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<p>This study applies joint modeling (JM) of longitudinal and time-to-event data to circulating tumor DNA (ctDNA) dynamics measured by liquid biopsy in metastatic breast cancer (mBC), with a focus on dynamic prediction. Unlike traditional prognostic approaches that rely on static biomarkers, JM captures the continuous evolution of a methylation-based tumor fraction (TF) and links these changes to clinical outcomes. Serial liquid biopsies from 49 patients with hormone receptor–positive/HER2-negative mBC treated with endocrine therapy plus a CDK4/6 inhibitor were analyzed using the Guardant Reveal assay. JM combined a flexible longitudinal sub-model to characterize temporal TF trajectories with a Cox proportional hazards model for overall survival (OS) and time to treatment discontinuation (TTD). The most recent TF estimate was strongly associated with both OS and TTD (<i>p</i> &lt; 0.0001), demonstrating an inverse relationship between TF and prognosis. These findings highlight the value of JM for generating patient-specific, dynamically updated predictions that may support real-time, personalized clinical decision-making in mBC management.</p>

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Longitudinal evaluation of serial ctDNA kinetics using joint modeling in patients with metastatic breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月3日

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  • Christopher Pretz,
  • Jesús Fuentes-Antrás,
  • Sasha Main,
  • Aaron Dou,
  • Elizabeth Shah,
  • Emily Van de Laar,
  • Caroline M. Weipert,
  • Bryan Lin,
  • Amar Das,
  • Eitan Amir,
  • Michelle B. Nadler,
  • Celeste Yu,
  • Hal K. Berman,
  • Lillian L. Siu,
  • Philippe L. Bedard,
  • Mitchell J. Elliott,
  • David W. Cescon

摘要

This study applies joint modeling (JM) of longitudinal and time-to-event data to circulating tumor DNA (ctDNA) dynamics measured by liquid biopsy in metastatic breast cancer (mBC), with a focus on dynamic prediction. Unlike traditional prognostic approaches that rely on static biomarkers, JM captures the continuous evolution of a methylation-based tumor fraction (TF) and links these changes to clinical outcomes. Serial liquid biopsies from 49 patients with hormone receptor–positive/HER2-negative mBC treated with endocrine therapy plus a CDK4/6 inhibitor were analyzed using the Guardant Reveal assay. JM combined a flexible longitudinal sub-model to characterize temporal TF trajectories with a Cox proportional hazards model for overall survival (OS) and time to treatment discontinuation (TTD). The most recent TF estimate was strongly associated with both OS and TTD (p < 0.0001), demonstrating an inverse relationship between TF and prognosis. These findings highlight the value of JM for generating patient-specific, dynamically updated predictions that may support real-time, personalized clinical decision-making in mBC management.