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Abstract
Purpose: 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.

Results: 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.

Conclusion: 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.

기존의 MRI 또는 암표지자의 반응과는 다른 세포유리 DNA의 반응이 환자의 예후를 보다 정확하게 예측하는 표. 만약 이를 임상에 적용한다면 최소 침습적인 검사 (혈액)로 방사선치료를 받은 여러 환자에게 큰 도움을 줄 수 있다.

Affiliations

Jae Sik Kim 1 2, Sunah Yang 3, Kyeonghun Jeong 4, Dong-Yun Kim 1 5, Kwangsoo Kim 3, Hyun-Cheol Kang 1 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.