Combined Analysis of Concordance between Liquid and Tumor Tissue Biopsies for <i>RAS</i> Mutations in Colorectal Cancer with a Single Metastasis Site: The METABEAM Study

Kagawa, Yutaka; Élez, Elena; Garcı́a-Foncillas, Jesús; Bando, Hideaki; Taniguchi, Hiroya; Vivancos, Ana; Akagi, Kiwamu; García, Ariadna; Denda, Tadamichi; Ros, Javier; Nishina, Tomohiro; Baraibar, Iosune; Ciardiello, Davide; Oki, Eiji; Kudo, Toshihiro; Kato, Takeshi; Yamanaka, T.; Tabernero, Josep; Yoshino, Takayuki

doi:10.1158/1078-0432.ccr-20-3677

Cited by 52 publications

(53 citation statements)

References 20 publications

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“…TriMeth was particularly sensitive towards patients with liver recurrence (100%), while it was less sensitive towards lung recurrences (76.5%) (P Z 0.0432). The observations are consistent with other ctDNA studies [33,34] and may be related to the high radiographic resolution in the lungs, i.e. lung lesions can be detected while very small, and potentially too small in some cases to shed enough tumour DNA for detection by ctDNA analysis.…”

Section: Discussionsupporting

confidence: 91%

Tumour-agnostic circulating tumour DNA analysis for improved recurrence surveillance after resection of colorectal liver metastases: A prospective cohort study

Øgaard

Reinert

Henriksen

et al. 2022

European Journal of Cancer

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Nearly 50% of patients recur within two years after curatively intended resection of colorectal cancer liver metastasis (CRLM). The optimal surveillance strategy is unknown due to the lack of evidence. Here, we explored the potential for improving postoperative CRLM surveillance by performing serial circulating tumour DNA (ctDNA) assessments parallel to standard-of-care surveillance. Experimental design: 499 prospectively collected serial plasma samples from 96 patients undergoing CRLM resection were analysed using the tumour-agnostic methylation multiplex droplet-digital PCR test 'TriMeth'. Results: Patients with ctDNA postoperatively or post adjuvant chemotherapy experienced a significant lower recurrence-free survival than patients without ctDNA (hazard ratio (HR)

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Section: Discussionsupporting

confidence: 91%

Tumour-agnostic circulating tumour DNA analysis for improved recurrence surveillance after resection of colorectal liver metastases: A prospective cohort study

Øgaard

Reinert

Henriksen

et al. 2022

European Journal of Cancer

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“…21,22 Another possibility that may cause the above discordant status between the ctDNA and CEA levels is the intrinsic biological characteristics between metastatic sites. [23][24][25] A significant association was observed between the ctDNA level and liver metastasis, whereas no association was observed in patients without liver metastasis. Similarly, Vidal et al reported that the site of peritoneal and lung metastases and the mucinous histology of the tumor negatively affect the detection of ctDNA.…”

Section: Discussionmentioning

confidence: 92%

Correlation between circulating tumor DNA and carcinoembryonic antigen levels in patients with metastatic colorectal cancer

et al. 2021

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Background: Circulating tumor DNA (ctDNA) is a biomarker with potential to reflect comprehensive genomic information and overcome intratumor heterogeneity. In contrast, carcinoembryonic antigen (CEA) is a conventional tumor marker for predicting recurrence, survival, and chemotherapeutic efficacy in patients with metastatic colorectal cancer (mCRC). However, the relationship between them remains unclear. Here, the relationship between plasma ctDNA and CEA levels was evaluated to clarify the advantages and disadvantages of their clinical use. Methods:A total of 110 patients with mCRC underwent chemotherapy were enrolled. Amplicon-based plasma genomic profiling of 14 genes that are commonly mutated in CRC by next-generation sequencing was compared to the CEA level and tumor diameter using Spearman's correlation coefficient. Results:The overall concordance rate between the ctDNA and CEA levels was 75.5% (83/110). The correlation coefficient between the ctDNA and CEA levels was lower in the group of patients without liver and lymph node metastases (r = 0.18, p = 0.44) than in the group of patients with liver metastasis (r = 0.48, p < 0.0001). Although the correlation coefficients between tumor diameter and both ctDNA and CEA levels were high in the group of patients with liver metastasis, only the CEA correlation coefficient was maintained in the group of patients without liver and lymph node metastases (r = 0.53, p = 0.01). The characteristics that influenced discordance were liver metastasis and the sum of tumor diameter. Conclusions:The status of ctDNA and CEA may not be consistent in patients with mCRC without liver metastasis or with a low tumor volume; both results should be considered when deciding a treatment strategy.

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“…Thus, plasma-based MSI assessment may be less likely to detect MSI-H in patients with tumor characteristics, which likely results in a low ctDNA fraction, such as low tumor burden, no liver metastasis, isolated lung metastases, and specific cancer types (eg, primary brain tumors and renal cell carcinoma). [20][21][22][23][24][25] Conversely, some patients had tissue-negative but ctDNApositive MSI-H tumors. The NGS-based MSI assessment supposedly has higher performance in the evaluation of MSI status in non-CRCs compared with PCR-based testing developed primarily for CRC.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical Validity of Plasma-Based Genotyping for Microsatellite Instability Assessment in Advanced GI Cancers: SCRUM-Japan GOZILA Substudy

Nakamura

Okamoto

Denda

et al. 2022

JCO Precision Oncology

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PURPOSE Circulating tumor DNA (ctDNA) genotyping may guide targeted therapy for patients with advanced GI cancers. However, no studies have validated ctDNA genotyping for microsatellite instability (MSI) assessment in comparison with a tissue-based standard. PATIENTS AND METHODS The performance of plasma-based MSI assessment using Guardant360, a next-generation sequencing–based ctDNA assay, was compared with that of tissue-based MSI assessment using a validated polymerase chain reaction–based method in patients with advanced GI cancers enrolled in GOZILA study, a nationwide ctDNA profiling study. The primary end points were overall percent agreement, positive percent agreement (PPA), and negative percent agreement. The efficacy of immune checkpoint inhibitor therapy was also evaluated. RESULTS In 658 patients with advanced GI cancers who underwent both plasma and tissue testing for MSI, the overall percent agreement, PPA, and negative percent agreement were 98.2% (95% CI, 96.8 to 99.1), 71.4% (95% CI, 47.8 to 88.7), and 99.1% (95% CI, 98.0 to 99.7), respectively. In patients whose plasma samples had a ctDNA fraction ≥ 1.0%, the PPA was 100.0% (15/15; 95% CI, 78.2 to 100.0). Three patients with MSI-high (MSI-H) tumors detected only by ctDNA genotyping achieved clinical benefits after receiving anti–programmed cell death 1 therapy with the progression-free survival ranging from 4.3 to 16.7 months. One patient with an aggressive cancer of an unknown primary site benefited from pembrolizumab after rapid detection of MSI-H by ctDNA genotyping. CONCLUSION ctDNA genotyping was able to detect MSI with high concordance to validated tissue-based MSI testing, especially in patients with tumors that have sufficient ctDNA shedding. Furthermore, ctDNA genotyping enabled identification of patients with MSI-H tumors who benefited from immune checkpoint inhibitor treatment.

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Combined Analysis of Concordance between Liquid and Tumor Tissue Biopsies for RAS Mutations in Colorectal Cancer with a Single Metastasis Site: The METABEAM Study

Cited by 52 publications

References 20 publications

Tumour-agnostic circulating tumour DNA analysis for improved recurrence surveillance after resection of colorectal liver metastases: A prospective cohort study

Tumour-agnostic circulating tumour DNA analysis for improved recurrence surveillance after resection of colorectal liver metastases: A prospective cohort study

Correlation between circulating tumor DNA and carcinoembryonic antigen levels in patients with metastatic colorectal cancer

Clinical Validity of Plasma-Based Genotyping for Microsatellite Instability Assessment in Advanced GI Cancers: SCRUM-Japan GOZILA Substudy

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