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Annals of Surgical Oncology

, Volume 23, Issue 6, pp 1890–1896 | Cite as

KRAS Mutation Status Predicts Site-Specific Recurrence and Survival After Resection of Colorectal Liver Metastases Irrespective of Location of the Primary Lesion

  • Junichi Shindoh
  • Yujiro Nishioka
  • Ryuji Yoshioka
  • Toshitaka Sugawara
  • Yoshihiro Sakamoto
  • Kiyoshi Hasegawa
  • Masaji Hashimoto
  • Norihiro Kokudo
Colorectal Cancer

Abstract

Background

The KRAS mutation status is reportedly correlated with poor survival outcome in patients with colorectal liver metastases (CLM); however, its true prognostic impact and the reason for the poor prognosis remain unclear.

Methods

Data on 163 patients with a known KRAS mutation status who underwent curative resection for CLM were retrospectively reviewed. The long-term survival and site-specific incidence of recurrence were then compared between patients with a KRAS mutation (mtKRAS) and those without a mutation (wtKRAS).

Results

The mtKRAS group had a poorer 3-year disease-specific survival (DSS) rate (59.8 vs. 83.6 %, p = 0.016), 3-year recurrence-free survival (RFS) rate (0 vs. 20.2 %, p = 0.069), and median time to surgical failure (TSF) [18.8 vs. 39.7 months, p = 0.001] than the wtKRAS group. The cumulative incidences of liver recurrence and lung recurrence at 3 years were also higher in the mtKRAS group (76.2 vs. 54.7 %, p = 0.060; and 71.9 vs. 37.3 %, p < 0.001, respectively). A multivariate analysis confirmed that an mtKRAS status had a significant effect on the DSS rate (hazard ratio [HR] 2.9, p = 0.006), RFS (HR 2.0, p = 0.004), TSF (HR 2.4, p < 0.001), liver recurrence (HR 1.7, p < 0.001), and lung recurrence (HR 2.6, p < 0.001). Lung-related unresectable recurrences were more frequent (41 vs. 18 %, p = 0.048) and were associated with an earlier TSF (9.6 vs. 14.0 months, p = 0.14) in the mtKRAS group, regardless of the location of the primary lesions.

Conclusions

mtKRAS is associated with poor survival outcome after CLM resection because of a relatively high incidence of lung recurrence and a relatively short TSF.

Keywords

Primary Lesion Colorectal Liver Metastasis Future Liver Remnant KRAS Mutation Status Poor Survival Outcome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

This study was supported by a study grant from Okinaka Memorial Institute for Medical Disease (No. 2015-15) and JSPS KAKENHI Grant No. 26861063.

Conflict of interest

Junichi Shindoh, Yujiro Nishioka, Ryuji Yoshioka, Toshitaka Sugawara, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Masaji Hashimoto, and Norihiro Kokudo have no conflicts of interest to declare that are directly relevant to the content of this study.

Supplementary material

10434_2016_5087_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 23 kb)

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Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • Junichi Shindoh
    • 1
    • 2
  • Yujiro Nishioka
    • 1
    • 3
  • Ryuji Yoshioka
    • 3
  • Toshitaka Sugawara
    • 1
  • Yoshihiro Sakamoto
    • 3
  • Kiyoshi Hasegawa
    • 3
  • Masaji Hashimoto
    • 1
  • Norihiro Kokudo
    • 3
  1. 1.Hepatobiliary-Pancreatic, Surgery Division, Department of Digestive SurgeryToranomon HospitalTokyoJapan
  2. 2.Okinaka Memorial Institute for Medical DiseaseTokyoJapan
  3. 3.Hepatobiliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of MedicineThe University of TokyoTokyoJapan

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