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1、Name of presenterFunction of presenter,Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: final analysis of the EORTC AMAROS trial,By the EORTC Breast Cancer Group andRadiation Oncology Group In collaboration with the Dutch BOOG Group and ALMANAC Trialist
2、s Group,Emiel J.T. Rutgers The Netherlands Cancer Institute, AmsterdamClinical trial information: NCT00014612,Background,Sentinel node (SN) biopsy has replaced the axillary lymph node dissection (ALND) if cN0If axillary SN+ (AxSN+) and indication for axillary treatment, ALND is standard of careALND
3、is associated with high rates of side effectsAxillary radiotherapy (AxRT) provides good regional control with limited side effects in cN0,Deutsch et al, IJROBP 2008 Hoebers et al, Cancer 2000Fisher et al, NEJM 2002Louis-Sylvestre et al, JCO 2004,Hypothesis,Axillary radiotherapy provides local contro
4、l and survival comparable to ALND with fewer side effects in women with a positive axillary SN,Eligibility Criteria,InclusionInvasive breast cancer 0.5-5 cmClinically N0BCT or mastectomy Any age Informed consent,ExclusionMulticentric diseaseNeoadjuvant systemic treatmentPrevious axillary treatmentPr
5、ior malignancy,Trial design,cT1-2N0,R,SNB,Stratification: institutionAdjuvant systemic therapy by choice,ALND,AxRT,AxSN+,AxSN-,Objectives,Primary: To demonstrate non-inferiority in axillary recurrence rateSecondary: 1. To compare overall survival (OS) and disease-free survival (DFS) 2. To compare ly
6、mphedema, shoulder function and Quality of Life (QoL),Endpoints and statistical design,Primary: 5-years axillary recurrence free rate Non inferiority hypothesis (design): assumption: ALND 98%; AxRT 96%one-sided log-rank; alpha = 0.05; power = 80%52 events neededSecondary: Efficacy: OS and DFSSafety:
7、 shoulder function, lymphedema, QoL,AxRT,Timing:Start 12 weeks after SNBExtent:level I + II + III + medial SCDose & schedule:25 x 2 Gy or equivalentQuality control: dummy run,Hurkmans et al, Radiother Oncol 2003,Timing: 12 weeks after SNBExtent:Level I + II mandatoryLevel III optionalAdditional AxRT
8、: 4 positive nodes,ALND,RESULTS,2001- 2010: 4806 patients enrolled (4766 required),All included patientsn = 4806,SNB negativeN = 3131 (65.1%),ALND N = 744,ALND N = 598,AxRT N = 681,AxRT N = 535,ExcludedN = 146,Intent-to-treat (ITT) sample,AxSNB positiveN = 1425 (29.7%),SNB not identifiedN = 132 (2.7
9、%),SNB other N = 120 (2.5%),ExcludedN = 146,Per Protocol (PP) sample,10 not eligible 885 ITC only (before amendment)6751 Non-compliance 71,Efficacy analyses (OS and DFS): per protocol (PP)by intent-to-treat (ITT) Both PP and ITT analyses gave similar results Intent-to-treat analysis reported,Treatme
10、nt compliance,Randomized treatmentBoth treatmentsCross-overNo axillary treatment,631 (84.8 %)41 (5.5 %)46 (6.2 %)24 (3.2 %),590 (86.6 %)1 (0.1 %) 68 (10.0 %)22 (3.2 %),ALND (744 pts),AxRT(681 pts),Median age (Q1-Q3)Menopausal stagepre-menopausalpost-menopausalMedian tumor size (Q1-Q3)Grade123Pre-ope
11、rative ultrasound axilla,56 (48 - 64)38.1 %57.7 %17 mm (13 - 22)24.1 %47.8 %25.8 %59.2 %,Baseline clinical,ALND (744 pts),AxRT(681 pts),55 (48 - 63)42.5 %54.5 %18 mm (13 - 23)22.6 %45.7 %29.4 %61.5 %,Breast surgery BCSMastectomy,Systemic treatmentchemotherapyhormonal therapyimmunotherapy no systemic
12、 treatment,81.9 %17.1 %,60.9 %78.6 %6.0 %9.0 %,84.8 %,61.3 %77.1 %6.4 %9.4 %,81.8 %17.8 %,RT breast/chest wall,87.7 %,ALND (744 pts),AxRT(681 pts),Baseline treatment,SN results,ALND (744 pts),AxRT(681 pts),Median number of SN removed (Q1-Q3)Size of metastases in SN macrometastasesmicrometastasesITC,
13、59.4 %28.9 %11.7 %,2 (1-3),2 (1-3),Straver et al, Ann Surg Oncol 2010,61.5 %28.6 %9.8 %,ALND results,Median number of all nodes removed (Q1-Q3)Number of additional positive nodes (besides SN)01-3 4,15 (12-20)67.1 %25.0 %7.8 %,ALND (744 pts),5-years axillary recurrence rate: ALND 0.43% (4 / 744 event
14、s (0.54%) AxRT 1.19% (7 / 681 events (1.03%) hypothesis (2%)Consequence: planned comparison is underpowered,Axillary recurrence rate,Axillary recurrence rate SN-,5-years axillary recurrence rate: 0.72% (25/3131 events (0.80%),Disease-free survival,HR:1.17; 95%CI: 0.93-1.51P = 0.18,Overall survival,H
15、R:1.17; 95%CI: 0.85-1.62P = 0.34,Breast cancer specific deaths:ALND: 53 (7.1 %)AxRT: 54 (7.9 %),Results side effects,50-70% form compliance at all time points,Lymphedema of the arm,Measured: 1, 3 and 5 years after treatmentItems:Clinical observationTreatment for edema:- sleeve garment- lymph drainage therapy- compression therapy,24,40.0%,29.8%,21.7%,16.7%,13.6%,Years after randomization,%,Lymphedema: clinical observation and/or treatment,
