• Seung-Hyun Jung, Choong-Kun Lee, Woo Sun Kwon, Sujin Yun, Minkyu Jung, Hyo Song Kim, Hyun Cheol Chung, Yeun-Jun Chung, and Sun Young Rha.
• Department of Biochemistry, IRCGP, College of Medicine, The Catholic University of Korea, Seoul, Korea.
• Yonsei Med. J. 2023 Sep 1; 64 (9): 531540531-540.

PurposeFor precision medicine, exploration and monitoring of molecular biomarkers are essential. However, in advanced gastric cancer (GC) with visceral lesions, an invasive procedure cannot be performed repeatedly for the follow-up of molecular biomarkers.Materials And MethodsTo verify the clinical implication of serial liquid biopsies targeting circulating tumor DNA (ctDNA) on treatment response, we conducted targeted deep sequencing for serially collected ctDNA of 15 HER2-positive metastatic GC patients treated with anti-PD-1 inhibitor in combination with standard systemic treatment.ResultsIn the baseline ctDNAs, 14 patients (93%) harbored more than one genetic alteration. A number of mutations in well-known cancer-related genes, such as KRAS and PIK3CA, were identified. Copy number alterations were identified in eight GCs (53.3%), and amplification of the ERBB2 gene (6/15, 40.0%) was the most recurrent. When we calculated the mean variant allele frequency (VAF) of mutations in each ctDNA as the molecular tumor burden index (mTBI), the mTBI trend was largely consistent with the VAF profiles in both responder and non-responder groups. Notably, in the longitudinal analysis of ctDNA, mTBI provided 2-42 weeks (mean 13.4 weeks) lead time in the detection of disease progression compared to conventional follow-up with CT imaging.ConclusionOur data indicate that the serial genetic alteration profiling of ctDNA is feasible to predict treatment response in HER2-positive GC patients in a minimally invasive manner. Practically, ctDNA profiles are useful not only for the molecular diagnosis of GC but also for the selection of GC patients with poor prognosis for systemic treatment (ClinicalTrials.gov identifier: NCT02901301).© Copyright: Yonsei University College of Medicine 2023.

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