Frontiers in immunology · 2026
Stratified lymph node yield thresholds after neoadjuvant immunochemotherapy: a surgical benchmark for survival in oral squamous cell carcinoma.
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Yuan Shuai, Hu Yunshuang, Hou Yalin, Wei Yunzhe, Fang Qigen, Liu Fei
Аннотация
BACKGROUND: The adequacy of neck dissection following neoadjuvant immunotherapy combined with chemotherapy (NICT) for locally advanced oral squamous cell carcinoma (OSCC) lacks evidence-based benchmarks. This study aimed to define and validate extent-specific lymph node dissection (LND) adequacy thresholds associated with survival outcomes.
METHODS: In a development and validation study, the training cohort comprised 256 consecutive patients with locally advanced OSCC treated with NICT and surgery at Henan Cancer Hospital (2019-2022). An independent cohort of 199 patients from the First Affiliated Hospital of Zhengzhou University (2020-2022) served for validation. Patients were stratified by surgical extent: unilateral (Group Un) or bilateral (Group Bi) neck dissection. Optimal LND thresholds predictive of 3-year overall survival (OS) were determined using restricted cubic splines and maximally selected rank statistics. For Group Un, the threshold (LND-Un) was based on total lymph node yield; for Group Bi, the threshold (LND-Bi) was based on the average yield per side. Survival and safety outcomes were compared between patients meeting ("Adequate") or not meeting ("Inadequate") these thresholds.
RESULTS: The optimal thresholds were 20 total lymph nodes for unilateral dissections (LND-Un) and 18 nodes per side on average for bilateral dissections (LND-Bi). In the training cohort, inadequate LND was independently associated with worse OS (Group Un: adjusted hazard ratio [aHR] 2.42, 95% CI 1.47-3.99, p<0.001; Group Bi: aHR 2.29, 95% CI 1.20-4.37, p=0.012) and disease-free survival (DFS). Inadequate LND was also linked to a higher risk of major complications in Group Un (adjusted odds ratio 2.15, 95% CI 1.06-4.38, p=0.034). These findings were robustly validated in the external cohort, where the LND-based model demonstrated good discrimination (C-index for OS: 0.71), excellent calibration, and positive net benefit on decision curve analysis.
CONCLUSION: This study establishes and validates stratified, surgical extent-specific thresholds for lymph node dissection adequacy after NICT in OSCC. Achieving a yield of ≥20 nodes in unilateral dissection or an average of ≥18 nodes per side in bilateral dissection is independently associated with significantly improved survival and an acceptable safety profile. These benchmarks provide a tangible, evidence-based guide for surgical quality assessment and decision-making in the post-NICT setting.
METHODS: In a development and validation study, the training cohort comprised 256 consecutive patients with locally advanced OSCC treated with NICT and surgery at Henan Cancer Hospital (2019-2022). An independent cohort of 199 patients from the First Affiliated Hospital of Zhengzhou University (2020-2022) served for validation. Patients were stratified by surgical extent: unilateral (Group Un) or bilateral (Group Bi) neck dissection. Optimal LND thresholds predictive of 3-year overall survival (OS) were determined using restricted cubic splines and maximally selected rank statistics. For Group Un, the threshold (LND-Un) was based on total lymph node yield; for Group Bi, the threshold (LND-Bi) was based on the average yield per side. Survival and safety outcomes were compared between patients meeting ("Adequate") or not meeting ("Inadequate") these thresholds.
RESULTS: The optimal thresholds were 20 total lymph nodes for unilateral dissections (LND-Un) and 18 nodes per side on average for bilateral dissections (LND-Bi). In the training cohort, inadequate LND was independently associated with worse OS (Group Un: adjusted hazard ratio [aHR] 2.42, 95% CI 1.47-3.99, p<0.001; Group Bi: aHR 2.29, 95% CI 1.20-4.37, p=0.012) and disease-free survival (DFS). Inadequate LND was also linked to a higher risk of major complications in Group Un (adjusted odds ratio 2.15, 95% CI 1.06-4.38, p=0.034). These findings were robustly validated in the external cohort, where the LND-based model demonstrated good discrimination (C-index for OS: 0.71), excellent calibration, and positive net benefit on decision curve analysis.
CONCLUSION: This study establishes and validates stratified, surgical extent-specific thresholds for lymph node dissection adequacy after NICT in OSCC. Achieving a yield of ≥20 nodes in unilateral dissection or an average of ≥18 nodes per side in bilateral dissection is independently associated with significantly improved survival and an acceptable safety profile. These benchmarks provide a tangible, evidence-based guide for surgical quality assessment and decision-making in the post-NICT setting.