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Introduction <p>Kirsten rat sarcoma viral oncogene (KRAS) mutations account for 86% of all RAS mutations and 30–50% of colorectal cancer mutations (CRC). The KRAS mutation may have prognostic implications in CRC. The impact of RAS/BRAF mutations on pathological complete response (pCR) after total neoadjuvant therapy (TNT) in patients with rectal cancer is unclear. This study aims to assess pCR rates following TNT in RAS/BRAF mutant rectal cancer. </p> Methods <p>Adult patients with rectal cancer who underwent TNT and curative surgery at a large academic institution between 2018 and 2023 were retrospectively reviewed. Patients were divided into two groups based on RAS/BRAF mutation status: mutant RAS/BRAF (RAS+) and wild-type RAS/BRAF (RAS−). Patients with other or concurrent mutations were excluded. </p> Results <p>Of 146 patients, 69 (47.3%) were RAS+, whereas 77 (52.7%) were RAS−. In the RAS+ group, five patients (7.2%) were BRAF mutants. There was no significant difference in magnetic resonance imaging rate between groups. However, RAS mutation status was significantly associated with differences in pCR; specifically, a higher proportion of RAS- patients achieved pCR (20.8% vs. 8.7%; <i>p</i> = 0.042). Subgroup analysis revealed that RAS+ (20.8%, 8.7%; <i>p</i> = 0.042) and codons 12 and 13 (20.8%, 7.3%; <i>p</i> = 0.033) were associated with a less pathologic complete response rate. Three-year disease-free survival was significantly associated with RAS mutation status, being higher in the RAS− group compared with the RAS+ group (80% vs. 65%; <i>p</i> = 0.038).</p> Conclusions <p>In the era of TNT and nonoperative management strategies, RAS/BRAF mutations are more likely associated with a lower pCR rate in locally advanced rectal cancer patients. Moreover, these mutations are associated with worse disease-free survival.</p>

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The Impact of RAS/BRAF Mutation on Pathological Complete Response After Total Neoadjuvant Therapy in Rectal Cancer

  • 期刊论文

  • 发表日期：

    2025年7月17日

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  • Sara Aboelmaaty,
  • Ibrahim A. Gomaa,
  • Annaclara Sileo,
  • Richard Sassun,
  • Jyi Cheng Ng,
  • Nouran O. Keshk,
  • Nicholas P. McKenna,
  • William R. Perry,
  • David W. Larson

摘要

Introduction

Kirsten rat sarcoma viral oncogene (KRAS) mutations account for 86% of all RAS mutations and 30–50% of colorectal cancer mutations (CRC). The KRAS mutation may have prognostic implications in CRC. The impact of RAS/BRAF mutations on pathological complete response (pCR) after total neoadjuvant therapy (TNT) in patients with rectal cancer is unclear. This study aims to assess pCR rates following TNT in RAS/BRAF mutant rectal cancer.

Methods

Adult patients with rectal cancer who underwent TNT and curative surgery at a large academic institution between 2018 and 2023 were retrospectively reviewed. Patients were divided into two groups based on RAS/BRAF mutation status: mutant RAS/BRAF (RAS+) and wild-type RAS/BRAF (RAS−). Patients with other or concurrent mutations were excluded.

Results

Of 146 patients, 69 (47.3%) were RAS+, whereas 77 (52.7%) were RAS−. In the RAS+ group, five patients (7.2%) were BRAF mutants. There was no significant difference in magnetic resonance imaging rate between groups. However, RAS mutation status was significantly associated with differences in pCR; specifically, a higher proportion of RAS- patients achieved pCR (20.8% vs. 8.7%; p = 0.042). Subgroup analysis revealed that RAS+ (20.8%, 8.7%; p = 0.042) and codons 12 and 13 (20.8%, 7.3%; p = 0.033) were associated with a less pathologic complete response rate. Three-year disease-free survival was significantly associated with RAS mutation status, being higher in the RAS− group compared with the RAS+ group (80% vs. 65%; p = 0.038).

Conclusions

In the era of TNT and nonoperative management strategies, RAS/BRAF mutations are more likely associated with a lower pCR rate in locally advanced rectal cancer patients. Moreover, these mutations are associated with worse disease-free survival.