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Monitoring the Outcomes of Systemic Chemotherapy Including Immune Checkpoint Inhibitor for HER2-Positive Metastatic Gastric Cancer by Liquid Biopsy

 Seung-Hyun Jung  ;  Choong-Kun Lee  ;  Woo Sun Kwon  ;  Sujin Yun  ;  Minkyu Jung  ;  Hyo Song Kim  ;  Hyun Cheol Chung  ;  Yeun-Jun Chung  ;  Sun Young Rha 
 YONSEI MEDICAL JOURNAL, Vol.64(9) : 531-540, 2023-09 
Journal Title
Issue Date
Administration, Cutaneous ; Circulating Tumor DNA* / genetics ; Humans ; Immune Checkpoint Inhibitors ; Liquid Biopsy ; Stomach Neoplasms* / drug therapy ; Stomach Neoplasms* / genetics
Gastric cancer ; circulating tumor DNA ; immune checkpoint inhibitor ; liquid biopsy ; molecular tumor burden index
Purpose: For 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 methods: To 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.

Results: In 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.

Conclusion: Our 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).
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Woo Sun(권우선) ORCID logo https://orcid.org/0000-0003-0268-5624
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Lee, Choong-kun(이충근) ORCID logo https://orcid.org/0000-0001-5151-5096
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
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