is there enough evidence to shift to sentinel lymph node...
TRANSCRIPT
Is there enough evidence to shift to
Sentinel Lymph Node Concept
in Cervical Cancer?
Mustafa Erkan Sarı, MDAnkara Training and Research HospitalDepartment of Gynecologic Oncology
November 2018
2013 NCCN Guidelines
2014 NCCN Guidelines
Approximately 50% of cervical cancers are limited to cervix
For most cases standard treatment is radical hysterectomy / trachelectomy and bilateral pelvic LND
however, usually lymphatic metastasis will not be seen(15% LN METASTASIS IN STAGE 1A2-1B1 PATIENTS)
CERVICAL CANCER
Can we determine if there is lymphatic spread without a complete lymphadenectomy?Sentinel Lymph Node Concept
Risks of Lymphadenectomy-Morbidity
•Vessel and nerve injuries (%3.9)
•Venous trombosis (%5)
•Pulmoner emboli (%2.8)
•Lymphosel (%13.5)
•Lymphedema•Pelvic LND ( % 5-38)•Bad QOL•Sellulitis
Advantages of Sentinel Lymph Node Mapping
✓ Reduction of morbidity
✓ Direction of intraoperative surgery
✓ Detection of micrometasis and isolated tumor cells
✓ Detection of lymph nodes in atypical localization
• Blue Dyes
• Metilen Blue, Patent Blue, Isosulfan Blue
• Radioactive tracer: Technetium-99(Tc-99)
• Long
• Short
• Ultrashort
• Fluorescence-guided imaging• Indocyanine green (ICG)
Indicators
Why is ICG in the foreground?
• SLN selectable brightness
• SLN can be detected even in the case of bleeding
• ICG application is easy and does not require preop preparation like Tc99
• ICG success is higher than blue dye alone
• Equal to blue dye and Tc99 combination
Ann Nucl Med (2008) 22:487–494
Conclusions
• Bilateral SLNsmapping using ICG issuperior to othermodalities
Ann Surg Oncol (2016) 23:2183–2191
Nodal staging with an intracervicalinjection of ICG is accurate, safe, andreproducible in patients with cervicalcancer
Ann Surg Oncol (2016) 23:2959–2965
Rates of Bilateral Mapping
Tc99+MM MM ICG
Number of Patients 77 38 48
SLN detection rate (%) 97 89 100
Bilateral SLN detection rate(%) 58 54 85
Sensitivity ve NPV(%) 100 100 100
Buda et al. Ann Surg Oncol 2016
p=0.001
Tecrübe önemli> 30 vaka
Laparoscopic identification of the sentinel node after injection of Patent Blue Violet (PBV)
around early tumors of the cervix
If the sensitivity of the assessment of the BDLN is confirmed to be 100%, this laparoscopic approach
could transform the management of early cervical cancer
Gynecologic Oncology 79, 411–415 (2000)
SLN procedure performs well diagnostically for the assessment of nodalmetastases in patients with early stage cervical cancer
MedOncol (2015) 32:385
%88
Gynecologic Oncology 116 (2010) 28–32
SENTICOL
•139 early stage cervix ca (1A1-1B1)
•Tc99 and blue dye combination
•SLN complete pelvic lymph node dissection
•Detection Rate %97.8
•Sensitivity %92
•2/139 False Negative
• SLN biopsy was fully reliable only when SLNs were detected bilaterally
104 patients (76.5%) Lecuru F. J Clin Oncol 2011
SLN Detects Unexpected Drainage Pathways:Insights From the SENTICOL Study
• 5% had SLNs only in unexpected areas
• Positive SLNs were located inunexpected areas in 17% of patients
Mapping scheme of expected (areas 3 and 4) and unexpected (others)
Bats AS, et al. Ann Surg Oncol. 2013;20(2):413-422.
MSKCC SLN Algorithm
• 122 patients were included. Median SLN count was 3 and median total LN count was 20
• At least one SLN was identified in 93%
• Optimal (bilateral) mapping was achieved in 75% of cases
• SLN correctly diagnosed 21 of 25 patients with nodal spread
• When the algorithm was applied, all patients with LN metastasis were detected
• With optimal bilateral mapping, pelvic LND could have been avoided in 75% of cases
Cormier B, et al. Gynecol Oncol. 2011;122(2):275-280.
Gynecologic Oncology 122 (2011) 275–280Cormier B, et al. Gynecol Oncol. 2011;122(2):275-280.
Gynecologic Oncology 122 (2011) 275–280
†Cormier B, et al. Gynecol Oncol. 2011;122(2):275-280.††Intracervcal injection with dye, 99m technetium, or both.†††Including interiliac/subaortic nodes.††††Exceptions made for select case (see CERV-A 1 of 7).
Note: all recommendations are category 2A unless otherwise indicated.Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology (NCCN Guidelines): Cervical cancer. V1.2014.
• 188 patients, 35 (19%) LN metastases
• SLN identified in 90%, bilateral in 62%
• The false-negative rate was 3.6% (1 case)– Sensitivity of 96%, NPV of 99%
• Applying the NCCN algorithm identified 100% of patients who had (+) LN
• CONCLUSIONS: We believe it is time to change the standard of care for women with early-stage cervical cancer to SLN biopsy only
Salvo G, et al. Gynecol Oncol. 2017;145(1):96-101.
G. Salvo & P. Ramirez (MDACC) Gyn Onc 2017
47 çalışma, n=4130
Gynecologic Oncology 139 (2015) 559–567
Gynecologic Oncology 139 (2015) 559–567
Routine H&E (1st cut)
Additional H&E & IHC stains (Ultrastaging)
Additional H&E & IHC stains (Ultrastaging)
50 mm
50 mm
Ultrastaging is for Negative SLN on Initial H&E Evaluation
Kim CH, et al. Int J Gynecol Cancer. 2013;23(5):964-970.
• Macrometastasis (> 2mm)
• Micrometastasis (0.2-2 mm)
• Isolated tumor cell (<0.2 mm)
Variable N (%)
Ultrastaging (96 of 114 who mapped)
No disease
Isolated cytokeratin-staining cells
Positive on H&E
Macrometastasis
Micrometastasis
Positive on ultrastaging only
Macrometastasis
Micrometastasis
Isolated tumor cells
77 (63.1)
8 (6.6)
6 (4.9)
1 (0.8)
1 (0.8)
2 (1.6) 41 (0.8)
Ultrastaging not performed (N = 26)
Failed mapping, no disease
SLN positive on H&EReason not specified, no disease
7 (5.7)14 (11.5)5 (4.1)
D. Cibula et al. / Gynecologic Oncology 124 (2012) 496–501
• Adjuvant Rx given to:– 85% of Macromets
– 83% of Micromets
– 52% of ITC
– 10% of node negative
• OS reduced in micro & macrometastasis, but not ITC
Significance of Low-Volume SLN Metastasis (N = 645)
ITC
LN(-)
MM & Macro
Overa
ll S
urv
ival
Cormier B, et al. Gynecol Oncol. 2011;122(2):275-280.
D. Cibula et al. / Gynecologic Oncology 124 (2012) 496–501
D. Cibula et al. / Gynecologic Oncology 124 (2012) 496–501
Risk of Micrometastases in Nonsentinel Pelvic Lymph Nodes
• 17 cases Stage IB1-IIA all >3cm
• Mean 30 pelvic nodes
• After processing all pelvic LNs by pathologic ultrastaging, there were no false-negative cases
Cibula D, et al. Gynecol Oncol. 2016
BMC Cancer 11, 2011
99mTc phytate
radical abdominal trachelectomy (RAT)
n=18, conization + vs. n=32, conization -
Int J Gynecol Cancer 2011;21: 1491Y1494
Does tm size effect rate of mapping?
2 cm-cut off
•<2 cm detection rate %95 ve sensitivity %100
•>2 cm detection rate %80 ve sensitivity %89
Lukas R. Exp Rev Anticancer Ther 2013
•Tumor size is not significant <2 cm vs 2-4 cm vs >4 cm
Cibula D. Gynecol Oncol 2018
•Tumor size >2 cm ICG is more effective
Di Martino G. JMIG 2017
Tm Size and Detection Rate
SLN Biyopsi - Survival
Lennox GK. Gynecol Oncol 2017
2Y-RFS: %97 vs 955Y-RFS: %93 vs 92
Ongoing Research: SENTICOL III Accepted by the French National Cancer Institute (Fabrice Lécuru)
• A prospective multicenter international randomizedstudy
• Compare the outcome of patients with negative bilateral SLN (SLN Algorithm) vs. patients with negative SLN + pelvic lymph node dissection
SENTIX Protocol
• A prospective observational trial on sentinel lymph
node biopsy in patients with early-stage cervical cancer
• The null hypothesis is that the recurrence rate after SLN
biopsy is noninferior to the reference recurrence rate of
7% (at the 24th month of follow-up) in patients after
systematic pelvic lymphadenectomy, but that the less
radical surgery is associated with significantly lower
postoperative morbidity
There are many studies reporting high sensitivity from multiple centers
According to these results the number of patients calculated for randomized study is 1400
Frumovitz M. Gynecol Oncol 2017
Summary
• SLN algorithm is a standard of care in many practices
• Its a reasonable strategy for
Stage IA1 with LVI, IA2, and IB1 tumors
THANK YOU…