乳腺癌前哨淋巴結(jié)與放療

1、乳腺癌前哨淋巴結(jié)乳腺癌前哨淋巴結(jié) 與放療與放療 保乳手術(shù)保乳手術(shù) breast conservative treatment (BCT) safe- results of randomized trials in the 1980s patients with early breast cancer 前哨淋巴結(jié)活檢前哨淋巴結(jié)活檢 a high level accuracy false negative rate around 7% equivalent oncological outcomes in terms of distant disease-free and overall survi

2、val surprisingly low regional recurrence rate of less than 1% 前哨淋巴結(jié)活檢前哨淋巴結(jié)活檢 negative SN-completion ALND is not required 前哨淋巴結(jié)活檢前哨淋巴結(jié)活檢 axillary metastasis are limited the SN in 60-70% overall 90% for low volume involvement (micrometastasis/isolated tumour cells detected by immunohistochemical stain

3、ing only) 前哨淋巴結(jié)活檢前哨淋巴結(jié)活檢 patients with involved SN omit the completion ALND no apparent detriment to oncological outcomes ACOSOG-Z0011ACOSOG-Z0011 American College of Surgeons Oncology Group (ACOSOG)-Z0011 axillary dissection vs. no axillary dissection ACOSOG-Z0011ACOSOG-Z0011 May 1999-Dec 2004 115

4、sites ACOSOG-Z0011ACOSOG-Z0011 Eligibility criteria older than 18 years, T1-2invasive breast cancer, no palpable axillary adenopathy, and 1 or 2 SN metastasis without extranodal extension ACOSOG-Z0011ACOSOG-Z0011 Exclusion criteria Clinically node positive disease more than 2 positive sentinel nodes

5、, matted nodes, gross extranodal disease Preoperative systemic treatments isolated tumour cells (ITC) in the SN ACOSOG-Z0011ACOSOG-Z0011 Stratification age (younger or older than 50 years) ER status tumour size (2 cm) ACOSOG-Z0011ACOSOG-Z0011 BCS and SNB SN metastasis in 1 or 2 nodes randomly assign

6、ed ALND or no further axillary ALND a dissection of at least 10 lymph WBI Systemic adjuvant therapy ACOSOG-Z0011ACOSOG-Z0011 The main outcome measure overall survival Secondar youtcome measure disease free survival ACOSOG-Z0011ACOSOG-Z0011 noninferiority trial the SNB-only group having a 5-year OS n

7、ot less than 75% of ALND group Targeted enrolment was 1900 women with a final analysis after 500 deaths. ACOSOG-Z0011ACOSOG-Z0011 The trial was closed 891 patients due to lower than expected accrual and event rates ACOSOG-Z0011ACOSOG-Z0011 445 ALND 446 SN biopsy alone 35 patients (25 on the ALND arm

8、 and 10 on the SNB arm) excluded because withdrew consent ACOSOG-Z0011ACOSOG-Z0011 ACOSOG-Z0011ACOSOG-Z0011 ACOSOG-Z0011ACOSOG-Z0011 ACOSOG-Z0011ACOSOG-Z0011 ACOSOG-Z0011ACOSOG-Z0011 ACOSOG-Z0011ACOSOG-Z0011 ACOSOG-Z0011ACOSOG-Z0011 limited SN metastatic breast cancer Breast conservation and systemi

9、c therapy, SNB alone compared with ALND did not result in inferior survival ACOSOG-Z0011ACOSOG-Z0011 Potential problems statistical design and interpretation enrolment of patients imbalances between the treatment groups and missing data ACOSOG-Z0011ACOSOG-Z0011 The planned target accrual 1900 patien

10、ts -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), was unable to complete enr

11、olment, and therefore closed early with less than 50% of the targeted accrual and with lower-than- expected event rates ACOSOG-Z0011ACOSOG-Z0011 a significant amount of missing data 98 cases (11%) -the number of lymph node metastases was missing, 217 cases (32%) -tumour grade was missing 20 cases (2

12、%) -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-Z0011ACOSOG-Z0011 27% patients in the ALND arm had further posi

13、tive 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-Z0011ACOSOG-Z0011 This statistically significant imbalance between the groups raises the question the SNB g

14、roup had 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-Z0011ACOSOG-Z0011 The most critical issue - eligibility criteria included patients over 18 years old with tumour 5cmwithmacrometast

15、ases in2 sentinel nodes 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 repre

16、sented in the cohort of patients in the trial. ACOSOG-Z0011ACOSOG-Z0011 Another concern the high proportion of patients lost to follow-up 21% ALND and 17% SN ACOSOG-Z0011ACOSOG-Z0011 WBI with opposing standard tangential fields the fields were not uniform between the randomization arms the radiation

17、 oncologists not blinded 前哨淋巴結(jié)活檢微轉(zhuǎn)移前哨淋巴結(jié)活檢微轉(zhuǎn)移 Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 2301) a phase 3 randomised controlled trial IBCSG 2301IBCSG 2301 no axillary dissection non-inferior to axillary dissection one or more micrometastati

18、c (2 mm) sentinel nodes tumour of maximum 5 cm one or more micrometastatic (2 mm) sentinel lymph nodes with no extracapsular extension IBCSG 2301IBCSG 2301 randomly assigned (in a 1:1 ratio) Randomisation was stratified by centre and menopausal status Treatment assignment was not masked IBCSG 2301IB

19、CSG 2301 primary endpoint disease-free survival Non-inferiority as a hazard ratio (HR) of less than 1.25 for no axillary dissection versus axillary dissection The analysis - intention to treat IBCSG 2301IBCSG 2301 IBCSG 2301IBCSG 2301 IBCSG 2301IBCSG 2301 IBCSG 2301IBCSG 2301 IBCSG 2301IBCSG 2301 IBCSG 2301IBCSG 2301 IBCSG 2301IBCSG 2301 IBCSG 2301IBCSG 2301 IBCSG 2301IBCSG 2301 IBCSG 2301IBCSG 2301 Analysis of subgroups defined by tumour size, OR, Analysis of subgroups defined by tumour size, OR, PR, tumour grade, and ty