Purpose: The validity of sentinel lymph node biopsy (SLNB) for T1 or T2, clinically N0, oral cancer was tested by correlation of sentinel node pathologic status with that of nodes within the completion neck dissection. Methods: This prospective, cooperative group trial involved 25 institutions over a 3-year period. One hundred forty patients with invasive oral cancers, stage T1 and T2, N0 including 95 cancers of the tongue, 26 of the floor of mouth, and 19 other oral cancers were studied. The study excluded lesions with diameter smaller than 6 mm or minimal invasion. Imaging was used to exclude nonpalpable gross nodal disease. Patients underwent injection of the lesion with ^99mTc-sulfur colloid, nuclear imaging, narrow-exposure SLNB, and completion selective neck dissection. The major end point was the negative-predictive value (NPV) of SLNB. Results: In the 106 SLNBs, which were found to be pathologically and clinically node-negative by routine hematoxylin and eosin stain, 100 patients were found to have no other pathologically positive nodes, corresponding to a NPV of 94%. With additional sectioning and immunohistochemistry, NPV was improved to 96%. In the forty patients with proven cervical metastases, the true-positive rate was 90.2% and was superior for tongue tumors relative to floor of mouth. For T1 lesions, metastases were correctly identified in 100%. Conclusion: For T1 or T2 N0 oral squamous cell carcinoma, SLNB with step sectioning and immunohistochemistry, performed by surgeons of mixed experience levels, correctly predicted a pathologically negative neck in 96% of patients (NPV, 96%).

Oral premalignancy serves as an ideal model for study of chemopreventive agents. Although 13-cis-retinoic acid showed reversal of oral premalignancy, toxicity, and reversal of clinical response after cessation of therapy obviated its widespread use. A search for nontoxic agents with cancer preventive activity led us to evaluate Bowman Birk Inhibitor (BBI) formulated as BBI Concentrate (BBIC). We previously reported encouraging results in a phase IIa trial of BBIC in patients with oral leukoplakia with measurable clinical responses and favorable biomarker changes. On the basis of these results, we undertook a randomized, placebo controlled phase IIb trial with patients receiving BBIC or placebo for 6 months, with assessment of clinical response and change in lesion area as primary end point and an intent-to-treat analysis. One hundred and thirty two subjects were randomized; and 89 subjects completed six months on study drug or placebo. Both placebo and BBIC showed a statistically significant decrease in mean lesion area of 17.1% and 20.6%, respectively, and partial or greater clinical responses of 30% and 28% respectively. No significant difference between placebo and study drug arms was observed. Histologic review, review of photographs of lesions, and comparison of serum neu protein and oral mucosal cell protease activity also did not show significant differences between study arms. Probable reasons for these negative results were considered, are discussed, and include a placebo with non-BBIC clinical activity and reduced pharmacokinetic availability of the second batch of BBIC. This experience should be a strong cautionary note to those considering “Green” chemoprevention. Cancer Prev Res; 6(5); 410–8. ©2013 AACR.