4961 - Validation of GAME score risk groups in resected colorectal cancer liver metastases and the prognostic relevance of KRAS, NRAS and BRAF mutation analysis

Background

Hepatic resection of liver metastases is considered the optimal potentially curative treatment for colorectal liver metastases. Numerous clinical and pathological factors have been proved to be prognostic. The Genetic And Morphological Evaluation (GAME) has been proposed as a preoperative prognostic tool to select patients candidates for liver resection. This study aimed to validate the utility of GAME score risk groups in patients with colorectal liver metastases that underwent hepatic resection.

Methods

Clinical and pathological data were collected from 142 metastatic colorectal cancer patients undergoing liver resection (48% after neoadjuvant chemotherapy) between August 1999 and February 2018 at Sant Pau Hospital. The GAME score was calculated allocating points for KRAS mutation, CEA levels, lymph node metastasis, Tumour Burden score (TBS) and extrahepatic disease. We analysed the progression free survival (PFS) and overall survival (OS) according to the GAME score risk groups. Additionally, we considered other KRAS, NRAS and BRAF mutations not included in the original GAME score. Histopathological changes in malignant tissue and liver parenchyma were documented to identify potential prognostic factors for tumor recurrence.

Results

The high-risk group (GAME score ≥ 4 points) had a median PFS of 15.8 months compared with 24.2 months for the low-risk group (GAME score 0–1 point; p = 0.019). The high-risk group had a medium OS of 38.6 months compared with 68.8 months for the low-risk group (p = 0.05). When all RAS and BRAF status was considered regardless of the GAME score a median OS of 66.2 months was observed in wild type tumours compared to 44.5 months for mutated tumours (p = 0.005). Histological examination showed that a mixed and infiltrative growth pattern and the absence of a fibrotic pseudocapsule or liver cell rosettes were associated with a worse outcome.

Conclusions

The GAME score was validated as a useful preoperative prognostic tool in our cohort of patients. However, in our series, molecular profile was a prognostic factor regardless of the GAME score. Some pathologic characteristics may help on further clinical decisions after liver resection.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.