2017 Section 7 Green Book

SLNB process. The use of [ 99 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. 2 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. 5 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.

No. of Patients

False-Negative Rate

Negative Predictive Value (95% CI)

Study

Thompson et al.

631

1.9% 96% (93%–99%)

Civantos et al.

140

9.8% 96% (90%–98%) 2.6% 98% (88%–99%)

Agrawal et al.

83

CI 5 confidence interval.

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 1 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 1 non-SLN in levels outside of the SLN ( P 5 .04 and .01, respectively). In breast disease, those patients with 1 non-SLNs in differ- ent fields receive more aggressive adjuvant therapy, and nomograms have been developed to predict the presence of 1 non-SLNs in these fields. Similar approaches could be taken with OSCC. The SLNB is traditionally performed by injecting the primary site with unfiltered 99 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

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