Prognostic impact of preoperative imaging-detected extranodal extension in head and neck squamous cell carcinoma treated with postoperative chemoradiotherapy.

6063 Background: In 2024, the Head and Neck Cancer International Group (HNCIG) newly defined imaging-detected and pathological extranodal extension (iENE/pENE). We previously reported the utility of iENE in induction chemotherapy followed by definitive chemoradiotherapy (Onaga R, et al. ASCO Annual Meeting, 2024). However, the significance of iENE in surgically treated head and neck squamous cell carcinoma (HNSCC) remains unclear, particularly in high-risk populations with positive pENE. We aimed to investigate the prognostic value of iENE in patients treated with completed surgery and postoperative chemoradiotherapy (poCRT) due to pENE-positivity. Methods: We retrospectively analyzed patients with HNSCC (oral cavity, oropharynx, hypopharynx, or larynx) who underwent surgical resection between 2013 and 2023 at our hospital. pENE-positive patients who received poCRT (cisplatin ≥ 200 mg/m² and radiation therapy ≥ 60 Gy) were included, excluding those with positive surgical margins of the primary site. iENE grading on preoperative CT or MRI and pENE assessment in surgical specimens were re-evaluated according to HNCIG consensus recommendations. Relapse-free survival (RFS) and Overall survival (OS) were analyzed using the log-rank test. Results: We identified 95 patients with a median age of 62 years (range: 16-76). The primary tumor sites included oral cavity (58 patients), hypopharynx (29), larynx (5), and oropharynx (3). iENE grades were 0/1/2/3 in 24/29/13/29 patients, and pENE was categorized as minor ENE/major ENE/soft tissue metastasis (STM) in 40/20/35 patients. With a median follow-up of 42.1 months, 43 patients developed recurrence (local/regional/distant/regional and distant: 1/7/30/5). In the iENE classification, the 5-year RFS for iENE Grades 0/1/2/3 was 77.8%, 60.3%, 35.9%, and 33.4% (p=0.003), and the 5-year OS was 88.8%, 70.5%, 37.8%, and 63.0% (p=0.021), respectively. When iENE grades were grouped into Grade 0/1 and Grade 2/3, the latter group had significantly shorter RFS (5-year RFS: 68.0% vs. 34.2%, p < 0.001) and OS (5-year OS: 78.3% vs. 55.9%, p = 0.008). In the pENE classification, no significant differences in RFS and OS were observed among minor ENE, major ENE, and STM (p=0.380 for RFS, p=0.617 for OS). Conclusions: Our study revealed for the first time that preoperative iENE was a significant prognostic factor for pENE-positive patients treated with poCRT. Specifically, patients with iENE grade 2/3 exhibited a poor prognosis, emphasizing the need for additional treatment strategies tailored to this very high-risk group. Prognosis based on iENE grades and pENE category. N=95 5-year RFS p-value 5-year OS p-value iENE Grade 0 24 77.8% 0.003 88.8% 0.021 Grade 1 29 60.3% 70.5% Grade 2 13 35.9% 37.8% Grade 3 29 33.4% 63.0% pENE Minor ENE 40 60.9% 0.380 70.6% 0.617 Major ENE 20 56.4% 70.1% Soft tissue metastasis 35 45.1% 66.6%