Circulating Tumor DNA Predicts Response After Definitive Radiation Therapy for Merkel Cell Carcinoma

Area of Science:

• Oncology
• Genetics
• Medical Diagnostics

Background:

• Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a high risk of recurrence.
• Circulating tumor DNA (ctDNA) assays are emerging tools for monitoring treatment efficacy and detecting cancer recurrence.
• Definitive radiation therapy (dRT) is a standard treatment for MCC, but its effectiveness and patient outcomes require robust monitoring methods.

Purpose of the Study:

• To evaluate the clinical utility of ctDNA levels in assessing treatment response and predicting recurrence in patients with MCC undergoing definitive radiation therapy (dRT).
• To determine the correlation between ctDNA dynamics and disease status (no evidence of disease vs. clinical evidence of disease) following dRT.

Main Methods:

• A cohort of 48 MCC patients treated with dRT was analyzed.
• ctDNA levels were measured using a tumor-informed multiplex PCR assay before and after dRT.
• Patient outcomes were categorized as no evidence of disease (NED) or clinical evidence of disease, and ctDNA dynamics were compared between groups.

Main Results:

• Median ctDNA levels were higher in stage I vs. stage I-II MCC at baseline.
• ctDNA levels significantly decreased during and after dRT (P = .0125 and P = .0004, respectively).
• Persistent or rising ctDNA levels post-dRT were strongly associated with recurrence (90% of patients with detectable ctDNA after dRT recurred).

Conclusions:

• ctDNA levels decline rapidly during and after dRT in MCC patients, especially those achieving NED.
• Detectable ctDNA after dRT is a significant predictor of recurrence.
• ctDNA serves as a valuable noninvasive biomarker for monitoring treatment response and guiding post-treatment surveillance in MCC.