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Related Experiment Video

Updated: Jun 13, 2025

Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
06:53

Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids

Published on: June 8, 2019

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Ultrasensitive detection and tracking of circulating tumor DNA to predict relapse and survival in patients with

J Mayadev1, J C Vázquez Limón2, F J Ramírez Godinez3

  • 1Radiation Medicine and Applied Sciences Department, University of California San Diego Medical Center, San Diego, USA.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|June 11, 2025
PubMed
Summary

Ultrasensitive circulating tumor DNA (ctDNA) detection shows promise as a prognostic biomarker for locally advanced cervical cancer (LACC) patients, predicting disease progression and survival independently of stage. This finding offers new hope for personalized treatment strategies.

Keywords:
cHPVctDNAefficacy outcomeslocally advanced cervical cancerpredictive markerultrasensitive

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Detection of Rare Mutations in CtDNA Using Next Generation Sequencing
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Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Biomarker Discovery

Background:

  • Locally advanced cervical cancer (LACC) has a high relapse rate (30-50%) after chemoradiotherapy (CRT), indicating a need for prognostic biomarkers.
  • The CALLA trial found durvalumab plus CRT did not improve progression-free survival (PFS) in unselected LACC patients.
  • Ultrasensitive circulating tumor DNA (ctDNA) and circulating human papillomavirus (cHPV) DNA are explored as potential prognostic markers.

Purpose of the Study:

  • To analyze the association between ultrasensitive ctDNA and cHPV DNA detection and outcomes in LACC patients from the CALLA trial.
  • To evaluate ctDNA and cHPV DNA as predictive and prognostic markers for disease progression and survival.
  • To assess the utility of these biomarkers independent of disease stage and lymph node status.

Main Methods:

  • Randomized controlled trial (CALLA) comparing durvalumab + CRT versus CRT alone in LACC patients.
  • Ultrasensitive tumor-informed ctDNA and cHPV DNA analysis using the NeXT Personal® assay at baseline, post-CRT (C3D1), and 3 months post-CRT (C6D1).
  • Correlation analysis between ctDNA/cHPV DNA detection levels and progression-free survival (PFS) and overall survival (OS).

Main Results:

  • ctDNA was detected in 98.9% of baseline samples, with detection levels predicting disease progression and survival.
  • Baseline ctDNA levels showed a trend towards better PFS and OS in lower ctDNA subgroups across both treatment arms.
  • Post-treatment ctDNA detection preceded clinical progression by a median of 164 days, independent of stage or node status. cHPV DNA became predictive after treatment.

Conclusions:

  • Ultrasensitive ctDNA detection is a promising predictive and prognostic marker for disease progression and OS in LACC.
  • ctDNA utility is demonstrated to be independent of LACC disease stage.
  • This approach may aid in refining risk stratification and guiding treatment decisions for LACC patients.