Zhang Xu, Fang Qigen, Yuan Junhui, Dai Liyuan, Luo Ruihua, Huang Tao, Wu Yinfei
Department of Head Neck and Thyroid, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
Department of Radiology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
Front Immunol. 2025 Aug 7;16:1576042. doi: 10.3389/fimmu.2025.1576042. eCollection 2025.
BACKGROUND: While circulating tumor DNA (ctDNA) assessment after surgery has emerged as a promising biomarker for minimal residual disease detection in solid tumors, its clinical utility for guiding the selection between postoperative radiotherapy (PORT) and chemoradiotherapy (POCRT) in head and neck squamous cell carcinoma (HNSCC) remains poorly characterized. We evaluated whether ctDNA-directed stratification could optimize locoregional control in HNSCC patients following neoadjuvant chemoimmunotherapy. METHODS: In this comparative cohort study, consecutive HNSCC patients treated with neoadjuvant chemoimmunotherapy were stratified into two management groups: a ctDNA-guided cohort where tumor-informed ctDNA testing determined POCRT administration given only for detectable ctDNA, and a traditional cohort where all patients received PORT, with postoperative chemotherapy decisions made by multidisciplinary team review based on pathologic response status and pretreatment imaging findings. The primary endpoint was 3-year locoregional control, with secondary analysis of POCRT utilization rates. RESULTS: Among 257 patients who completed neoadjuvant chemoimmunotherapy, 209 (81.3%) underwent surgery with 187 (72.8% of treated patients) achieving major pathological response and comprising our study population. Of these, 69 (36.9%) received ctDNA-guided management, while 118 (63.1%) followed traditional protocols. POCRT utilization was significantly lower in the ctDNA-guided group (27.5% [19/69] vs 42.4% [50/118]; absolute difference -14.9%, p=0.042). ctDNA positivity rates were comparable between groups (ctDNA-guided: 27.5% [19/69] vs traditional: 29.6% [35/118], p=0.867). ctDNA-guided management demonstrated superior outcomes, with a 15% reduction in locoregional recurrence risk (adjusted HR 0.85, 95%CI 0.70-0.94; p=0.013) versus traditional management. Among ctDNA-positive patients, POCRT benefit was significantly greater in the ctDNA-guided cohort (HR 0.73, 95%CI 0.57-0.83; p=0.026) compared to ctDNA-positive patients receiving traditional management (HR 0.87, 95%CI 0.73-0.93; p=0.047; interaction p=0.039). CONCLUSION: Postoperative ctDNA analysis identifies HNSCC patients who benefit most from POCRT, enabling a 41% relative reduction in treatment utilization while maintaining superior locoregional control. The enhanced therapeutic effect observed in ctDNA-guided patients supports ctDNA's role as a decision-modifying biomarker for personalization management following neoadjuvant chemoimmunotherapy.
背景：虽然手术后循环肿瘤DNA（ctDNA）评估已成为实体瘤微小残留病检测的一种有前景的生物标志物，但其在指导头颈部鳞状细胞癌（HNSCC）术后放疗（PORT）和放化疗（POCRT）选择方面的临床效用仍未得到充分表征。我们评估了ctDNA指导的分层是否能优化接受新辅助化疗免疫治疗后的HNSCC患者的局部区域控制。 方法：在这项比较队列研究中，接受新辅助化疗免疫治疗的连续HNSCC患者被分为两个管理组：一个ctDNA指导组，其中肿瘤信息ctDNA检测确定仅对可检测到ctDNA的患者给予POCRT；另一个传统组，所有患者接受PORT，术后化疗决策由多学科团队根据病理反应状态和治疗前影像学检查结果进行审查。主要终点是3年局部区域控制，对POCRT利用率进行次要分析。 结果：在257例完成新辅助化疗免疫治疗的患者中，209例（81.3%）接受了手术，其中187例（占治疗患者的72.8%）达到主要病理反应并纳入我们的研究人群。其中，69例（36.9%）接受ctDNA指导的管理，而118例（63.1%）遵循传统方案。ctDNA指导组的POCRT利用率显著较低（27.5% [19/69] 对42.4% [50/118]；绝对差异-14.9%，p = 0.042）。两组之间的ctDNA阳性率相当（ctDNA指导组：27.5% [19/69] 对传统组：29.6% [35/118]，p = 0.867）。ctDNA指导的管理显示出更好的结果，与传统管理相比，局部区域复发风险降低了15%（调整后HR 0.85，95%CI 0.70 - 0.94；p = 0.013）。在ctDNA阳性患者中，与接受传统管理的ctDNA阳性患者（HR 0.87，95%CI 0.73 - 0.93；p = 0.047；交互作用p = 0.039）相比，ctDNA指导组的POCRT获益显著更大（HR 0.73，95%CI 0.57 - 0.83；p = 0.026）。 结论：术后ctDNA分析可识别出从POCRT中获益最大的HNSCC患者，在保持优异的局部区域控制的同时，使治疗利用率相对降低41%。在ctDNA指导的患者中观察到的增强治疗效果支持ctDNA作为新辅助化疗免疫治疗后个性化管理的决策修正生物标志物的作用。
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