2024 World Conference on Lung Cancer (WCLC) - Posters-P3.13C.04 Assessing ctDNA using a Methylation-informed Molecular Response Algorithm in Extensive-Stage Small Cell Lung Cancer Patients

P3.13C.04 Assessing ctDNA using a Methylation-informed Molecular Response Algorithm in Extensive-Stage Small Cell Lung Cancer Patients

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This study investigates the use of a methylation-informed circulating tumor DNA (ctDNA) molecular response algorithm in assessing survival outcomes for patients with extensive-stage small cell lung cancer (ES-SCLC). The research builds on prior work assessing the efficacy of nivolumab and temozolomide in these patients. Traditionally, ctDNA analysis has focused on identifying specific somatic mutations from the blood, which, while specific, often suffers from low sensitivity. This study explores the potential for using methylation markers, which may enhance detection sensitivity by identifying cancer-specific methylation patterns in ctDNA.<br /><br />The study involved 27 patients with relapsed ES-SCLC, treated with a combination of nivolumab and temozolomide. Plasma was collected before cycles 1, 2, and 5, and analyzed using the Guardant Infinity assay to evaluate genomic alterations and methylation-based tumor fraction (TF). Molecular response was defined by a significant decrease in ctDNA levels (either genomic or methylation-based).<br /><br />Results indicated a high correlation between genomic-based and methylation-based ctDNA dynamics (Pearson R = 0.957). Methylation-influenced ctDNA detection was successful in 92% of samples. A notable finding was a patient whose genomic ctDNA indicated a mere 33% reduction, while methylation indicators showed a 98% reduction, aligned with a prolonged treatment response lasting over 700 days. This suggests that methylation-based assessments might provide a more accurate representation of molecular responses for some patients.<br /><br />Survival outcomes were assessed via Kaplan-Meier analysis, comparing responders with non-responders. Patients with concurrent TP53 and RB1 loss of heterozygosity had significantly shorter median overall survival than those without these alterations.<br /><br />The study acknowledges contributors and highlights the potential for methylation-informed ctDNA assessments to serve as critical indicators for survival in ES-SCLC patients, potentially complementing genomic ctDNA assessments.

Asset Subtitle

Jinesh Gheeya

Meta Tag

Speaker Jinesh Gheeya

Topic SCLC & Neuroendocrine Tumors

Keywords

methylation-informed ctDNA

circulating tumor DNA

extensive-stage small cell lung cancer

ES-SCLC

nivolumab

temozolomide

methylation markers

genomic alterations

molecular response

survival outcomes