed in 8 patients ( 3.3 % ) at a median of 73months after APBI . The 5- and 10-year cumulative incidences were respectively , 1.8 % ( 95%CI : 0.6 - 4.3 ) and 6.6 % ( 95%CI : 2.7 - 12.9 ) . Regional recurrences developed in 5 patients ( 2 % ) at a median of 28months and distant metastases in 8 ( 3.3 % ) at a median of 32.5months . Breast cancer specific mortality occurred in 6 patients ( 2.5 % ) at a median of 60months . Acute toxicity developed in 71 ( 29.6 % ) patients ( G1 in 60 and G2 in 11 ) . Almost all were skin toxicity and hematomas . Late toxicity was observed in 90 patients ( 37.5 % ) , G1 in 97 cases and G2 in 11 . Some patients presented with more than one type of toxicity . Teleangectasia and fibrosis were the most common ( 48 and 44 cases respectively ) , followed by fat necrosis ( in 18 patients ) Tamoxifen emerged as the only risk factor for breast fibrosis ( p=0.007 ) . Cosmetic results were judged by the physicians as excellent in 174 ( 83.7 % ) patients , good in 25 ( 12 % ) fair in 8 ( 3.8 % ) and poor in 1 ( 0.5 % ) ; 174 patients ( 83.7 % ) judged outcomes as excellent , 26 ( 12.4 % ) as good , 7 ( 3.4 % ) as fair and 1 ( 0.5 % ) as poor . Physician/patient agreement was good ( weighted k-value 0.72 ) . CONCLUSIONS APBI with interstitial multi-catheter brachytherapy was associated with good outcomes , low relapse and toxicity rates . Few events during this long-term follow-up preclude identifying specific features of patients at risk of relapse and illustrate the need for a large data -base PURPOSE To evaluate with a r and omized clinical trial the possibility of treating the index quadrant with external intensity-modulated radiotherapy ( IMRT ) in a selected group of patients with early-stage breast cancer and to analyze the acute toxicity . METHODS AND MATERIAL S From September 2005 , a r and omized Phase III clinical trial has been conducted to compare conventional ( tangential field ) fractionated whole breast treatment ( Arm A ) with accelerated partial breast irradiation plus intensity-modulated radiotherapy ( Arm B ) . For intensity-modulated radiotherapy , the clinical target volume was drawn with a uniform 1-cm margin around the surgical clips in three dimensions . The ipsilateral and contralateral breast , ipsilateral and contralateral lung , heart , and spinal cord were contoured as organs at risk . All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations . RESULTS In September 2008 , 259 patients were r and omized and treated . The mean clinical target volume in Arm B was 44 cm(3 ) and the mean planning target volume was 123 cm(3 ) . The mean value of the ratio between the planning target volume and the ipsilateral breast volume was 21 % . The rate of Grade 1 and Grade 2 acute skin toxicity was 22 % and 19 % in Arm A ( Radiation Therapy Oncology Group scale ) , respectively . The tolerance in Arm B was excellent with only 5 % Grade 1 and 0.8 % Grade 2 acute skin toxicity . The planning constraints were fully satisfied in most patients . In a very few cases , this was not possible because of very unfavorable anatomy . Quality assurance procedures were performed according to our internal quality assurance protocol , with excellent results . CONCLUSION In the present preliminary analysis , we have demonstrated that accelerated partial breast irradiation is feasible , with very low acute toxicity PURPOSE To analyze the feasibility , reproducibility , and impact on functional status of postoperative accelerated and partial breast irradiation ( APBI ) using interstitial high-dose rate-brachytherapy in women older than 70 years . METHODS AND MATERIAL S From July 2004 to April 2008 , 46 patients were screened for enrollment in a nationwide prospect i ve Phase II trial . A total of 40 patients were eligible according to the inclusion criteria ( aged > 70 years , T1 - 2 < 30 mm , and pN0 ) . The total delivered dose was 34Gy of 10 fractions for 5 days . Feasibility and reproducibility were evaluated using a Quality Index ( QI ) defined as ( V100%- clinical target volume)/V100 % . Skin toxicity was reported using Common Terminology Criteria for Adverse Events version 3.0 . ABPI impact on functional dependence was evaluated using the Activity of Daily Living and Instrumental Activity of Daily Living scales . Reproducibility and feasibility were assessed with the optimal two-stage design of Simon . RESULTS Median age was 74 years ( 70 - 87 years ) . All patients were treated according to the protocol . Median Quality Index calculated for the 40 eligible patients was 13.3 % ( 1 - 70 % ) . It was considered acceptable , partially acceptable , and nonacceptable in 10 , 28 , and 2 patients , respectively . Within 12 months after APBI , overall rates of toxicity were 59 % , 28 % , and 2 % for Grade 1 , 2 , and 3 events , respectively . Twelve months after APBI , 35 patients ( 87 % ) achieved excellent/good cosmetic result . Compared with baseline values , Activity of Daily Living and Instrumental Activity of Daily Living scores remained unchanged 6 and 12 months after APBI . CONCLUSIONS APBI by means of high-dose rate-brachytherapy is a feasible/reproducible technique without significant impact on functional dependence in the treatment of elderly women with early breast cancer To study the role of radiotherapy and tamoxifen after breast-conserving surgery ( BCS ) in patients with a favourable prognosis , a clinical trial was initiated by the German Breast Cancer Study Group ( GBSG-V ) . Between 1991 and 1998 , 361 patients ( pT 1pN0M0 , aged 45 - 75 years , receptor positive , grade s I and II ) were r and omised to radiotherapy ( yes/no ) and tamoxifen for 2 years ( yes/no ) in a 2 x 2-factorial design ; the exclusion of seven centres ( 14 patients ) left 347 patients for the analysis . First results after a median follow-up of 5.9 years were published . Herein we present up date d results after a median follow-up of about 10 years . Hundred and eleven events concerning event-free survival ( EFS ) have been observed . Since a strong interactive effect between radiotherapy and tamoxifen has been established , the results are presented in terms of the treatment effects for all four treatment groups separately . Mainly due to the presence of local recurrences , the event rate was much higher in the group with BCS only than in the other three groups . No significant difference could be established between the four treatment groups for distant disease-free survival rates ( DDFS ) . Up date d results give further evidence that even in patients with a favourable prognosis , the avoidance of radiotherapy and tamoxifen after BCS increases the rate of local recurrences substantially . Rates are about three times higher in the BCS only group . For the two outcomes EFS and DDFS , no important difference could be seen between the three groups with an additional treatment . However , because of the limited sample size with corresponding low power the strength of evidence for such a comparison is weak Background To analyze the clinical outcome of elderly women with early breast cancer who underwent accelerated partial breast irradiation ( APBI ) based on a post-operative single fraction of multicatheter interstitial high dose – rate brachytherapy ( MIB ) . Methods A single institution retrospective cohort study was performed focusing on elderly patients ( ≥ 65 years old ) presenting a low-risk breast carcinoma treated by lumpectomy plus axillary evaluation followed by MIB .  A single fraction of 16 Gy was prescribed on the 100 % isodose . Clinical outcome at 3 years was reported based on local relapse free survival ( 3-y LRFS ) , specific survival ( SS ) and overall survival ( OS ) . Acute ( < 180 days after APBI ) and late toxicity were evaluated . Cosmetic results were clinical ly evaluated by the physician . Results Between January 2012 and August 2015 , 48 women ( 51 lesions ) were treated . Median age was 77.7 years ( range : 65–92 ) with a median tumor size of 12 mm ( range : 3–32 ) . Five patients ( pts ) presented an axillary lymph node involvement ( 4 Nmic , 1 N1 ) . Invasive ductal carcinoma was the most frequent histology type ( 86.3 % ) . With a median follow – up of 40 months ( range : 36–42 ) , no local relapse occurred while 1 pt . developed axillary relapse ( 2.1 % ) . The 3-y LRFS , SS and OS rates were 100 % , 100 % and 93.1 % respectively . Forty-five acute events were remained . The most frequent acute toxicity was grade ( G ) 1 hyperpigmentation ( 26.7 % ) , 3 pts . ( 6.3 % ) presented G3 acute toxicity ( 2 breast hematomas , 1 breast abscess ) . No ≥ G3 late toxicity was observed while 15 late toxicities occurred ( G1 : 13 events - 86.7 % ) mainly breast fibrosis ) . The rate of excellent cosmetic outcome was 76.4 % . Conclusion We reported promising and encouraging clinical outcome of a post-operative single fraction of MIB ABPI in the elderly . This approach leads to consider a sfAPBI as an attractive alternative to intra-operative radiation therapy while all the patients will be good c and i date s for APBI in regards to the post-operative pathological report . More mature results ( number of patients and follow-up ) are needed PURPOSE This trial was prompted by uncertainty about the need for breast irradiation after lumpectomy in node-negative women with invasive breast cancers of < /= 1 cm , by speculation that tamoxifen ( TAM ) might be as or more effective than radiation therapy ( XRT ) in reducing the rate of ipsilateral breast tumor recurrence ( IBTR ) in such women , and by the thesis that both modalities might be more effective than either alone . PATIENTS AND METHODS After lumpectomy , 1,009 women were r and omly assigned to TAM ( n = 336 ) , XRT and placebo ( n = 336 ) , or XRT and TAM ( n = 337 ) . Rates of IBTR , distant recurrence , and contralateral breast cancer ( CBC ) were among the end points for analysis . Cumulative incidence of IBTR and of CBC was computed accounting for competing risks . Results with two-sided P values of.05 or less were statistically significant . RESULTS XRT and placebo result ed in a 49 % lower hazard rate of IBTR than did TAM alone ; XRT and TAM result ed in a 63 % lower rate than did XRT and placebo . When compared with TAM alone , XRT plus TAM result ed in an 81 % reduction in hazard rate of IBTR . Cumulative incidence of IBTR through 8 years was 16.5 % with TAM , 9.3 % with XRT and placebo , and 2.8 % with XRT and TAM . XRT reduced IBTR below the level achieved with TAM alone , regardless of estrogen receptor ( ER ) status . Distant treatment failures were infrequent and not significantly different among the groups ( P = .28 ) . When TAM-treated women were compared with those who received XRT and placebo , there was a significant reduction in CBC ( hazard ratio , 0.45 ; 95 % confidence interval , 0.21 to 0.95 ; P = .039 ) . Survival in the three groups was 93 % , 94 % , and 93 % , respectively ( P = .93 ) . CONCLUSION In women with tumors < /= 1 cm , IBTR occurs with enough frequency after lumpectomy to justify considering XRT , regardless of tumor ER status , and TAM plus XRT when tumors are ER positive PURPOSE To up date the accelerated partial breast irradiation Consensus Statement published in 2009 and provide guidance on use of intraoperative radiation therapy ( IORT ) for partial breast irradiation in early-stage breast cancer , based on published evidence complemented by expert opinion . METHODS AND MATERIAL S A systematic PubMed search using the same terms as the original Consensus Statement yielded 419 articles ; 44 articles were selected . The authors synthesized the published evidence and , through a series of conference calls and e-mails , reached consensus regarding the recommendations . RESULTS The new recommendations include lowering the age in the " suitability group " from 60 to 50 years and in the " caution ary group " to 40 years for patients who meet all other elements of suitability ( Table 1 ) . Patients with low-risk ductal carcinoma in situ , as per Radiation Therapy Oncology Group 9804 criteria , were categorized in the " suitable " group . The task force agreed to maintain the current criteria based on margin status . Recommendations for the use of IORT for breast cancer patients include : counseling patients regarding the higher risk of ipsilateral breast tumor recurrence with IORT compared with whole breast irradiation ; the need for prospect i ve monitoring of long-term local control and toxicity with low-energy radiograph IORT given limited follow-up ; and restriction of IORT to women with invasive cancer considered " suitable . " CONCLUSION These recommendations will provide up date d clinical guidance regarding use of accelerated partial breast irradiation for radiation oncologists and other specialists participating in the care of breast cancer patients
Introduction .
Elderly patients are underrepresented from a majority of clinical trials and the choice of the best treatment becomes a challenge .
The optimal treatment should be personalized and based on a multidisciplinary approach that includes radiation oncologists , surgeons , geriatricians , medical oncologists , social workers , and support services .
The global evaluation of the patients and the creation of nomograms may facilitate the definition of long-term treatment benefits minimizing the use of unnecessary therapy .