Clearance of circulating tumor DNA (ctDNA) during radiotherapy strongly correlates with treatment response and improved outcomes in patients with gynecologic malignancies, according to research presented at the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting. The study, led by Gabriella Wernicke, MD, MSc, indicates that ctDNA could serve as a valuable biomarker for assessing treatment efficacy and predicting disease progression.
The research team collected data from 29 patients with gynecologic cancers undergoing radiotherapy. At baseline, ctDNA was detectable in 83% of patients (n = 24/29). Following radiotherapy, a significant reduction in ctDNA levels was observed across the cohort. Specifically, from pre-treatment to post-treatment, 88% of patients achieved a complete metabolic response (cMR), where ctDNA became undetectable, while 12% experienced a partial metabolic response (pMR). Mid-treatment to post-treatment, cMR rate was 67% and pMR rate was 33%.
Correlation with Imaging and Disease Burden
The study also revealed a strong correlation between ctDNA levels and disease burden as assessed by imaging. A decrease in ctDNA levels correlated with a reduction of disease burden on MRI before the brachytherapy phase of radiation. Elevated ctDNA levels were significantly associated with measurable disease on MRI or elevated standardized uptake value (SUV) on PET scans (correlation coefficient of 0.67, P = 0.002). Undetectable ctDNA levels correlated with complete resolution of SUV at 3 to 6 months post-radiation (P = 0.02).
Clinical Implications
"Patients with undetectable ctDNA by the end of treatment were seen to have metabolic response and remained without evidence of disease, with undetectable ctDNA at 3 to 6 months following radiation or chemoradiation," Wernicke noted. Only one patient exhibited persistent ctDNA after therapy and subsequently developed metastatic disease in the lung and liver within three months.
The findings suggest that ctDNA monitoring could provide an early indication of treatment response and potential disease recurrence, allowing for timely intervention. The ability to non-invasively assess treatment efficacy through ctDNA analysis represents a significant advancement in the management of gynecologic cancers undergoing radiotherapy.
