IMBdx

コア技術

がんの早期発見

発表

게시물 목록
番号	年度	題名	雑誌	リンクを見る
11	2025	Multi-cancer detection: Is it appropriate for early detection of pancreatic cancer with plasma WGS - Multi-cancer detection: Is it appropriate for early detection of pancreatic cancer with plasma WGS	International Pancreatobiliary Meeting (IPBM)
10	2025	Detection of mutations in Homologous Recombination Repair (HRR) pathway genes using liquid biopsy in metastatic, castration-resistant prostate cancer (mCRPC) patients without tumor tissue availability Background: Blood samples (20ml of whole blood) were collected fr\|om 760 mCRPC patients in 10 Asian countries. Samples were collected once for each patient, regardless of treatment type or cycles as long as the patients were followed up for their mCRPC. All patients included were confirmed fr\|om each participating site to have no tissue available for genomic analysis. Blood samples were analyzed using a next-generation sequencing (NGS) based ctDNA assay, covering 15 genes in the HRR pathway (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L). Results: ctDNA testing for HRR gene mutations offers a practical tool for therapy selection in mCRPC patients. This non-invasive approach enables testing for patients who were not eligible for evaluation by tissue-based methods and can expand access to adequate targeted therapies. Detection of mutations in Homologous Recombination Repair (HRR) pathway genes using liquid biopsy in metastatic, castration-resistant prostate cancer (mCRPC) patients without tumor tissue availability リンクを見る	ASCO GU	リンクを見る
9	2024	Enhancing Lung Nodule Discrimination with a Novel cfDNA Test The Cancer Signature Ensemble (CSE) Approach Background Lung cancer is the leading cause of cancer-related deaths worldwide, with over 40% of patients diagnosed at stage IV, mainly due to difficulties in early detection. Although low-dose CT (LDCT) screening assists in early diagnosis, its high false-positive rate demands more accurate and minimally invasive biomarkers. In LDCT screening, about 5% of cases exhibit lung nodules with a 5% or higher risk of malignancy (Lung-RADS category 4); however, most are benign, with actual lung cancers representing only 0.6% of the total screened population. A diagnostic test is essential to avoid unnecessary invasive examinations and identify individuals at higher lung cancer risk. Other liquid biopsy approaches using restricted range of biomarkers have diagnostic limitations for early-stage cancers. Enhancing Lung Nodule Discrimination with a Novel cfDNA Test The Cancer Signature Ensemble (CSE) Approach	European Association for Cancer Research (EACR)
8	2024	Pairwise analysis of plasma cell-free DNA before and after paclitaxel plus ramucirumab treatment in patients with metastatic gastric cancer Abstract Background Plasma cell-free DNA (cfDNA) analysis has emerged as an appealing alternative to detect somatic mutations. This study compared cfDNA at baseline (baseline-cfDNA) and progressive disease (PD-cfDNA) and tumor tissue DNA (ttDNA) in patients with metastatic gastric cancer who underwent palliative second-line paclitaxel+ramucirumab treatment. Methods We conducted targeted sequencing of 106 cancer-related genes using germline DNA, baseline-cfDNA, and PD-cfDNA samples. The results were then compared with conventional cancer panel results using ttDNA. Results Of 76 consecutively enrolled patients who received paclitaxel+ramucirumab treatment, 46 patients (27 males; median age 57.5 [range, 32-73] years) with access to all three samples were analyzed along with their ttDNA data. A total of 138, 145, and 80 mutations were detected in baseline-cfDNA, PD-cfDNA, and ttDNA respectively. Combined analysis of baseline-cfDNA and ttDNA revealed that TP53 (56.5%) was the most frequently mutated gene, followed by CDH1 (26.1%), KRAS (21.7%), and APC (13.5%). For the top four genes, the sensitivity and positive predictive value of baseline-cfDNA compared with ttDNA were 71.8% and 51.9%, respectively. Compared with ttDNA alone, 32 patients (70.0%) benefited fr\|om baseline-cfDNA in detecting novel mutations. When combined with baseline-cfDNA and PD-cfDNA, novel mutations were discovered in 34 patients (73.9%). Of note, PD-cfDNA analysis detected 9 novel pathogenic mutations in TP53, APC, PIK3CA, CDH1, RNF43, CTNNB1, and BRCA2 genes in 8 patients (17.4%) after treatment. In baseline-cfDNA, patients with a circulating ttDNA fraction concentration at 110-160 bp of >4.3777 ng/µL had significantly shorter progression-free survival (PFS) (median 3.5 vs. 5.3 months, P=0.016). In addition, maximal variant allele frequency (VAF) values of >0.1045 (median 3.4 vs. 5.2 months, P=0.022) and the sum of VAF values of >0.2071 (median 3.4 vs. 5.2 months, P=0.028) were significantly associated with shorter PFS. In patients with TP53 mutations, those with TP53 VAF values of >0.1014 significantly had worse PFS (median 4.6 vs. 6.4 months, P=0.022). Conclusions Although cfDNA could not entirely take over the role of ttDNA, cfDNA analysis identified additional somatic mutations that were otherwise missed by ttDNA alone. Moreover, PD-cfDNA analysis detected novel pathogenic mutations that developed during treatment, implicating the clonal evolution of cancer. In addition, baseline cfDNA predicted PFS of patients receiving paclitaxel+ramucirumab therapy. Pairwise analysis of plasma cell-free DNA before and after paclitaxel plus ramucirumab treatment in patients with metastatic gastric cancer	KSMO
7	2024	High circulating tumor DNA (ctDNA) concentration was associated with shorter progression free survival in patients with metastatic breast cancer Abstract Background Metastatic breast cancer can be classified into different subtypes depending on hormone receptor (HR) and HER2 status. The subtype can change during tumor progression, and repeated biopsy is needed to deliver the most appropriate treatment every time a new lesion is found. It is not always possible to get a new biopsy fr\|om metastatic sites, and therefore liquid biopsy using circulating tumor DNA (ctDNA) is suggested as an alternative method to replace conventional biopsy. Methods We performed a prospective serial collection of 65 ctDNA samples fr\|om 17 patients with metastatic breast cancer (mBC) at Seoul National University Hospital fr\|om October 2020 to March 2022. We used IMBdx AlphaLiquid®100 method to detect the genetic changes and analyzed the correlation with clinical outcomes. Results Median age was 45 (range 32 – 62). Fifteen patients (88.2%) were relapsed mBC and most of the patients (14/17: 82.4%) were HR-positive and HER2-negative. Most of the patients had their ctDNA examined at baseline and at the time of maximal response and/or at progression. Fifteen patients (88.2%) received systemic therapy including hormone therapy, anti-HER2 therapy, and cytotoxic chemotherapy. Eight patients (47.1%) were on the first-line treatment for mBC, and 7 patients (41.2%) were on the second or later lines for mBC at the time of baseline sampling. The concentration of ctDNA and the sum of mutated allelic frequency was calculated for each sample. The ctDNA concentration ranged fr\|om 0.71 to 1386.00 ng/mL, and the median value was 5.37 ng/mL. We dichotomized these samples into two groups, with ctDNA concentration either higher or lower than the median value. Then we analyzed progression free survival (PFS) of each group. Patients with higher ctDNA concentration showed shorter PFS (7 mo. vs. not reached, p< 0.001). The sum of mutated allelic frequency ranged fr\|om 0.00% to 223.46% and the median value was 6.36%. Patients with higher mutated allelic frequency showed shorter PFS (6 mo. vs. 22 mo., p< 0.001). In addition, the PFS was significantly worse in patients who had mutated PIK3CA (5 mo vs. 22 mo, p< 0.001). The patients with mutated TP53 also showed shorter PFS (6 mo vs. 17 mo, p< 0.001) in univariate analysis. High estrogen receptor positivity in immunohistochemistry was correlated with lower mutated allelic frequency in ctDNA (p=0.003) but had no impact on the concentration of ctDNA (p=0.165). The concentration of ctDNA differed by metastatic sites. Patients with metastases to bones (p=0.007), liver (p< 0.001), soft tissue or lymph nodes (p=0.002) were more likely to have higher concentrations of ctDNA, while patients with brain metastases had significantly lower ctDNA concentration (p=0.006). When the sum of mutated allelic frequency of ctDNA and metastatic sites was analyzed, bone (p=0.001), liver (p< 0.001), and soft tissue or lymph node (p< 0.001) metastases had a positive correlation, while brain had negative correlation (p=0.017). Lung or pleural metastases had no significant correlation with ctDNA, neither concentration (p=0.271) nor mutated allelic frequency (p=0.965). Conclusion Patients with mBC with higher concentrations of ctDNA or higher mutated allelic frequency of ctDNA at baseline showed significantly shorter PFS. PIK3CAmt and TP53mt detected by liquid biopsy could be used as a poor prognostic biomarkers for mBC patients. High circulating tumor DNA (ctDNA) concentration was associated with shorter progression free survival in patients with metastatic breast cancer リンクを見る	AACR	リンクを見る