Clinical Application of Genomic Profiling With Circulating Tumor DNA for Management of Advanced Non–Small-cell Lung Cancer in Asia

With the rapid development of targeted therapies for the treatment of cancer, methods for predicting response and outcome are in high demand. Non-small cell lung cancer driven by genomic rearrangements of the anaplastic lymphoma kinase (ALK) gene can be successfully treated with ALK-targeted therapy. Unfortunately, a subset of patients does not respond, and all patients ultimately acquire resistance, highlighting the need for better clinical tools to manage these patients. Here, we performed targeted next-generation sequencing on plasma circulating tumor DNA (ctDNA) from 24 patients to assess the clinical utility of ctDNA genomic profiling. Patients with detectable ctDNA prior to treatment had worse progression-free survival (PFS) than those without (median 8.7 vs. 15.2 months, p = 0.028). In addition, the presence of ctDNA within two months after treatment initiation predicted inferior PFS (median 4.6 vs. 14.5 months, p = 0.028). Longitudinal monitoring of ctDNA with droplet digital PCR during treatment reflected the radiological response and revealed potential acquired resistance mutations. Interestingly, an increase in the ctDNA concentration was evident prior to the determination of progressive disease by conventional radiological imaging, with a median lead time of 69 days (range 30–113). Genomic profiling of ctDNA is a promising tool for predicting outcome and monitoring response to targeted therapy.

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Hybrid Capture–Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Non–Small Cell Lung Cancer

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2018.10.008 ◽

2019 ◽

Vol 14 (2) ◽

pp. 255-264 ◽

Cited By ~ 15

Author(s):

Alexa B. Schrock ◽

Allison Welsh ◽

Jon H. Chung ◽

Dean Pavlick ◽

Eric H. Bernicker ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Circulating Tumor Dna ◽

Small Cell ◽

Genomic Profiling ◽

Small Cell Lung ◽

Hybrid Capture ◽

Tumor Dna

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Pan-cancer circulating tumor DNA detection in over 10,000 Chinese patients

Nature Communications ◽

10.1038/s41467-020-20162-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yongliang Zhang ◽

Yu Yao ◽

Yaping Xu ◽

Lifeng Li ◽

Yan Gong ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Circulating Tumor Dna ◽

Small Cell ◽

Chinese Patients ◽

Plasma Samples ◽

Small Cell Lung ◽

Pan Cancer ◽

Tumor Dna

AbstractCirculating tumor DNA (ctDNA) provides a noninvasive approach to elucidate a patient’s genomic landscape and actionable information. Here, we design a ctDNA-based study of over 10,000 pan-cancer Chinese patients. Using parallel sequencing between plasma and white blood cells, 14% of plasma cell-free DNA samples contain clonal hematopoiesis (CH) variants, for which detectability increases with age. After eliminating CH variants, ctDNA is detected in 73.5% of plasma samples, with small cell lung cancer (91.1%) and prostate cancer (87.9%) showing the highest detectability. The landscape of putative driver genes revealed by ctDNA profiling is similar to that in a tissue-based database (R2 = 0.87, p < 0.001) but also shows some discrepancies, such as higher EGFR (44.8% versus 25.2%) and lower KRAS (6.8% versus 27.2%) frequencies in non-small cell lung cancer, and a higher TP53 frequency in hepatocellular carcinoma (53.1% versus 28.6%). Up to 41.2% of plasma samples harbor drug-sensitive alterations. These findings may be helpful for identifying therapeutic targets and combined treatment strategies.

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