Patterns of tumor regression after neoadjuvant immunochemotherapy in oral squamous cell carcinoma and their surgical margin implications.

6098 Background: Neoadjuvant immunochemotherapy (nICT) has been increasingly applied in locally advanced oral squamous cell carcinoma (OSCC), demonstrating promising tumor downstaging and improved pathological response rates. However, the spatial patterns of tumor regression after nICT and their implications for surgical margin design and potential de-escalation of surgery remain poorly defined. Methods: We retrospectively analyzed 36 hemiglossectomy specimens from OSCC patients treated with nICT. All specimens were entirely embedded and evaluated using large-format histopathology. Tumor regression patterns were classified based on the distribution of residual viable tumor into central necrotic regression, peripheral regression, and patchy ablation types, each with distinct morphological subtypes. The relationship between pathological residual tumor foci, margin distance (1 mm vs 5 mm), and multicentricity was systematically assessed. Results: Distinct tumor regression patterns were observed following nICT. Most cases exhibited predominantly unicentric residual disease, while a small proportion demonstrated multicentric pathological residuals. Using a 1-mm pathological distance threshold, 1 cases were classified as multicentric, whereas no case met multicentric criteria using a 5-mm threshold. Notably, cases achieving major pathological response (MPR) or near pathological response (NPR) showed minimal residual tumor burden, though isolated satellite foci were occasionally detected. These findings suggest that regression morphology directly influences margin risk distribution and surgical safety. Conclusions: Tumor regression patterns after nICT in OSCC are heterogeneous and play a critical role in determining optimal surgical resection boundaries. While surgical de-escalation may be feasible in selected responders, careful assessment of residual tumor distribution is essential to ensure oncologic safety. Our findings support the development of an integrated preoperative regression assessment and postoperative margin reconstruction framework to guide individualized, function-preserving surgical strategies in OSCC.