PO.BCS01.17 · 生物信息与计算
ctDNA先于影像学：一种用于HPV相关肛门鳞状细胞癌实时治疗调整的预测模型
ctDNA precedes imaging: A predictive model for real-time treatment adaptation in HPV-associated anal squamous cell carcinoma
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：HPV相关肛门鳞状细胞癌(ASCC)治疗应答的实时评估仍具挑战性。传统的肿瘤体积测量需要连续影像，成本高、耗时长，并延迟临床决策。因此，患者可能接受长时间的次优治疗，或因过度治疗而承受不必要的毒性。循环肿瘤DNA(ctDNA)提供了一种更易获取的实时替代生物标志物——但其对指导治疗调整的预测价值和临床实用性仍未明确。
方法：我们开发了一个肿瘤体积-ctDNA动力学的机制性数学模型，并将其参数化并校准至32例接受免疫治疗(pembrolizumab，每3周一次，最长2年)的HPV相关ASCC患者的纵向数据。该模型在三种临床情景下拟合：同时测量(8例患者)、体积先于ctDNA(14例患者)以及ctDNA先于体积(2例患者)。我们量化了ctDNA对早期治疗应答评估的预测能力。
结果：ctDNA与肿瘤负荷(SLD)显示出强正相关，并在治疗开始后4周内预测临床应答状态。至关重要的是，ctDNA动力学在多例患者中先于体积变化，在影像学确认之前为应答评估提供了早期信号。该数学模型稳健地捕捉了所有测量情景下的异质性患者动力学，验证了其预测框架。
结论：ctDNA作为一种先导指标生物标志物，能够早期识别HPV相关ASCC的治疗应答。我们的定量框架将这一生物标志物转化为可操作的临床预测，使临床医生能够就治疗递增、维持或递减做出实时决策。这种方法通过用可及的血液监测取代繁琐的影像学，增强了精准肿瘤学——对影像获取有限的服务不足人群尤为有益。未来研究将前瞻性验证该模型，以指导个体化的适应性治疗策略。
查看英文原文 English abstract
Background: Real-time assessment of treatment response in HPV-associated anal squamous cell carcinoma (ASCC) remains challenging. Traditional tumor volume measurements require serial imaging that is costly, time-intensive, and delays clinical decision-making. Consequently, patients may receive prolonged suboptimal therapy or unnecessary toxicity from over-treatment. Circulating tumor DNA (ctDNA) offers a more accessible, real-time alternative biomarker-yet its predictive value and clinical utility for guiding treatment adaptation remain undefined.
Methods: We developed a mechanistic mathematical model of tumor volume-ctDNA dynamics which we parameterized and calibrated to longitudinal data from 32 HPV-associated ASCC patients who received immunotherapy (pembrolizumab, once every 3 weeks, up to 2 years). The model was fit across three clinical scenarios: simultaneous measurements (8 patients), volume preceding ctDNA (14 patients), and ctDNA preceding volume (2 patients). We quantified ctDNA's predictive capacity for early treatment response assessment.
Results: ctDNA demonstrated strong positive correlation with tumor burden (SLD) and predicted clinical response status within 4 weeks of treatment initiation. Critically, ctDNA kinetics preceded volume changes in multiple patients, providing early signal for response assessment before imaging confirmation. The mathematical model robustly captured heterogeneous patient dynamics across all measurement scenarios, validating its predictive framework.
Conclusions: ctDNA functions as a leading indicator biomarker enabling early identification of treatment response in HPV-associated ASCC. Our quantitative framework translates this biomarker into actionable clinical predictions, allowing clinicians to make real-time decisions on treatment escalation, maintenance, or de-escalation. This approach enhances precision oncology by replacing burdensome imaging with accessible blood-based monitoring-particularly impactful for underserved populations with limited imaging access. Future studies will prospectively validate this model to inform personalized, adaptive treatment strategies.
利益披露 Disclosure
P. M. Havor, None..
B. Huffman, None..
J. Cleary, None..
R. Brady-Nicholls, None.