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Research communication
Dynamic changes in TP53 mutated circulating tumor DNA predicts outcome of patients with high-grade ovarian carcinomas
  1. Maria Kfoury1,2,
  2. Clément Bonnet3,
  3. Nicolas Delanoy4,
  4. Karen Howarth5,
  5. Christophe Marzac6,
  6. Etienne Rouleau7,
  7. Jean-Baptiste Micol6,8 and
  8. Alexandra Leary1
    1. 1 Medical Oncology Department, Institut Gustave-Roussy, Villejuif, Île-de-France, France
    2. 2 Medical Oncology Department, Institut Paoli-Calmettes, Marseille, France
    3. 3 Medical Oncology Department, Institut Curie, Paris, France
    4. 4 Medical Oncology Department, Université de Paris, Paris, France
    5. 5 Inivata Ltd, Cambridge, UK
    6. 6 Université Paris-Saclay, Gif-sur-Yvette, France
    7. 7 Medical Biology and Pathology Department, Institut Gustave-Roussy, Villejuif, Île-de-France, France
    8. 8 Hematology Department, Institut Gustave-Roussy, Villejuif, Île-de-France, France
    1. Correspondence to Dr Maria Kfoury; kfourym{at}ipc.unicancer.fr

    Abstract

    There is a lack of biomarkers to predict outcome following initial treatment in patients with high-grade ovarian cancer. We hypothesized that monitoring TP53 mutation (TP53m) in circulating tumor DNA (ctDNA) could be a tumor-specific biomarker. Patients enrolled in a prospective study (NCT03010124) consented to analysis of biological samples through the disease course. ctDNA was extracted and analyzed to detect the presence of TP53m. Next-generation sequencing was performed on tumor tissue to detect TP53m and on whole blood to detect clonal hematopoiesis of indeterminate potential (CHIP).

    A total of 102 samples were sequentially collected from 26 patients. ctDNA was detected in all patients at diagnosis. The same TP53m was found in ctDNA and tumor tissue in 77% of patients. TP53m in ctDNA was not CHIP related. During neoadjuvant chemotherapy, increasing ctDNA was associated with failure to achieve complete interval cytoreductive surgery in 60% of patients. Rising ctDNA or de novo TP53m seemed to be associated with a trend for worst survival compared with decrease or complete clearance: progression-free survival 10 versus 26.5 months, HR 3.2. Despite macroscopically complete surgery, 30% of patients had detectable ctDNA post-operatively and had worse survival than those with undetectable ctDNA. Monitoring TP53m in ctDNA during chemotherapy or after surgery could help guide the best adjuvant therapy.

    • Ovarian Cancer

    https://doi.org/10.1136/ijgc-2024-005581

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      Footnotes

      • X @kfoury_maria

      • Contributors AL and ER contributed to conceptualization. MK, CB, and ND contributed to data curation. MK, ER, CM, and JBM contributed to formal analysis. KH, CM, and AL contributed to funding acquisition. AL, JBM, and ER contributed to supervision and validation. EL contributed to project administration. MK contributed to original draft and writing. All authors contributed to reviewing and editing of the manuscript. MK is the guarantor.

      • Funding The analysis of ctDNA was funded by INIVATA.

      • Competing interests MK: advisory boards/honoraria: GSK, AstraZeneca; travel, accommodations: Pfizer, GSK, Eisai. ND: travel, accommodations: GSK; advisory boards/honoraria: GSK, AstraZeneca, MSD, Clovis Oncology, EISAI. KH: shareholder/stockholder/stock options, full/part-time employment: Inivata. ER: honoraria: AstraZeneca (Inst), Roche (Inst), BMS (Inst), GlaxoSmithKline (Inst), Clovis Oncology (Inst); consulting or advisory role: AstraZeneca; research funding: AstraZeneca (Inst); travel, accommodations, expenses: AstraZeneca, BMS. JBM : honoraria: Jazz Pharmaceuticals, Astellas Pharma; consulting or advisory role: AbbVie, Servier; travel, accommodations, expenses: AbbVie. AL: honoraria (self): Medscape; AZ, Clovis, GSK, Kephren; advisory/consultancy: AZ, Clovis, GSK, Biocad, Ability Pharma, Merck Serono, Tesaro, MSD, Seattle Genetics, Gamamabs, Gritstone; research grant/funding (self): Inivata, Sanofi, AZ, OSE Immuno; travel/accommodation/expenses: AZ, Roche, Clovis, Tesaro. All other authors have declared no conflicts of interest.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.