New Artificial Intelligence Score and Immune Infiltrates as Prognostic Factors in Colorectal Cancer With Brain Metastases

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.

Single-fraction SRS and multiple-fraction SRT for brain metastases from colorectal cancer

“…Complete response (CR): All target lesions disappeared completely ( 2 ). Partial response (PR): The total diameter of the target lesion was reduced by ≥30% ( 3 ). Progressive disease (PD): The total diameter of the target lesion increased by ≥20% ( 4 ).…”

“…The ratio of CR+PR is defined as the objective response rate (ORR), while the ratio of CR+PR+SD is defined as the local control rate (LCR). Radiation-induced brain necrosis was diagnosed when at least 2 of the criteria listed below were fulfilled ( 8 ) ( 1 ): On enhanced MRI or CT images, the lesions showed irregular borderP enhancement with obvious oedema ( 2 ); MRI or CT perfusion imaging showed hypoperfusion in the lesion ( 3 ); MRS suggested a decreased Cho value in the enhanced area ( 4 ); PET revealed that the uptake of 18 F-FDG in the enhanced area was significantly decreased. Overall survival (OS) was defined as the time from the diagnosis of brain metastasis to death or the end of the follow-up period.…”

“…CRC is one of the most common tumours worldwide, and the survival time of these patients has gradually improved with advancements in systemic therapy. Brain metastasis from CRC is also becoming increasingly common ( 3 ).…”

Changes in Tumor Immune Microenvironment after Radiotherapy Resistance in Colorectal Cancer: A Narrative Review

“…They are the most studied TIME-associated immune cells and play important parts in the anti-tumor immune response [97]. Studies have found that CRC tumors with fewer tumorinfiltrating T cells are not sensitive to radiotherapy [98][99][100][101]. With regard to T cell subtypes, lower proportions of CD4+ T and CD8+ T cells have been observed in the TIME of radiotherapy-resistant CRC tumors [54,91,[102][103][104][105][106][107][108], with a greater proportion of regulatory T cells (Tregs) [75,[109][110][111].…”

Potential role of PRKCSH in lung cancer: bioinformatics analysis and a case study of Nano ZnO

“…PRKCSH expression is correlated with immune cell infiltration in patients with lung carcinoma Previous studies have reported that the survival time of cancer patients depends on the quantity and activity of tumour-infiltrating lymphocytes. 24,25 Therefore, we used the TIMER database to investigate the association between PRKCSH expression and immune cell infiltration in various types of cancer. We found that PRKCSH expression levels in bladder urothelial carcinoma, breast invasive carcinoma, LUAD, and lung squamous cell carcinoma cancer tissues were negatively correlated with tumour purity and the infiltration of B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells (Fig.…”