Pre- operative staging of the axilla
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1 Pre- operative staging of the axilla Anthony J Maxwell University Hospital of South Manchester
2 Outline Why stage the axilla? Optimising conventional US & needle sampling Other imaging and needle sampling techniques inc. round- up of current UK studies How might changes in the management of the axilla affect what we do? 2
3 Why stage? To diagnose the presence of axillary metastatic disease avoids unnecessary surgical SLNB reduces the number of women who need repeat axillary operations To assess the extent of axillary metastatic disease 3
4 Pre- op diagnosis rate with axillary ultrasound and needle sampling 50 60% ~ 15% of US- negative axillae contain mets 4
5 Optimising current axillary staging practice Ultrasound Needle sampling of nodes 5
6 Axillary ultrasound Anatomy Technique Criteria for abnormality Limitations of US 6
7 RadioGraphics 2013; 33:
8 Position of the SLN Lowest visible node in 81% Second lowest in 11% Third lowest in 8% Britton PD, Moyle P, Benson JR, et al. Ultrasound of the axilla: where to look for the sentinel lymph node. Clin Radiol 2010; 65:
9 Technique Methodical and meticulous Appropriate frequency, depth and focus settings Positive identification of nodes Scan down to nipple level and into axillary tail Transverse and longitudinal planes Colour Doppler 9
10 Criteria for abnormality Diffuse cortical thickening (2 3mm) Focal bulge / eccentric cortical thickening Rounded shape (length/width <2) Partial or complete loss of fatty hilum Non- hilar blood flow Partial or complete replacement with mass 10
11 11
12 Limitations of ultrasound Absence of contour change Low volume disease Invasive lobular carcinoma Poor conspicuity of nodes 12
13 Needle sampling of nodes FNA or core biopsy? 13
14 Audience vote Which do you use most frequently for axillary lymph node sampling? 1. FNA 2. Core biopsy 14
15 FNA or core? The evidence Rao et al - retrospective study FNA +ve in 12/16 cases (75%) 18G core biopsy +ve in 18/22 (82%) (p=0.11) Rao R, Lilley L, Andrews V, et al. Axillary staging by percutaneous biopsy: Sensitivity of fine- needle aspiration versus core needle biopsy. Ann Surg Oncol 2009; 16:
16 FNA or core? The evidence 66 axillae 21 or 22G FNA and 16G core biopsy (median 2 samples, range 1-6) Sensitivity FNA 37/51 (72.5%) core biopsy 45/51 (88.2%) (p=0.008) Rautiainen S, Masarwah A, Sudah M, et al. Axillary lymph node biopsy in newly diagnosed invasive breast cancer: comparative accuracy of fine- needle aspiration biopsy versus core- needle biopsy. Radiology 2013; 269:
17 Core biopsy technique Rotate patient so almost in lateral position Inferior or inferomedial approach 5-10mls 1-2% lidocaine with adrenaline Infiltrate if necessary between node and adjacent structures 14- gauge needle Semi- automatic needle or open notch technique 17
18 18
19 Why does core biopsy fail? 139 patients 121 had core biopsy of abnormal/lowest node 73 CB negative for metastases evidence of CB in 47 mets at surgery in 22/71 (30%) failure to sample SN in 10 (45%) failure to sample metastatic disease in 12 (55%) Britton PD, Provenzano E, Barter S, et al. Ultrasound guided percutaneous axillary lymph node core biopsy: How often is the sentinel lymph node being biopsied? Breast 2009; 18:
20 How can we improve pre- op axillary staging? Improve identification of sentinel/metastatic nodes Improve sampling of target node Specifically identify and optimally biopsy the sentinel node (i.e. percutaneous SLNB) 20
21 Identification of involved nodes Assume lowest visible node (if US normal) Second look ultrasound US elastography CT MRI PET/CT 21
22 Biopsy lowest axillary node 139 patients 121 had (16G) core biopsy if no abnormal node on US then lowest visible node biopsied 41 cores positive in 63 women with mets 65% sensitivity Britton PD, Provenzano E, Barter S, et al. Ultrasound guided percutaneous axillary lymph node core biopsy: How often is the sentinel lymph node being biopsied? Breast 2009; 18:
23 Second look US Repeat axillary US after histological confirmation of breast cancer Could use a nomogram to aid prediction of likelihood of axillary disease Rescan if above certain threshold 23
24 Memorial Sloan- Kettering nomograms.mskcc.org/breast/breastslnodemetastasispage.aspx 24
25 CancerMath.net 25
26 Elastography 26
27 Elastography Cambridge study 21/50 cases positive at surgery Sensitivity: conventional US 76% visual elastography 90% strain scoring 100% Taylor K, O Keeffe S, Britton PD, et al. Ultrasound elastography as an adjuvant to conventional ultrasound in the preoperative assessment of axillary lymph nodes in suspected breast cancer: A pilot study. Clin Radiol 2011; 66:
28 CT MISO- BC CI: Dr Julie Cox, County Durham & Darlington NHS Foundation Trust Randomisation to CT or no CT pre- op 247/300 recruited to date 28
29 72 year old with lump in left breast 33 mm on mammograms (M4) 26 mm on ultrasound (U4) One mildly abnormal left axillary node, cortical thickness 2.4 mm Breast lesion: G3 IDC with DCIS Axillary core: fibrofatty tissue only Courtesy of Dr Julie Cox 29
30 Entered MISO BC trial; randomised to CT Normal apical nodes but one abnormal lower axillary node, lower than the node which had been core biopsied Repeat FNA lower node: malignant infiltration. Had mastectomy and Ax clearance (1/13 +) Learning Point: The axilla is a large space; beware focussing on the apex alone 30
31 MRI Gd enhanced MRI Ultrasmall superparamagnetic iron oxide (USPIO) DWI 31
32 Gd CE MRI lymph node criteria Baltzer PAT, Dietzel M, Burmeister HP, et al. Application of MR mammography beyond local staging: Is there a potential to accurately assess axillary lymph nodes? Evaluation of an extended protocol in an initial prospective study. AJR Am J Roentgenol 2011; 196: w
33 Gd- enhanced MRI Some correlation between enhancement and metastatic infiltration less intensely enhancing nodes more likely to be benign 33
34 MRI with USPIO Harada T, Tanigawa N, Matsuki M, et al. Evaluation of lymph node metastases of breast cancer using ultrasmall superparamagnetic iron oxide- enhanced magnetic resonance imaging. Eur J Radiol 2007; 63:
35 MRI sensitivity & specificity Sensitivity Specificity Gd CE MRI (3 studies) 88% 73% USPIO (5 studies) 98% 96% Harnan SE, Cooper KL, Meng Y, et al. Magnetic resonance for assessment of axillary lymph node status in early breast cancer: A systematic review and meta- analysis. Eur J Surg Oncol 2011; 37:
36 DWI 36 cases: Sensitivity 84% Specificity 88% Luo N, Su D, Jin G, et al. Apparent diffusion coefficient ratio between axillary lymph node with primary tumor to detect nodal metastasis in breast cancer patients. J Magn Reson Imaging 2013; 38:
37 PET/CT 61 patients CT sensitivity 46% specificity 89% FDG PET/CT sensitivity 58% specificity 92% Heusner TA, Kuemmel S, Hahn S, et al. Diagnostic value of full- dose FDG PET/CT for axillary lymph node staging in breast cancer patients. Eur J Nucl Med Mol Imaging 2009; 36:
38 PET- CT Staging the axilla in breast cancer: PET/CT CI: Professor Steven Heys, University of Aberdeen T2, randomised to PET/CT or no PET/CT pre- op No. of surgical procedures No. of radiological investigations post- op Cost- effectiveness 160/208 recruited 38
39 Improve sampling of target node Vacuum- assisted biopsy Manchester study funded by BSBR research grant A feasibility study comparing the safety and acceptability of vacuum- assisted biopsy and conventional 14- gauge core biopsy in the diagnosis of ultrasonically indeterminate and abnormal axillary lymph nodes CI: Dr Anthony Maxwell 23/80 recruited; 11 13G VABs performed 39
40 Mammotome Elite 40
41 41
42 Manchester VAB study Technique No. of cases Time (mins) No. of cores Pain (0-10) (procedure) Pain (0-10) (1 st 3 days) 14G core 12 3 (2 5) 3 (3) 0 (0 3) 1 (0 5) 13G VAB 11 3 (2 10) 7 (4 15) 1 (0 7) 1 (1 10) 42
43 Percutaneous sentinel lymph node biopsy Sentinel node localisation methods 99m Tc nanocolloid microbubbles indocyanine green SentiMag 43
44 Gamma probe and US Subareolar/peritumoural 99m Tc nanocolloid Steve Parker (2000) insertion of guide wire Andy Evans (Dundee) insertion of guide wire (44/59 = 75% hit rate) VAB Parker SH, Dennis MA, Kaske TI. Identification of the sentinel node in patients with breast cancer. Radiol Clin North Am 2000; 38:
45 Gamma probe and US VAPSLNB CI: Andy Evans (Dundee) Pre- op 7G EnCor VAB of SLN 5 cases to date 9 nodes, 7 hot only 1 partial residual hot node at surgery 2 minimal haematomas 1 pneumothorax Data courtesy of Professor Andrew Evans 45
46 US microbubbles 46
47 US microbubbles and core biopsy/ FNA - Maidstone 136 women with normal axillary US 16G core bx or FNA of SLN in 126 positive in 17 9 false negative (4 micromets) sensitivity 65% Sever AR, Mills P, Weeks J, et al. Preoperative needle biopsy of sentinel lymph nodes using intradermal microbubbles and contrast- enhanced ultrasound in patients with breast cancer. AJR Am J Roentgenol 2012; 199:
48 US microbubbles and clip/vab CI: Peter Britton (Cambridge) Part 1: clip insertion in 36 patients Part 2: VAB & clip 3/120 to date 48
49 US microbubbles and core biopsy with clip - Leeds normal axillary US or abnormal US & normal core/fna subareolar sulphur hexafluoride (SonoVue) injection 14G core bx of SLN and marker clip 22 women 4 failed to identify SLN 4 malignant 14 benign (inc. 1 inadequate) 2 positive at surgical SLNB Data courtesy of Dr Nisha Sharma 49
50 Indocyanine green 50
51 SentiMag 51
52 What s happening with surgical management of the axilla? ACOSOG Z0011 No difference in survival or axillary recurrence rates between women in ANC arm and no ANC arm 52
53 What does this mean? Excision of low volume disease does not appear to affect outcome Treatment based more on biology of disease than stage Can SLNB be avoided for some women? Can we replace it with imaging that will identify which women need ANC? 53
54 US appearances and pn stage pn1 pn2/3 Moore A, Hester M, Nam M- W, et al. Distinct lymph nodal sonographic characteristics in breast cancer patients at high risk for axillary metastases correlate 54 with the final axillary stage. Br J Radiol 2008; 81: 630 6
55 US appearances and pn stage 439 axillary US node positive at FNA or SLNB 4 nodes involved in 54% with US suspicious/malignant nodes 19% with US indeterminate nodes 21% with US normal nodes Amonkar SJ, Oates E, McLean L, et al. Pre- operative staging of the axilla in primary breast cancer. By redefining the abnormal appearing node can we reduce investigations without affecting overall treatment? Breast 2013; 22:
56 Conclusion Optimise axillary US (and audit results) Core biopsy (?VAB) of abnormal nodes rather than FNA?Percutaneous SLNB with microbubbles and VAB if US normal Improve non- invasive imaging of the axilla
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