Tomoharu Sugie, MD , Terumasa Sawada, MD, Nobumi Tagaya, MD,Takayuki Kinoshita MD, Kazuhiko Yamagami, MD, Hirofumi Suwa,MD, Takafumi Ikeda, PhD, Kenichi Yoshimura, PhD, Miyuki Niimi,PhD, Akira Shimizu, MD, and Masakazu Toi, MDAnn Surg Oncol 2013; 20:2213-2218

Background Sentinel lymph node (SLN) biopsy using indocyanine green (ICG)
fluorescence method is a technique that utilizes the fluorescing property ofICG reagent that is used in the dye method.
 This florescence technique leads to the first SLN as a real time image fromoutside the body, and enables orderly and sequential dissection along thelymphatic flow.
 ICG fluorescence detection was superior to the blue dye in terms of thenumber of SLNs identified and detection rate in early stage breast cancer.
 No statistical analyses has clearly demonstrated the superiority of the ICG
fluorescence method over the dye method following a standard procedure.

Objectives
 Primary Objective:

Compare the number of lymph nodes identified by the ICG fluorescence or the bluedye method
 Secondary Objectives:
1. Identification rate, metastasis rate of SLN
2. Metastasis rate according to the order of SLN
3. Identification rate by age and BMI
4. Items of adverse reactions and the prevalenceStudy Design

Primary breast cancer of
T1-3N0Acquisition ofconsent
Case registration

Detection of sentinel lymph
node (ICG fluorescencemethod, dye method)

Detection of sentinel lymph
node (ICG fluorescencemethod, dye method)

Surgery (primary lesion)

Surgery (primary lesion)
Lymph node dissection

Lymph nodedissection

Detection of sentinel lymph
node (ICG fluorescencemethod, dye method)

Preoperative adjuvant
chemotherapy

Surgery (primarylesion)
Lymph nodedissection

Observation, evaluation

Surgery(primary lesion)

Patients and tumor characteristics (n=99)
Characteristics

ValuesAge

Mean (range)

60 (29-75)

Pathology

Invasive
Noninvasive

92 (93%)
7 (7%)

Tumor size

Tis
T1a
T1b
T1c
T2
T3Tx

4 (4%)
4 (4%)
15 (15%)39 (39%)34 (34%)
1 (1%)
2 (2%)

Grade

12
3
Unknown

36 (36%)37 (37%)23 (23%)3 (3%)ER

Negative
Positive
Unknown

17 (17%)81 (81%)1 (1%)

Characteristics

ValuesPR

Negative
Positive
Unknown

24 (24%)73 (73%)2 (2%)HER2

Negative
1+2+3+
Unknown

37 (37%)32 (32%)15 (15%)12 (12 %)
3 (3%)BMI (kg/m2)<18.5(11%)>18.5, <22>22, <25>25, <30>30

11
39 (39%)32 (32%)13 (13%)
4 (4%)

Comparison of SLN detection between the ICG fluorescence method andthe dye method
Resultsp

1.0 (rage, 0-6)

<0.00199% (98/99)
78% (77/99)<0.001

Difference in number of nodes identified

Differences ( ICG fluorescence – blue dye)

Detection rate
ICG fluorescence
Dye
Ann Surg Oncol 2013; 20:2213-2218

Classification of SLN in terms of fluorescence and dye% patients (n=99)% SLNs identified (n=340)

Flu+dye+78 (77/99)

36 ( 121/340)

Flu+dye-69 (68/99)

47 (160/340)

Flu-dye+0(0/99)0( 0/340)

Flue-dye-35 (35/99)

17(59/340)

Flu ; fluorescence

Ann Surg Oncol 2013; 20:2213-2218

SLN detection rate according to age and BMI using the ICG fluorescence method
and the dye method
ICG (%)

pDye (%)

p100 (30/30)
100 (19/19)
97 (34/35)
100 (15/15)

1.00

87 (26/30)
95 (18/19)
69 (24/35)
60 (9/15)

0.03

100 (11/11)
100 (39/39)
97 (31/32)
100 (13/13)
100 (4/4)

0.61

100 (11/11)
79 (31/39)
75 (24/32)
62 (8/13)
75 (3/4)

0.20

Age<50>50, <60>60, <70>70
BMI
<18.5
>18.5, <22>22, <25>25, <30>30

Ann Surg Oncol 2013; 20:2213-2218

SLN and non-SLN involvement in terms of the order of SLN removal
Characteristics% Patients

Patients with positive SLNs

20 ( 20/99)

Positive SLN identified byICG
Dye

100 (20/20)
70 (14/20)

1st SLN positive alone

60 (12/20)

Completion of ALND

67(8/12)

Non SLN negative

100 (8/8)

Non SLN positive0(0/8)

1st SLN and 2nd or further positive

40 (8/20)

Completion of ALND

100 (8/8)

Non SLN negative

50 (4/8)

Non SLN positive

50 (4/8)

Ann Surg Oncol 2013; 20:2213-2218

Conclusions
 ICG fluorescence method leads to a high rate of SLN detection
 The detection rate of SLN is stable irrelevant to age and BMI .
 The first SLN identified by fluorescence imaging represents theexact axillary status.
 The patients with the isolated involvement in the first SLN canbe spared subsequent completion of ALND.