Comparison of false negative rates (FNR) & overall accuracy (AC) of sentinel lymph node biopsy (SLNB) in phase 3 ^99mTc-tilmanocept (TcTM) vs ACOSOG Z-0360 ^99mTc-sulfur colloid (TcSC) in head/neck squamous cell cancer (SCC)

Objectives Intraoperative lymphatic mapping (ILM) & SLNB in SCC patients (pts) is conducted with a ^99mTc-radiotracing agent (RTA). Currently no RTAs are FDA-approved for SLNB in SCC. The particulate TcSC (50-800nm) is the only US commercially available RTA; it is used off-label for SCC SLNB. TcSC was used in a prospective study of SLNB in SCC (published JCO 2010;28:1395-400). Recently, a phase 3 study of TcTM (≤ 7nm) (Navidea Biopharmaceuticals, Dublin, OH), a novel soluble, receptor-targeted (CD206) molecular RTA, was evaluated in SCC SLNB. We completed a meta-contrast of 2 key parameters for SLNB in SCC between the studies.

Methods A meta-analysis from phase 3 TcTM data vs JCO TcSC data was conducted for key ILM/SLNB performance parameters: FNR & AC. All pts in the studies received SLNB & complete elective head/neck dissection; all nodes were evaluated for tumor. The histological methods, RTA administration & demographics were similar. The endpoints were: 1] FNR (% of pts that the SLN failed to correctly stage the pt) and 2] AC (correctness; sensitivity & specificity). Both metrics define the potential for RTA performance for ILM & evaluation of nodal metastasis.

Results The FNR for TcSC was 0.10 (95% CI=0.027,0.231; n=41). The FNR for TcTM was 0.03 (95% CI=0.001,0.138; n=38); p<0.0006 vs TcSC. The AC for TcSC was 0.97 (95% CI=0.928,0.992; n=140). The AC for TcTM was 0.99 (95% CI=0.934,1.000; n=82); p<0.0161 vs TcSC.

Conclusions Based on a meta-analysis of clinical data, TcTM provided statistically significantly better performance than TcSC in the key metrics of FNR & AC in SCC SLNB. While other factors, such as improvements in surgical or pathological techniques over time, may play a role, these data suggest that receptor targeted TcTM may provide improved diagnostic ILM vs the currently employed nonspecific ILM RTA, TcSC.