2023 North America Conference on Lung Cancer (NACLC) - Posters and Abstracts-PP01.92 (Poster) Analytical Performance of a Cell-free DNA Targeted Methylation Test for Early Lung Adenocarcinoma (LUAD) Recurrence Prediction

PP01.92 (Poster) Analytical Performance of a Cell-free DNA Targeted Methylation Test for Early Lung Adenocarcinoma (LUAD) Recurrence Prediction

Back to course

Pdf Summary

Researchers have conducted an analytical performance evaluation of a blood-based, tissue-free lung prognosis test for the risk of recurrence in lung adenocarcinoma (LUAD). The study used cell-free DNA (cfDNA) samples from healthy individuals and LUAD patients to assess the sensitivity, specificity, precision, input titration, interferent effect, and whole blood stability of the test.<br /><br />The test demonstrated robust analytical performance at low cfDNA input mass in early-stage LUAD. The median limit of detection with 95% probability (LoD95) was determined to be 0.0044% tumor methylated fraction (TMeF), or 44 parts per million (PPM), from 5 unique LUAD samples tested. The analytical sensitivity at 6 ng cfDNA input was 97.9%, and at 20 ng cfDNA input was 100%. The analytical specificity, assessed using non-cancer samples, was 96.9%.<br /><br />Positive precision, measuring the repeatability and reproducibility of ctDNA classification in LUAD samples, demonstrated 100% repeatability and 99.1% reproducibility. Negative precision in non-cancer samples showed 100% repeatability and reproducibility. The test accurately classified samples with a tumor methylation score above its threshold as ctDNA positive and those below as ctDNA negative.<br /><br />The test also showed accurate classification across a range of cfDNA input amounts, with a binary coverage threshold indicating sample quality. Endogenous interfering substances, such as bilirubin and hemoglobin, did not cause misclassification of LUAD samples. Whole blood stability was evaluated at different temperatures and storage durations, showing no impact on the classification of non-cancer samples.<br /><br />In conclusion, the blood-based, tissue-free lung prognosis test demonstrated robust analytical performance in predicting the risk of LUAD recurrence. Future studies will assess the clinical utility of ctDNA detection above a predetermined threshold in early-stage LUAD.

Asset Subtitle

Manami Roychowdhury-Saha

Keywords

lung prognosis test

recurrence risk

lung adenocarcinoma

analytical performance

sensitivity

specificity

precision

ctDNA classification

methylation score

clinical utility