Significance of imaging-detected extranodal extension (iENE) in locally advanced head and neck squamous cell carcinoma (LASCCHN) treated with induction chemotherapy followed by chemoradiotherapy.

person Ryutaro Onaga National Cancer Center Hospital East, Japan, Chiba, Japan info_outline Ryutaro Onaga, Tomohiro Enokida, Takashi Hiyama, Nobukazu Tanaka, Yuta Hoshi, Hideki Tanaka, Takao Fujisawa, Susumu Okano, Hirofumi Kuno, Makoto Tahara

Authors person Ryutaro Onaga National Cancer Center Hospital East, Japan, Chiba, Japan info_outline Ryutaro Onaga, Tomohiro Enokida, Takashi Hiyama, Nobukazu Tanaka, Yuta Hoshi, Hideki Tanaka, Takao Fujisawa, Susumu Okano, Hirofumi Kuno, Makoto Tahara Organizations National Cancer Center Hospital East, Japan, Chiba, Japan, Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Japan, Chiba, Japan, National Cancer Center Hospital East, Kashiwa, Chiba, Japan, National Cancer Center Hospital East, Kashiwa-Shi, Japan Abstract Disclosures Research Funding No funding sources reported Background: Extranodal extension (ENE) of nodal metastasis is a significant prognostic factor in p16-negative SCCHN and is classified as N3b by the AJCC 8th edition. Therefore, pretreatment determination of ENE has significant clinical implications in SCCHN, and iENE has just recently been proposed. We previously discussed association with pathological ENE and iENE (Jpn J Radiol. 2020;38(6):489-506.). However, the role of iENE in non-surgical sequential therapy remains unclear. Methods: We retrospectively reviewed patients with LASCCHN originating from the oropharynx, hypopharynx, and larynx who received enhanced computed tomography (CT), then treated with induction chemotherapy (IC) with paclitaxel, carboplatin, and cetuximab followed by chemoradiotherapy (CRT) from 2013 to 2022 in our hospital. Two radiologists specializing in head and neck cancer blindly annotated the status of iENE in baseline CT images by the previously reported criteria (Oral Oncol. 2022;125:105716.). Multivariate analysis variables for event-free survival (EFS) and overall survival (OS) included the presence or absence of iENE, a response to IC, clinical T-category, performance status, smoking status, etc. Results: In the 88 patients, 67 (76.1%) had iENE and 21 (23.9%) did not at baseline. In the former and latter group, stage II/III/IV were 10.4%/26.9%/62.7% and 0%/28.6%/71.4%, HPV-positive were 37.3% and 28.6%, respectively. With the median follow-up of 37.4 months (range: 6.7-108.8), the former had significantly shorter EFS (3-y EFS: 41.9% vs. 75.6%, hazard ratio [HR]; 2.9 (1.2-7.4), p -value; 0.02) and OS (3-y OS: 72.8% vs. 100%, HR; Inf (0.01-Inf), p -value=0.003). Multivariate analysis identified the presence of iENE (HR for EFS: 2.80, 95%CI: 0.97-8.05, HR for OS: 2.93, 95%CI: 1.01-8.44) and unresponsiveness to IC (HR for EFS: 2.47, 95%CI: 1.31-4.68, HR for OS: 2.87, 95%CI: 1.13-7.26) as mutually independent unfavorable prognostic factors for both EFS and OS. Furthermore, classification based on the two factors could identify the population with a worse prognosis (Table). Conclusions: In the sequential therapy of IC followed by CRT, the current study revealed for the first time that subjects with an iENE at baseline, together with an unsatisfactory response to IC would require special attention, such as more intensified post-treatment follow-up as well as additional therapeutic interventions to improve their prognosis. Prognosis by the status of imaging-detected extranodal extension (iENE) and response to induction chemotherapy (IC). iENE at Baseline Response to IC n 3-y EFS p-Value 3-y OS p-Value Negative Positive (CR/PR) 9 89% 0.08 100% 0.01 Negative Negative (SD/PD) 5 27% 100% Positive Positive (PR/CR) 42 49% 89% Positive Negative (SD/PD) 22 35% 51%