Circulating tumor DNA Dynamics as a Leading Indicating Biomarker for Time to Progression in HPV-associated Anal Squamous Cell Carcinoma

Phebe MHavor

Moffitt Cancer Center/University of South Florida

"Circulating tumor DNA Dynamics as a Leading Indicating Biomarker for Time to Progression in HPV-associated Anal Squamous Cell Carcinoma"

Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for monitoring cancer progression and treatment response in real time. In anal squamous cell carcinoma (ASCC), where 80-90% of cases are linked to human papillomavirus (HPV), ctDNA demonstrates high sensitivity in tracking disease dynamics, often detecting progression earlier than imaging while enabling frequent assessment and correlating with tumor burden. Our study examined how patient-specific modeling of ctDNA dynamics can predict time to progression in HPV-associated ASCC. We analyzed longitudinal data from 32 ASCC patients receiving immunotherapy every 3 weeks for up to 2 years, exploring correlations between tumor volume and ctDNA levels. We developed a mathematical model calibrated to patient-specific tumor volume and ctDNA dynamics during immunotherapy. Results show that relative changes in ctDNA positively correlate with tumor volume changes, with lower baseline ctDNA associated with better clinical responses. In some complete responders, ctDNA became undetectable before radiological confirmation, demonstrating both tumor reduction and ctDNA clearance. However, all patients eventually progressed. Parameter analysis revealed that treatment efficacy significantly impacts ctDNA shedding patterns, often causing characteristic peaks in ctDNA levels. These dynamics could serve as an early warning system for progression, potentially enabling more timely intervention. The model effectively characterizes patient-specific tumor and ctDNA dynamics. Results suggest alternative strategies, including chemotherapy, could optimize dosing regimens based on ctDNA patterns to improve responses and extend time to progression. This work establishes a foundation for integrating ctDNA surveillance into treatment monitoring for ASCC patients.
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