乳腺癌前哨淋巴结与放疗

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 1980s patients with early breast cancer,前哨淋巴结活检,a high level accuracy false negative rate around 7% equivalent oncological outcomes in terms of distant disease-free and overall survival surprisingly low re

2、gional 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 invol

3、ved SN omit the completion ALND no apparent detriment to oncological outcomes,ACOSOG-Z0011,American College of Surgeons Oncology Group (ACOSOG)-Z0011 axillary dissection vs. no axillary dissection,ACOSOG-Z0011,May 1999-Dec 2004 115 sites,ACOSOG-Z0011,Eligibility criteria older than 18 years, T1-2inv

4、asive breast 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 disease Preoperative systemic treatments isolated tumour ce

5、lls (ITC) in the SN,ACOSOG-Z0011,Stratification age (younger or older than 50 years) ER status tumour size (2 cm),ACOSOG-Z0011,BCS and SNB SN 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

6、 main outcome measure overall survival Secondar youtcome measure disease free survival,ACOSOG-Z0011,noninferiority trial the SNB-only group having a 5-year OS not less than 75% of ALND group Targeted enrolment was 1900 women with a final analysis after 500 deaths.,ACOSOG-Z0011,The trial was closed 8

7、91 patients due to lower than expected accrual and event rates,ACOSOG-Z0011,445 ALND 446 SN biopsy alone 35 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 meta

8、static breast cancer Breast conservation and systemic therapy, SNB alone compared with ALND did not result in inferior survival,ACOSOG-Z0011,Potential problems statistical design and interpretation enrolment of patients imbalances between the treatment groups and missing data,ACOSOG-Z0011,The planne

9、d target accrual 1900 patients -a prediction of an overall survival rate of 80% at 5 years for women with optimally treated node-positive breast cancer The 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)

10、, was unable to complete 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 miss

11、ing 20 cases (2%) -tumour size was missing 81 cases(9%) - receptor status was missing The size of the SN metastasis was unknown in 125 cases (15%), 33 cases (4%) had no lymph node metastases 15 cases in the SN arm had more than 2 nodes involved,ACOSOG-Z0011,27% patients in the ALND arm had further p

12、ositive nodes Thus 27% of the 388 patients in the SNB arm may have had undissected disease Macrometastases in the SN 62.5% of patients in the ALND group 55.2% of patients in the SNB group.,ACOSOG-Z0011,This statistically significant imbalance between the groups raises the question the SNB group had

13、less tumour burden in their nodes and, consequently, a more favourable prognosis the 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 nod

14、es the patients recruited to the study were generally low risk cancers The majority of patients had small (T1) ER positive invasive ductal carcinomas over 50 years old raising the question many patients with cancers that would have met the eligibility criteria but were not represented in the cohort

15、of patients in the trial.,ACOSOG-Z0011,Another concern the high proportion of patients lost to follow-up 21% ALND and 17% SN,ACOSOG-Z0011,WBI with opposing standard tangential fields the fields were not uniform between the randomization arms the radiation oncologists not blinded,前哨淋巴结活检微转移,Axillary

16、dissection versus no axillary dissection 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 cm one or more microm

17、etastatic (2 mm) sentinel lymph nodes with no extracapsular extension,IBCSG 2301,randomly assigned (in a 1:1 ratio) Randomisation was stratified by centre and menopausal status Treatment assignment was not masked,IBCSG 2301,primary endpoint disease-free survival Non-inferiority as a hazard ratio (HR

18、) of less than 1.25 for no axillary dissection versus axillary dissection The 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 regression analysis of disease-free survival,IBCSG 2301,This trial and ACOSOG Z0011-change clinical practice, sparing many patients with early breast-cancer axillary dissection