2017 Section 7 Green Book

disease only in the same level as the positive SLNs, 21/

42 patients (50%) had additional disease in an adjacent

nodal level (7/21 higher and 14/21 lower) from the posi-

tive SLN, and 3/42 patients (7.1%) had disease in a non-

adjacent level. Only one ND yielded neck nodes in levels

other than I to III. The three factors that predicted

non-SLN in multivariate analysis were lymphovascu-

lar invasion, positive margins, and non-SLN extracapsu-

lar spread. Only 15 patients (13.7%) developed

recurrence, with six of those being regional. Kaplan-

Meier and log-rank analyses showed only two variables

to be significant for nodal recurrence: positive lymph

nodes in addition to the SLN and

non-SLN in levels

outside of the SLN (

.04 and .01, respectively). In

breast disease, those patients with

non-SLNs in differ-

ent fields receive more aggressive adjuvant therapy, and

nomograms have been developed to predict the presence

non-SLNs in these fields. Similar approaches could

be taken with OSCC.

The SLNB is traditionally performed by injecting

the primary site with unfiltered

Tc-sulfur colloid

within 18 hours of the procedure. Dosages are adjusted

based on the timing. Serial nuclear imaging is then per-

formed. Some authors advocate injecting methylene blue

at the time of resection. After removal of the primary,

the SLNB is performed utilizing a small incision within

the planned END incision, with the SLNs identified

using the gamma probe. Any lymph node exhibiting

10% of the radioactivity of the most active node are

removed. The SLNs are then sectioned from hilum to

periphery, longitudinally, at 2- to 3-mm thickness and

hematoxylin and eosin stained for immediate analysis. If

the lymph nodes are not grossly positive, the central lab-

oratory evaluates the nodes in permanent section and

stains the slides for cytokeratin using IHC. Any IHC

cytokeratin-positive clusters are further reviewed for

morphology consistent with metastatic SCC. Two novel

methods have recently emerged that could improve the

SLNB process. The use of [

Tc]tilmanocept, a novel

radiopharmaceutical that specifically target CD206

mannose-binding receptors on reticuloendothelial cells

within lymph nodes, was recently investigated in a

phase III multi-institutional trial.

Incorporating tilma-

nocept resulted in an NPV of 97.8%, an FNR of 2.56%,

and an overall accuracy in correctly determining the

nodal status of 98.8% (Table I). Quantitative real-time

polymerase chain reaction (qRT-PCR) has also shown

potential to increase the sensitivity of SLNB in detecting

carcinoma microdeposits. Ferris et al. demonstrated in a

validation set of 102 nodes that a multiplexed assay

using two markers for squamous cell carcinoma demon-

strated excellent reproducibility, linearity, and accuracy

(96% NPV) for identifying positive and negative nodal

status.

BEST PRACTICE

SLNB has emerged as a powerful adjunct to END

in early-stage OSCC to identify cervical metastases,

which can have significant therapeutic and prognostic

implications. The method has shown excellent NPV that

can be even more effective with novel radiopharmaceuti-

cals and qRT-PCR. This technique, when properly con-

ducted, can reliably be done in lieu of an END for cT1/2

N0 OSCC, thereby avoiding unnecessary morbidity and

cost.

LEVEL OF EVIDENCE

Recommendations for SLNB for early stage OSCC

is based on level II evidence, with a meta-analysis con-

ducted of level II studies.

BIBLIOGRAPHY

1. Civantos FJ, Zitsch RP, Schuller DE, et al. Sentinel lymph node biopsy

accurately stages the regional lymph nodes for T1-T2 oral squamous cell

carcinomas: results of a prospective multi-institutional trial.

J Clin

Oncol

2010;28:1395–1400.

2. Agrawal A, Civantos FJ, Brumund KT, et al. [Tc]Tilmanocept accurately

detects sentinel lymph nodes and predicts node pathology status in

patients with oral squamous cell carcinoma of the head and neck:

results of a phase III multi-institutional trial [published on line Febru-

ary 11, 2015.

Ann Surg Oncol

. doi:

10.1245/s10434-015-4382-x.

3. Thompson CF, St John MA, Lawson G, Grogan T, Elashoff D, Mendelsohn

AH. Diagnostic value of sentinel lymph node biopsy in head and neck

cancer: a meta-analysis.

Eur Arch Otorhinolaryngol

2013;270:2115–2122.

4. Gurney BA, Schilling C, Putcha V, et al. Implications of a positive sentinel

node in oral squamous cell carcinoma.

Head Neck

2012;34:1580–1585.

5. Ferris RL, Stefanika P, Xi L, Gooding W, Seethala RR, Godfrey TE. Rapid

molecular detection of metastatic head and neck squamous cell

carcinoma as an intraoperative adjunct to sentinel lymph node biopsy.

Laryngoscope

2012;122:1020–1030.

TABLE I.

False Negative Rates and NPV of SLNB for OSCC.

Study

No. of

Patients

False-Negative

Rate

Negative Predictive

Value (95% CI)

Thompson et al.

631

1.9% 96% (93%–99%)

Civantos et al.

140

9.8% 96% (90%–98%)

Agrawal et al.

2.6% 98% (88%–99%)

confidence interval.

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