865P - Molecular analysis of surgical margins in early oral carcinomas (OSCC)

Background

The prognosis of early OSCC is strongly correlated with local disease control. However, patients with T1-T2 OSCC and clear margins have a 5-year local relapse rate of around 15%. The evaluation of the quality of surgical resection is therefore essential.

Methods

A prospective multicenter trial based on patients with T1-T2 OSCC treated surgically with clear margins, showed the interest of a molecular analysis (microsatellite instability (MSI)) of surgical margins to evaluate the minimal residual disease (MRD) while adapting the postoperative strategy (NCT00232960). Recently, innovative techniques for detecting circulating tumor DNA have been developed. Our main objective was, then, to evaluate the feasibility of detecting MRD by identifying specific molecular abnormalities with Whole Exom Sequencing (WES) and Shallow Whole Genome Sequencing (ShWGS) in the primary tumor and looking for it on the margins.

Results

310 patients were included initially with 216 tumor/margins samples available for molecular analysis. Tumor was informative for MSI analysis in 63% of cases (n=133). Positive molecular margins were observed in 23 cases, leading to a postoperative treatment. Median follow-up was 58 months [30;83]. In informative tumor, molecularly driven treatment seemed to lower the 5-year local recurrence rate from 14.1% to 6.4% (p=0.15). Among the initial cohort, 108 primary tumors were secondary screened by WES with an informative rate of 78.6%. With a 10X depth for molecular analysis, we observed 13 patients with at least one positive margin. Then, analyzing retrospectively the oncologic outcomes, we observed a significant benefit for local control at 5 years for patients with WES negative margins (91.7% versus 64.1%, p=0.02). We, then, performed a ShWGS analysis on a sub-group of 39 patients. Patients with positive margins both in WES and ShWGS had a higher risk of local relapse at 5 years (p<10-3).

Conclusions

Molecular analysis of surgical margins for early OSCC lead to a better assessment of microscopic residual disease while postoperative decision making according to WES and ShWGS could improve local control.

Clinical trial identification

NCT00232960.

Editorial acknowledgement

Legal entity responsible for the study

GETTEC group (French Group for Study of Head and Neck Tumors).

Funding

PHRC program from INCA (French National Cancer Institute) PRISM program from Gustave Roussy Cancer Campus.

Disclosure

All authors have declared no conflicts of interest.