ctDNA-Guided Cetuximab or Bevacizumab Plus Trifluridine/Tipiracil in RAS/BRAF Wild-Type mCRC

Inclusion Criteria: * Histologically confirmed colorectal adenocarcinoma * Initial RAS/BRAF wild-type status * Received first-line treatment with FOLFOX, FOLFIRI, or FOLFOXIRI combined with cetuximab, with documented clinical benefit (CR/PR/SD) and progression-free survival (PFS) ≥ 6 months * Disease progression occurred during or within 3 months after cetuximab-based first-line therapy * Experienced further tumor progression after receiving second-line or subsequent treatments * At least 4 months have elapsed since the last administration of cetuximab * At least one measurable lesion according to RECIST v1.1 * RAS/BRAF wild-type status confirmed by blood-based ctDNA testing * Normal hematologic function (platelets \> 90 × 10⁹/L; white blood cells \> 3 × 10⁹/L; neutrophils \> 1.5 × 10⁹/L; hemoglobin \> 10.0 g/100 ml) * Serum bilirubin ≤ 1.5 × upper limit of normal (ULN), transaminases ≤ 5 × ULN * No ascites, normal coagulation function, serum albumin ≥ 35 g/L * Child-Pugh class A liver function * Serum creatinine below ULN or calculated creatinine clearance \> 50 ml/min (using the Cockcroft-Gault formula) * ECOG performance status of 0-1 * Expected survival \> 3 months * Signed written informed consent * Willing and able to undergo follow-up until death, study completion, or study termination Exclusion Criteria: * Presence of RAS or BRAF gene mutations * Severe arterial embolism or ascites * Bleeding tendency or coagulation disorders * Hypertensive crisis or hypertensive e…