Maximum allele frequency observed in plasma: A potential indicator of liquid biopsy sensitivity

Abstract

Personalized medicine is revolutionizing the diagnosis and treatment of cancer; however, for personalized medicine to be used accurately, patient information is essential to determine the appropriate diagnosis, prognosis and treatment. The detection of genomic mutations in liquid biopsy samples is a non-invasive method of characterizing the genotype of a tumor. However, next generation sequencing-based plasma genotyping only has a sensitivity of ~70%. Identifying potential indicators that may reflect the sensitivity of a liquid biopsy analysis could offer important information for its clinical application. In the present study, 47 pairs of patient-matched plasma and tumor tissue samples obtained from patients with advanced lung cancer were sequenced using a panel of 56 cancer-associated genes. The plasma maximum allele frequency (Max AF) was identified as a novel biomarker to indicate the sensitivity of plasma genotyping. Using the identified somatic mutations in patient tissue biopsy samples as a reference, the sensitivity of the corresponding patient plasma test was investigated. The by-variant sensitivity of the plasma test was 68.1%, with 79 matched and 37 missed genetic aberrances. The by-patient sensitivity was calculated as 83%. Patients with a high plasma Max AF value (>2.2%) demonstrated a higher concordance with the range of mutations identified in the patient-matched tissue samples. The Max AF observed in patient plasma samples was positively correlated with liquid biopsy sensitivity and could be used as a potential indicator of liquid biopsy sensitivity. Therefore, patients with a low plasma Max AF (≤2.2%) may need to undergo further tissue biopsy to allow personalized oncology treatment. In summary, the present study may offer a non-invasive testing method for a subgroup of patients with advanced lung cancer.

Efficacy of erlotinib in NSCLC harboring rare EGFR extracellular domain mutation (T263P) and common mutations: Case report and literature review

“…Unfortunately, it was not successful due to insufficient tissue in the supraclavicular lymph nodes. Interestingly, a prospective study observed only a 62.0% by variant concordance rate among primary tumor, metastatic lymph nodes, and plasma, suggesting that there is some deviation between the detection of plasma samples and the detection of primary tumor samples (5). Therefore, the genetic test results of the first blood sample do not reflect the actual mutation status of the patient.…”

Maximum Somatic Allele Frequency-Adjusted Blood-Based Tumor Mutational Burden Predicts the Efficacy of Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer

“…Distinct from tTMB, the analysis of bTMB had been found to be impacted by several factors in the blood, including ctDNA, AF, MSAF grouping, ITH, etc. [ 13 , 20 , 21 , 22 , 23 , 24 ]. Considering that a patient with advanced NSCLC is characterized by high tumor burden and ITH, the relationship among bTMB, MSAF, and ITH has been analyzed.…”

Sintilimab with two cycles of chemotherapy for the treatment of advanced squamous non-small cell lung cancer: a phase 2 clinical trial

“…Sequence data analysis was conducted with a bioinformatics pipeline as previously described 45 . The maximum allele frequency of somatic mutations in plasma was used to determine the changes of ctDNA 46 .…”