Introduction: Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker for monitoring treatment response and residual disease in solid tumors. However, its prognostic value during neoadjuvant chemotherapy (NAC) for localized pancreatic ductal adenocarcinoma (PDAC) has not been well established.
Introduction:
Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker for monitoring treatment response and residual disease in solid tumors. However, its prognostic value during neoadjuvant chemotherapy (NAC) for localized pancreatic ductal adenocarcinoma (PDAC) has not been well established. This study evaluated whether mutant KRAS ctDNA measured by digital droplet PCR (ddPCR) predicts survival in patients undergoing NAC and surgical resection.
Why was this study needed?
Reliable biomarkers are needed to assess response to neoadjuvant therapy in localized PDAC.
Radiologic assessment alone often fails to accurately reflect tumor biology.
The prognostic significance of serial KRAS ctDNA measurements during treatment remains unclear.
ctDNA could help identify patients at high risk of recurrence after surgery.
Results:
Among 84 patients with localized PDAC receiving NAC, mutant KRAS ctDNA was detected in approximately half at diagnosis and in nearly 70% after NAC and after surgery. Around 18% of patients achieved complete ctDNA clearance during treatment, which was associated with significantly improved overall survival. In contrast, persistent detection of the KRAS G12V mutation after NAC and especially after surgical resection identified patients with substantially poorer survival outcomes. On multivariable analysis, postoperative detection of KRAS G12V was one of the strongest predictors of reduced overall survival, suggesting persistent molecular disease despite apparently curative treatment.
Clinical Impact:
Serial KRAS ctDNA monitoring may provide valuable prognostic information beyond conventional imaging and pathology. Clearance of ctDNA during neoadjuvant therapy identifies patients with favorable tumor biology, whereas persistent postoperative KRAS mutations may indicate minimal residual disease and identify candidates for intensified surveillance, additional systemic therapy, or enrollment in clinical trials.
Bottom Line:
Serial KRAS ctDNA monitoring during neoadjuvant treatment is a promising prognostic biomarker in localized PDAC, with postoperative persistence of KRAS G12V identifying patients at particularly high risk of poor survival.
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