| Impact of Margin-to-Depth of Invasion Ratio on Oncologic Outcomes in Locally Advanced Oral Cancer Treated With Surgery and Chemoradiotherapy |
Ming-Hsien Tsai1,2,3,4
, Yu-Tsai Lin1,2,3,4
, Hui-Ching Chuang1,3,4
, Chao-Hui Yang1,3,4
, Tai-Lin Huang5, Hui Lu6
, Wen-Ling Tsai7
, Chih-Yen Chien1,6
, Fu-Min Fang3,4,8
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1Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
3School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
4School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
5Department of Hematology and Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
6Doctoral Program of Clinical and Experimental Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
7Department of Cosmetics and Fashion Styling, Center for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung, Taiwan
8Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan |
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Received: November 12, 2025; Revised: December 22, 2025 Accepted: January 17, 2026. Published online: January 19, 2026. |
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| ABSTRACT |
Objectives.
This study aimed to evaluate the prognostic value of the margin-to-depth of invasion ratio (MDR) in patients with locally advanced oral squamous cell carcinoma (LAOSCC) who underwent curative surgery followed by adjuvant concurrent chemoradiotherapy (CCRT).
Methods.
We analyzed 422 consecutive patients with LAOSCC treated at a single institution between 2007 and 2017. MDR was defined as the ratio of the closest surgical margin (mm) to the tumor depth of invasion (mm). Survival outcomes, including overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS), were assessed. The optimal MDR cutoff was determined by X-tile analysis and validated using repeated k-fold cross-validation.
Results.
The optimal MDR cutoff for predicting survival was 0.35. Patients with MDR ≥0.35 (high MDR, n=205) demonstrated significantly better 5-year OS (66.1% vs. 47.6%, P<0.001), CSS (77.5% vs. 57.4%, P<0.001), and RFS (71.5% vs. 53.8%, P=0.001) than those with MDR <0.35 (low MDR, n=217). In multivariate analysis, low MDR remained an independent adverse prognostic factor for OS (hazard ratio [HR], 1.612; P=0.005), CSS (HR, 2.028; P=0.001) and RFS (HR, 1.501; P=0.033). Among patients with adequate margins (≥5 mm), MDR retained significant prognostic value (OS, P=0.008; CSS, P=0.001; RFS, P=0.015). Cross-validation confirmed the robustness of the MDR threshold value of 0.35 across all survival endpoints.
Conclusion.
MDR is an independent prognostic marker in LAOSCC treated with surgery and adjuvant CCRT. A cutoff of 0.35 effectively stratifies survival risk, even among patients with adequate surgical margins. Incorporating MDR into postoperative assessment could refine risk stratification and guide individualized follow-up and adjuvant treatment planning. |
| Keywords:
Oral Squamous Cell Carcinoma; Neoplasm Invasiveness; Surgical Margins; Prognosis; Concurrent Chemoradiotherapy; Survival |
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