Coupled Modeling of Tumor Volume and ctDNA Dynamics in HPV-Associated Anal Squamous Cell Carcinoma

ctDNA after one pembrolizumab cycle drops more in responders than non-responders with advanced HPV-associated anal squamous cell carcinoma, about six weeks before the next scan.

• Why it matters: Imaging during anti-PD-1 therapy is infrequent and can lag behind tumor biology, leaving response classification uncertain despite frequent ctDNA sampling.
• What they did: In 26 patients, longitudinal tumor volume and HPV ctDNA were modeled with an ordinary differential equation linking tumor volume to ctDNA release, then reduced to two patient-specific parameters.
• The result: The model reproduced individual tumor and ctDNA trajectories, including a transient ctDNA spike at treatment onset, and found faster proliferation in non-responders, enabling ctDNA-guided monitoring.

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