Peri-treatment ctDNA dynamics in locally advanced cervical cancer: pilot study from a safety-net hospital

Real-time kinetics of circulating tumor DNA (ctDNA) during active concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) remain poorly characterized. We evaluated peri-treatment ctDNA dynamics in a real-world safety-net cohort using a commercially available tumor-informed assay.

We retrospectively reviewed serial ctDNA measurements (Signatera) in 17 LACC patients who underwent definitive CCRT, with or without induction chemotherapy and immune checkpoint inhibitor therapy. Patients were classified by longitudinal ctDNA kinetics as Sustained clearance, Persistent/Re-positive, or Negative.

Baseline ctDNA was detectable in 15 of 17 patients (88%); patients were classified as Sustained clearance (n = 8), Persistent/Re-positive (n = 7), or Negative (n = 2). With mean follow-up of 273 ± 148 days, all 5 clinical recurrences occurred in the Persistent/Re-positive group (5/7 vs 0/8; Fisher's exact P = 0.007), representing a strong but preliminary association. Among 8 non-induction-treated patients with detectable baseline ctDNA and ≥ 2 assessments spanning baseline and intra-CCRT, molecular clearance during active CCRT occurred in 5 (62.5%), first observed between days 27 and 43; none developed recurrence. Trajectories were frequently non-monotonic, with isolated negative results within otherwise-positive courses. ctDNA preceded imaging-based recurrence in three of five recurrent patients by a median of 124 days (range 70-240). Three recurrent patients were considered candidates for total pelvic exenteration.

Detectable ctDNA declined rapidly during CCRT but frequently followed a non-monotonic trajectory. Serial rather than isolated measurements appear necessary to interpret molecular response during active treatment. Prospective studies are warranted to determine whether trajectory-based ctDNA monitoring can improve risk stratification and recurrence detection.