1、乳腺癌前哨淋巴结与放疗,保乳手术,breast conservative treatment (BCT) safe- results of randomized trials in the 1980spatients with early breast cancer,前哨淋巴结活检,a high level accuracyfalse negative rate around 7%equivalent oncological outcomes in terms of distant disease-free and overall survivalsurprisingly low region
2、al recurrence rate of less than 1%,前哨淋巴结活检,negative SN-completion ALND is not required,前哨淋巴结活检,axillary metastasis are limited the SN in 60-70% overall 90% for low volume involvement (micrometastasis/isolated tumour cells detected by immunohistochemical staining only),前哨淋巴结活检,patients with involved
3、SN omit the completion ALNDno apparent detriment to oncological outcomes,ACOSOG-Z0011,American College of Surgeons Oncology Group (ACOSOG)-Z0011axillary dissection vs. no axillary dissection,ACOSOG-Z0011,May 1999-Dec 2004 115 sites,ACOSOG-Z0011,Eligibility criteria older than 18 years,T1-2invasive b
4、reast cancer,no palpable axillary adenopathy, and 1 or 2 SN metastasis without extranodal extension,ACOSOG-Z0011,Exclusion criteria Clinically node positive disease more than 2 positive sentinel nodes, matted nodes, gross extranodal diseasePreoperative systemic treatmentsisolated tumour cells (ITC)
5、in the SN,ACOSOG-Z0011,Stratification age (younger or older than 50 years)ER statustumour size (2 cm),ACOSOG-Z0011,BCS and SNBSN metastasis in 1 or 2 nodes randomly assigned ALND or no further axillary ALND a dissection of at least 10 lymph WBI Systemic adjuvant therapy,ACOSOG-Z0011,The main outcome
6、 measure overall survivalSecondar youtcome measure disease free survival,ACOSOG-Z0011,noninferiority trial the SNB-only group having a 5-year OS not less than 75% of ALND groupTargeted enrolment was 1900 women with a final analysis after 500 deaths.,ACOSOG-Z0011,The trial was closed 891 patients due
7、 to lower than expected accrual and event rates,ACOSOG-Z0011,445 ALND446 SN biopsy alone35 patients (25 on the ALND arm and 10 on the SNB arm) excluded because withdrew consent,ACOSOG-Z0011,ACOSOG-Z0011,ACOSOG-Z0011,ACOSOG-Z0011,ACOSOG-Z0011,ACOSOG-Z0011,ACOSOG-Z0011,limited SN metastatic breast can
8、cer Breast conservation and systemic therapy, SNB alone compared with ALND did not result in inferior survival,ACOSOG-Z0011,Potential problems statistical design and interpretationenrolment of patientsimbalances between the treatment groups and missing data,ACOSOG-Z0011,The planned target accrual 19
9、00 patients -a prediction of an overall survival rate of 80% at 5 years for women with optimally treated node-positive breast cancerThe study had a slow accrual (115 sites over 4 years leading to 900 patients e some centres entered less than 3 patients which is not many per site), was unable to comp
10、lete enrolment, and therefore closed early with less than 50% of the targeted accrual and with lower-than-expected event rates,ACOSOG-Z0011,a significant amount of missing data 98 cases (11%) -the number of lymph node metastases was missing,217 cases (32%) -tumour grade was missing20 cases (2%) -tum
11、our size was missing 81 cases(9%) - receptor status was missingThe size of the SN metastasis was unknown in 125 cases (15%),33 cases (4%) had no lymph node metastases15 cases in the SN arm had more than 2 nodes involved,ACOSOG-Z0011,27% patients in the ALND arm had further positive nodesThus 27% of
12、the 388 patients in the SNB arm may have had undissected diseaseMacrometastases in the SN 62.5% of patients in the ALND group 55.2% of patients in the SNB group.,ACOSOG-Z0011,This statistically significant imbalancebetween the groups raises the question the SNB group had less tumour burden in their
13、nodes and, consequently, a more favourable prognosisthe axillary recurrence rate was double in the SNB group(0.9% vs. 0.5%),ACOSOG-Z0011,The most critical issue - eligibility criteria included patients over 18 years old with tumour 5cmwithmacrometastases in2 sentinel nodesthe patients recruited to t
14、he study were generally low risk cancersThe majority of patients had small (T1)ER positive invasive ductal carcinomasover 50 years oldraising the questionmany patients with cancers that would have met the eligibility criteria but were not represented in the cohort of patients in the trial.,ACOSOG-Z0
15、011,Another concern the high proportion of patients lost to follow-up 21% ALND and 17% SN,ACOSOG-Z0011,WBI with opposing standard tangential fieldsthe fields were not uniform between the randomization armsthe radiation oncologists not blinded,前哨淋巴结活检微转移,Axillary dissection versus no axillary dissect
16、ion in patients with sentinel-node micrometastases (IBCSG 2301)a phase 3 randomised controlled trial,IBCSG 2301,no axillary dissection non-inferior to axillary dissection one or more micrometastatic (2 mm) sentinel nodes tumour of maximum 5 cmone or more micrometastatic (2 mm) sentinel lymph nodes w
17、ith no extracapsular extension,IBCSG 2301,randomly assigned (in a 1:1 ratio) Randomisation was stratified by centre and menopausal statusTreatment assignment was not masked,IBCSG 2301,primary endpoint disease-free survivalNon-inferiority as a hazard ratio (HR) of less than 1.25 for no axillary disse
18、ction versus axillary dissectionThe analysis - intention to treat,IBCSG 2301,IBCSG 2301,IBCSG 2301,IBCSG 2301,IBCSG 2301,IBCSG 2301,IBCSG 2301,IBCSG 2301,IBCSG 2301,IBCSG 2301,Analysis of subgroups defined by tumour size, OR, PR, tumour grade, and type of surgery,Multivariable proportional-hazards r
19、egression analysis of disease-free survival,IBCSG 2301,This trial and ACOSOG Z0011-change clinical practice, sparing many patients with early breast-cancer axillary dissectionthe sentinel node is minimally involved thus reducing surgical complications Axillary dissection with no adverse effect on survival,IBCSG 2301,the 2011 St Gallen Consensus Conference recommending that micrometastases in a single sentinel node should not be an indication for axillary dissection,
