翁長 龍太郎

6034 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. [Table: see text]

頭頸部扁平上皮癌に対する薬物療法は,この20年間に目覚ましい発展を遂げている.古くはシスプラチンをキードラッグとした治療のみがエビデンスの確立した薬物療法であった.2000年代に入り導入化学療法や術後補助化学放射線療法の概念が登場し,殺細胞性抗がん薬の併用療法のエビデンスも出現した.さらに,2012年には分子標的薬であるセツキシマブ,2017年以降には免疫チェックポイント阻害薬であるニボルマブやペムブロリズマブが登場したことで,再発転移例においてもより多くの治療選択肢を得ることとなった.頭頸部扁平上皮癌は一般に予後不良な固形癌であるが,数々の臨床試験が行われ,予後向上と機能温存を目指した治療法が模索されている.また,治療に結びつく頻度は高くないものの,遺伝子異常に対するゲノム医療も研究が進んでいる.本稿では治療セッティング毎に既存の標準治療の要点と問題点を概説したうえで,今後期待される最新免疫・薬物療法を含め紹介する.(著者抄録)