Application of Cell-free DNA Analysis to Cancer Treatment

Corcoran, Ryan B.; Chabner, Bruce A.

doi:10.1056/nejmra1706174

Cited by 733 publications

(594 citation statements)

References 62 publications

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“…6 ccfDNA is one tool capable to represent at once every metastasis and to follow them during the time showing clonal evolution of cancer driver genes which may play a major role in the therapy escaping mechanism. 11 Previous studies indicate the amount of cfDNA as a prognostic factor. 17 Results presented here confirmed the prognostic role of cfDNA plasma level demonstrating that the detection of more than 27.2 ng (per 4 mL of plasma) allowed to stratify the patient's' overall survival.…”

Section: Discussionmentioning

confidence: 99%

“…The usefulness of cfDNA sequencing for identifying markers of disease progression is well established. 11,12 The European Medicines Agency (EMA) in 2015, and the Food and Drug Administration (FDA) in 2016 approved the use of cfDNA extracted from plasma for detection of EGFR mutations in non-small-cell lung cancer (NSCLC) patients without tissue available or after resistance to a first or second generation TKIs. 13 Notwithstanding the potential game-changing role of cfDNA assessments, its clinical utility is still under investigation and translational trials focused on the impact of its integration in the therapeutic algorithm are pivotal and of great impact to further develop precision medicine approaches.…”

Section: Introductionmentioning

confidence: 99%

“…Among patients with distant metastatic disease, the visceral metastasis was the most common metastatic site (32.4%) followed by coexistence of both bone and visceral (19.1%) (Table 1). The median follow-up of OS for all patients was 3.2 months (range[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. At the time of survival analysis, death by tumor progression occurred in 12/68 (17.6%) patients.…”

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confidence: 99%

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Two‐point‐NGS analysis of cancer genes in cell‐free DNA of metastatic cancer patients

et al. 2020

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Background Although the efficacy of molecularly target agents in vitro, their use in routine setting is limited mainly to the use of anti‐HER2 and antiEGFR agents in vivo. Moreover, core biopsy of a single cancer site may not be representative of the whole expanding clones and cancer molecular profile at relapse may differ with respect to the primary tumor. Methods We assessed the status of a large panel of cancer driver genes by cell‐free DNA (cfDNA) analysis in a cohort of 68 patients with 13 different solid tumors at disease progression. Whenever possible, a second cfDNA analysis was performed after a mean of 2.5 months, in order to confirm the identified clone(s) and to check the correlation with clinical evolution. Results The approach was able to identify clones plausibly involved in the disease progression mechanism in about 65% of cases. A mean of 1.4 mutated genes (range 1‐3) for each tumor was found. Point mutations in TP53, PIK3CA, and KRAS and copy number variations in FGFR3 were the gene alterations more commonly observed, with a rate of 48%, 20%, 16%, and 20%, respectively. Two‐points‐Next‐Generation Sequencing (NGS) analysis demonstrated statistically significant correlation between allele frequency variation and clinical outcome (P = .026). Conclusions Irrespective of the primary tumor mutational burden, few mutated genes are present at disease progression. Clinical outcome is consistent with variation of allele frequency of specific clones indicating that cfDNA two‐point‐NGS analysis of cancer driver genes could be an efficacy tool for precision oncology.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Two‐point‐NGS analysis of cancer genes in cell‐free DNA of metastatic cancer patients

et al. 2020

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“…17 Studies have shown a high degree of concordance of cfDNA analysis with tissue testing. 18 In the IFUM study, the mutation status of EGFR in blood and matched tissues of 652 patients with NSCLC cancer was detected by ARMS. The concordance, sensitivity, and specificity of EGFR mutation detection in blood and tissue samples were 94.3%, 65.7%, and 99.8%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Detection of plasmaEGFRmutations for personalized treatment of lung cancer patients without pathologic diagnosis

et al. 2020

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Introduction Next‐generation sequencing (NGS) and digital polymerase chain reaction (PCR) based platforms have been used to detect EGFR mutations in plasma circulating tumor DNA (ctDNA) with high accuracy. Generally, molecular testing is performed after histopathological analysis. However, many patients with suspected advanced nonsmall cell lung cancer are unable to undergo biopsy thus forgoing potential treatment with highly effective tyrosine kinase inhibitors (TKIs) in patients with sensitizing EGFR mutations. We examined the utility of ctDNA testing to detect EGFR mutations in patients' plasma, where tissue biopsy is not feasible. Methods We conducted a single‐center, prospective study of 30 Chinese patients with suspected advanced lung cancer, who were unable to undergo a biopsy for initial diagnosis due to comorbidities or poor performance status. Patients with plasma EGFR sensitizing mutations were treated with first‐generation EGFR TKIs. Results Twenty of 30 patients enrolled had sensitizing EGFR mutations in ctDNA and were started on EGFR TKIs. After a median follow‐up of 12 months, median progression‐free survival (PFS) was 10 months and median overall survival (OS) was not reached. The median OS for the 10 untreated patients was 3 months. Conclusions In our study, patients with plasma EGFR mutations treated with TKIs showed disease control rate (DCR) and PFS similar to historical controls that were treated based on tissue testing. This is the first prospective study showing that ctDNA genotyping provides a feasible diagnostic approach for frail lung cancer patients who are unable to undergo biopsy, which subsequently leads to EGFR‐targeted therapy, and improved outcomes in this subgroup of patients.

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“…[1][2][3][4][5][6] Potential applications of ctDNA are far-reaching, including cancer screening and diagnosis, noninvasive tumor profiling and identification of targetable somatic variants, pretreatment risk stratification, tracking of treatment response, detection of minimal residual disease, and surveillance for relapse. [7][8][9] For children with cancer, these applications could reduce exposure to anesthesia and radiation by decreasing reliance on surgical biopsies and serial imaging for diagnosis, staging, and disease monitoring. Furthermore, the opportunity to analyze serial liquid biopsy samples could vastly increase our understanding of tumor evolution and genomic patterns of treatment resistance in children with relapsed cancer.…”

Section: Introductionmentioning

confidence: 99%

Assessment of circulating tumor DNA in pediatric solid tumors: The promise of liquid biopsies

Abbou

Shulman

DuBois

et al. 2019

Pediatric Blood & Cancer

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Circulating tumor DNA (ctDNA) can be detected in the blood and body fluids of patients using ultra-sensitive technologies which have the potential to improve cancer diagnosis, risk stratification, non-invasive tumor profiling, and tracking of treatment response and disease recurrence. As we begin to apply “liquid biopsy” strategies in children with cancer, it is important to tailor our efforts to the unique genomic features of these tumors and address the technical and logistical challenges of integrating biomarker testing. This article reviews the literature demonstrating the feasibility of applying liquid biopsy to pediatric solid malignancies and suggests new directions for future studies.

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Application of Cell-free DNA Analysis to Cancer Treatment

Cited by 733 publications

References 62 publications

Two‐point‐NGS analysis of cancer genes in cell‐free DNA of metastatic cancer patients

Two‐point‐NGS analysis of cancer genes in cell‐free DNA of metastatic cancer patients

Detection of plasmaEGFRmutations for personalized treatment of lung cancer patients without pathologic diagnosis

Assessment of circulating tumor DNA in pediatric solid tumors: The promise of liquid biopsies

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