(Press-News.org) Can fragments of tumor DNA in the blood predict whether chemotherapy will be effective? Researchers at the Princess Máxima Center investigated this question together with experts from Italy and Slovakia. They focused specifically on young adults with germ cell tumors for whom standard chemotherapy doesn't work well.
Blood samples from young adults treated at hospitals in Italy and Slovakia were analyzed before and during chemotherapy. The researchers searched these samples for fragments of tumor DNA circulating in the blood. They identified specific changes in the genetic material that came from cancer cells resistant to standard chemotherapy. The team then looked at whether these characteristics were linked with how long the cancer stayed away after treatment in young adults with germ cell tumors.
The findings are promising: a blood test could potentially help doctors make more personalized decisions about whether initiating this intensive therapy is worthwhile, particularly in what may be the patient’s final phase of life.
Further research is required before this approach can be implemented in clinical practice. The next step is to confirm these findings in a larger group of people, including blood samples from children with germ cell tumors.
This research was made possible by Stichting Kinderen Kankervrij (KiKa) and the Italian Ministry of Health.
Germ Cell Tumors
Germ cells are responsible for the development of sperm in men and eggs in women. The precursor cells of these germ cells can develop into cancer. This happens mainly in boys and young men, both in the testis and in other places in the body.
In the Netherlands, approximately 30 children are diagnosed with a germ cell tumor each year, as well as around 850 young men with testicular germ cell tumors. Testicular cancer is the most common cancer in young men aged 15 to 35. In one in ten of these young adults, standard chemotherapy doesn't work well enough. Despite treatment with high-dose chemotherapy, half of this group ultimately dies.
For this reason, researchers from the Looijenga group at the Máxima Center worked with scientists from the Italian IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” to study biomarkers that could predict clinical response and treatment outcome. In the future, this could help improve the quality of life in the patient’s final phase of life.
The study was published today in the Journal of Clinical Oncology.
Tumor Fraction and Copy Number Alterations
Blood samples from 69 patients receiving high-dose chemotherapy and 26 patients receiving standard chemotherapy were analyzed using shallow whole genome sequencing. In circulating tumor DNA (cfDNA), the researchers assessed tumor fraction (TF) and copy number alterations (CNAs). These results were compared with an existing biomarker, miR‑371a‑3p. The team then evaluated associations with progression-free survival and overall survival.
Key findings:
Tumor fraction exceeded the detection threshold—indicating the presence of tumor DNA—in 75% of patients treated with high-dose chemotherapy. A high tumor fraction was strongly associated with poorer survival, both in patients receiving high-dose and standard-dose chemotherapy.
miR‑371a‑3p proved more informative than the established biomarker for detecting the presence of disease, but it was not a good predictor of survival.
Specific genetic alterations (a high frequency of 3p gain, 9q and 11q gains, and 6q loss) were more common in patients receiving high-dose chemotherapy who had a poor prognosis.
Histological subtypes—tumors with distinct microscopic appearances—also showed specific patterns of genetic alterations. Patients whose tumors exhibited abnormalities consistent with extra-embryonic histology (yolk sac tumor and choriocarcinoma) had worse survival outcomes.
High-dose chemotherapy appears to be more effective than standard chemotherapy in patients with a high tumor fraction.
Conclusion
Analysis of cfDNA provides valuable prognostic information in germ cell tumors that do not respond adequately to, or recur after, standard chemotherapy. These minimally invasive biomarkers may refine risk stratification and support decision-making about whether to initiate a final, highly intensive course of chemotherapy in relapsed germ cell tumors. The insights gained could also help identify new targets for the development of less toxic treatments.
Next Steps
The researchers now plan to validate these results in a larger cohort of adolescents and children with germ cell tumors, within an international collaboration. If the follow-up study confirms the findings, clinicians may be able to use them in practice to determine the most appropriate treatment for patients with germ cell tumors. Researchers will also be able to more effectively explore alternative treatments that are both more effective and associated with fewer side effects.
Dr. Thomas Eleveld, postdoctoral researcher, and Ferd Janssen, PhD candidate, both members of the Looijenga group, conducted the study together with Dr. Milena Urbini (IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori”, Meldola, Italy) and Dr. Maurizio Polano (IRCCS Centro di Riferimento Oncologico di Aviano, Aviano, Italy).
The research was led by Prof. Dr. Leendert Looijenga, in collaboration with Prof. Dr. Migal Mego (Comenius University and National Cancer Institute, Bratislava, Slovakia) and Prof. Dr. Ugo De Giorgi (IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori”, Meldola, Italy).
END
Blood test could help guide treatment decisions in germ cell tumors
2026-02-19
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