Circulating Tumor DNA Profiling Reveals Genomic Evolution in Recurrent Gastric or Gastroesophageal Junction Cancer

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Recurrent gastric and gastroesophageal junction cancers present significant challenges due to limited treatment options.
• Archival tumor tissue may not accurately represent the molecular landscape of recurrent disease.

Purpose of the Study:

• To evaluate the effectiveness of circulating tumor DNA (ctDNA) analysis in identifying actionable genomic alterations in recurrent gastric cancer.
• To compare ctDNA findings with genomic profiles from archival primary tumors.

Main Methods:

• A prospective observational study involving 50 patients with recurrent gastric or gastroesophageal junction adenocarcinoma.
• Guardant360 assay used for ctDNA analysis at recurrence, with comparison to comprehensive genomic profiling of primary tumors.
• Primary endpoint: detection rate of actionable genomic alterations (OncoKB level ≥ 3).

Main Results:

• ctDNA was detected in 78% of patients, with actionable genomic alterations found in 36%.
• Key alterations included PIK3CA mutations (18%), ARID1A mutations (10%), and ERBB2 amplification (6%).
• Significant genomic evolution was observed, with 66.7% of paired samples showing altered actionable genomic alterations, including new findings exclusively in ctDNA.

Conclusions:

• ctDNA analysis successfully captures genomic evolution in recurrent gastric cancer, identifying clinically relevant alterations.
• These findings advocate for the incorporation of liquid biopsies into clinical practice for guiding treatment strategies in recurrent disease.