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  9. Predictive And Prognostic Markers
  11. Dynamic Changes In Tp53 Mutated Circulating Tumor Dna Predicts Outcome Of Patients With High-grade Ovarian Carcinomas

Dynamic changes in TP53 mutated circulating tumor DNA predicts outcome of patients with high-grade ovarian carcinomas

Maria Kfoury1,2, Clément Bonnet3, Nicolas Delanoy4

  • 1Medical Oncology Department, Institut Gustave-Roussy, Villejuif, Île-de-France, France kfourym@ipc.unicancer.fr.

International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society
|September 23, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Monitoring TP53 mutations in circulating tumor DNA (ctDNA) can predict high-grade ovarian cancer outcomes. Rising ctDNA levels during chemotherapy or post-surgery indicate worse survival, guiding adjuvant therapy decisions.

Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Genetics

Background:

  • High-grade ovarian cancer lacks reliable biomarkers for predicting treatment response.
  • TP53 mutations are common in ovarian cancer, but their utility as a dynamic biomarker is underexplored.

Purpose of the Study:

  • To investigate the potential of monitoring TP53 mutations in circulating tumor DNA (ctDNA) as a predictive biomarker in high-grade ovarian cancer.
  • To correlate ctDNA TP53 mutation dynamics with treatment response and patient survival.

Main Methods:

  • Prospective study (NCT03010124) involving sequential collection of biological samples from ovarian cancer patients.
  • Analysis of ctDNA for TP53 mutations using next-generation sequencing.
  • Comparison of ctDNA TP53 mutations with tumor tissue and assessment for clonal hematopoiesis of indeterminate potential (CHIP).
Keywords:
Ovarian Cancer

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Main Results:

  • ctDNA was detected in all patients at diagnosis, with 77% concordance of TP53 mutations between ctDNA and tumor tissue.
  • Increasing ctDNA levels during neoadjuvant chemotherapy correlated with failure to achieve complete cytoreductive surgery (60% of patients).
  • Rising or de novo TP53 mutations in ctDNA trended towards worse progression-free survival (10 vs 26.5 months). Detectable ctDNA post-surgery was associated with poorer survival.

Conclusions:

  • Monitoring TP53 mutations in ctDNA serves as a reliable, tumor-specific biomarker in high-grade ovarian cancer.
  • ctDNA dynamics during and after treatment can predict treatment failure and patient survival.
  • TP53 mutation monitoring in ctDNA may guide optimal adjuvant therapy selection for ovarian cancer patients.