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

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.

Informations de copyright

2021 Annals of Translational Medicine. All rights reserved.

Déclaration de conflit d'intérêts

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.