The Sentinel Node Concept in Patients with Cervical Cancer -A Multicenter Validation Study- of the...
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Transcript of The Sentinel Node Concept in Patients with Cervical Cancer -A Multicenter Validation Study- of the...
The Sentinel Node Concept in Patients with Cervical Cancer
-A Multicenter Validation Study- of 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
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
Gynecol Oncol update Leuven
5. May
-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
5-year survival drops from 85% to 50%.
Introduction
Gynecol Oncol update Leuven
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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.
Introduction
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prospective studies
Author Tc/Blue Patients Detection (n) (%)
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 41 75,6Niikura et al. 2004 Tc + blue 20 90
Li et al. 2004 Tc 75 96,4
Rob et al. 2004 blue 100 60-90,5
Plante et al. 2003 blue +/- Tc 70 87-93
Wuppertal 2004
-evaluation of detection rate and diagnostic accuracy of sentinel lymph nodes
-patients with cervical cancer
-all stages
-to predict the histopathologic pelvic nodal status
Aim
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1998-2006
-prospective multi-center cohort study
-Technetium, Patent Blue®, or both to identify sentinel lymph nodes
-pelvic (and para-aortic) node dissection
-sentinel nodes and non-sentinel nodes were histopathologically examined
The study
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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, -neoadjuvant therapyGynecol Oncol update
Leuven 5. May
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
Statistics
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Tracer application
Tc-albumines
60 MBq the day prior (1ml)
Blue dye (Patent Blue®)
4 ml after anesthesia
subepithelially
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laparoscopic pelvic lymphadenectomy (left)
surgical procedure
N. obturatorius
N. genito-femoralis
Vasa iliacaexterna
M. psoas
laparoscopic paraaortic lymphadenectomy
A. mesenterica inferior
V. renalis
positive pelvic lymphnode left side
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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
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Patients fulfilling inclusion but not
exclusion criteria n = 603
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)
Positiven = 82
Negativen = 422
Pelvic nodal status (Reference)
Positiven = 82
Positiven = 24
Negative (impos. by definition)
Neg.n = 398
Positiven = 3
Negative (impos. by definition)
Inconclusive 2
n = 3
Pelvic nodal status (Reference)
Pelvic nodal status (Reference)
Pelvic SLN nodal status (Index test)
Excluded patients:(n =13) Reasons: No marker applied (n = 1)No searching for SLN (n = 12)
Population for analysis of detect- ion rate n = 590
Population for analysis of diagnostic accuracy n= 507
n=590
n=507
n=603
n=82 n=422
n=24!!
-flowchart-
disposition of patients eligiblefor analysis
median age 41 years (range 16-79 years)
squamous cell carcinoma 383 patients (75.5%) adenocarcinoma 97 patients (19.1%)
(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%)
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Results
cervical cancer were removed vaginally and lymph nodes were harvested endocopically in 283 patients (56%),
open approach was chosen in 224 Patients (44%)
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Results
over all detection rate: 89,7% (CI95 86.9-92%)
pelvic: 88,6% (CI95 85,8-91,1%)
Tc alone (n=55) 82% detection ratePatent Blue® alone (n=195) 82% detection rateTc+Patent Blue® (n=340) 94% detection rate (p<0,001)
Gynecol Oncol update Leuven
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Resultsindentification of sentinel lymph nodes
median number of sentinel lymph nodespelvic: 2 (2-24)
paraaortic: 1 (1-9)
>5 sentinel nodes identified in 103 patients (20,3%)
median number of all lymph nodespelvic: 24 (2-70); n=507 patients
paraaortic: 13 (1-47); n=190 patientsGynecol Oncol update Leuven
5. May
Resultsindentification of sentinel lymph nodes
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 94,3% (CI 83-99,4%)
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Resultsaccuracy of diagnostic test
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). Gynecol Oncol update Leuven
5. May
Resultsindentification of sentinel lymph nodes
sensitivity in subgroups of women with tumors
<21mm =90.9%(70,8-98,9%),
>21mm =72,7% (61,3-82,3%)
(p=0.091)
Gynecol Oncol update Leuven
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Resultsaccuracy 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)
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Resultsaccuracy of diagnostic test
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Probability of diagnostic outcome in all patients –flowchart-
SLN not detected
0.114
SLN detected
0.886
Reference positive1.000
Reference positive0.057
Reference negative0.943
SLN positive
0.163
SLN negative0.837
True positive0.144
False negative0.042
True negative0.700
0.114
Probability of diagnostic outcome
SLN: Pelvic SLN (Index test)Reference: Pelvic nodal status
SLN not detected
0.114
SLN detected
0.886
Reference positive1.000
Reference positive0.057
Reference negative0.943
SLN positive
0.163
SLN negative0.837
True positive0.144
False negative0.042
True negative0.700
0.114
Probability of diagnostic outcome
SLN: Pelvic SLN (Index test)Reference: Pelvic nodal status
4 patients!100
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Probability of diagnostic outcome in patients with cervival cancer ≤20mm -flowchart-
Reference positive1.000
Reference positive0.009
Reference negative0.991
True positive0.081
False negative0.008
True negative0.851
0.060
Probability of diagnostic outcome in patients with tumor size 20 mm
SLN: Pelvic SLN (Index test)Reference: Pelvic nodal status
Reference positive1.000
Reference positive0.009
Reference negative0.991
True positive0.081
False negative0.008
True negative0.851
0.060
Probability of diagnostic outcome in patients with tumor size 20 mm
SLN: Pelvic SLN (Index test)Reference: Pelvic nodal status
100 1 patient!
Our data suggest that the sentinel concept is NOT applicable in patients with cervical cancer.
Sensitivity is to low.
Gynecol Oncol update Leuven
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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
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Conclusion