Dataset Information

White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer.

ABSTRACT: Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.

SUBMITTER: Leal A

PROVIDER: S-EPMC6985115 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer.

Leal Alessandro A van Grieken Nicole C T NCT Palsgrove Doreen N DN Phallen Jillian J Medina Jamie E JE Hruban Carolyn C Broeckaert Mark A M MAM Anagnostou Valsamo V Adleff Vilmos V Bruhm Daniel C DC Canzoniero Jenna V JV Fiksel Jacob J Nordsmark Marianne M Warmerdam Fabienne A R M FARM Verheul Henk M W HMW van Spronsen Dick Johan DJ Beerepoot Laurens V LV Geenen Maud M MM Portielje Johanneke E A JEA Jansen Edwin P M EPM van Sandick Johanna J Meershoek-Klein Kranenbarg Elma E van Laarhoven Hanneke W M HWM van der Peet Donald L DL van de Velde Cornelis J H CJH Verheij Marcel M Fijneman Remond R Scharpf Robert B RB Meijer Gerrit A GA Cats Annemieke A Velculescu Victor E VE

Nature communications 20200127 1

Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized c ...[more]

PMID: 31988276

Similar Datasets

Project description:ImportanceLeptomeningeal disease (LMD) is a devastating complication of cancer that is frequently underdiagnosed owing to the low sensitivity of cerebrospinal fluid (CSF) cytologic assessment, the current benchmark diagnostic method. Improving diagnostic sensitivity may lead to improved treatment decisions.ObjectiveTo assess whether cell-free DNA (cfDNA) analysis of CSF may be used to diagnose LMD more accurately than cytologic analysis.Design, setting, and participantsThis diagnostic study conducted in a neuro-oncology clinic at 2 large, tertiary medical centers assessed the use of genomic sequencing of CSF samples obtained from 30 patients with suspected or confirmed LMD from 2015 through 2018 to identify tumor-derived cfDNA. From the same CSF samples, cytologic analyses were conducted, and the results of the 2 tests were compared. This study consisted of 2 patient populations: 22 patients with cytologically confirmed LMD without parenchymal tumors abutting their CSF and 8 patients with parenchymal brain metastases with no evidence of LMD. Patients were considered positive for the presence of LMD if previous CSF cytologic analysis was positive for malignant cells. The analysis was conducted from 2015 to 2018.Main outcomes and measuresThe primary outcome was the diagnostic accuracy of cfDNA analysis, defined as the number of tests that resulted in correct diagnoses out of the total number of tests assayed. Hypotheses were formed before data collection.ResultsIn total, 30 patients (23 women [77%]; median age, 51 years [range, 28-81 years]), primarily presenting with metastatic solid malignant neoplasms, participated in this study. For 48 follow-up samples from patients previously diagnosed via cytologic analysis as having LMD with no parenchymal tumor abutting CSF, cfDNA findings were accurate in the assessment of LMD in 45 samples (94%; 95% CI, 83%-99%), whereas cytologic analysis was accurate in 36 samples (75%; 95% CI, 60%-86%), a significant difference (P = .02). Of 43 LMD-positive samples, CSF cfDNA analysis was sensitive to LMD in 40 samples (93%; 95% CI, 81%-99%), and cytologic analysis was sensitive to LMD in 31 samples (72%; 95% CI, 56%-85%), a significant difference (P = .02). For 3 patients with parenchymal brain metastases abutting the CSF and no suspicion of LMD, cytologic findings were negative for LMD in all 3 patients, whereas cfDNA findings were positive in all 3 patients.Conclusions and relevanceThis diagnostic study found improved sensitivity and accuracy of cfDNA CSF testing vs cytologic assessment for diagnosing LMD with the exception of parenchymal tumors abutting CSF, suggesting improved ability to diagnosis LMD. Consideration of incorporating CSF cfDNA analysis into clinical care is warranted.

Project description:ObjectiveAlthough driver mutation status is crucial to targeted therapy decision-making in non-small cell lung cancer (NSCLC), due to unavailable or inadequate biopsies, there are still many patients with unknown mutation status. A promising way to solve this problem is liquid biopsy, such as cell-free DNA (cfDNA) in peripheral blood. Additionally, due to the little amount of cfDNA, detecting methods with high sensitivity, specificity and economy are required in clinical practice. Here, we explored the feasibility of Competitive Allele-Specific TaqMan® PCR (CastPCR) detecting driver mutations in cfDNA from plasma in lung adenocarcinoma patients.ResultsSensitivity, specificity, concordance, PPV and NPV of CastPCR detecting EGFR mutations in cfDNA was 56.4% (31/55), 94.2% (49/52), 74.8% (80/107), 91.2% (31/34) and 67.1% (49/73), respectively. Notably, specificity and PPV for p.T790M both reached 100.0%. For BRAF detection, it was 28.6% (2/7), 93.0% (93/100), 88.8% (95/107), 22.2% (2/9) and 94.9% (93/98), respectively.Materials and methodsPlasma specimens of 107 lung adenocarcinoma patients and their matched tumor formalin fixed paraffin embedded (FFPE) samples were analyzed. CastPCR was used to detect EGFR (c.2235_2249del, c.2236_2250del, c.2369C>T p.T790M, c.2573T>G p.L858R) and BRAF (c.1406G>C p.G469A, c.1799T>A p.V600E, c.1781A>G p.D594G) mutations. Mutation results of tumor tissue was set as gold standard, and the sensitivity, specificity, concordance, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each mutation.ConclusionsFor patients whose tumor tissue is unavailable or inadequate, EGFR mutation detection in cfDNA with CastPCR could be first choice. Mutation positive results may provide reference for further clinical medication. While negative results indicate that detection in tissue should be considered as the following step. In this way, tumor tissue could be economized to the maximum extent and the risk of repeated percutaneous transthoracic lung biopsy could also be lowered to the maximum extent. For BRAF detection in cfDNA, CastPCR is a specific method while the sensitivity needs further exploration.

Dataset Information

White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer.

Publications

White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets