Ruiz-Torres Daniel A, Merkin Ross D, Bryan Michael, Mendel Julia, Efthymiou Vasileios, Roberts Thomas, Patel Manisha, Park Jong C, Chevalier Amber, Murray Clodagh, Gates Lisa, Pipinikas Christodoulos, Stott Shannon L, Fisch Adam S, Wirth Lori J, Faden Daniel L
Massachusetts Eye and Ear, 243 Charles St, Boston, MA 02114.
Massachusetts General Hospital Cancer Center, 55 Fruit St, Boston, MA 02114.
medRxiv. 2025 Jan 28:2025.01.27.25321198. doi: 10.1101/2025.01.27.25321198.
Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is an aggressive cancer with a median overall survival of only 12 months. Existing biomarkers have limited ability to predict treatment response or survival, exposing many patients to the potential toxicity of treatment without certain clinical benefit. Circulating tumor DNA (ctDNA) has emerged as a non-invasive, real-time biomarker that could address these challenges.
We analyzed 137 plasma samples from 16 patients with R/M HNSCC undergoing immune checkpoint blockade (ICB)-based therapy. A tumor-informed, highly sensitive next-generation sequencing liquid biopsy assay (RaDaR, NeoGenomics Laboratories, Inc.) was applied to track ctDNA changes at baseline and throughout treatment. Univariable and multivariable analyses were used to assess the association between ctDNA negativity and key clinical outcomes: disease control (best objective response of stable disease, partial response, or complete response), three-year overall survival (OS), and three-year progression-free survival (PFS). We also assessed a machine learning model to predict disease progression based on ctDNA dynamics.
Multivariable analysis revealed that ctDNA negativity during treatment was significantly associated with improved disease control (OR 21.7, 95% CI 1.86-754.88, p=0.0317), three-year OS (HR 0.04, 95% CI 0.00-0.47, p=0.0103), and three-year PFS (HR 0.03, 95% CI 0.00-0.37, p=0.0057). The machine learning model predicted disease progression with 88% accuracy (AUC 0.89).
Serial ctDNA monitoring predicted disease control, survival, and progression in patients with R/M HNSCC receiving treatment with ICB, suggesting that incorporation of ctDNA into clinical practice could enhance treatment decision-making for clinicians and improve patient outcomes.
复发/转移性头颈部鳞状细胞癌（R/M HNSCC）是一种侵袭性癌症，中位总生存期仅为12个月。现有的生物标志物预测治疗反应或生存期的能力有限，导致许多患者在没有明确临床获益的情况下承受治疗的潜在毒性。循环肿瘤DNA（ctDNA）已成为一种可应对这些挑战的非侵入性实时生物标志物。
我们分析了16例接受基于免疫检查点阻断（ICB）治疗的R/M HNSCC患者的137份血浆样本。采用一种肿瘤知情的高灵敏度下一代测序液体活检检测方法（RaDaR，NeoGenomics Laboratories公司）来追踪基线及整个治疗过程中ctDNA的变化。采用单变量和多变量分析来评估ctDNA阴性与关键临床结局之间的关联：疾病控制（最佳客观反应为病情稳定、部分缓解或完全缓解）、三年总生存期（OS）和三年无进展生存期（PFS）。我们还评估了一个基于ctDNA动态变化预测疾病进展的机器学习模型。
多变量分析显示，治疗期间ctDNA阴性与改善疾病控制（比值比21.7，95%置信区间1.86 - 754.88，p = 0.0317）、三年OS（风险比0.04，95%置信区间0.00 - 0.47，p = 0.0103）和三年PFS（风险比0.03，95%置信区间0.00 - 0.37，p = 0.0057）显著相关。机器学习模型预测疾病进展的准确率为88%（曲线下面积0.89）。
连续ctDNA监测可预测接受ICB治疗的R/M HNSCC患者的疾病控制、生存期和进展情况，这表明将ctDNA纳入临床实践可增强临床医生的治疗决策能力并改善患者预后。
