Prognostic impact of early ctDNA dynamics during chemotherapy of metastatic cancer

Abstract

Aim: Clinical utility of the dynamics of ctDNA is sparse. This study aimed at evaluating the prognostic impact of early ctDNA dynamics in patients with metastatic cancer treated with chemotherapy. Materials & methods: The ctDNA dynamics were evaluated in 595 patients with metastatic cancer using droplet digital PCR. Results: Patients with an increase in ctDNA after one treatment cycle (n = 73; 12.2%) had an overall survival of 5.6 months compared with 8.6 months in patients with stable or decreasing ctDNA (n = 328; 55.1%) and 21.0 months in patients with undetectable ctDNA (p < 0.001; hazard ratio: 0.47; 95% CI: 0.41–0.53). Conclusion: Early ctDNA dynamics hold important prognostic information and have great implications for evaluation with the perspective of a more individualized treatment strategy.

Keywords::

• ctDNA
• droplet digital PCR
• dynamics
• HOXA9
• methylation
• NPY
• prognosis

Author contributions

L Faaborg: conceptualization, investigation, writing – original draft; RF Andersen: data curation, investigation, writing – review and editing; SWC Wen: data curation, writing – review and editing; CB Thomsen: data curation, writing – review and editing; L Raunkilde: data curation, writing – review and editing; TF Hansen: resources, data curation, writing – review and editing; LH Jensen: resources, data curation, writing – review and editing; KD Steffensen: resources, data curation, writing – review and editing; A Jakobsen: conceptualization, supervision, writing – original draft, writing – review and editing.

Acknowledgments

The authors would like to thank Karin Larsen for linguistic editing of the manuscript.

Financial disclosure

This work was financially supported by the Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest or financial conflict with the subject matter or materials discussed in the manuscript.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

The authors certify that this manuscript reports the secondary analysis of clinical trial data that have been shared with them and that the use of this shared data is in accordance with the terms (if any) agreed upon their receipt. The source of this data is NCT02399592 ClinicalTrials.gov

Additional information

Funding

This work was financially supported by the Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest or financial conflict with the subject matter or materials discussed in the manuscript.