THE IMPACT OF LIVER SURGERY AND MARGIN STATUS ON SURVIVAL ACCORDING TO KRAS MUTATIONAL STATUS IN COLORECTAL LIVER METASTASES

Authors

  • Mariana Peyroteo Surgical Oncology Department, Instituto Português de Oncologia do Porto, Portugal
  • Rita Canotilho Surgical Oncology Department, Instituto Português de Oncologia do Porto, Portugal
  • Alexandre Sousa Surgical Oncology Department, Instituto Português de Oncologia do Porto, Portugal
  • Fernanda Sousa Surgical Oncology Department, Instituto Português de Oncologia do Porto, Portugal
  • Manuel Fernandes Surgical Oncology Department, Instituto Português de Oncologia do Porto, Portugal
  • Belarmino Gonçalves
  • José Flávio Videira Surgical Oncology Department, Instituto Português de Oncologia do Porto, Portugal
  • Maria Fragoso Medical Oncology Department, Instituto Português de Oncologia do Porto, Portugal
  • Lúcio Lara Santos Surgical Oncology Department, Instituto Português de Oncologia do Porto, Portugal; Experimental Pathology and Therapeutics Group, Instituto Português de Oncologia do Porto Francisco Gentil, EPE, Porto, Portugal
  • Joaquim Abreu de Sousa Surgical Oncology Department, Instituto Português de Oncologia do Porto, Portugal

DOI:

https://doi.org/10.34635/rpc.815

Keywords:

colorectal liver metastasis, KRAS status, liver margin, recurrence free survival

Abstract

Introduction: The impact of kirsten rat sarcoma viral oncogene homolog (KRAS) mutational status on surgery planning for colorectal liver metastases (CRLM) remains unknown. The aim of the study was to evaluate the impact of type of liver surgery and margin status in recurrence free survival (RFS) of patients with CRLM, according to KRAS mutational status.

Materials and methods: Retrospective review of all patients consecutively submitted to CLRM surgery between January 2011 and December 2016 with KRAS determination. Exclusion criteria were 2-stage hepatectomy strategy, loss to follow up and non-anatomical and anatomical resections performed simultaneously.

Results: 114 patients were included, with a median age of 61 [31-80] years old. 67.5% of patients were male. KRAS mutation was present in 46.5% of patients, 58.8% had non-anatomical resections and R0 surgery was obtained in 69.3%. With a median follow up of 43 [4-105] months, recurrence rate was 86.8%, median overall survival and RFS were 53 and 11 months, respectively. In the mutated KRAS (mKRAS) group, the detection of R1 margins was the only predictor of worse RFS (31 versus 13 months, p=0.022). In the wild-type KRAS (wtKRAS) group a similar difference was not observed (24 versus 19 months, p=0.310). The most common form of recurrence after R1 resections in the mKRAS group was extra-hepatic, while in the wtKRAS was isolated hepatic recurrence.

Conclusion: In patients with mKRAS, R1 resection was associated with a decreased RFS, mainly due to extra-hepatic recurrence. These findings were not replicated in the wtKRAS group. KRAS mutational status should be considered while planning liver resection for CRLM, namely when deciding optimal margin width. 

Downloads

Download data is not yet available.

References

1. Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg. 2006;244(2):254-9.

2. Van Cutsem E, Nordlinger B, Adam R, Kohne CH, Pozzo C, Poston G, et al. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer. 2006;42(14):2212-21.

3. Jones RP, Kokudo N, Folprecht G, Mise Y, Unno M, Malik HZ, et al. Colorectal Liver Metastases: A Critical Review of State of the Art. Liver Cancer. 2016;6(1):66-71.

4. Lan YT, Jiang JK, Chang SC, Yang SH, Lin CC, Lin HH, et al. Improved outcomes of colorectal cancer patients with liver metastases in the era of the multidisciplinary teams. Int J Colorectal Dis. 2016;31(2):403-11.

5. Weledji EP. Centralization of Liver Cancer Surgery and Impact on Multidisciplinary Teams Working on Stage IV Colorectal Cancer. Oncol Rev. 2017;11(2):331.

6. Pawlik TM, Schulick RD, Choti MA. Expanding criteria for resectability of colorectal liver metastases. Oncologist. 2008;13(1):51-64.

7. Chow FC, Chok KS. Colorectal liver metastases: An update on multidisciplinary approach. World J Hepatol. 2019;11(2):150-72.

8. Kanas GP, Taylor A, Primrose JN, Langeberg WJ, Kelsh MA, Mowat FS, et al. Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors. Clin Epidemiol. 2012;4:283-301.

9. Sasaki K, Andreatos N, Margonis GA, He J, Weiss M, Johnston F, et al. The prognostic implications of primary colorectal tumor location on recurrence and overall survival in patients undergoing resection for colorectal liver metastasis. J Surg Oncol. 2016;114(7):803-9.

10. Ribero D, Vigano L, Amisano M, Capussotti L. Prognostic factors after resection of colorectal liver metastases: from morphology to biology. Future Oncol. 2013;9(1):45-57.

11. Jones RP, Brudvik KW, Franklin JM, Poston GJ. Precision surgery for colorectal liver metastases: Opportunities and challenges of omics-based decision making. Eur J Surg Oncol. 2017;43(5):875-83.

12. Amikura K, Akagi K, Ogura T, Takahashi A, Sakamoto H. The RAS mutation status predicts survival in patients undergoing hepatic resection for colorectal liver metastases: The results from a genetic analysis of all-RAS. J Surg Oncol. 2018;117(4):745-55.

13. Umeda Y, Nagasaka T, Mori Y, Sadamori H, Sun DS, Shinoura S, et al. Poor prognosis of KRAS or BRAF mutant colorectal liver metastasis without microsatellite instability. J Hepatobiliary Pancreat Sci. 2013;20(2):223-33.

14. Margonis GA, Buettner S, Andreatos N, Sasaki K, Ijzermans JNM, van Vugt JLA, et al. Anatomical Resections Improve Diseasefree Survival in Patients With KRAS-mutated Colorectal Liver Metastases. Ann Surg. 2017;266(4):641-9.

15. Margonis GA, Sasaki K, Andreatos N, Kim Y, Merath K, Wagner D, et al. KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients Undergoing Resection of Colorectal Liver Metastases. Ann Surg Oncol. 2017;24(1):264-71.

16. Pang YY. The Brisbane 2000 terminology of liver anatomy and resections. HPB 2000; 2:333-39. HPB (Oxford). 2002;4(2):99; author reply –100.

17. Fong Y, Salo J. Surgical therapy of hepatic colorectal metastasis. Semin Oncol. 1999;26(5):514-23.

18. Elias D, Lasser P, Rougier P, Debaene B. [Another failure in the attempt of definition of the indications to the resection of liver metastases of colorectal origin]. J Chir (Paris). 1992;129(2):59-65.

19. Cucchetti A, Ercolani G, Cescon M, Bigonzi E, Peri E, Ravaioli M, et al. Impact of subcentimeter margin on outcome after hepatic resection for colorectal metastases: a meta-regression approach. Surgery. 2012;151(5):691-9.

20. Kokudo N, Tada K, Seki M, Ohta H, Azekura K, Ueno M, et al. Anatomical major resection versus nonanatomical limited resection for liver metastases from colorectal carcinoma. Am J Surg. 2001;181(2):153-9.

21. Zorzi D, Mullen JT, Abdalla EK, Pawlik TM, Andres A, Muratore A, et al. Comparison between hepatic wedge resection and anatomic resection for colorectal liver metastases. J Gastrointest Surg. 2006;10(1):86-94.

22. Guzzetti E, Pulitano C, Catena M, Arru M, Ratti F, Finazzi R, et al. Impact of type of liver resection on the outcome of colorectal liver metastases: a case-matched analysis. J Surg Oncol. 2008;97(6):503-7.

23. Vauthey JN, Zimmitti G, Kopetz SE, Shindoh J, Chen SS, Andreou A, et al. RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg. 2013;258(4):619-26; discussion 26-7.

24. Kemeny NE, Chou JF, Capanu M, Gewirtz AN, Cercek A, Kingham TP, et al. KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases. Cancer. 2014;120(24):3965-71.

25. Brudvik KW, Mise Y, Chung MH, Chun YS, Kopetz SE, Passot G, et al. RAS Mutation Predicts Positive Resection Margins and Narrower Resection Margins in Patients Undergoing Resection of Colorectal Liver Metastases. Ann Surg Oncol. 2016;23(8):2635-43.

26. Lipsyc M, Yaeger R. Impact of somatic mutations on patterns of metastasis in colorectal cancer. J Gastrointest Oncol. 2015;6(6):645-9.

27. Kokudo N, Miki Y, Sugai S, Yanagisawa A, Kato Y, Sakamoto Y, et al. Genetic and histological assessment of surgical margins in resected liver metastases from colorectal carcinoma: minimum surgical margins for successful resection. Arch Surg. 2002;137(7):833-40.

28. Holdhoff M, Schmidt K, Diehl F, Aggrawal N, Angenendt P, Romans K, et al. Detection of tumor DNA at the margins of colorectal cancer liver metastasis. Clin Cancer Res. 2011;17(11):3551-7.

29. Procopio F, Vigano L, Cimino M, Donadon M, Del Fabbro D, Torzilli G. Does KRAS mutation status impact the risk of local recurrence after R1 vascular resection for colorectal liver metastasis? An observational cohort study. Eur J Surg Oncol. 2020;46(5):818-24.

30. Knijn N, Mekenkamp LJ, Klomp M, Vink-Borger ME, Tol J, Teerenstra S, et al. KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients. Br J Cancer. 2011;104(6):1020-6.

31. Wan JCM, Massie C, Garcia-Corbacho J, Mouliere F, Brenton JD, Caldas C, et al. Liquid biopsies come of age: towards implementation
of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223-38.

Downloads

Published

2020-09-30

Issue

Section

Original Papers

Most read articles by the same author(s)

<< < 1 2