Sep 29

QP 29 - Response Assessment and Risk Stratification in Gynecologic Cancers: Biomarkers, Imaging, and Outcomes

1171 - Association Between Plasma and Urine HPV Circulating Tumor DNA and Early Treatment Response in Locally Advanced Cervical Cancer Treated with Concurrent Chemoradiation

05:30pm - 05:35pm ET

Room 257

Presenter(s)

Chinnavuth Vatanashevanopakorn, MD, PhD - Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkoknoi, Krung Thep

C. Vatanashevanopakorn¹, P. Dankulchai¹, T. Prasartseree¹, W. Sittiwong¹, R. Romrattaphan¹, P. Tuntapakul¹, N. Apiwarodom¹, C. Metheetrairut², K. Trakarnsanga², P. Jintanapunya², and W. Thaweerat¹; ¹Division of Radiation Oncology, Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, ²Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

Purpose/Objective(s):

Plasma human papillomavirus (HPV) circulating tumor DNA (ctDNA) is a promising biomarker for recurrence inlocally advanced cervical cancer (LACC). Its association with early radiation response, particularly tumor regression during external beam radiation therapy (EBRT) prior to brachytherapy (BT), remains unclear. Given the non-invasive nature of urine sampling, we evaluated whether urine HPV ctDNA parallels plasma kinetics and correlates with early treatment response.

Materials/Methods:

In this prospective single-center study, 11 patients with HPV16-positive LACC (FIGO 2018 stage IB3–IVA) received definitive concurrent chemoradiation (CCRT) followed by BT. Blood and urine samples were collected at four time points, treatment day 15, end of treatment, 1 month post-treatment and 3 months post-treatment. Plasma and urine HPV ctDNA was quantified using multiplex digital PCR targeting HPV16 E6/E7. Mid-EBRT response was defined as percentage reduction in gross tumor volume (GTV) between baseline (GTVinitial) and pre-BT (GTVpreBT) imaging. Statistical analyses included Mann–Whitney test and Pearson or Spearman correlation.

Results:

With a mean follow-up of 5.5 ± 1.7 months, no residual or recurrent disease was identified at last follow-up, except for two patients with residual disease at 1 month post-treatment assessment. HPV ctDNA was detectable in both plasma and urine in all patients, with higher levels in urine. Plasma and urine HPV ctDNA levels declined over time. Plasma and urine ctDNA levels at corresponding time points were not correlated.

Plasma HPV ctDNA at day 15 and end of treatment showed a trend toward inverse correlation with mid-EBRT response (R=-0.5000, p=0.1217; R=-0.5448, p=0.0862, respectively). Plasma HPV ctDNA at 1 month post-treatment was strongly inversely correlated with mid-EBRT response (R=-0.8581, p=0.0016). In contrast, urine HPV ctDNA levels at all time points were not associated with mid-EBRT response. Notably, the plasma-urine ctDNA difference at day 15inversely correlated with mid-EBRT response (R=-0.6507, p=0.0302).

Patients with residual tumor at 1 month post-treatment had higher plasma HPV ctDNA at day 15 and end of treatment compared with responders (p=0.0364 for both time points). No differences in urine HPV ctDNA levels were observed between these groups.

Conclusion:

Plasma HPV ctDNA kinetics during chemoradiation are associated with early tumor response in LACC. Elevated plasma HPV ctDNA levels and greater plasma–urine ctDNA difference during treatment were associated with inferior mid-EBRT response and early residual disease. Despite higher levels, urine HPV ctDNA did not correlate with early treatment response. These findings support plasma HPV ctDNA as a potential early response biomarker during definitive CCRT for LACC.