Clinical significance of circulating-tumour DNA analysis by metastatic sites in pancreatic cancer

• Published in: British journal of cancer 2023-04, Vol.128 (8), p.1603-1608
• Main Authors: Umemoto, Kumiko, Sunakawa, Yu, Ueno, Makoto, Furukawa, Masayuki, Mizuno, Nobumasa, Sudo, Kentaro, Kawamoto, Yasuyuki, Kajiwara, Takeshi, Ohtsubo, Koushiro, Okano, Naohiro, Matsuhashi, Nobuhisa, Itoh, Shinji, Matsumoto, Toshihiko, Shimizu, Satoshi, Otsuru, Toru, Hasegawa, Hiroko, Okuyama, Hiroyuki, Ohama, Hideko, Moriwaki, Toshikazu, Ohta, Takashi, Odegaard, Justin I., Nakamura, Yoshiaki, Bando, Hideaki, Yoshino, Takayuki, Ikeda, Masafumi, Morizane, Chigusa
• Format: Article
• Language: English
• Subjects: 631/67/1504/1713; 631/67/69; Adenocarcinoma; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Biopsy; Cancer Research; Carcinoma, Pancreatic Ductal - pathology; Circulating Tumor DNA - genetics; Clinical Relevance; Clinical significance; Drug Resistance; Epidemiology; Gene frequency; Genomics; Genotyping; Humans; K-Ras protein; Liver; Lymph nodes; Metastases; Metastasis; Molecular Medicine; Mutation; Oncology; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - pathology; Patients; Peritoneum; Proto-Oncogene Proteins p21(ras) - genetics; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-023-02189-y

Background Liquid biopsy is an alternative to tissue specimens for tumour genotyping. However, the frequency of genomic alterations with low circulating-tumour DNA (ctDNA) shedding is shown in pancreatic ductal adenocarcinoma (PDAC). We, therefore, investigated the prevalence of KRAS mutations and ctDNA fraction by the metastatic site in patients with PDAC. Methods This study enrolled previously treated PDAC patients from a plasma genomic profiling study; ctDNA analysis was performed using Guardant360 at disease progression before initiating subsequent treatment. Results In 512 patients with PDAC, KRAS mutations were detected in 57%. The frequency of KRAS mutation in ctDNA differed depending on the metastatic organ; among patients with single-organ metastasis ( n  = 296), KRAS mutation detection rate was significantly higher in patients with metastasis to the liver (78%). In addition, the median maximum variant allele frequency (VAF) was higher with metastasis to the liver (1.9%) than with metastasis to the lungs, lymph nodes, peritoneum or with locally advanced disease (0.2%, 0.4%, 0.2% and 0.3%, respectively). Conclusion The prevalence of KRAS mutations and maximum VAF were higher in patients with metastasis to the liver than in those with metastasis to other sites. This study indicated the clinical utility of ctDNA analysis, especially in PDAC with liver metastases.