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Cancer Research and Treatment > Accepted Articles
doi: https://doi.org/10.4143/crt.2022.1440    [Accepted]
Plasma Cell-Free DNA in Uterine Cervical Cancer: Therapeutic Monitoring and Prognostic Values after Radical Radiotherapy
Jae Sik Kim1,2 , Sunah Yang3 , Kyeonghun Jeong4, Dong-Yun Kim1,5, Kwangsoo Kim3, Hyun-Cheol Kang1,6
1Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
2Department of Radiation Oncology, Soonchunhyang University Seoul Hospital, Seoul, Korea
3Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul, Korea
4Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, Korea
5Department of Radiation Oncology, Kyung Hee University Hospital at Gangdong, Seoul, Korea
6Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea
Correspondence  Hyun-Cheol Kang ,Tel: 82-2-2072-2526, Fax: 82-2-765-3317, Email: shule@snu.ac.kr
Received: November 2, 2022;  Accepted: December 11, 2022.  Published online: December 12, 2022.
*Jae Sik Kim and Sunah Yang contributed equally to this work.
In the present study, we aimed to establish a liquid biopsy-based monitoring method using peripheral blood cell-free DNA (cfDNA) for patients with cervical cancer who underwent radical radiotherapy (RT).
Materials and Methods
Twenty-five patients with cervical cancer were prospectively recruited and treated with external beam RT and brachytherapy. In all patients, except one, chemotherapy was administered concurrently during RT. Whole peripheral blood samples were obtained at least twice from each patient. We performed next-generation sequencing (NGS) for the target-captured libraries (67 oncogenes and human papillomavirus [HPV] type 16/18) using 64 plasma cfDNA samples from the 25 participants. The ratio of HPV cfDNA and the variant allele frequency (VAF) in cfDNA was calculated, and their dynamic changes were monitored. The median follow-up duration was 25.4 months.
In total, we identified 21,866 cfDNA variants. ARID1A and frameshift variants occupied the largest portion of altered genes and HIGH-grade variant types, respectively. In most cases, tumor shrinkage was followed by a decrease in the HPV ratio; however, an increase in HPV ratio indicated distant metastasis, despite the reduced tumor size. The initial HPV ratio reflecting the tumor burden was likely associated with treatment outcomes (p = 0.16). We did not determine a role for serial changes in the VAF in cfDNA.
Our findings suggest that the HPV cfDNA ratio, calculated after targeted NGS, may be valuable for monitoring and predicting treatment responses. Accordingly, further validation of these findings is warranted.
Key words: Cell-free DNA, Uterine cervical neoplasms, Human papillomavirus viruses, Variant allele frequency
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