The identification of circulating tumour DNA using MassARRAY technology in non-small-cell lung cancer (NSCLC)

Abstract

Attaining tumour material from lung cancer patients can be challenging with limited sample availability. Therefore, non-invasive means of assessing tumour material is becoming increasingly more important. Circulating tumour DNA (ctDNA), extracted from a blood sample is appealing for the patient, and can be performed serially over the course of treatment. Materials and Methods: Here, we describe an approach for profiling the blood samples of 103 NSCLC patients for 73 variants in ctDNA across a panel of actionable lung cancer mutations using the UltraSEEK lung Panel (Agena Biosciences). Results: Our cross-sectional study showed tumour and blood concordance in the detection of KRAS mutations (G12C, G12D, G12A/V, G12R, G12RC, Q61H) in 17/27 (63%), EGFR mutations (e746_a750del, e747_A750, T790M, L861Q) in 16/20 (80%) with additional PIK3CA_p545K mutations across both cohorts. In patients without reported tumour mutations, 11/56 (19.6%) presented with plasma mutations across EGFR, KRAS and PIK3CA. Where ctDNA mutations were measured longitudinally (n = 4 patients), the individual mutations mirrored the response to therapy/progression of disease. Conclusion: Whilst preliminary, this study demonstrates the utility of detecting clinically actionable mutations in the blood samples of NSCLC patients at the time of presentation, and over the course of therapy.

Detection and Monitoring of Tumor-Derived Mutations in Circulating Tumor DNA Using the UltraSEEK Lung Panel on the MassARRAY System in Metastatic Non-Small Cell Lung Cancer Patients

“…However, when tissue is not available or adequate for NGS analysis, tumor-derived mutation testing in plasma serves as an alternative method. Our results demonstrated concordant results in 68% of the patients between routine diagnostic NGS analysis on the pretreatment tissue biopsy and UltraSEEK ® analysis in 66 matched baseline plasma samples, comparable to previous data [28,32]. In 23% of the patients with a known driver mutation in the tumor tissue, this variant could not be detected in the matched baseline plasma sample.…”

“…A recent comparison study showed comparable sensitivity and specificity in EGFR mutation detection between the PCR-based Cobas ® EGFR Mutation Test v2 and UltraSEEK ® Lung Panel, especially with an optimal ccfDNA input for UltraSEEK ® (≥10 ng) [27]. Furthermore, it was demonstrated previously that clinically relevant variants beyond EGFR could be identified as well [27,28], including in patients with limited oligobrain metastatic disease [29]. Within the framework of the Innovative Medicines Initiative (IMI) program CANCER-ID (http://www.cancer-id.eu, accessed on 14 June 2023), the UltraSEEK ® Lung Panel on the MassARRAY ® System to detect tumor-derived driver mutations in ccfDNA of NSCLC patients at diagnosis and at progression was evaluated, as well as its ability to quantify changes in ctDNA levels during treatment as a monitoring tool.…”

Monitoring cfDNA in Plasma and in Other Liquid Biopsies of Advanced EGFR Mutated NSCLC Patients: A Pilot Study and a Review of the Literature

“…Also, with our study, we underlined the utility of plasma ctDNA during the treatment as prognostic factor and as complementary or exclusive source to identify targetable resistance mechanisms. Finally, liquid biopsy could play a key role also in the detection of other driver-genes such as KRAS, in NSCLC patients treated with specific TKI [ 43 ].…”

Detection of KRAS mutation using plasma samples in non-small-cell lung cancer: a systematic review and meta-analysis

“…UltraSEEK lung panel (Agena Biosciences), a commercial MassARRAY panel, was used in a 103-patient cohort, and sensitivity, specificity, and concordance rate were 62.96%, 92.11%, and 84.47%, respectively ( 56 ). Pyrosequencing was used in an early study ( 57 ), and sensitivity and specificity were 75% and 100%, respectively, resulting in a concordance rate of 97.67%.…”