The NeoRAS phenomenon is defined as the conversion of tumor RAS status from mutant-type (MT) to wild-type (WT) after systemic chemotherapy in metastatic colorectal cancer (mCRC). Cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody, is effective in patients with RAS WT mCRC but ineffective in those with RAS MT mCRC; however, its outcome in patients with NeoRAS WT mCRC is unclear. Herein, we report two cases of NeoRAS WT mCRC that responded clinically to anti-EGFR treatment. The first was a 40-year-old man with synchronous peritoneal metastatic rectosigmoid cancer. The first RAS testing on tumor tissue revealed a KRAS G12C mutation, which was converted to RAS WT after two lines of chemotherapy, as assessed by liquid biopsy. After initiating irinotecan plus cetuximab treatment, a computed tomography (CT) scan revealed that malignant ascites had resolved. The treatment was discontinued after 4 months because of disease progression. The second was a 68-year-old male patient with synchronous liver metastasis from sigmoid colon cancer. The KRAS G12D mutation, initially detected in tumor tissue, was not detected by liquid biopsy after six lines of chemotherapy. Cetuximab monotherapy was initiated, and the liver metastases shrank significantly. The patient continued cetuximab monotherapy for 8 months without disease progression. Our cases demonstrate the efficacy of anti-EGFR therapy for NeoRAS WT mCRC and highlight the importance of capturing the gene mutation profile throughout the clinical course for optimal treatment selection.

中文翻译：

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NeoRAS野生型转移性结直肠癌患者的抗表皮生长因子受体治疗：附2例病例报告

NeoRAS现象被定义为转移性结直肠癌（mCRC）全身化疗后肿瘤RAS状态从突变型（MT）转变为野生型（WT）。西妥昔单抗是一种抗表皮生长因子受体（EGFR）抗体，对 RAS WT mCRC 患者有效，但对 RAS MT mCRC 患者无效；然而，其在 NeoRAS WT mCRC 患者中的结果尚不清楚。在此，我们报告了两例对抗 EGFR 治疗有临床反应的 NeoRAS WT mCRC 病例。第一个患者是一名 40 岁男性，患有同步性腹膜转移性直肠乙状结肠癌。对肿瘤组织的首次 RAS 检测发现存在 KRAS G12C 突变，经液体活检评估，该突变在两线化疗后转变为 RAS WT。开始伊立替康联合西妥昔单抗治疗后，计算机断层扫描（CT）显示恶性腹水已消退。4个月后由于疾病进展而停止治疗。第二例是一名68岁男性乙状结肠癌同步肝转移患者。KRAS G12D 突变最初在肿瘤组织中检测到，但在六线化疗后液体活检未检测到。开始西妥昔单抗单药治疗后，肝转移灶明显缩小。患者继续西妥昔单抗单药治疗 8 个月，疾病没有进展。我们的案例证明了抗 EGFR 疗法对 NeoRAS WT mCRC 的疗效，并强调了在整个临床过程中捕获基因突变谱以实现最佳治疗选择的重要性。