Abstract
Incidence of brain metastases has increased in patients with colorectal cancer (CRC) as their survival has improved. CD3 T-cells and, lately, DGMate (DiGital tuMor pArameTErs) score, have been identified as prognostic factors in locally advanced CRC. Until now, there is no data concerning the prognostic value of these markers in patients with CRC-derived brain metastases. All consecutive patients with CRC-derived brain metastases diagnosed between 2000 and 2017 were retrospectively included. Staining for CD3, CD8, PD-1, PD-L1 and DGMate analyses were performed using tissue micro-array from primary tumors and, if available, brain metastases. All in all, 83 patients were included with 80 primary tumor samples and 37 brain metastases samples available. CD3 and CD8 T-cell infiltration was higher in primary tumors compared to brain metastases. We observed a significant higher DGMate score in rectal tumors compared to colon tumors (p=0.03). We also noted a trend of higher CD3 T-cell infiltration in primary tumors when brain metastases were both supra and subtentorial compared to brain metastases that were only subtentorial or supratentorial (p=0.36 and p=0.03, respectively). No correlation was found between CD3 or CD8 infiltration or DGMate score in primary tumors or brain metastases and overall survival (OS) in the overall population. In patients with rectal tumors, a high DGMate score in brain metastases was associated with longer OS (13.4 ± 6.1 months versus 6.1 ± 1.4 months, p=0.02). High CD3 T-cell infiltration in brain metastases was associated with lower OS in patients with supratentorial brain metastases (9.8 ± 3.3 months versus 16.7 ± 5.9 months, p=0.03). PD-L1 overexpression was rare, both in primary tumors and brain metastases, but PD-L1 positive primary tumors were associated with worse OS (p=0.01). In contrast to breast and lung cancer derived brain metastases, CD3 and CD8 infiltration and DGMate score are not major prognostic factors in patients with CRC-derived brain metastases.
Highlights
The prognosis of patients with metastatic colorectal cancer has improved and median overall survival (OS) is about three years
Eighty-three patients were included with primary tumors (PT) samples available in 80 cases and brain metastases (BM) tissues available for 37 patients
Since CD3 T-cell infiltration and/or DiGital tuMour pArameTErs (DGMate) scores were different according to PT site, BMs location and BMs number, we looked for a potential prognostic impact in these subgroups
Summary
The prognosis of patients with metastatic colorectal cancer (mCRC) has improved and median overall survival (OS) is about three years. The percentage of CD3+ T cells at the invasive margin of locally advanced CRC is a predictive factor of metachronous metastases [7] It remains a robust prognostic factor at the metastatic stage [8]. More biological insight is needed to characterize dynamic and prognostic significance of immune infiltration, especially by CD3+ T cells, in this rare subgroup of CRC with BMs. An artificial intelligence software device, using a LASSO algorithm called DiGital tuMour pArameTErs (DGMate), was shown in the PETACC08 study to predict the prognosis of locally advanced colon cancers (stage III) [11]. A predictive nomogram based on DGMate, CD3 TIL and clinical variables has identified a group of patients with less than 10% relapse risk and another group with a 50% relapse risk in stage III CRC These tools are not yet validated in mCRC. We analyzed both CD3 infiltration and DGMate score in a rare series of CRC-derived BM to assess whether CD3 infiltration and/or DGMate score were prognostic factors in CRC-derived BMs
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