New Insights from Long-Term Clinical Use of Circulating Tumor DNA-Based Minimal Residual Disease Monitoring in Translocation-Associated Sarcomas
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Tumor-informed ctDNA monitoring in osteosarcoma and breakpoint-guided ctDNA monitoring in translocation-associated sarcomas currently have the clearest longitudinal clinical support.
“Tumor-informed ctDNA monitoring in osteosarcoma and breakpoint-guided ctDNA monitoring in translocation-associated sarcomas currently have the clearest longitudinal clinical support, although both still require prospective multicenter validation before routine treatment decisions can be based on ctDNA alone [ 13 , 16 , 17 , 22 , 23 , 24 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [22]
In Ewing sarcoma and other breakpoint-defined tumors, the disease-defining structural variant provides a stable and highly specific target for longitudinal monitoring.
“In Ewing sarcoma and other breakpoint-defined tumors, the disease-defining structural variant provides a stable and highly specific target for longitudinal monitoring [ 13 , 22 , 23 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [22]
Unilocular or low-volume recurrence may remain undetected by ctDNA in translocation-associated sarcomas.
“However, unilocular or low-volume recurrence may remain undetected, emphasizing that ctDNA should not replace imaging [ 22 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [22]
Ewing sarcoma and other translocation-associated sarcomas provide a different model because disease-defining structural variants can serve as highly specific molecular targets for longitudinal monitoring.
“Ewing sarcoma and other translocation-associated sarcomas provide a different model because disease-defining structural variants can serve as highly specific molecular targets for longitudinal monitoring [ 13 , 22 , 23 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Grünewald, T. G. P., Cidre-Aranaz, F., Surdez, D., Tomazou, E. M., de Álava, E., Kovar, H., Sorensen, P. H., Delattre, O., & Dirksen, U. (2018) · Nature Reviews Disease Primers · doi:10.1038/s41572-018-0003-x · Cited by 873 · see citing works
Senescence, Necrosis, and Apoptosis Govern Circulating Cell-free DNA Release Kinetics
Rostami, A., Lambie, M., Yu, C. W., Stambolic, V., Waldron, J. N., & Bratman, S. V. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107830 · Cited by 204 · see citing works
Shulman, D. S., Klega, K., Imamovic-Tuco, A., Clapp, A., Nag, A., Thorner, A. R., Van Allen, E., Ha, G., Lessnick, S. L., Gorlick, R., et al. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0212-9 · Cited by 149 · see citing works
Genomic EWSR1 Fusion Sequence as Highly Sensitive and Dynamic Plasma Tumor Marker in Ewing Sarcoma
Krumbholz, M., Hellberg, J., Steif, B., Bäuerle, T., Gillmann, C., Fritscher, T., Agaimy, A., Frey, B., Juengert, J., Wardelmann, E., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-3028 · Cited by 96 · see citing works
Assessment of circulating tumor DNA in pediatric solid tumors: The promise of liquid biopsies
Abbou, S. D., Shulman, D. S., DuBois, S. G., & Crompton, B. D. (2019) · Pediatric Blood & Cancer · doi:10.1002/pbc.27595 · Cited by 72 · see citing works
Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors
Christodoulou, E., Yellapantula, V., O’Halloran, K., Xu, L., Berry, J. L., Cotter, J. A., Zdanowicz, A., Mascarenhas, L., Amatruda, J. F., Ostrow, D., et al. (2023) · npj Precision Oncology · doi:10.1038/s41698-023-00357-0 · Cited by 55 · see citing works
Genotyping of circulating cell-free DNA enables noninvasive tumor detection in myxoid liposarcomas
Braig, D., Becherer, C., Bickert, C., Braig, M., Claus, R., Eisenhardt, A. E., Heinz, J., Scholber, J., Herget, G. W., Bronsert, P., et al. (2019) · International Journal of Cancer · doi:10.1002/ijc.32216 · Cited by 42 · see citing works
Krumbholz, M., Eiblwieser, J., Ranft, A., Zierk, J., Schmidkonz, C., Stütz, A. M., Peneder, P., Tomazou, E. M., Agaimy, A., Bäuerle, T., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1324 · Cited by 39 · see citing works
Schmidkonz, C., Krumbholz, M., Atzinger, A., Cordes, M., Goetz, T. I., Prante, O., Ritt, P., Schaefer, C., Agaimy, A., Hartmann, W., et al. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04649-1 · Cited by 29 · see citing works
Genomic profiling in GIST: Implications in clinical outcome and future challenges
Calderillo-Ruiz, G., Pérez-Yépez, E.-A., García-Gámez, M., Millán-Catalán, O., Díaz-Romero, C., Ugalde‐Silva, P., Salas-Benavides, R., Pérez‐Plasencia, C., & Carbajal-López, B. (2024) · Neoplasia · doi:10.1016/j.neo.2023.100959 · Cited by 27 · see citing works
Seidel, M. G., Kashofer, K., Moser, T., Thueringer, A., Liegl-Atzwanger, B., Leithner, A., Szkandera, J., Benesch, M., El-Heliebi, A., & Heitzer, E. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2022.926405 · Cited by 24 · see citing works
Self-citationAnderson, P. M., Ghisoli, M. L., Crompton, B. D., Klega, K. S., Wexler, L. H., Slotkin, E. K., Stanbery, L., Manning, L., Wallraven, G., Manley, M., et al. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-2292 · Cited by 24 · see citing works
Clinical significance of circulating tumor cells and cell‐free DNA in pediatric rhabdomyosarcoma
Tombolan, L., Rossi, E. M. C., Binatti, A., Zin, A., Manicone, M., Facchinetti, A., Lucchetta, S., Affinita, M. C., Bonvini, P., Bortoluzzi, S., et al. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13197 · Cited by 23 · see citing works
Stegmaier, S., Sparber‐Sauer, M., Aakcha‐Rudel, E., Münch, P., Reeh, T., Feuchtgruber, S., Hallmen, E., Blattmann, C., Bielack, S., Klingebiel, T. E., et al. (2022) · Pediatric Blood & Cancer · doi:10.1002/pbc.29652 · Cited by 19 · see citing works
Genotyping of Circulating Free DNA Enables Monitoring of Tumor Dynamics in Synovial Sarcomas
Eisenhardt, A. E., Brugger, Z., Lausch, U., Kiefer, J., Zeller, J., Runkel, A., Schmid, A., Bronsert, P., Wehrle, J., Leithner, A., et al. (2022) · Cancers · doi:10.3390/cancers14092078 · Cited by 18 · see citing works
Self-citationCirculating Plasma Tumor DNA Is Superior to Plasma Tumor RNA Detection in Ewing Sarcoma Patients
Bodlak, A., Chang, K., Channel, J., Treece, A. L., Donaldson, N., Cost, C. R., Garrington, T. P., Greffe, B., Luna-Fineman, S., Sopfe, J., et al. (2021) · The Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2021.04.003 · Cited by 12 · see citing works
Kjær, E. K. R., Vase, C. B., Rossing, M., Ahlborn, L. B., & Hjalgrim, L. L. (2023) · Translational Oncology · doi:10.1016/j.tranon.2023.101690 · Cited by 11 · see citing works
Anderson, C. J., Yang, H., Parsons, J., Ahrens, W. A., Jagosky, M. H., Hsu, J. H., Patt, J. C., Kneisl, J. S., & Steuerwald, N. M. (2025) · Clinical Orthopaedics & Related Research · doi:10.1097/corr.0000000000003161 · Cited by 10 · see citing works
Rapid and highly sensitive approach for multiplexed somatic fusion detection
Abbou, S. D., Finstuen-Magro, S., McDannell, B., Feenstra, M., Ward, A., Shulman, D. S., Geoerger, B., Duplan, J., Comeau, H., Janeway, K. A., et al. (2022) · Modern Pathology · doi:10.1038/s41379-022-01058-y · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Alabid, I., Yousef, A. J., Patni, M. M., Aloti, R. A., Qassim, Z. A.-A. M., Alothman-Agha, A. A., Hamdy, H. A., Noury, F. M., & Abdelfattah, M. T. (2026) · Cells · doi:10.3390/cells15141271
- Authors
- Joch, S., Smolle, M. A., Kashofer, K., Thüringer, A., Szkandera, J., Benesch, M., El-Heliebi, A., Liegl-Atzwanger, B., Leithner, A., & Seidel, M. G.
- Affiliations
- Medical University of Graz (AT)
- University of Graz (AT)
- Corresponding author
- Smolle, Maria Anna
- Kashofer, Karl
- ORCID
- Venue
- Oncology Research and Treatment
- Publisher
- S. Karger AG
- Published
- 2024-12-23
- Volume
- 48
- Issue
- 4
- Pages
- 186-196
- ISSN
- 2296-5262 (ISSN-L)
- 2296-5270
- PMC
- PMC11974511
- OpenAlex
- W4405720397
- Cited by
- 2
- References
- 19
- Citations by year
- 2026: 2
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Oncology Research and Treatment (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Amgen
- CSL Behring
- Eisai
- Medizinische Universität Graz
- PharmaMar
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Keywords
- circulating tumor DNA, minimal residual disease, liquid biopsy, recurrence detection, disease progression, prognostic factors, long-term follow-up, Ewing sarcoma family of tumors, rhabdomyosarcoma, osteosarcoma, soft tissue sarcoma, image correlation, treatment response monitoring
- MeSH terms
- Circulating Tumor DNA, Adolescent, Adult, Aged, Child, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Retrospective Studies, Sarcoma, Translocation, Genetic, Biomarkers, Tumor, Neoplasm, Residual, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
