Cavalieri Stefano, Brakenhoff Ruud H, Leemans C René, Hoebers Frank J P, Poli Tito, Scheckenbach Kathrin, Iacovelli Nicola Alessandro, Franceschini Marzia, Orlandi Ester, Licitra Lisa, De Cecco Loris
Head and Neck Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.
Amsterdam UMC location Vrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, De Boelelaan 1117, Amsterdam, the Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands.
Radiother Oncol. 2025 Jul;208:110900. doi: 10.1016/j.radonc.2025.110900. Epub 2025 Apr 17.
Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer-related deaths worldwide, with HPV-negative cases being particularly aggressive. These cases often show poor prognosis and low responsiveness to radiotherapy. Improved prognostic tools and treatment strategies are needed to enhance outcomes.
To evaluate the prognostic value of various gene expression signatures in predicting survival outcomes in HPV-negative HNSCC patients receiving radiotherapy and to compare their accuracy against the current TNM staging system.
This observational cohort study used data from the European BD2Decide project, systematically analyzing gene expression in loco-regionally advanced, non-metastatic HPV-negative HNSCC patients (stage III-IVa/b) treated with curative radiotherapy (post-operative or definitive) between 2008 and 2017. The primary outcome was overall survival (OS), with secondary outcomes including disease-free survival (DFS), distant metastasis-free survival (DMFS), and loco-regional recurrence-free survival (LRRFS). The prognostic performance of selected gene expression signatures was evaluated using receiver operating characteristic (ROC) curves and hazard ratios (HR) from Cox models.
The study included 783 patients, with a median age of 63 years, mostly male (68 %), with significant tobacco (84 %) and alcohol (69 %) exposure. The 172-gene signature (172GS) showed the highest prognostic accuracy, outperforming the TNM system in predicting OS, DFS, DMFS, and LRRFS. Multivariable analysis confirmed its independent prognostic value.
The 172GS gene signature offers superior prognostic information compared to TNM staging, supporting its potential use for better risk stratification and personalized treatment planning in HPV-negative HNSCC. Future trials should consider tumor biology and gene signatures for better patient selection.
NCT02832102.
头颈部鳞状细胞癌（HNSCC）是全球癌症相关死亡的主要原因，HPV阴性病例尤其具有侵袭性。这些病例通常预后较差，对放疗的反应性较低。需要改进预后工具和治疗策略以提高治疗效果。
评估各种基因表达特征在预测接受放疗的HPV阴性HNSCC患者生存结局中的预后价值，并将其准确性与当前的TNM分期系统进行比较。
这项观察性队列研究使用了来自欧洲BD2Decide项目的数据，系统分析了2008年至2017年间接受根治性放疗（术后或根治性）的局部区域晚期、非转移性HPV阴性HNSCC患者（III-IVa/b期）的基因表达。主要结局是总生存期（OS），次要结局包括无病生存期（DFS）、无远处转移生存期（DMFS）和无局部区域复发生存期（LRRFS）。使用来自Cox模型的受试者工作特征（ROC）曲线和风险比（HR）评估所选基因表达特征的预后性能。
该研究纳入了783例患者，中位年龄为63岁，大多数为男性（68%），有大量吸烟（84%）和饮酒（69%）史。172基因特征（172GS）显示出最高的预后准确性，在预测OS、DFS、DMFS和LRRFS方面优于TNM系统。多变量分析证实了其独立的预后价值。
与TNM分期相比，172GS基因特征提供了更好的预后信息，支持其在HPV阴性HNSCC中用于更好的风险分层和个性化治疗计划的潜在用途。未来的试验应考虑肿瘤生物学和基因特征以更好地选择患者。
NCT02832102。
