Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients

被引：265

作者：

Vidal, J. ^{[1
,2
]}

Muinelo, L. ^{[3
]}

Dalmases, A. ^{[4
]}

Jones, F. ^{[5
]}

Edelstein, D. ^{[5
]}

Iglesias, M. ^{[1
,4
]}

Orrillo, M. ^{[2
]}

Abalo, A. ^{[3
]}

Rodriguez, C. ^{[3
]}

Brozos, E. ^{[3
]}

Vidal, Y. ^{[3
]}

Candamio, S. ^{[3
]}

Vazquez, F. ^{[3
]}

Ruiz, J. ^{[3
]}

Guix, M. ^{[2
]}

Visa, L. ^{[2
]}

Sikri, V. ^{[5
]}

Albanell, J. ^{[1
,2
,6
]}

Bellosillo, B. ^{[2
,3
]}

Lopez, R. ^{[3
]}

Montagut, C. ^{[1
,2
]}

机构：

[1] FIMIM Hosp Mar, Canc Res Program, Barcelona, Spain

[2] Hosp Mar, Med Oncol Dept, Passeig Maritim 25-29, Barcelona 08003, Spain

[3] Complexo Hosp Univ Santiago de Compostela SERGAS, Hlth Res Inst Santiago IDIS, Liquid Biopsy Anal Unit, Traslat Med Oncol Grp Oncomet, Santiago De Compostela, Spain

[4] Hosp Mar, Pathol Dept, Barcelona, Spain

[5] Sysmex Inost Inc, Mundelein, IL USA

[6] Univ Pompeu Fabra, Barcelona, Spain

来源：

ANNALS OF ONCOLOGY | 2017年 / 28卷 / 06期

关键词：

ctDNA; RAS mutations; colorectal cancer; liquid biopsy; tumor dynamics; heterogeneity; CIRCULATING TUMOR DNA; KRAS MUTATIONS; EGFR BLOCKADE; RESISTANCE; EMERGENCE;

D O I：

10.1093/annonc/mdx125

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: RAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct) DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice. Patients and methods: RAS mutational status in plasma was evaluated in mCRC patients by OncoBEAMTM RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated. RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients. Results: Analysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment. Conclusion: The high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAMTM as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAMTM is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments.

引用

页码：1325 / 1332

页数：8

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