tumor size and sentinel node procedure
DESCRIPTION
Tumor Size and Sentinel Node Procedure. A. Ph. MAKAR, MD, Ph.D . R. Van Den Broecke, MD, Ph.D . Depart of Senology & Gynaecologic Oncology The Middelheim Hospital University Hospital of Ghent. Tumor size. I .Carcinoma in situ II. T1 & T2 (TRANSCRIPT
Tumor Size and Sentinel Node
Procedure
A. Ph. MAKAR, MD, Ph.D.
R. Van Den Broecke, MD, Ph.D.
Depart of Senology & Gynaecologic OncologyThe Middelheim Hospital
University Hospital of Ghent
Tumor size
I. Carcinoma in situ II. T1 & T2 (<3cm ) tumorsIII. Large T2 & T3 tumorsIV. Inflammatory breast cancerV. Multi-centric / multi-focal disease
Prospective analysis Middelheim hospital 1998-2001, 268 patients, single surgeon
Sense of SN procedure
• Impact on further surgical management, postoperative treatment or prognosis
• False negative rate: acceptable
• Number to be saved complete ALND: high
• Number that needs second surgery: low
– increased morbidity: swelling, numbness, pain– increased coasts– completeness of axillary dissection ?
I. Ductal Carcinoma In Situ
• Silverstein: rate of axillary metastases < 1%
• Survival rate > 98%
• Axillary staging is generally not necessary
• IHC: micro-metastases in 5-15% of cases • Lara (2003) & Broekhuizen & Marby (2006):
– No impact on local failure or distant metastasis
ADH/DCIS in core biopsy: underestimation risk
• Underestimation risk of invasive
disease : 20-40%• SN procedure can be justified:
– Mammographic lesion >5cm– Underlying mass/distortion – Palpable lesion & Core biopsy under
sonography– High grade lesion & micro-invasion &LVSI
II. T1 &T2 tumors (<3cm)
• Extensive evaluation: ASCO guide lines
• Identification rate >95%– Failed identification:
• Age >60 years
• Capsular invasion, high number of positive nodes
• FNR <10%: removal of all radioactive nodes
• IHC: more micro-metastases 15% (10-67%)
• SN metastases in <50% of tumors
• SN only site of metastases in 40%
Positive SNmacro-metasmicro-metas
Complete ALND Alternatives ? ?
Radiotherapy Observation(EORTC) ACSOG00Z11
Historical NSBAP-04
Micro-metastases in SN: Risk factors predicting Non-SN metastases
• LVSI
• Tumor size
• Extra-nodal spread
• Micro-metastasis:– Size of micro-metastasis– Micro-metastasis detected by HES vs IHC– Location of micro-metas: sinusal vs intranodal
• Number of pos SN/total nr of SN: (1/3)
Rate of Non-SN involved in case of micro-metastases in SN according to tumor size
Tumor size (mm) Involved Non-SN %
0-5
6-10
11-20
0-20
21-50
>50
4.8%
8.2%
15.3%
13.4%
30.8%
50%
T1 tumors & micro-metastasis in SN
Houvenaeghel (2006) & Leikola (2006):
• pT1a, pT1b (IHC)
• pT1a- pT1c of tubular, colloid or medullary types– Risk of Non-SN involvement: <5%– Risk of involvement of >1 Non-SN : 0%– ALND can be omitted with minimal risk
Prediction of Non-SN metastases in case of micro-metstases in SN
• Turner (2000): likelihood model
• Van Zee (2003): nanogram (9 variables)
• Meta-analysis:– No combination of factors was able to predict
non-SN metastases – 10% of the micro-metastases in the SN were
associated with one or more macro-metastases in Non-SN
ALND dissection is recommended in every case with micro-metastases in the SN
The prognostic significance micro-metastases:
The Ludwig Breast Cancer Study Group
NSABP-32ACSOG Z0010
III. Large T2 & T3 tumors
Authors No SN LN False
pts identified metas neg rate
O’Hea (1998)
Winchester (1999)
Bedrosian (2000)
Cohen (2001)
Wong (2002)
Chung (2001)
Leidenius (2005)
Makar
25 82% 25%
31 90% 20%
104 99% 63% 2%
83 82% 58% 10%
59 100% 73% 4%
41 100% 76% 3%
70 95% 71% NS
106 82% 52% 2%
SN in tumors <=3cm vs >3 cmLeidenius 2005
<= 3cm > 3cm P value
Axillary metas %
Micro-metas/ITC %
Pos para-sternal SN %
AD omitted (neg SN)%
38%
38%
1.9%
T1a-b: 72%
T1c: 57%
71%
20%
2.8%
28.5%
<.0001
<.02
NS
<.001
% patients with tumors > 3cm and pos SN that have an additional disease in Non-SN
0%10%20%30%40%50%60%70%80%90%
100%
SNmicrometastasis
SNmacrometastasis
% patients
SN with T3 tumors
• The high risk of nodal metastases warrants complete ALND unless:– Motivated patient to have LN conservation
SN procedure following pre-operative CT: Meta analysis
• Identification rate (IR): 91% – IR isotope 95% vs 93% blue dye– No serious concern regarding the fibrotic effect of
CT on lymphatic pathways
• False negative rate: 12%
Neo-adjuvant chemotherapy & axillary downstaging
• Anthracyclin / cyclophosph based CT provides up to 30 % axillary down staging– Size of residual LN metastases after neo-adjuvant
CT is of prognostic significance
• Changing concept:– SN prior to neo-adjuvant CT followed by
“2nd look” axillary dissection post CT
= better prognostic information
Tumors >3cm with macro-metastases in SN
= almost 100% non-SN metastases
SN prior to CT (better staging)
Axillary dissection post CT
Pathologic remission Persistent disease
Less morbidity
IV. Inflammatory breast cancer
• Insufficient data.
• High risk of nodal spread
• False negative rate:– Occlusion of subdermal lymphatics (tumor
emboli)
V. Multicentric tumors
• Occurs in up to 10% of cases
• Were excluded by most SN investigators
• Hypothesis “sentinel for the entire breast”:– High success ratio– No increase in false negative ratio– Peri-areolar injection
Increased risk of nodal metastases with multi-focal tumors
Tumor size (mm)
Uni-focal Multi-focal
( 877 tumors) (107 tumors)
1-10
11-20
21-30
>30
22% 45%
37% 51%
53% 72%
68% 100%
Conclusions-1
• DCIS: – In some cases of core biopsy with risk of
underestimation:• Lesions > 5cm
• Underlying lesion: density/distortion
• High grade tumors & micro-invasion, LVSI
• Immediate reconstruction
Conclusions-2
• T1 –T2 (< 3cm):– Standard procedure with N0– With few exceptions “T1a and T1a-T1c of certain
pathology”, a full ALND is indicated in case of microscopic disease in the SN
– The prognostic significance of micro-metastases needs further evaluation
Conclusions-3
• Large T2 & T3 tumors:– IR and FNR are comparable with T1 tumors– Yet the high incidence of LN metastases makes
the clinical relevance of SN procedure of limited value except in case of neo-adjuvant CT
• Multi-centric /multi-focal disease: – More reports suggest safety of the procedure– Yet multifocal tumors have higher risk of nodal
spread than unifocal ones of same diameter
Conclusion-4
• 2nd axillary surgery carries more morbidity:
Prospective multi-centric trial comparing immediate versus “second-look” axillary surgery post chemotherapy in patients with positive SN:
Welcome to participate
Sentinel Node Team
• Nuclear medicine:– K. Melis
– F. Van Acker
• Pathology:– S. Declercq
– L. Van Leuevn
– C.Mattelaer
• Radiotherapy:– D. Van denWeyngaert
– S. Vanderkam
– I. Jacobs
• Medical Oncology– E. Joossens
– D. Becquart
– A..Vandebroek