2022 World Conference on Lung Cancer (ePosters)-EP08.01-035. Personalized ctDNA Detection to Monitor Outcome and Predict Immunotherapy Benefit in Locally Advanced and Metastatic NSCLC

EP08.01-035. Personalized ctDNA Detection to Monitor Outcome and Predict Immunotherapy Benefit in Locally Advanced and Metastatic NSCLC

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A study was conducted to evaluate the use of personalized ctDNA detection as a biomarker for monitoring therapeutic efficacy in patients with non-small-cell lung cancer (NSCLC) receiving immunotherapy. The study included 16 NSCLC patients who underwent first-line immunotherapy combined with chemotherapy. Tumor tissues and matched peripheral blood samples were collected before treatment, and whole exome sequencing was performed. Serial plasma samples were collected at baseline and the beginning of immunotherapy cycles. The ctDNA burden, measured as mean mutant tumor molecules per mL of plasma, was calculated based on variant allele fraction (VAF) and cfDNA yield.<br /><br />The results showed that personalized ctDNA detection was more sensitive than tumor-agnostic ctDNA detection. Among the three patients who underwent both assays, tumor-informed detection detected ctDNA in all three patients, while tumor-agnostic detection failed to detect ctDNA in two of the patients. The study also found that the trend of ctDNA levels from baseline to the first assessment timepoint was consistent with disease progression. Patients who had a partial response to immunotherapy showed a decrease in ctDNA burden to 17.9% of baseline level, while patients with stable disease/progressive disease showed a decrease to 88.3% of baseline level.<br /><br />Furthermore, the decrease in ctDNA burden was found to be associated with patient prognosis. Patients with a ctDNA drop of at least 0.5-fold from baseline had significantly longer progression-free survival compared to those without a significant ctDNA drop. Additionally, patients with a more than 50% decrease in ctDNA had significantly longer overall survival compared to those with less than a 50% decrease.<br /><br />In conclusion, personalized ctDNA detection can serve as a valuable biomarker for monitoring therapeutic efficacy and predicting outcomes in NSCLC patients receiving immunotherapy. This tumor-informed assay demonstrated higher sensitivity compared to tumor-agnostic assays and showed consistent changes in ctDNA levels with disease progression. The decrease in ctDNA burden was associated with improved prognosis in patients receiving immunotherapy. These findings highlight the potential of ctDNA detection as a personalized tool in cancer care.

Asset Subtitle

Guanghui Gao

Meta Tag

Speaker Guanghui Gao

Topic Metastatic Non-small Cell Lung Cancer - Immunotherapy

Keywords

personalized ctDNA detection

biomarker

therapeutic efficacy

NSCLC

immunotherapy

ctDNA burden

disease progression

patient prognosis

progression-free survival

overall survival