Circulating tumor DNA in advanced solid tumors: Clinical relevance and future directions

Cheng, Michael L.; Pectasides, Eirini; Hanna, Glenn J.; Parsons, Heather A.; Choudhury, Atish D.; Oxnard, Geoffrey R.

doi:10.3322/caac.21650

Cited by 128 publications

(114 citation statements)

References 150 publications

(207 reference statements)

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“…It’s groundbreaking that, not like any other conventional factors for recurrence risk stratification (high versus low), detection of ctDNA is the reflection of MRD itself (yes versus no). As the ctDNA measuring technology continues to evolve and manifest its significance [ 19 ], the real-time detection of MRD using ctDNA may help guide the precise administration of ACT, evaluation of ACT efficacy, and monitoring of disease recurrence. The potential paradigm-changing clinical applications of this ctDNA-guided strategy can be summarized as follows.…”

Section: Discussionmentioning

confidence: 99%

Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer

et al. 2021

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Background Precise methods for postoperative risk stratification to guide the administration of adjuvant chemotherapy (ACT) in localized colorectal cancer (CRC) are still lacking. Here, we conducted a prospective, observational, and multicenter study to investigate the utility of circulating tumor DNA (ctDNA) in predicting the recurrence risk. Methods From September 2017 to March 2020, 276 patients with stage II/III CRC were prospectively recruited in this study and 240 evaluable patients were retained for analysis, of which 1290 serial plasma samples were collected. Somatic variants in both the primary tumor and plasma were detected via a targeted sequencing panel of 425 cancer-related genes. Patients were treated and followed up per standard of care. Results Preoperatively, ctDNA was detectable in 154 of 240 patients (64.2%). At day 3–7 postoperation, ctDNA positivity was associated with remarkably high recurrence risk (hazard ratio [HR], 10.98; 95%CI, 5.31–22.72; P < 0.001). ctDNA clearance and recurrence-free status was achieved in 5 out of 17 ctDNA-positive patients who were subjected to ACT. Likewise, at the first sampling point after ACT, ctDNA-positive patients were 12 times more likely to experience recurrence (HR, 12.76; 95%CI, 5.39–30.19; P < 0.001). During surveillance after definitive therapy, ctDNA positivity was also associated with extremely high recurrence risk (HR, 32.02; 95%CI, 10.79–95.08; P < 0.001). In all multivariate analyses, ctDNA positivity remained the most significant and independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors. Serial ctDNA analyses identified recurrence with an overall accuracy of 92.0% and could detect disease recurrence ahead of radiological imaging with a mean lead time of 5.01 months. Conclusions Postoperative serial ctDNA detection predicted high relapse risk and identified disease recurrence ahead of radiological imaging in patients with stage II/III CRC. ctDNA may be used to guide the decision-making in postsurgical management.

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Section: Discussionmentioning

confidence: 99%

Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer

et al. 2021

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“…Although several studies have reported associations between each somatic mutation and the clinicopathological characteristics of EC [8] , [9] , [10] , few studies have focused on a comprehensive somatic mutation analysis [6] . More recently, plasma circulating tumor DNA (ctDNA) has been reported to be effective in early diagnosis and therapeutic monitoring in human cancers [11] . As blood samples are easy to obtain multiple times on demand in a non-invasive method compared with standard tumor biopsy, somatic mutations become increasingly important as clinically useful biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Clinical relevance of oncogenic driver mutations identified in endometrial carcinoma

Watanabe

Nanamiya

Kojima

et al. 2021

Translational Oncology

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“…Therapies at baseline in advanced NSCLC rely on many different factors ( Figure 2 ). A LB at diagnosis in late stage NSCLC was initially performed to detect genomic alterations in EGFR [ 20 , 21 , 34 , 35 ]. Notably activating EGFR mutations can be detected in LB from NSCLC, which is now performed in the daily practice of many clinical centers [ 36 , 37 , 38 ].…”

Section: Ngs With Blood Samples At Diagnosis Of Advanced Non-small Cell Lung Carcinomamentioning

confidence: 99%

Next-Generation Sequencing with Liquid Biopsies from Treatment-Naïve Non-Small Cell Lung Carcinoma Patients

Hofman

2021

Cancers

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Recently, the liquid biopsy (LB), a non-invasive and easy to repeat approach, has started to compete with the tissue biopsy (TB) for detection of targets for administration of therapeutic strategies for patients with advanced stages of lung cancer at tumor progression. A LB at diagnosis of late stage non-small cell lung carcinoma (NSCLC) is also being performed. It may be asked if a LB can be complementary (according to the clinical presentation or systematics) or even an alternative to a TB for treatment-naïve advanced NSCLC patients. Nucleic acid analysis with a TB by next-generation sequencing (NGS) is gradually replacing targeted sequencing methods for assessment of genomic alterations in lung cancer patients with tumor progression, but also at baseline. However, LB is still not often used in daily practice for NGS. This review addresses different aspects relating to the use of LB for NGS at diagnosis in advanced NSCLC, including its advantages and limitations.

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Circulating tumor DNA in advanced solid tumors: Clinical relevance and future directions

Cited by 128 publications

References 150 publications

Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer

Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer

Clinical relevance of oncogenic driver mutations identified in endometrial carcinoma

Next-Generation Sequencing with Liquid Biopsies from Treatment-Naïve Non-Small Cell Lung Carcinoma Patients

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