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ctDNA Clearance Mirrors Clinical Response to TKI Treatment

Category:

Early-stage Cancer Studies

Source:

JCO Oncology Advances

Cancer type:

Lung Cancer

In advanced non-small cell lung cancer (NSCLC), precision medicine need 2 critical information: the identification of actionable driver mutations and the ability to monitor real-time response. The case of a 65-year-old woman with EGFR-mutant illustrates how genomic profiling and ctDNA monitoring work hand-in-hand to guide therapy and track response — well before imaging changes become apparent.

Patient ZML513 A 65-year-old woman

Genomic Profiling: Setting the Stage for Targeted Therapy

At diagnosis, Ms. L underwent tissue and plasma-based genomic profiling. The results revealed:

EGFR exon 19 deletion, a well-characterized driver mutation predictive of response to first- and third-generation EGFR TKIs (1)
KEAP1 E192K, a mutation increasingly associated with aggressive disease and potential resistance mechanisms in NSCLC (2)

These findings directly informed the decision to initiate gefitinib, a first-line EGFR inhibitor, offering a targeted alternative to cytotoxic chemotherapy. Importantly, genomic profiling also established a personalized molecular profile to monitor treatment efficacy through tumor-informed ctDNA monitoring.

ctDNA Monitoring: A Real-Time Indicator of Response

Baseline ctDNA analysis showed a variant allele frequency (VAF) of 3.60%, confirming the presence of circulating tumor DNA in plasma — a reflection of active tumor burden.

As treatment with gefitinib progressed, so did the molecular response:

January 2024 (6 months post-treatment): ctDNA became negative (VAF < 0.05%), indicating molecular clearance
This preceded continued imaging responses and reflected deep biological suppression of tumor activity

By March 2024, radiological imaging confirmed partial response and tumor size decrease, consistent with RECIST 1.1 criteria.

ctDNA was cleared after 6 months of treatment, corresponding with the partial response evaluated by RECIST 1.1 criteria at the 9-month visit, supporting its use as a dynamic biomarker for treatment response assessment.

This case demonstrates how these two tools operate on different yet synergistic levels:

Genomic Profiling: Identifies therapeutic targets and resistance markers, Establishes a personalized molecular profiling for monitoring
Tracks response non-invasively and Offers real-time insight into tumor biology between scans

Reference:

Truini A, Starrett JH, Stewart T, et al. The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma. Clinical Cancer Research. 2019;25(21):6382-6391. doi:10.1158/1078-0432.ccr-19-0780
Hellyer JA, Stehr H, Das M, et al. Impact of KEAP1/NFE2L2/CUL3 mutations on duration of response to EGFR tyrosine kinase inhibitors in EGFR mutated non-small cell lung cancer. Lung Cancer. 2019;134:42-45. doi:10.1016/j.lungcan.2019.05.002

This is the story of a 60-year-old man with stage IV NSCLC, whose case demonstrates how ctDNA monitoring predicted disease progression ahead of imaging, offering a critical opportunity for earlier intervention.

The case of a 66-year-old woman with metastatic lung cancer, illustrates how genomic profiling and ctDNA monitoring together provide a sharper, more dynamic view of tumor evolution — even when conventional markers appear to improve.

The story of Rajesh, a 75-year-old man diagnosed with stage IA lung adenocarcinoma, reminds us that while CT scans remain a staple in surveillance, molecular recurrence can emerge well before structural changes are visible.

This real-world case of Long, a 46-year-old man diagnosed with stage III sigmoid colon cancer, illustrates how both approaches informed risk stratification and a tailored adjuvant treatment strategy.

Meet Maya, a 35-year-old woman diagnosed with HER2-positive breast cancer. Her story highlights the real-world impact of using both technologies to personalize treatment, track progress, and achieve long-term disease control.

The K-CONNECT Platform creates as a collaborative initiative that brings together leading oncologists and researchers from across the region. The platform serves as a bridge between cutting-edge technology and expert practitioners, aiming to unlock the potential of ctDNA-MRD for precision and personalized oncology.

Terms and Conditions

ctDNA Clearance Mirrors Clinical Response to TKI Treatment

Table of Contents

Genomic Profiling: Setting the Stage for Targeted Therapy

ctDNA Monitoring: A Real-Time Indicator of Response

Reference:

Table of Contents

Patient ZML514

Patient ZML512

Patient ZMB501

Patient ZMC502

Patient ZMB501

ctDNA Clearance Mirrors Clinical Response to TKI Treatment

Table of Contents

Genomic Profiling: Setting the Stage for Targeted Therapy

ctDNA Monitoring: A Real-Time Indicator of Response

Reference:

Table of Contents

Patient ZML514

Patient ZML512

Patient ZMB501

Patient ZMC502

Patient ZMB501

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