The eukaryotic initiation factor 4E (eIF4E) as a predictive biomarker in the negative margins of resected head and neck and oral cancers: Is there a role for tailoring adjuvant radiotherapy

Introduction: The eukaryotic translation initiation factor 4E (eIF4E) is a protein that plays a key role in the tumourigenesis and metastasis. eIF4E overexpression usually precede morphological changes. The amplification of this biomarker in the surgically negative margins of resected Head and Neck cancer patients is associated with early recurrence and failure in several earlier studies. This subset may benefit from adjuvant radiotherapy even in the absence of morphological risk factors. We evaluated the pattern of expression of eIF4E protein in the surgically negative margins of Head and Neck cancer patients and its role in the treatment and outcome. Material and Methods: Twenty-nine patients with Oral and 14 patients with Head and Neck cancers having surgically negative margins were analyzed for the expression of eIF4E with relation to local failure and treatment outcome. Results: There were 11 local failures with 9 deaths, all within 6 months documented. The overall median survival was 12 months. Notably patients who had received adjuvant radiotherapy had a 45% better chance of survival 29.5 months vs 13.5 months (p=0.79). The clinical features of size, grade and co-expression of p53 did not correlate significantly with eIF4E overexpression. The Oral cancer subset when individually analyzed; showed a similar pattern of outcome with 17% (5/29) failing locally. Patients who had received adjuvant radiotherapy fared better with a 30% higher chance of survival 30.8 months vs 15.7 months. In Head and Neck cancer patients the failure rate was 57.8% (8/14). Patients who received radiotherapy had a median survival of 15.43 months vs 10.85 months (p=0.28). Conclusion: The overexpression of eIF4E in surgically negative margins of resected Head & Neck and oral cancers may predict a more unfavorable microenvironment at risk for early recurrence and mortality within 6 months. The addition of adjuvant radiotherapy or targeting the eIF4E pathway may benefit these patients.