The effects of KRAS Mutations on the Prognosis of Rectal Cancer Following Neoadjuvant Chemoradiotherapy and Surgery

Park, Ji Sun; Lee, Soon Seong; Choi, Yoon Sun

doi:10.31557/APJCP.2024.25.7.2337

The effects of KRAS Mutations on the Prognosis of Rectal Cancer Following Neoadjuvant Chemoradiotherapy and Surgery

Document Type : Research Articles

Authors

¹ Department of Nuclear Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea.

² Department of Radiation Oncology, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea.

10.31557/APJCP.2024.25.7.2337

Abstract

Background: Rectal cancers with mutations in the KRAS gene have worse prognoses than wild-type malignancies. Variants at codon 12 of KRAS have particularly detrimental effects on prognosis. We aimed to analyze whether KRAS mutations act as adverse prognostic factors following neoadjuvant concurrent chemoradiotherapy (CRT) and surgery for rectal cancer treatment. Methods: We analyzed the effects of KRAS mutations on disease-free survival (DFS) and locoregional recurrence-free survival (LRFS) in 125 patients with cT2-4N0-2M0 rectal cancer who underwent surgery following CRT between June 2014 and March 2023 Inje University Busan Paik Hospital. Results: The median follow-up period was 39.7 (range, 7.5–98.2) months. There were 25 patients (20.0%) who harbored KRAS mutations. Among them, 22 patients (17.6%) had codon 12 variants. Overall, 43 patients (34.4%) showed recurrence, of which 10 (8.0%) had locoregional recurrence and 35 (28.0%) had distant metastases (two occurred simultaneously). DFS was significantly reduced in the patients with KRAS mutations (p = 0.005). LRFS was also reduced in patients with KRAS mutations (p = 0.039). DFS and LRFS were also relatively low in the subgroup with KRAS mutations at codon 12 (n = 22) (p = 0.003 and p = 0.017, respectively). However, pathologic complete response rate following CRT was not affected by KRAS mutations (p = 0.197). Overall survival was also not associated with KRAS mutations (p = 0.486).Conclusion: KRAS mutation is related to decreased DFS and LRFS, when surgery is performed following neoadjuvant CRT to treat rectal cancer. These effects are particularly pronounced for KRAS mutations at codon 12.

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