***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 : The purpose of this study was to determine the optimal timing of delayed abdominal free flap breast reconstruction following postmastectomy radiation therapy .  The authors evaluated the association between timing of delayed abdominal free flap breast reconstruction following postmastectomy radiation therapy and postoperative complications . Methods : The authors review ed a prospect ively maintained data base of  delayed abdominal free flap breast reconstruction performed between July of 2005 and December of 2009 . Data regarding demographics , operative variables , and clinical outcomes were collected . Patients were classified as having undergone reconstruction less than 12 months after postmastectomy radiation therapy ( group I ) or 12 months or more after postmastectomy radiation therapy ( group II ) . Complications were compared between groups , including microvascular thrombosis , flap loss , reoperation , wound dehiscence , and fat necrosis . Results : One hundred eighty-nine patients were identified , 82 ( 43.4 percent ) in group I and 107 ( 56.6 percent ) in group II . The total flap loss rate was 2.6 percent , with all flap losses occurring in group I ( p = 0.014 ) . The reoperation rate was higher in group I ( 14.6 percent versus 4.7 percent ; p = 0.022 ) . In addition , group I patients trended toward a higher incidence of microvascular thrombosis , infection , and wound dehiscence . Conclusions : Patients who underwent delayed abdominal free flap breast reconstruction after 12 months from the completion of postmastectomy  radiation therapy developed fewer complications , including microvascular thrombosis and total flap loss , than those who underwent delayed abdominal free flap breast reconstruction within 12 months of completing postmastectomy radiation therapy . Allowing an interval of 12 months between the completion of postmastectomy radiation therapy and delayed abdominal free flap breast reconstruction will likely minimize complications and optimize outcomes in free flap breast reconstruction in patients receiving postmastectomy radiation & NA ; Immediate breast reconstruction has important advantages over delayed reconstruction , including a shorter operative time and decreased psychological distress for the patient . However , the authors ’ experiences with the deep inferior epigastric perforator flap demonstrate variable aesthetic outcomes among patients who undergo radiation postoperatively . To establish an association between radiation and poor postoperative results , a matched‐pairs analysis was conducted . Thirty irradiated patients were paired with 30 nonirradiated patients , according to age and body mass index . For each group , the incidence of fat necrosis , fibrosis/ shrinkage , and flap contracture was recorded . In addition , an aesthetic evaluation was conducted to compare before and ‐after images of 10 irradiated patients with those of 10 nonirradiated patients from similar time periods . The images were r and omized and blindly evaluated by a panel of eight judges . A five‐point scale was used to evaluate symmetry , aesthetic proportion , and the appearance of the superior pole . Statistical analysis demonstrated a significant difference in the score changes for irradiated and nonirradiated patients , according to all three criteria . Nonirradiated patient scores increased by one‐half point , and irradiated patient scores decreased by one‐half point . In addition , the incidences of fat necrosis , fibrosis , and flap contracture were all significantly higher among the irradiated group . These results suggest that when possible , reconstruction should be delayed until after radiation therapy is complete . Persons who smoke or are obese may be at particular risk for complications following radiation therapy . ( Plast . Reconstr . Surg . 109 : 1919 , 2002 . Background Skin-sparing mastectomy ( SSM ) with immediate breast reconstruction ( IBR ) is increasingly used in invasive breast cancer . However , adjuvant chemotherapy ( CT ) and radiotherapy ( RT ) can increase the rate of local complications . Objective The aim of this study was to assess the morbidity of SSM – IBR after neoadjuvant CT and RT . Methods A French prospect i ve pilot study of women aged 18–75 years with invasive breast cancer requiring mastectomy after CT and RT .  Reconstruction was performed using autologous latissimus dorsi flap with or without prosthesis . The primary endpoint was the skin necrosis rate within 6 months , while secondary endpoints included pathological complete response rate ( pCR ) and global morbidity . Results Among 94 patients included in this study , 83 were analyzed ( mean age 45.2 ± 9.5 years , T1 23.6 % , T2 55.6 % , T3 18.1 % ) . All but one patient received anthracyclines and taxanes , and all patients received RT ( 49.3 ± 5.2 Gy ) before SSM – IBR . Prostheses were used for IBR in 32 patients ( mean volume 256 ± 73 mm3 ) . Five patients had necrosis ( ≤2 cm2 , 2–10 cm2 and > 10 cm2 , in three , one , and one cases , respectively ) , and they all recovered without revision surgery . Among 50 patients who underwent upfront mastectomy , 36 % achieved pCR . Conclusions SSM – IBR performed after CT and RT  is safe , with an acceptable local morbidity rate . Long-term data are needed to evaluate recurrence rates Background Patients considering postmastectomy radiation and reconstruction  require information regarding expected outcomes to make preference-concordant decisions . Methods A prospect i ve multicenter cohort study of women diagnosed with breast cancer at 11 centers between 2012 and 2015 compared complications and patient-reported outcomes of 622 irradiated and 1625 unirradiated patients who received reconstruction .  Patient characteristics and outcomes between irradiated and unirradiated patients were analyzed using ttests for continuous variables and chi-square tests for categorical variables . Multivariable mixed-effects regression modelsassessed the impact of reconstruction type and radiotherapy on outcomes after adjusting for relevant covariates . All statistical tests were two-sided . Results  Autologous reconstruction was more commonly received by irradiated patients ( 37.9 % vs 25.0 % , P < .001 ) . Immediate reconstruction was less common in irradiated patients ( 83.0 % vs 95.7 % , P < .001 ) . At least one breast complication had occurred by two years in 38.9 % of irradiated patients with implant reconstruction , 25.6 % of irradiated patients with autologous reconstruction , 21.8 % of unirradiated patients with implant reconstruction , and 28.3 % of unirradiated patients with autologous reconstruction . Multivariable analysis showed bilateral treatment and higher body mass index to be predictive of developing a complication , with a statistically significant interaction between radiotherapy receipt and reconstruction type . Among irradiated patients , autologous reconstruction was associated with a lower risk of complications than implant-based reconstruction at two years ( odds ratio [ OR ] = 0.47 , 95 % confidence interval [ CI ] = 0.27 to 0.82 , P = .007 ) ; no between-procedure difference was found in unirradiated patients . The interaction was also statistically significant for satisfaction with breasts at two years ( P = .002 ) , with larger adjusted difference in satisfaction between autologous vs implant approaches ( 63.5 , 95 % CI = 55.9 to 71.1 , vs 47.7 , 95 % CI = 40.2 to 55.2 , respectively ) in irradiated patients than between autologous vs implant approaches ( 67.6 , 95 % CI = 60.3 to 74.9 , vs 60.5 , 95 % CI = 53.6 to 67.4 ) in unirradiated patients . Conclusions Autologous reconstruction appears to yield superior patient-reported satisfaction and lower risk of complications than implant-based approaches among patients receiving postmastectomy radiotherapy Purpose In oncology , RCTs are often beset by slow recruitment , limited generalizability , and strong preferences for interventions by patients and physicians . The cohort multiple r and omized controlled trial ( cm RCT ) is an innovative design with the potential to overcome those challenges . In cm RCT , a prospect i ve cohort serves as an infrastructure for multiple RCTs . We implemented cm RCT in a clinical breast cancer setting by creating UMBRELLA — a large prospect i ve cohort of breast cancer and DCIS patients /survivors . Methods For all participants , clinical data and patient-reported outcomes ( PROs , i.e. , quality of life , fatigue , anxiety and depression , physical activity , work ability , and cosmetic satisfaction ) are being collected at regular time-intervals for a period of 10 years . These data are being used both for observational and r and omized studies . For each intervention to be tested against st and ard care , a subcohort of eligible patients is identified within UMBRELLA . From this subcohort , a r and om sample of patients is offered the intervention . Their outcomes are compared to the outcomes of patients receiving st and ard care . Results So far , between October 2013 and July 2016 , we have recruited 1308 participants . In this period , 1308/1486 ( 88 % ) patients who were invited for participation in UMBRELLA consented to cohort participation . Of these patients , 1138 ( 87 % ) gave broad consent for r and omization to future interventions . Return rate for PROs at baseline were 80 % , and varied from 67 to 74 % during follow-up . Several observational studies — and the first r and omized intervention study —are currently ongoing . Conclusions Results from UMBRELLA show that this novel study design is feasible and acceptable to patients in a clinical breast cancer setting . We invite research ers who are interested in conducting r and omized or observational studies within the UMBRELLA cohort to contact the UMBRELLA scientific advisory board BACKGROUND If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node , axillary lymph node dissection is the present st and ard . Although axillary lymph node dissection provides excellent regional control , it is associated with harmful side-effects . We aim ed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects . METHODS Patients with T1 - 2 primary breast cancer and no palpable lymphadenopathy were enrolled in the r and omised , multicentre , open-label , phase 3 non-inferiority EORTC 10981 - 22023 AMAROS trial . Patients were r and omly assigned ( 1:1 ) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node , stratified by institution . The primary endpoint was non-inferiority of 5-year axillary recurrence , considered to be not more than 4 % for the axillary radiotherapy group compared with an expected 2 % in the axillary lymph node dissection group . Analyses were by intention to treat and per protocol . The AMAROS trial is registered with Clinical Trials.gov , number NCT00014612 . FINDINGS Between Feb 19 , 2001 , and April 29 , 2010 , 4823 patients were enrolled at 34 centres from nine European countries , of whom 4806 were eligible for r and omisation . 2402 patients were r and omly assigned to receive  axillary lymph node dissection and 2404 to receive axillary radiotherapy . Of the 1425 patients with a positive sentinel node , 744 had been r and omly assigned to axillary lymph node dissection and 681 to axillary radiotherapy ; these patients constituted the intention-to-treat population . Median follow-up was 6·1 years ( IQR 4·1 - 8·0 ) for the patients with positive sentinel lymph nodes . In the axillary lymph node dissection group , 220 ( 33 % ) of 672 patients who underwent axillary lymph node dissection had additional positive nodes . Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group . 5-year axillary recurrence was 0·43 % ( 95 % CI 0·00 - 0·92 ) after axillary lymph node dissection versus 1·19 % ( 0·31 - 2·08 ) after axillary radiotherapy . The planned non-inferiority test was underpowered because of the low number of events . The one-sided 95 % CI for the underpowered non-inferiority test on the hazard ratio was 0·00 - 5·27 , with a non-inferiority margin of 2 . Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year , 3 years , and 5 years . INTERPRETATION Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1 - 2 primary breast cancer and no palpable lymphadenopathy . Axillary radiotherapy results in significantly less morbidity . FUNDING EORTC Charitable Trust Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r 
    Output:
    
The impact of PMRT and neoadjuvant radiotherapy appeared to be similar