Mirko Manojlovic-Kolarski, Susie Su, Ilian Weinreb, Robert Calvisi, Bayardo Perez-Ordonez, Stephen Smith, Snehal Patel, Cristina Valero, Bin Xu, Ronald Ghossein, Nora Katabi, Jonathan Clark, Tsu-Hui Hubert Low, Ruta Gupta, Evan Graboyes, Joel Davies, Mary Richardson, David Goldstein, Shao Hui Huang, Brian O'Sullivan, Weu Xu, Aaron Hansen, John R de Almeida
{"title":"辅助放化疗治疗伴大、小结外扩张的口腔鳞状细胞癌。","authors":"Mirko Manojlovic-Kolarski, Susie Su, Ilian Weinreb, Robert Calvisi, Bayardo Perez-Ordonez, Stephen Smith, Snehal Patel, Cristina Valero, Bin Xu, Ronald Ghossein, Nora Katabi, Jonathan Clark, Tsu-Hui Hubert Low, Ruta Gupta, Evan Graboyes, Joel Davies, Mary Richardson, David Goldstein, Shao Hui Huang, Brian O'Sullivan, Weu Xu, Aaron Hansen, John R de Almeida","doi":"10.1001/jamaoto.2025.1721","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>Extranodal extension (ENE) in oral cavity squamous cell carcinoma (OSCC) is a poor prognostic feature and an indication for adjuvant chemoradiotherapy. ENE is stratified into minor (≤2 mm) or major (>2 mm) extent. The role of adjuvant chemoradiotherapy, particularly for the minor ENE subgroup, is unclear.</p><p><strong>Objective: </strong>To determine the impact of adjuvant chemoradiotherapy on oncological outcomes depending on the extent of ENE.</p><p><strong>Design, setting, and participants: </strong>This retrospective, multicenter cohort study was conducted across 4 high-volume head and neck surgery centers in Australia, the US, and Canada. The study included patients with surgically resected OSCC with pathologic positive nodal disease treated between 2005 and 2018. Statistical analysis took place between 2022 and 2025; final follow-up was in 2022.</p><p><strong>Exposures: </strong>Extent of ENE was restaged on archived tissue. Adjuvant radiotherapy or chemoradiotherapy was recommended per standard guidelines.</p><p><strong>Outcomes: </strong>Univariable and multivariable analysis were used to assess the effect of chemotherapy for the entire group and for propensity score-matched cohorts on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) stratified by minor vs major ENE.</p><p><strong>Results: </strong>A total of 755 patients (mean [SD] age, 61.7 [12.9] years; 36% female) were included in the study: 126 (17%) with minor ENE and 243 (32%) with major ENE. A total of 50 (39.7%) patients with minor ENE and 116 (47.8%) with major ENE received adjuvant chemotherapy. On multivariable analysis, chemotherapy was not associated with improved LRC (hazard ratio [HR], 1.07 [95% CI, 0.49-2.32]), DFS (HR, 0.96 [95% CI, 0.56-1.66]), or OS (HR, 0.97 [95% CI, 0.55-1.73]) in patients with minor ENE. However, in patients with major ENE, chemotherapy improved DFS (HR, 0.58 [95% CI, 0.41-0.81]) and OS (HR, 0.61 [95% CI, 0.38-0.98]). In propensity score-matched cohorts, chemotherapy did not improve LRC (71% vs 75%; difference, 4% [95% CI, -18% to 26%]), DFS (56% vs 56%; difference, 0% [95% CI, -25% to 25%]), or OS (57% vs 57%; difference, 0% [95% CI, -25% to 25%]) for patients with minor ENE, but improved DFS (33% vs 11%; difference, 22% [95% CI, 5%-38%]) and OS (41% vs 15%; difference, 26% [95% CI, 8%-44%]) but not LRC (61% vs 62%; difference, 1% [95% CI, -17% to 21%]) in patients with major ENE.</p><p><strong>Conclusions: </strong>This multicenter cohort study found that in patients with OSCC, adjuvant chemotherapy is beneficial in patients with major ENE, but may not be beneficial in patients with minor ENE.</p>","PeriodicalId":14632,"journal":{"name":"JAMA otolaryngology-- head & neck surgery","volume":" ","pages":"785-794"},"PeriodicalIF":5.6000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177724/pdf/","citationCount":"0","resultStr":"{\"title\":\"Adjuvant Chemoradiotherapy for Oral Cavity SCC With Minor and Major Extranodal Extension.\",\"authors\":\"Mirko Manojlovic-Kolarski, Susie Su, Ilian Weinreb, Robert Calvisi, Bayardo Perez-Ordonez, Stephen Smith, Snehal Patel, Cristina Valero, Bin Xu, Ronald Ghossein, Nora Katabi, Jonathan Clark, Tsu-Hui Hubert Low, Ruta Gupta, Evan Graboyes, Joel Davies, Mary Richardson, David Goldstein, Shao Hui Huang, Brian O'Sullivan, Weu Xu, Aaron Hansen, John R de Almeida\",\"doi\":\"10.1001/jamaoto.2025.1721\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Importance: </strong>Extranodal extension (ENE) in oral cavity squamous cell carcinoma (OSCC) is a poor prognostic feature and an indication for adjuvant chemoradiotherapy. ENE is stratified into minor (≤2 mm) or major (>2 mm) extent. The role of adjuvant chemoradiotherapy, particularly for the minor ENE subgroup, is unclear.</p><p><strong>Objective: </strong>To determine the impact of adjuvant chemoradiotherapy on oncological outcomes depending on the extent of ENE.</p><p><strong>Design, setting, and participants: </strong>This retrospective, multicenter cohort study was conducted across 4 high-volume head and neck surgery centers in Australia, the US, and Canada. The study included patients with surgically resected OSCC with pathologic positive nodal disease treated between 2005 and 2018. Statistical analysis took place between 2022 and 2025; final follow-up was in 2022.</p><p><strong>Exposures: </strong>Extent of ENE was restaged on archived tissue. Adjuvant radiotherapy or chemoradiotherapy was recommended per standard guidelines.</p><p><strong>Outcomes: </strong>Univariable and multivariable analysis were used to assess the effect of chemotherapy for the entire group and for propensity score-matched cohorts on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) stratified by minor vs major ENE.</p><p><strong>Results: </strong>A total of 755 patients (mean [SD] age, 61.7 [12.9] years; 36% female) were included in the study: 126 (17%) with minor ENE and 243 (32%) with major ENE. A total of 50 (39.7%) patients with minor ENE and 116 (47.8%) with major ENE received adjuvant chemotherapy. On multivariable analysis, chemotherapy was not associated with improved LRC (hazard ratio [HR], 1.07 [95% CI, 0.49-2.32]), DFS (HR, 0.96 [95% CI, 0.56-1.66]), or OS (HR, 0.97 [95% CI, 0.55-1.73]) in patients with minor ENE. However, in patients with major ENE, chemotherapy improved DFS (HR, 0.58 [95% CI, 0.41-0.81]) and OS (HR, 0.61 [95% CI, 0.38-0.98]). 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引用次数: 0
摘要
重要性：结外延伸（ENE）在口腔鳞状细胞癌（OSCC）是一个预后不良的特征，是辅助放化疗的指征。ENE分为轻度（≤2mm）和重度（bb0 ~ 2mm）。辅助放化疗的作用，特别是对于较小的ENE亚组，尚不清楚。目的：探讨辅助放化疗对肿瘤预后的影响。设计、环境和参与者：这项回顾性、多中心队列研究在澳大利亚、美国和加拿大的4个大容量头颈外科中心进行。该研究包括2005年至2018年间接受手术切除的伴有病理阳性淋巴结疾病的OSCC患者。统计分析在2022年至2025年之间进行；最后一次跟进是在2022年。暴露：在存档组织上重新测定ENE的范围。根据标准指南推荐辅助放疗或放化疗。结果：单变量和多变量分析用于评估化疗对整个组的影响，以及倾向评分匹配队列对局部区域控制（LRC）、无病生存（DFS）和总生存（OS）的影响，按轻微和严重ENE分层。结果：共755例患者(平均[SD]年龄61.7[12.9]岁；36%为女性)，126例（17%）为轻度ENE， 243例（32%）为重度ENE。共有50例（39.7%）轻度ENE患者和116例（47.8%）重度ENE患者接受了辅助化疗。在多变量分析中，化疗与轻度ENE患者的LRC（风险比[HR]， 1.07 [95% CI, 0.49-2.32]）、DFS（风险比[HR]， 0.96 [95% CI, 0.56-1.66]）或OS（风险比，0.97 [95% CI, 0.55-1.73]）改善无关。然而，在严重ENE患者中，化疗改善了DFS （HR, 0.58 [95% CI, 0.41-0.81]）和OS （HR, 0.61 [95% CI, 0.38-0.98]）。在倾向评分匹配的队列中，化疗没有改善LRC (71% vs 75%；差异，4% [95% CI， -18%至26%]),DFS (56% vs 56%；差异，0% [95% CI， -25%至25%])或OS (57% vs 57%；轻度ENE患者的差异为0% [95% CI， -25%至25%]，但改善了DFS (33% vs 11%；差异为22% [95% CI， 5%-38%])和OS (41% vs 15%；差异为26% [95% CI， 8%-44%])，但LRC无差异(61% vs 62%；严重ENE患者的差异为1% [95% CI， -17%至21%]。结论：这项多中心队列研究发现，在OSCC患者中，辅助化疗对严重ENE患者有益，但对轻微ENE患者可能没有好处。
Adjuvant Chemoradiotherapy for Oral Cavity SCC With Minor and Major Extranodal Extension.
Importance: Extranodal extension (ENE) in oral cavity squamous cell carcinoma (OSCC) is a poor prognostic feature and an indication for adjuvant chemoradiotherapy. ENE is stratified into minor (≤2 mm) or major (>2 mm) extent. The role of adjuvant chemoradiotherapy, particularly for the minor ENE subgroup, is unclear.
Objective: To determine the impact of adjuvant chemoradiotherapy on oncological outcomes depending on the extent of ENE.
Design, setting, and participants: This retrospective, multicenter cohort study was conducted across 4 high-volume head and neck surgery centers in Australia, the US, and Canada. The study included patients with surgically resected OSCC with pathologic positive nodal disease treated between 2005 and 2018. Statistical analysis took place between 2022 and 2025; final follow-up was in 2022.
Exposures: Extent of ENE was restaged on archived tissue. Adjuvant radiotherapy or chemoradiotherapy was recommended per standard guidelines.
Outcomes: Univariable and multivariable analysis were used to assess the effect of chemotherapy for the entire group and for propensity score-matched cohorts on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) stratified by minor vs major ENE.
Results: A total of 755 patients (mean [SD] age, 61.7 [12.9] years; 36% female) were included in the study: 126 (17%) with minor ENE and 243 (32%) with major ENE. A total of 50 (39.7%) patients with minor ENE and 116 (47.8%) with major ENE received adjuvant chemotherapy. On multivariable analysis, chemotherapy was not associated with improved LRC (hazard ratio [HR], 1.07 [95% CI, 0.49-2.32]), DFS (HR, 0.96 [95% CI, 0.56-1.66]), or OS (HR, 0.97 [95% CI, 0.55-1.73]) in patients with minor ENE. However, in patients with major ENE, chemotherapy improved DFS (HR, 0.58 [95% CI, 0.41-0.81]) and OS (HR, 0.61 [95% CI, 0.38-0.98]). In propensity score-matched cohorts, chemotherapy did not improve LRC (71% vs 75%; difference, 4% [95% CI, -18% to 26%]), DFS (56% vs 56%; difference, 0% [95% CI, -25% to 25%]), or OS (57% vs 57%; difference, 0% [95% CI, -25% to 25%]) for patients with minor ENE, but improved DFS (33% vs 11%; difference, 22% [95% CI, 5%-38%]) and OS (41% vs 15%; difference, 26% [95% CI, 8%-44%]) but not LRC (61% vs 62%; difference, 1% [95% CI, -17% to 21%]) in patients with major ENE.
Conclusions: This multicenter cohort study found that in patients with OSCC, adjuvant chemotherapy is beneficial in patients with major ENE, but may not be beneficial in patients with minor ENE.
期刊介绍：
JAMA Otolaryngology–Head & Neck Surgery is a globally recognized and peer-reviewed medical journal dedicated to providing up-to-date information on diseases affecting the head and neck. It originated in 1925 as Archives of Otolaryngology and currently serves as the official publication for the American Head and Neck Society. As part of the prestigious JAMA Network, a collection of reputable general medical and specialty publications, it ensures the highest standards of research and expertise. Physicians and scientists worldwide rely on JAMA Otolaryngology–Head & Neck Surgery for invaluable insights in this specialized field.
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