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ctDNA RAS Evolution CRC — SCE Medical Oncology MCQ

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HardGI CancersctDNA RAS Evolution CRCSCE Medical Oncology

A 60-year-old man with metastatic CRC has ctDNA testing showing loss of previously detected KRAS G12D mutation after 12 months of FOLFOX + bevacizumab. His RAS status on ctDNA is now wild-type. What therapeutic opportunity does this create?

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Correct answer: A — RAS clonal evolution under anti-VEGF pressure may restore anti-EGFR sensitivity

Clonal evolution during CRC treatment can result in loss of RAS-mutant clones (which were the dominant population at diagnosis) and emergence/selection of RAS-WT clones. ctDNA monitoring can detect this shift, creating an opportunity for anti-EGFR therapy in patients who were initially RAS-mutant. The CHRONOS trial demonstrated that ctDNA-guided anti-EGFR rechallenge in patients with acquired RAS-WT status achieves meaningful response rates (~30%). This represents a paradigm of adaptive, biomarker-guided treatment.

Reference: https://www.nice.org.uk/guidance/conditions-and-diseases/cancer