Circulating tumor DNA tracking in patients with pancreatic cancer using next-generation sequencing

Herreros-Villanueva, Marta; Bujanda, Luís; Ruiz-Rebollo, Lourdes; Torremocha, Rosana; Ramos, Ricardo; Martín, Rubén; Artigas, María Consuelo

doi:10.1016/j.gastrohep.2021.12.011

Cited by 6 publications

(4 citation statements)

References 32 publications

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“…Recently, liquid biopsy testing of blood and other body-fluid specimens has been developed as a new analytic method [ 27 , 28 , 29 ], and the F-One Liquid CDx Cancer Genome Profile [ 30 ] test for blood specimens is now covered by insurance programs in Japan. Although the liquid biopsy test is very useful for pancreaticobiliary cancers, for which the collection of samples for genetic testing is difficult, its sensitivity for detecting KRAS abnormalities is lower than that of the test using tumor tissue specimens [ 31 ], and tumor tissue specimens are superior in terms of certainty.…”

Section: Results Of Genomic Medicine Using Eus-ta In Pancreaticobilia...mentioning

confidence: 99%

Endoscopic Ultrasound-Guided Tissue Acquisition of Pancreaticobiliary Cancer Aiming for a Comprehensive Genome Profile

Hijioka¹,

Nagashio²,

Maruki³

et al. 2023

Diagnostics

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In recent years, cancer genomic medicine centered on comprehensive genome profile (CGP) analysis has become widely used in the field of pancreatic cancer. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has played an important role in pancreatic cancer, and recently, more EUS-TA tissue samples are considered for CGP analysis. Differences exist between the Oncoguide NCC Oncopanel System and Foundation One CDx Cancer Genome Profile, which are CGP tests approved by insurance programs in Japan, including the analysis criteria, optimal needle selection for meeting these criteria, and puncture target. It is important to understand not only the specimen collection factors, but also the specimen processing factors that can increase the success rate of CGP testing. Furthermore, cancer genome medicine is expected to enter an era of increasing turbulence in the future, and endoscopists need to respond flexibly to these changes. Herein, we review the current status of cancer genome medicine in pancreatic and biliary tract cancers and cancer gene panel testing using EUS-TA.

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Section: Results Of Genomic Medicine Using Eus-ta In Pancreaticobilia...mentioning

confidence: 99%

Endoscopic Ultrasound-Guided Tissue Acquisition of Pancreaticobiliary Cancer Aiming for a Comprehensive Genome Profile

Hijioka¹,

Nagashio²,

Maruki³

et al. 2023

Diagnostics

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“…Liquid biopsy refers to the non-invasive analysis of tumor-derived material, such ctDNA, circulating tumor cells (CTCs), RNA, and exosomes, present in bodily fluids like blood, urine, or cerebrospinal fluid. This approach offers a dynamic snapshot of cancer’s genetic landscape, enabling real-time tumor evolution assessment, resistance mechanisms, and treatment efficacy) ( Lin et al, 2021 ; Pesta et al, 2022 ; Herreros-Villanueva et al, 2022 ; Xia et al, 2023 ). Table 3 summarizes how liquid biopsies and NGS are transforming Oncology care.…”

Section: Next-generation Sequencing: a New Standard In Cancer Managementmentioning

confidence: 99%

Next-generation sequencing impact on cancer care: applications, challenges, and future directions

Zalis,

Viana Veloso,

Aguiar Jr.

et al. 2024

Front. Genet.

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Fundamentally precision oncology illustrates the path in which molecular profiling of tumors can illuminate their biological behavior, diversity, and likely outcomes by identifying distinct genetic mutations, protein levels, and other biomarkers that underpin cancer progression. Next-generation sequencing became an indispensable diagnostic tool for diagnosis and treatment guidance in current clinical practice. Nowadays, tissue analysis benefits from further support through methods like comprehensive genomic profiling and liquid biopsies. However, precision medicine in the field of oncology presents specific hurdles, such as the cost-benefit balance and widespread accessibility, particularly in countries with low- and middle-income. A key issue is how to effectively extend next-generation sequencing to all cancer patients, thus empowering treatment decision-making. Concerns also extend to the quality and preservation of tissue samples, as well as the evaluation of health technologies. Moreover, as technology advances, novel next-generation sequencing assessments are being developed, including the study of Fragmentomics. Therefore, our objective was to delineate the primary uses of next-generation sequencing, discussing its’ applications, limitations, and prospective paths forward in Oncology.

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“…Next Generation Sequencing (NGS) can generate valuable high-throughput genetic information when evaluating ctDNA. [ 17 ]…”

Section: Introductionmentioning

confidence: 99%

High somatic mutations in circulating tumor DNA predict response of metastatic pancreatic ductal adenocarcinoma to first-line nab-paclitaxel plus S-1: prospective study

Huang,

Lv,

Guan

et al. 2024

J Transl Med

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Aims We previously showed that the nab-paclitaxel plus S-1 (NPS) regimen had promising effects against metastatic pancreatic ducal adenocarcinoma (mPDAC), whose efficacy however could not be precisely predicted by routine biomarkers. This prospective study aimed to investigate the values of mutations in circulating tumor DNA (ctDNA) and their dynamic changes in predicting response of mPDAC to NPS chemotherapy. Methods Paired tumor tissue and blood samples were prospectively collected from patients with mPDAC receiving first-line NPS chemotherapy, and underwent next-generation sequencing with genomic profiling of 425 genes for ctDNA. High mutation allelic frequency (MAF) was defined as ≥ 30% and ≥ 5% in tumor tissue and blood, respectively. Kappa statistics were used to assess agreement between mutant genes in tumor and ctDNA. Associations of mutations in ctDNA and their dynamic changes with tumor response, overall survival (OS), and progression-free survival (PFS) were assessed using the Kaplan–Meier method, multivariable-adjusted Cox proportional hazards regression, and longitudinal data analysis. Results 147 blood samples and 43 paired tumor specimens from 43 patients with mPDAC were sequenced. The most common driver genes with high MAF were KRAS (tumor, 35%; ctDNA, 37%) and TP53 (tumor, 37%; ctDNA, 33%). Mutation rates of KRAS and TP53 in ctDNA were significantly higher in patients with liver metastasis, with baseline CA19-9 ≥ 2000 U/mL, and/or without an early CA19-9 response. κ values for the 5 most commonly mutated genes between tumor and ctDNA ranged from 0.48 to 0.76. MAFs of the genes mostly decreased sequentially during subsequent measurements, which significantly correlated with objective response, with an increase indicating cancer progression. High mutations of KRAS and ARID1A in both tumor and ctDNA, and of TP53, CDKN2A, and SMAD4 in ctDNA but not in tumor were significantly associated with shorter survival. When predicting 6-month OS, AUCs for the 5 most commonly mutated genes in ctDNA ranged from 0.59 to 0.84, larger than for genes in tumor (0.56 to 0.71) and for clinicopathologic characteristics (0.51 to 0.68). Repeated measurements of mutations in ctDNA significantly differentiated survival and tumor response. Among the 31 patients with ≥ 2 ctDNA tests, longitudinal analysis of changes in gene MAF showed that ctDNA progression was 60 and 58 days ahead of radiologic and CA19-9 progression for 48% and 42% of the patients, respectively. Conclusions High mutations of multiple driving genes in ctDNA and their dynamic changes could effectively predict response of mPDAC to NPS chemotherapy, with promising reliable predictive performance superior to routine clinicopathologic parameters. Inspiringly, longitudinal ctDNA tracking could predict disease progression about 2 months ahead of radiologic or CA19-9 evaluations, with the potential to precisely devise individualized therapeutic strategies for mPDAC.

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Circulating tumor DNA tracking in patients with pancreatic cancer using next-generation sequencing

Cited by 6 publications

References 32 publications

Endoscopic Ultrasound-Guided Tissue Acquisition of Pancreaticobiliary Cancer Aiming for a Comprehensive Genome Profile

Endoscopic Ultrasound-Guided Tissue Acquisition of Pancreaticobiliary Cancer Aiming for a Comprehensive Genome Profile

Next-generation sequencing impact on cancer care: applications, challenges, and future directions

High somatic mutations in circulating tumor DNA predict response of metastatic pancreatic ductal adenocarcinoma to first-line nab-paclitaxel plus S-1: prospective study

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