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. 2025;48(4):186-196.
doi: 10.1159/000543223. Epub 2024 Dec 23.

New Insights from Long-Term Clinical Use of Circulating Tumor DNA-Based Minimal Residual Disease Monitoring in Translocation-Associated Sarcomas

Sophie Joch  1 , Maria Anna Smolle  2 , Karl Kashofer  3 , Andrea Thüringer  3 , Joanna Szkandera  4 , Martin Benesch  5 , Amin El-Heliebi  6   7 , Bernadette Liegl-Atzwanger  3 , Andreas Leithner  2 , Markus G Seidel  5   8
Affiliations

New Insights from Long-Term Clinical Use of Circulating Tumor DNA-Based Minimal Residual Disease Monitoring in Translocation-Associated Sarcomas

Sophie Joch et al. Oncol Res Treat. 2025.

Abstract

Introduction: Assessment of circulating tumor DNA (ctDNA) as a means to monitor disease activity in translocation-associated tumors has become very popular in clinical practice. However, there are still few studies on its clinical application to date. Our study evaluates the clinical applicability of ctDNA as a biomarker for monitoring minimal residual disease (MRD) in patients with translocation-associated sarcomas.

Methods: In this retrospective study, we correlated 285 ctDNA samples from 34 patients diagnosed with translocation-associated sarcoma with the clinical course and images. Blood samples were collected at multiple time points during follow-up (median: 97 weeks, range: 7-398).

Results: We discovered a significant association between ctDNA levels and the clinical course of the disease, particularly noting differences between patients in remission or with progressive disease (p = 0.001). Furthermore, although we noted that ctDNA levels remained undetectable in a few cases of unilocular recurrence (n = 3), they were consistently higher in patients with multilocular recurrence (n = 14; p = 0.008).

Conclusion: Monitoring ctDNA levels provides highly specific, additional information enabling early recurrence detection in patients with translocation-associated sarcomas during the follow-up and can be integrated into clinical practice. However, MRD monitoring by ctDNA quantification alone does not allow the reliable detection of 100% of unilocular recurrences and should be complemented by the use of conventional imaging techniques.

Introduction: Assessment of circulating tumor DNA (ctDNA) as a means to monitor disease activity in translocation-associated tumors has become very popular in clinical practice. However, there are still few studies on its clinical application to date. Our study evaluates the clinical applicability of ctDNA as a biomarker for monitoring minimal residual disease (MRD) in patients with translocation-associated sarcomas.

Methods: In this retrospective study, we correlated 285 ctDNA samples from 34 patients diagnosed with translocation-associated sarcoma with the clinical course and images. Blood samples were collected at multiple time points during follow-up (median: 97 weeks, range: 7-398).

Results: We discovered a significant association between ctDNA levels and the clinical course of the disease, particularly noting differences between patients in remission or with progressive disease (p = 0.001). Furthermore, although we noted that ctDNA levels remained undetectable in a few cases of unilocular recurrence (n = 3), they were consistently higher in patients with multilocular recurrence (n = 14; p = 0.008).

Conclusion: Monitoring ctDNA levels provides highly specific, additional information enabling early recurrence detection in patients with translocation-associated sarcomas during the follow-up and can be integrated into clinical practice. However, MRD monitoring by ctDNA quantification alone does not allow the reliable detection of 100% of unilocular recurrences and should be complemented by the use of conventional imaging techniques.

Keywords: Cell-free circulating tumor DNA; Liquid biopsy; Minimal residual disease monitoring; Translocation-associated sarcomas.

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Conflict of interest statement

S.J., K.K., B.L.-A., and A.T. have no conflicts of interest to declare. M.A.S. has received travel support from ImplanTec, Alphamed, implantcast, and PharmaMar outside of the submitted work. J.S. has received sponsorship and research funds from Eisai, PharmaMar, and Roche and has received payment or other (financial) remuneration from Bayer, Amgen, PharmaMar, and Roche. M.G.S. has received research funding from Amgen and Takeda (paid to institution), consultancy honorary from Pharming, Amgen, and Novartis, and a conference travel grant from CSL Behring. A.E. has received research funding from Qiagen (paid to institution) and received remuneration from Illumina. A.L. reports receiving institutional educational grants by Alphamed, Medacta, and Johnson & Johnson. The funders had no role in the design of this study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Figures

Fig. 1.
Fig. 1.
Flowchart of included patients. LB, liquid biopsy.
Fig. 2.
Fig. 2.
ctDNA levels in liquid biopsy samples (copies/mL) depending on course of disease on imaging (a) and clinical follow-up (b).
Fig. 3.
Fig. 3.
ctDNA levels in samples of patients with recurrence and ctDNA levels in samples within 2 weeks before or after the recurrence. Each point represents one sample used for ctDNA detection. a All patients subjected to liquid biopsies since their initial sarcoma diagnosis. b All patients subjected to liquid biopsies since recurrence diagnosis.
Fig. 4.
Fig. 4.
Course of disease of patient ID 20.
See this image and copyright information in PMC

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References

    1. Grünewald TGP, Cidre-Aranaz F, Surdez D, Tomazou EM, De Álava E, Kovar H, et al. . Ewing sarcoma. Nat Rev Dis Primer. 2018;4(1):5. - PubMed
    1. Krumbholz M, Hellberg J, Steif B, Bäuerle T, Gillmann C, Fritscher T, et al. . Genomic EWSR1 fusion sequence as highly sensitive and dynamic plasma tumor marker in ewing sarcoma. Clin Cancer Res. 2016;22(17):4356–65. - PubMed
    1. Kjær EKR, Vase CB, Rossing M, Ahlborn LB, Hjalgrim LL. Detection of circulating tumor-derived material in peripheral blood of pediatric sarcoma patients: a systematic review. Transl Oncol. 2023;34:101690. - PMC - PubMed
    1. Anderson P, Ghisoli M, Crompton BD, Klega KS, Wexler LH, Slotkin EK, et al. . Pilot study of recurrent ewing’s sarcoma management with vigil/temozolomide/irinotecan and assessment of circulating tumor (ct) DNA. Clin Cancer Res. 2023;29(9):1689–97. - PMC - PubMed
    1. Tombolan L, Rossi E, Binatti A, Zin A, Manicone M, Facchinetti A, et al. . Clinical significance of circulating tumor cells and cell-free DNA in pediatric rhabdomyosarcoma. Mol Oncol. 2022;16(10):2071–85. - PMC - PubMed

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