Transcript Folie 1 - IGCS.org

The Sentinel Node Concept in Patients
with Cervical Cancer
-A Multicenter Validation Studyof the German
SUBMITTED
Hermann Hertel, Christopher Altgassen, Antje Brandstädt, Christhardt Köhler,
Matthias Dürst and Achim Schneider
for the AGO-study group
Introduction
-sentinel concept in the
surgical treatment of breast cancer
-minimize morbidity
-sensitivity 88.6 – 91.2%
-negative predictive value (NPV)
91.1 – 95.7%*
-without compromizing oncological safety
Today this technique has become method of choice in the
surgical treatment of breast cancer.
*Veronesi et al.: N Engl Med 2003;349:546-553, Krag et al.: N Engl Med 1998;339:991-995
Gynecol Oncol update
Leuven
5. May
Introduction
advantage of sentinel technique
-reduction of negative lymph node dissection
-sentinel lymph nodes predict accurately
the negative status of the
remaining regional lymph nodes
Introduction
-cervical cancer metastasize mainly lymphatic
-lymph node status is the most important
prognostic factor
-lymphadenectomy - gold standard
If lymph node metastases are present at the
time of primary surgery
Gynecol Oncol update
Leuven
5. May
5-year survival drops from 85% to 50%.
Introduction
Removal of lymph nodes can lead to:
-serocele formation
-lymphedema
-paraaesthesia
-voiding disorders
More than 90% of the removed lymph nodes are free of
metastatic disease.
Patients could be preserved from potential morbidity.
Sentinel concept might be applicable in cervical cancer.
Gynecol Oncol update
Leuven
5. May
prospective studies
Author
Tc/Blue
Patients
(n)
Detection
(%)
Hauspy et al. 2007 Tc + blue
39
98
Seong et al. 2007 blue
89
57,3%
Schwedinger et al. 2006
blue
47
83
Vieira et al. 2004
blue
51
62,7
Yuan et al. 2004 blue
Niikura et al. 2004 Tc + blue
41
20
75,6
90
Li et al. 2004
Tc
75
96,4
Rob et al. 2004
blue
100
60-90,5
70
87-93
Plante et al. 2003 blue +/- Tc
Wuppertal
2004
Aim
-evaluation of detection rate and diagnostic accuracy of
sentinel lymph nodes
-patients with cervical cancer
-all stages
-to predict the histopathologic pelvic nodal status
Gynecol Oncol update
Leuven
5. May
The study
1998-2006
-prospective multi-center cohort study
-Technetium, Patent Blue®, or both to identify sentinel
lymph nodes
Gynecol Oncol update
Leuven
5. May
-pelvic (and para-aortic) node dissection
-sentinel nodes and non-sentinel nodes were
histopathologically examined
inclusion criteria
-histological proven cervical cancer (all stages),
-signed informed consent,
-intension to surgical staging of the patient,
-complete pelvic lymphadenectomy,
exclusion criteria
-preoperative detected metastatic disease,
-previous pelvic or para-aortic lymphdenectomies,
-concurrent adnexal carcinoma,
-cervical extension which made injection in normal
cervical tissue impossible,
Gynecol Oncol update
-neoadjuvant therapy
Leuven
5. May
Statistics
primary objective:
-sentinel lymph node detection rate
-accuracy (sensitivity, negative predictive value)
Hypothesis
sensitivity: 96,5% should be achieved/ 90% clinically accepted
100 sentinel positive patients necessary
total sample size depended on prevalence of positive sentinel
nodes and detection rate
Gynecol Oncol update
Leuven
5. May
Tracer application
subepithelially
Gynecol Oncol update
Leuven
5. May
Tc-albumines
60 MBq the day prior
(1ml)
Blue dye (Patent Blue®)
4 ml after anesthesia
surgical procedure
laparoscopic pelvic lymphadenectomy (left)
N. obturatorius
surgical procedure
N. genitofemoralis
Vasa iliaca
externa
M. psoas
laparoscopic paraaortic lymphadenectomy
V. renalis
positive pelvic
lymphnode left side
A. mesenterica
inferior
Gynecol Oncol update
Leuven
5. May
Results
December 1998-October 2006
603 patients enrolled in 18 centers
-excluded 96 patients(in 64 patients no pelvic sentinel node was detected)
507 patients for analysis of accuracy
Gynecol Oncol update
Leuven
5. May
Patients fulfilling inclusion but not
exclusion criteria n = 603
n=603
Excluded patients:(n =13)
Reasons:
No marker applied (n = 1)
No searching for SLN (n = 12)
n=590
Population for analysis of detect- ion
rate n = 590
Excluded patients (n = 83)
Reasons:
Neo-adjuvant therapy (n = 12)
Pelvic SLN not detected (n = 64)
Pelvic nodal status (reference)
inconclusive or unknown (n = 7)
Population for analysis of diagnostic
accuracy n= 507
n=507
Pelvic SLN nodal status (Index test)
Positive
n = 82
n=82
Pelvic nodal status
(Reference)
Positive
n = 82
Negative
(impos. by
definition)
Negative
n = 422
n=422
Pelvic nodal status
(Reference)
Positive
n = 24
n=24!!
Neg.
n = 398
Inconclusive 2
n=3
Pelvic nodal status
(Reference)
Positive
n=3
Negative
(impos. by
definition)
-flowchartdisposition of
patients eligible
for analysis
Results
median age 41 years (range 16-79 years)
squamous cell carcinoma 383 patients (75.5%)
adenocarcinoma 97 patients (19.1%)
Gynecol Oncol update
Leuven
5. May
(5,4% others)
FIGO stage
-IA1 in 38 patients (7.5%),
-IA2 in 42 patients (8.3%),
-IB1 in 265 patients (52.3%),
-IB2 in 55 patients (10.8%),
-IIA or IIB in 91 patients (17.9%),
-IIIA to IVB in 15 patients (3%)
Results
cervical cancer were removed vaginally and lymph nodes
were harvested endocopically in 283 patients (56%),
open approach was chosen in 224 Patients (44%)
Gynecol Oncol update
Leuven
5. May
Results
indentification of sentinel lymph nodes
over all detection rate: 89,7%
(CI95 86.9-92%)
pelvic:
(CI95 85,8-91,1%)
88,6%
Tc alone (n=55)
Patent Blue® alone (n=195)
Tc+Patent Blue® (n=340)
Gynecol Oncol update
Leuven
5. May
82% detection rate
82% detection rate
94% detection rate
(p<0,001)
Results
indentification of sentinel lymph nodes
median number of sentinel lymph nodes
pelvic: 2 (2-24)
paraaortic: 1 (1-9)
>5 sentinel nodes identified in 103 patients (20,3%)
Gynecol Oncol update
Leuven
5. May
median number of all lymph nodes
pelvic: 24 (2-70); n=507 patients
paraaortic: 13 (1-47); n=190 patients
Results
accuracy of diagnostic test
pelvic lymph node metastasis
n=106 patients
sentinel lymph nodes
correctly predict metastatic disease
n=82 patients
Sensitivity
77,4% (CI 68,2-85%)
(<90% of clinically acceptability)
NPV
Gynecol Oncol update
Leuven
5. May
94,3% (CI 83-99,4%)
Gynecol Oncol update
Leuven
5. May
Results
indentification of sentinel lymph nodes
tumor size
lower or equal 20mm in 249 patients (45.8%)
larger than 20mm in 305 patients (47.7%)
(6,5% no data)
overall detection rate
94% in cancers smaller than 21mm
84% in cancers larger than 20mm (p<0.001).
Results
accuracy of diagnostic test
sensitivity in subgroups of women with tumors
Gynecol Oncol update
Leuven
5. May
<21mm =90.9%(70,8-98,9%),
>21mm =72,7% (61,3-82,3%)
(p=0.091)
Gynecol Oncol update
Leuven
5. May
Results
accuracy of diagnostic test
tumors < 21mm
NPV=99.1 (CI95 96.6 – 100%)
tumors >20mm
NPV=88.5% (CI95 82.9 – 92.8%),
(p<0.001)
Gynecol Oncol update
Leuven
5. May
Probability of diagnostic outcome in all patients –flowchart-
Probability of diagnostic outcome
itive
s
o
p
SLN .163
0
100
cted
e
t
e
d
SLN 0.886
Reference positive
1.000
True positive
0.144
Reference positive
0.057
False negative
0.042
SL
N
n
0. ega
83 ti
7 ve
SL
N
no
0. t de
11 te
4 cte
Reference negative
0.943
4 patients!
True negative
0.700
d
0.114
SLN: Pelvic SLN (Index test)
Reference: Pelvic nodal status
Probability of diagnostic outcome in patients with cervival cancer ≤20mm
-flowchart-
Gynecol Oncol update
Leuven
5. May
Probability of diagnostic outcome in patients with tumor size  20 mm
ive
osit
p
SLN .086
0
100
cted
e
t
e
d
SLN 0.940
Reference positive
1.000
True positive
0.081
Reference positive
0.009
False negative
0.008
SL
N
n
0. ega
91 ti
4 ve
SL
N
no
0. t de
06 te
0 cte
Reference negative
0.991
1 patient!
True negative
0.851
d
0.060
SLN: Pelvic SLN (Index test)
Reference: Pelvic nodal status
Conclusion
Our data suggest that the sentinel concept is NOT
applicable in patients with cervical cancer.
Gynecol Oncol update
Leuven
5. May
Sensitivity is to low.
Conclusion
Using the currently available concept, systematic
lymphadenectomy CAN NOT be omitted!
Ultrastaging of sentinel lymph nodes may have a future role in
addition to systematic lymphadenctomy.
HPV-associated markers have the highest potential of
accurate identification of viable tumor cells.
Gynecol Oncol update
Leuven
5. May