From Diagnosis, Therapy Decision-Making to Genetic Risk Assessment: The Impact of ctDNA Testing on Comprehensive...

Area of Science:

• Oncology
• Molecular Diagnostics
• Genetics

Background:

• Tissue biopsy limitations for inaccessible tumors or insufficient samples.
• Circulating tumor DNA (ctDNA) offers a minimally invasive method to capture tumor heterogeneity.
• Accurate diagnosis is crucial for effective cancer treatment and management.

Purpose of the Study:

• To illustrate the utility of ctDNA testing in diagnosing synchronous primary cancers.
• To demonstrate how ctDNA analysis can guide targeted therapy selection.
• To highlight the role of ctDNA in identifying actionable biomarkers and genetic risk.

Main Methods:

• Next-generation sequencing (NGS) of both tissue biopsy and ctDNA.
• Droplet digital PCR for targeted mutation detection.
• Immunohistochemistry for variant localization.
• Germline testing for hereditary cancer syndromes.

Main Results:

• ctDNA testing identified an EGFR p.L858R variant, indicative of non-small cell lung cancer (NSCLC), despite initial pancreatic adenocarcinoma diagnosis.
• EGFR variant localized to lymph nodes, not pancreatic tissue, supporting a synchronous lung primary.
• Pancreatic biopsy revealed a KRAS p.Q61 variant, absent in ctDNA, suggesting low ctDNA shedding from the pancreas.
• EGFR-mutant NSCLC treated with osimertinib resulted in a partial response.
• Germline testing identified a CDKN2A variant, indicating a hereditary cancer syndrome and prompting surveillance.

Conclusions:

• ctDNA testing is valuable for diagnosing synchronous primary cancers and overcoming tissue biopsy limitations.
• Identification of actionable mutations via ctDNA facilitates personalized treatment strategies.
• ctDNA analysis aids in comprehensive cancer evaluation, including genetic risk assessment and management.