The relationship between depth of invasion and adjuvant radiotherapy response in oral cavity tumors

The Relationship Between Depth of Invasion and Adjuvant Radiotherapy Response in Oral Cavity Tumors Background: The aim of this study was to evaluate the relationship between depth of invasion (DOI) and adjuvant radiotherapy (RT) response in oral cavity tumors, as well as its impact on survival outcomes. Materials and methods: This retrospective study included 44 patients who underwent surgery for oral cavity tumors between 2011 and 2024 and subsequently received adjuvant radiotherapy at the Department of Radiation Oncology, Çukurova University Faculty of Medicine. Tumor invasion depth (ID) was determined by re-examination of pathology specimens. In addition, pathological parameters such as surgical margin (SM), extranodal extension (ENE), and perineural invasion (PNI), as well as adjuvant treatment modalities (RT characteristics, chemotherapy status, etc.), were evaluated. The effects of these subgroups on recurrence and survival were compared. Results: The mean age of the 44 patients included in the study was 57.3 years, with a median follow-up of 60.5 months. Recurrence was observed in 36.4% of cases, with the most common tumor site being the lower lip (63.6%). The majority of patients were male (86.4%), while females comprised 13.6%. According to the AJCC 8th edition staging system, which incorporates invasion depth (ID) and extranodal extension (ENE), recurrence rates significantly increased with advancing stage (p=0.026). No statistically significant association was found between local-regional recurrence and ID in relation to radiotherapy response; however, higher ID values were associated with increased recurrence rates (≤0.5 cm: 21.4%; 0.5-1 cm: 37.5%; >1 cm: 50.0%; p=0.289). A significant correlation was observed between ID and lymph node metastasis (≤0.5 cm: 14.3% LN(+); >0.5 cm: 50.0% LN(+); p=0.023). ENE-positive cases had markedly higher recurrence rates compared to ENE-negative cases (71.4% vs. 29.7%; p=0.035), and positive surgical margins adversely affected overall survival (SM-: 109.5 months vs. SM+: 64.5 months; p=0.031). When radiotherapy-related parameters were analyzed, no statistically significant differences were found for RT versus CRT (OS p=0.080; DFS p=0.271), RT duration ≤44 vs. >44 days (OS p=0.587; DFS p=0.857), surgery-to-RT interval ≤7 vs. >7 weeks (OS p=0.357; DFS p=0.689), or total treatment time <13 vs. ≥13 weeks (OS p=0.751; DFS p=0.328). Conclusion: In our study, the impact of depth of invasion (DOI) on the response to adjuvant radiotherapy in patients with oral cavity tumors was evaluated based on the presence of locoregional recurrence. The findings indicate that DOI alone does not carry strong prognostic value; however, when assessed together with other pathological risk factors such as surgical margin, perineural invasion, and extranodal extension, it gains significant prognostic importance. Our results also suggest that optimal planning of radiotherapy schedules and DOI-based individualized radiotherapy strategies may play a critical role in improving both local control and overall survival. Keywords: Oral cavity cancer, depth of invasion, perineural invasion, extranodal extension, surgical margin, radiotherapy, survival.