Clémence Pleyers

Clinical characteristics of patients included in statistical analyses

Table S1 from Nonmetastatic Para-aortic Lymph Node Remodeling as a Predictor of Outcome in Locally Advanced Cervical Cancer

Table S8 from Nonmetastatic Para-aortic Lymph Node Remodeling as a Predictor of Outcome in Locally Advanced Cervical Cancer

Table S7 from Nonmetastatic Para-aortic Lymph Node Remodeling as a Predictor of Outcome in Locally Advanced Cervical Cancer

Table S2 from Nonmetastatic Para-aortic Lymph Node Remodeling as a Predictor of Outcome in Locally Advanced Cervical Cancer

Comparison of the model performance after inclusion of continuous PET-derived features

Clinical parameters 137 pPET+ and pPET-

TUMOR UNIVARIATE and MULTIVARIATE ANALYSIS

Purpose:Treatment of locally advanced cervical cancer (LACC) is guided notably by the European Society of Gynaecological Oncology guidelines; unfortunately, relapse remains frequent despite standard chemoradiotherapy and brachytherapy. We evaluated whether histologic assessment of nonmetastatic para-aortic lymph nodes (PAoLN) provides prognostic value in LACC.Experimental Design:Primary tumor and PAoLNs from 137 patients with nonmetastatic LACC were stratified by pretherapeutic 18F-2′-deoxy-2′-fluorodeoxyglucose PET/CT into pelvic PET–positive (pPET+, n = 72) and pelvic PET–negative (pPET−, n = 65) groups. Immunohistochemistry on whole sections assessed germinal centers, CD4+, CD8+, FOXP3+ cells, neutrophils [CD66b+, neutrophil extracellular traps (NET)], and high-endothelial venules (HEV). Associations with progression-free survival (PFS) were examined via uni- and multivariate analyses after a median follow-up of 55.4 months.Results:The primary tumor profile was not associated with outcome, whereas PAoLN features were strongly predictive. In pPET− patients, higher NETs were associated with shorter PFS [P = 0.015; hazard ratio (HR) = 2.768], whereas an elevated CD4/CD8 ratio improved outcomes (P = 0.047, HR = 0.497). In pPET+ patients, shorter PFS was linked to FOXP3+ (P = 0.04, HR = 1.918) and proliferating FOXP3+ cell (P = 0.018, HR = 1.668) density. Across the full cohort, abundant germinal centers (P = 0.0355, HR = 0.273) and an elevated CD4/CD8 ratio (P = 0.001, HR = 0.490) independently correlated with lower recurrence risk. Internal validation was conducted through a bootstrap resampling method. Combinatorial analyses revealed distinct predictive signatures according to pPET status: higher NETs, fewer germinal centers, and International Federation of Gynaecology and Obstetrics IIA1 to IIIB status predicted relapse in pPET− patients.Conclusions:Integrating pPET status with PAoLN histologic analyses improves recurrence risk stratification in LACC. PAoLN evaluation may serve as a complementary tool to guide treatment intensification and surveillance strategies.

Illustrative IHC of studied PAoLN biological parmaeters