Koos Boeve

135 Molecular biomarkers in SLNB staged early oral cancer DISCUSSION SLNB is nowadays used as neck staging strategy in early stage (cT1-2N0) OSCC. Although the SLNB procedure is less invasive compared to the conventional END, it is still an invasive staging technique while in ~70% of these early stage OSCCs no lymph node involvement is observed. In this study we analyzed the additional clinical value of molecular tumor biomarkers to select early stage OSCC patients with a low risk of occult metastasis for a watchful waiting strategy instead of performing a SLNB procedure. For that purpose, we selected patients with a pT1cN0 OSCC and a tumor infiltration depth <4 mm who were conventionally selected for a watchful waiting strategy instead of an END [15] and found that low cortactin expression selected true N-status negative patients with a 92% NPV. No association was found between any of the molecular markers and the true N-status in the total cohort or between the molecular markers and pT1 or pT2 tumors with a tumor infiltration depth ≥4 mm. In 2012, a diagnostic algorithm for early stage OSCC using gene-expression profiling of tumor biopsy specimens to select low risk patients for a watchful waiting strategy instead of a SLNB procedure has been proposed [10]. An 89% NPV for selecting patients for a watchful waiting strategy instead of SLNB was observed. In that study, 11% false negatives in patients selected as N-status negative by gene-expression profile but with lymph node involvement was found [10]. S100A9 was the only molecular biomarker of the current study which was also part of that gene-expression profile. Another study reported in 92 early stage OSCC patients staged by SLNB that tumor infiltration depth ≤2 mm might be used to select patients for watchful waiting, 2-5 mm for a SLNB and >5 mm for an END [11]. In a large cohort with data of 199 early stage OSCC patients with SLNB neck staging from two Dutch head and neck centers, a cut-off of 3.4 mm was reported as most optimal (sensitivity 83%, specificity 47%) between tumor infiltration depth and N-status based on a ROC-curve analysis [12]. Because a 15% risk for metastasis below the cutoff, the authors stated that tumor infiltration depth could not serve as an optimal predictive marker to select patients for a watchful waiting strategy instead of a SLNB procedure [12]. The difference with our study is that we used cortactin in combination with a tumor infiltration depth cut-off of 4 mm defined in a large cohort of OSCC to predict N-status [15]. Without cortactin, the risk for positive N-status is 18% in pT1cN0 and with cortactin that risk lowered to 8%. If we used the 3.4 mm cut-off as reported by den Toom [12] in combination with or without cortactin in our pT1cN0 patients, the metastasis risk lowered from 18% to 9% (data not shown). These data show that infiltration depth between 3 mm and 5 mm did not significantly affect the risk showing the potential additional value of cortactin to select patients with a low metastases risk for a watchful waiting strategy instead of a SLNB.