cfDNA-inferred putative clonal hematopoiesis during first-line platinum-to-PARP inhibitor maintenance in ovarian cancer
Year: 2026
Type: article
Abstract: OBJECTIVE: To describe cell-free DNA (cfDNA)-inferred putative clonal hematopoiesis (CH) candidates during first-line platinum-based chemotherapy followed by poly(ADP-ribose) polymerase inhibitor (PARPi) maintenance in ovarian cancer. METHODS: In SCRUM-Japan MONSTAR-SCREEN-1, we analyzed clinically reported paired tumor tissue and plasma cfDNA profiling (324-gene assays). Baseline (B1) data were assessed in 35 treatment-naïve patients; longitudinal cfDNA was available at B1, after platinum without progression (B2), and during/after PARPi without progression (B3) in 8 patients. Putative CH candidates were defined as pathogenic variants (variant allele frequency <40%) in prespecified CH-related genes detected in plasma but not detected in matched tumor tissue at clinical reporting thresholds. RESULTS: ) more frequently became detectable above the reporting threshold during B2-B3 than during B1-B2, while epigenetic-gene candidates showed relatively stable detectability. No therapy-related myeloid neoplasm events were observed during follow-up. CONCLUSION: This paired tissue-plasma longitudinal analysis highlights an interpretive challenge in cfDNA testing during first-line platinum-to-PARPi maintenance therapy: putative CH candidates may become detectable as tumor-derived cfDNA declines. Given cfDNA-only inference without matched WBC sequencing and the small serial cohort, these observations are supportive of prior reports of CH dynamics but require validation in larger WBC-integrated cohorts. TRIAL REGISTRATION: UMIN-CTR Clinical Trial Identifier: UMIN000036749.
Source: Journal of Gynecologic Oncology
Authors: Mika Okazawa-Sakai, Takao Fujisawa, Tatsuyuki Chiyoda, Hiroshi Yagi, Ichinosuke Hyodo, Shogen Boku, Yoh Hayasaki, Masanori Isobe, Daisuke Shintani, Kosei Hasegawa, Tomomi Egawa-Takata, Kimihiko Ito, Kei Ihira, Hidemichi Watari, Kazuhiro Takehara, Kiyoko Kato, Hiromichi Nakajima, Kenichi Harano, Yoshiaki Nakamura, Hideaki Bando, Takayuki Yoshino, Daisuke Aoki
Institutions: Shikoku Cancer Center, National Cancer Center Hospital East, Keio University, Kyushu University, Kansai Medical University Hospital, Gifu University, Saitama International Medical Center, Saitama Medical University, Kansai Rosai Hospital, Hokkaido University Hospital, International University of Health and Welfare
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7172306733