Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Sep;9(17):1372.
doi: 10.21037/atm-21-292.

Cancer gene related characterization of patterns and point of recurrence after resection of colorectal liver metastases

Hauke Lang  1 , Janine Baumgart  1 , Wilfried Roth  2 , Markus Moehler  3 , Michael Kloth  2
Affiliations

Cancer gene related characterization of patterns and point of recurrence after resection of colorectal liver metastases

Hauke Lang et al. Ann Transl Med. 2021 Sep.

Abstract

Background: Outcome after resection of CRLM is hampered by a high rate of recurrence. There are little data about the role of cancer related genes and their mutations in this scenario. The aim of our analysis was to assess the predictive power of cancer-related genes and their mutations on risk for and distribution of recurrence and the time of occurrence after resection of colorectal liver metastases (CRLM).

Methods: We included 130 patients with 167 liver resections. The work-up consisted of the analysis of a total of 720 cancer-related genes by next-generation sequencing (NGS). Results were correlated with the patterns and time of recurrence and survival.

Results: At the time of analysis, 89/130 patients (68%) had developed recurrence. This included liver only recurrence in 52%, lung only recurrence in 11% and disseminated disease in 37% of cases. In univariate analysis, alterations in the RAS/RAF pathway and in the SMAD family had significant predictive power for the time of recurrence (P<0.0001) whereas single mutations did not reach statistical significance in multivariate analysis. Mutations of PIK3CA were associated with a better prognosis and a later occurrence of relapse. A recurrence risk score (r-RS) based on mutations in these cancer related genes is predictive of the time of recurrence.

Conclusions: In conclusion, mutations in the RAS/RAF pathway and the SMAD family are risk factors for early recurrence. Mutations of PIK3CA are associated with a lower risk for recurrence after resection of CRLM. Cancer related genes and their mutations do not correlate with patterns of recurrence but are predictive for the timely onset of recurrence.

Keywords: Colorectal liver metastases (CRLM); liver resection; next generation sequencing (NGS); recurrence after liver resection.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-292). HL received a research grant by MSD SHARP & DOHME (MSD Germany). MM reports grants and non-financial support from EORTC, grants and non-financial support from AIO, grants and non-financial support from German Cancer Aid, grants and non-financial support from BMBF, during the conduct of the study; personal fees from Falk Foundation, personal fees from Lilly, grants and personal fees from MSD, personal fees from Roche, grants and personal fees from Pfizer, grants, personal fees and non-financial support from Amgen, grants, personal fees and non-financial support from Bristol-Myers Squibb, grants and personal fees from Merck Serono, personal fees from MCI Group, personal fees from Taiho, outside the submitted work. MK received a research grant of the Else-Kröner-Stiftung. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Patterns of recurrence.
Figure 2
Figure 2
Recurrence free survival depending on mutations in the RAS/RAF pathway, the SMAD family and PIK3CA (recurrence risk score).
See this image and copyright information in PMC

References

    1. Jones RP, Jackson R, Dunne DF, et al. Systematic review and meta-analysis of follow-up after hepatectomy for colorectal liver metastases. Br J Surg 2012;99:477-86. 10.1002/bjs.8667 - DOI - PubMed
    1. Rees M, Tekkis PP, Welsh FK, et al. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg 2008;247:125-35. 10.1097/SLA.0b013e31815aa2c2 - DOI - PubMed
    1. Vauthey JN, Kawaguchi Y. Innovation and Future Perspectives in the Treatment of Colorectal Liver Metastases. J Gastrointest Surg 2020;24:492-6. 10.1007/s11605-019-04399-3 - DOI - PubMed
    1. Folprecht G, Gruenberger T, Bechstein WO, et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol 2010;11:38-47. 10.1016/S1470-2045(09)70330-4 - DOI - PubMed
    1. Bonnot PE, Passot G. RAS mutation: site of disease and recurrence pattern in colorectal cancer. Chin Clin Oncol 2019;8:55. 10.21037/cco.2019.08.11 - DOI - PubMed