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Background <p>Expanded RAS analysis is essential for guiding targeted therapy in metastatic colorectal cancer (mCRC), as RAS mutations predicts resistance to anti-EGFR agents. This study aimed to evaluate the plasma RAS mutation status using liquid biopsy at disease progression and to assess the prognostic significance of RAS mutation clearance.</p> Methods <p>In this prospective study, 58 patients with mCRC harboring RAS mutations in baseline tumor tissue were enrolled. All patients experienced disease progression following first-line chemotherapy combined with bevacizumab. Plasma samples collected at progression were analyzed using the Idylla™ PCR-based system for detection of KRAS and NRAS mutations in circulating tumor DNA (ctDNA). Survival outcomes were estimated using the Kaplan–Meier method and compared with the log-rank test.</p> Results <p>The median age was 60&#xa0;years (IQR 35–83), and 60.3% of patients were male. The primary tumors were left sided in 81.0% of cases. At baseline, 94.8% of the patients had KRAS and 5.2% had NRAS mutations. At progression, ctDNA analysis revealed KRAS mutations in 56.9% and NRAS mutations in 3.4% of patients, while 39.7% showed no detectable RAS mutation in plasma. No significant differences in clinicopathological characteristics were observed between patients with persistent RAS mutations and those with RAS clearance. However, overall survival was significantly longer in patients with RAS wild-type conversion compared to those with persistent RAS mutations (44.3 vs. 19.6&#xa0;months, <i>p</i> = 0.002).</p> Conclusion <p>This study demonstrated that dynamic changes in plasma RAS mutation status may occur during disease progression in patients with mCRC, potentially reflecting tumor clonal evolution. The observed survival advantage in patients with RAS mutation clearance suggests potential prognostic relevance. Reassessment of RAS status using liquid biopsy at disease progression may provide clinically relevant information; however, these findings should be considered exploratory and require prospective validation in larger cohorts.</p>

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The temporal evaluation of RAS mutation by liquid biopsy at progression after bevacizumab-based treatment in patients with metastatic colorectal cancer

  • 期刊论文

  • 发表日期：

    2026年6月24日

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  • Irem Bilgetekin,
  • Umut Demirci,
  • Hasan Cagri Yildirim,
  • Mehmet Dogan,
  • Cengiz Karacin,
  • İlknur Deliktas Onur,
  • Fatma Bugdayci Basal,
  • Ece Esin,
  • Gokhan Ucar,
  • Ozlem Aydin Isak,
  • Inanc Imamoglu,
  • Gul Sema Yildiran Keskin,
  • Ismail Erturk,
  • Burak Yasin Aktas,
  • Naziyet Kose Baytemur,
  • Kubra Aydin,
  • Selcuk Cemil Ozturk,
  • Bulent Aksel,
  • Nuri Karadurmus,
  • Olcay Kandemir,
  • Suayib Yalcin,
  • Berna Oksuzoglu

摘要

Background

Expanded RAS analysis is essential for guiding targeted therapy in metastatic colorectal cancer (mCRC), as RAS mutations predicts resistance to anti-EGFR agents. This study aimed to evaluate the plasma RAS mutation status using liquid biopsy at disease progression and to assess the prognostic significance of RAS mutation clearance.

Methods

In this prospective study, 58 patients with mCRC harboring RAS mutations in baseline tumor tissue were enrolled. All patients experienced disease progression following first-line chemotherapy combined with bevacizumab. Plasma samples collected at progression were analyzed using the Idylla™ PCR-based system for detection of KRAS and NRAS mutations in circulating tumor DNA (ctDNA). Survival outcomes were estimated using the Kaplan–Meier method and compared with the log-rank test.

Results

The median age was 60 years (IQR 35–83), and 60.3% of patients were male. The primary tumors were left sided in 81.0% of cases. At baseline, 94.8% of the patients had KRAS and 5.2% had NRAS mutations. At progression, ctDNA analysis revealed KRAS mutations in 56.9% and NRAS mutations in 3.4% of patients, while 39.7% showed no detectable RAS mutation in plasma. No significant differences in clinicopathological characteristics were observed between patients with persistent RAS mutations and those with RAS clearance. However, overall survival was significantly longer in patients with RAS wild-type conversion compared to those with persistent RAS mutations (44.3 vs. 19.6 months, p = 0.002).

Conclusion

This study demonstrated that dynamic changes in plasma RAS mutation status may occur during disease progression in patients with mCRC, potentially reflecting tumor clonal evolution. The observed survival advantage in patients with RAS mutation clearance suggests potential prognostic relevance. Reassessment of RAS status using liquid biopsy at disease progression may provide clinically relevant information; however, these findings should be considered exploratory and require prospective validation in larger cohorts.