Histology-Specific Radiotherapy Target Volume Delineation for NSCLC Based on Distinct Lymph Node Metastasis Patterns of Adenocarcinoma and Squamous Cell Carcinoma

Background This study sought to characterize distinct regional lymph node metastasis (LNM) patterns of lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) using PET-CT imaging and postoperative pathology, and to provide evidence-based guidance for precise radiotherapy target volume delineation in NSCLC. Methods We retrospectively analyzed 422 PET-CT scans (281 LUAD, 141 LUSC) and 305 surgical pathology reports (236 LUAD, 69 LUSC) from our institution. Inter-group comparisons were performed using chi-square or Fisher’s exact tests. Binary logistic regression models were utilized for multivariate analyses. Results PET-CT and pathological data exhibited high concordance in LNM distribution. Compared with LUSC, LUAD displayed more aggressive LNM behavior, with significantly higher metastasis rates to supraclavicular, contralateral mediastinal, and contralateral hilar nodes. In contrast, LUSC showed increased level 8 LNM, especially in left inferior lobe origin. Multivariate analysis revealed: LUAD with mediastinal invasion, ipsilateral multi-lobar nodules, or LNM at levels 2L/2R/3a/6 had higher 1L/1R metastasis risk; left inferior lobe origin or larger tumor diameter in LUSC hinted level 8 metastasis. Significant inter-nodal metastatic correlations were identified across different levels. Conclusion LUAD and LUSC exhibit distinct histology- and subsite-specific LNM patterns and inter-nodal metastatic correlations. Two optimized CTVn delineation recommendations for definitive concurrent chemoradiotherapy of LUAD and LUSC were proposed to enhance targeting precision.