Neoadjuvant Chemotherapy and the search for optimum … of England BC Symposium Amit... ·...
Transcript of Neoadjuvant Chemotherapy and the search for optimum … of England BC Symposium Amit... ·...
Amit Goyal
Consultant Oncoplastic Breast Surgeon & Associate Professor
Royal Derby Hospital, Derby, United Kingdom
Neoadjuvant Chemotherapy and the search for optimum management of lymph node
positive breast cancer
Axillary Node Down-Staging with NAC
AC
NSABP B-18
50
40
30
20
10
0
%
Conversion
From
Node (+)
To
Node (-)
AT→CMF
ECTO
3037
FEC
EORTC
19
AC→TXT
NSABP B-27*
43
*Assuming 30% nodal down-staging with neoadjuvant AC
More than 40% of initially node-positive
women could potentially avoid ALND!
cN1 converts to N0 post NACT
Question
• Axillary lymph node dissection
• Axillary radiotherapy
• Sentinel node biopsy
cN1 convert to N0 (ATNEC EOI survey)
Axillary surgery after NACT
ACOSOG Z1071
n = 663 cN1
SN ID rate 95%
649 SN ALND
≥ 2 SN identified
n = 525, 79%
FNR
12.6% (9.9, 16.1)
EligibleT0-T4, N1-2, M0Biopsy Proven Nodal disease
Failed to meetprimary endpointFNR ≤ 10%
Boughey JC, JAMA 2013
ACOSOG Z1071FN rate by number of nodes removed
Boughey JC, JAMA 2013
SLN biopsy after NACTcN1 convert to N0
ACOSOG Z1071 SENTINA SN FNAC
N 649 592(cN+)* 153
Mapping Dual tracer
recommended (79%)
Technetium required Technetium required,
IHC
Pre-op biopsy? Yes Not required (biopsy
=25%)
Yes
Nodal pCR 41% 52% ypN0 (?) 35%
IR 92.7% 80.1% 87.6%
FNR (Overall) 12.6% 14.2% 8.4%
1 SLN 31.5% 24.3% 18.2%
2 SLN 21.1% 18.5% 4.9%
≥3SLN 9.1% 7.3%
*1737 patients enrolled in 4 arm multicenter trial. 592 ARM C were cN+ to cN0
Kuehn T et al. Lancet Oncol 2013; 14: 609–18 Boileau JF et al. JCO 2015; 33: 258–264
Pre vs. Post treatment nodal statusimpact on LRR
NSABP B-18 (AC)/B-27 (AC-T) Mamounas E et al JCO 2012
• Post NACT - SLN biopsy has higher FN rate
• Residual disease potentially resistant to treatment
• Do know importance of path node status in
predicting LRR … implications for RT
• cN1 to N0 post NACT - No data on LRR if ALND is
omitted
ALND remains standard of care outside clinical
trials
cN1 after neoadjuvant chemotherapy
Summary (1)
cN1 convert to N0 after NACT
Suggestions to minimise FNR
• Dual agent mapping
• Normal USS after chemotherapy
• Remove ≥ 3 SLN
• Include IHC detected disease as node positive
• Leave a clip at time of biopsy and localize for SLN
ACOSOG Z1071: 57% SENTINA: 34%
cN1 convert to N0 after NACT
Suggestions to minimise FNR
• Dual agent mapping
• Normal USS after chemotherapy
• Remove ≥ 3 SLN
• Include IHC detected disease as node positive
• Leave a clip at time of biopsy and localize for SLN
SLN biopsy AFTER NACT
cN1 convert to N0 after NACTACOSOG Z1071 SENTINA SN FNAC
N 649 592(cN+)* 153
Mapping Dual tracer
recommended (79%)
Technetium required Technetium required,
IHC
Pre-op biopsy? Yes Not required (biopsy
=25%)
Yes
Nodal pCR 41% 52% ypN0 (?) 35%
IR 92.7% 80.1% 87.6%
FNR (Overall) 12.6% 14.2% 8.4%
1 SLN 31.5% 24.3% 18.2%
2 SLN 21.1% 18.5% 4.9%
≥3SLN 9.1% 7.3%
*1737 patients enrolled in 4 arm multicentre trial. 592 ARM C were cN+ to cN0
Inclusion of mets <0.2mm in the definition of residual nodal
disease after NACT reduces the pCR rate and improves the
accuracy of SLN
2014 SABC, Boughey et al.
Evaluation of SLN after NACT
• Significance of residual ITC’s or disease <0.2mm (ypN0i+) after NACT
unclear
• 2012 WHO classification: small nodal mets and ITCs are evidence of
an incomplete response
• 7th (and 8th) edition AJCC TNM Staging Manual
ypN0i+ or ypN1mi residual nodal disease ALND remains
standard of care
cN1 convert to N0 after NACT
Suggestions to minimise FNR
• Dual agent mapping
• Normal USS after chemotherapy
• Remove ≥ 3 SLN
• Include IHC detected disease as node positive
• Leave a clip at time of biopsy and localize for SLN
Placement of a clip + identification of the clip during SLN and removal at least 2 SLN reduces FNR
20% pts clip not
in SLN
Clip placed 170 pts
2014 SABC, Boughey et al.
MD Anderson
Clipping the node for SLN after NACT
• Clipped node +/- SLN to reflect the status of the nodal basin in all-comers undergoing NAC
Also noted clipped node was not a SLN in ~ 20% pts
“Targeted Axillary Dissection”
Caudle AS et al JCO 2016;34(10):1072-8
Post NACT trials of axillary Management
Amit Goyal (Chief Investigator)
ATNEC trialAxillary management in T1-3N1M0 breast cancer patients with FNA or core
biopsy proven nodal metastases at presentation who convert to node negative after NEoadjuvant Chemotherapy
T1-3,N1,M0 breast cancer
FNA/core biopsy documented axillary metastasis
NEOADJUVANT CHEMOTHERAPY (NACT)
Breast conserving surgery or mastectomy + Targeted
(dual agent) sampling + at least 3 nodes removed + removal of clipped/tattooed node
Axillary ultrasound and FNA or core biopsy of abnormal nodes
Not malignant
No nodal metastasis
RANDOMISATION 1:1
Axillary treatment
ALND or ART
No Axillary
treatment
nodes positive
(micro or macrometastases)
Failed localisation of
clipped/tattooed node
Axillary lymph node
dissection(ALND)
malignant
Marking the positive node
• Clip placed• SPOT dye tattoo – anterior surface and perinodal tissue
cN1 convert to N0 (ATNEC EOI survey)
Axillary surgery – ATNEC Trial
Clipped/tattooed node + 2 more nodes
At least 3 nodes removed (clipped/tattooed node not mandatory)
Clipped/tattooed node + 1 more node
cN1 convert to N0 (ATNEC EOI survey)
Patient selection – ATNEC Trial
Marking and identifying positive node after NACT
• Clip
o Wire
• Radioactive seed
o Regulations
o Availability
o Cost
• Magseed
o Licensing issues
o Equipment –
o Cost - £200 per seed, probe >£10,000
• Tattooing
o £10 per syringe
o Feasibility
o No audio signal
Women undergoing axillary ultrasound and FNA or core biopsy of abnormal nodes
OUTCOMES
• Identification rate of tattooed node
• Concordance of tattooed node and
sentinel node (tattooed node
removed as part of sentinel node
biopsy)
• Migration of SPOT dye into other nodes
Not malignant
Mark the node with SPOT dye tattoo at the time of FNA or core biopsy
• cortex and perinodal tissue
Axillary lymph node
dissection(ALND)
malignant
OUTCOMES
• Identification rate of tattooed node in the
ALND specimen
• False negative rate of tattooed node (in
women undergoing ALND after NACT)
• Migration of SPOT dye into other nodes
(number of black nodes in ALND specimen)
Breast cancer treatment as per local MDT
(Neoadjuvant chemotherapy or No neoadjuvant chemotherapy)
Sentinel Node Biopsy• Sentinel node biopsy and
removal of tattooed node
PRE-ATNEC
• Carbon black tattooing ink
• Pre-loaded syringe
• Used routinely in GI tract
• £10 per syringe
• Removal of needle biopsy proven positive node
after NACT reduces FN rate
• Marking and visualizing the needle biopsy positive
node needs to be standardized
• Pre ATNEC – simple, low cost solution!
cN1 convert to N0 after NACT
Summary (2)
POSNOC Achievements
30
✓ Largest UK breast cancer surgical trial
✓ 1st UK led international breast cancer surgical trial
TOP 10 recruiting sitesSite Numbers
randomised
Derby 61
Oxford 28
Lincoln 27
Bristol 26
Aberdeen 26
Manchester 26
Belfast 24
Marsden 21
Melbourne (Australia) 21
Hull, Wycombe, Gillingham, Cambridge
20
Amendments• Sentinel node biopsy BEFORE Neoadjuvant Chemotherapy allowed
• Sentinel node biopsy tracer technique – as per local guidelines o Sentimag allowed
o Blue dye only allowed
Z11 POSNOC
Size of metastases micrometastasis or
macrometastasis
macrometastasis
Macrometastases 430 1020*
Extranodal invasion x √
Mastectomy x √
Radiotherapy quality
assurancex √
Mandatory pre-op
axillary ultrasoundx √
Sentinel node biopsy
before NACx √
*POSNOC recruitment ongoing (sample size 1900)
POSNOC vs. Z11
Recruitment end date Aug 2021