Primary tumor side is associated with prognosis of colorectal cancer patients with brain metastases

Bergen, Elisabeth; Scherleitner, Peter; Ferreira, Pedro; Kiesel, Barbara; Müller, Catharina; Widhalm, Georg; Dieckmann, Karin; Prager, Gerald W.; Preusser, Matthias; Berghoff, Anna Sophie

doi:10.1016/j.esmoop.2021.100168

Cited by 8 publications

(6 citation statements)

References 31 publications

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“…In a univariate analysis, Huerta et al [ 43 ] found that patients with RCC had a poorer survival rate than those with LCC (4.6 vs. 10.7 months; HR 3.5, p = 0.025), but in a multivariate Cox regression analysis, the difference was not significant. Another study found that CRC BMs patients with a left-sided primary tumor had a 1.5-fold better prognosis than those with a right-sided primary [ 14 ]. Right-sided CRC has a poorer prognosis than left-sided CRC, as evidenced by a greater prevalence of mucinous, undifferentiated, and signet-ring cell tumors, as well as a later stage of cancer at diagnosis [ 44 , 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…The prognosis of CRC BMs is also affected by the location of the underlying tumor. Compared to patients with left-sided CRC, those with right-sided CRC develop BMs much earlier and have a significantly worse prognosis [ 14 ]. The treatment of metastatic CRC has altered substantially in recent years, owing mostly to the development of targeted treatments and immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Primary Tumor Resection Provides Survival Benefits for Patients with Synchronous Brain Metastases from Colorectal Cancer

Cheng

Chen

et al. 2022

Diagnostics

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Background: Brain metastases (BMs), particularly synchronous brain metastases, in colorectal cancer (CRC) patients are uncommon. The survival benefit of primary tumor resection (PTR) in patients with metastatic colorectal cancer is controversial. Whether PTR can bring survival benefits to patients with BMs of CRC has not been reported. Methods: From 2010 to 2016, 581 CRC patients with BMs from the Surveillance, Epidemiology, and End Results (SEER) database were divided into PTR and non-PTR groups. The log-rank test was used to compare the survival distributions. The Kaplan-Meier method was used to estimate survival. By controlling additional prognostic factors, a Cox proportional multivariate regression analysis was used to estimate the survival benefit of PTR. Results: The median overall survival for CRC patients with synchronous BMs was 3 months, with a 1-year survival rate of 27.2% and a 2-year survival rate of 12.8%. The PTR group contained 171 patients (29.4%), whereas the non-PTR group had 410 patients (70.6%). Patients who underwent PTR had a 1-year survival rate of 40.2% compared to 21.7% in those who did not (p < 0.0001). Cox proportional analysis showed that patients ≥60 years (hazard ratio [HR] 1.718, 95% confidence interval [CI] 1.423–2.075, p < 0.0001) had a shorter OS than patients < 60 years of age. OS was better in CEA-negative than in CEA-positive patients (HR 0.652, 95% CI 0.472–0.899, p = 0.009). Patients in whom the primary tumor was removed had considerably improved prognoses (HR 0.654, 95% CI 0.531–0.805, p < 0.0001). Subgroup analysis revealed that the PTR group achieved a survival advantage except for patients with CEA negative. Conclusions: Patients with synchronous BMs from CRC may benefit from primary tumor resection (PTR). Age, CEA level, and PTR were independent prognostic risk factors for CRC patients with synchronous BMs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Primary Tumor Resection Provides Survival Benefits for Patients with Synchronous Brain Metastases from Colorectal Cancer

Cheng

Chen

et al. 2022

Diagnostics

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“…Even in recent reports, the prognosis of patients harboring CRC BMs generally remains dismal, with a median survival of 5-10 months [ 2 - 6 ]. In addition, right-sided CRC (including the appendix, cecum, and ascending colon) is associated with an unfavorable prognosis, compared with left-sided CRC (including the descending colon, sigmoid, and rectum) [ 7 ]. BMs from cecal cancer without any other simultaneous, distant metastases are extremely rare in either a synchronous or metachronous setting [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Five-Fraction Radiosurgery Using a Biologically Equivalent Dose of a Single Fraction of 24 Gy for a 3-cm Parasagittal Para-Central Sulcus Brain Metastasis From Adenocarcinoma of the Cecum

Ohtakara,

Kondo,

Obata

et al. 2023

Cureus

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An isolated single brain metastasis (BM) is an extremely rare manifestation of failure in patients with cecal adenocarcinoma (CAC). Total en bloc resection (while preserving function) of a 3-cm BM involving both the primary motor and sensory cortexes presents a conundrum: achieving long-term local control and safety of such a BM is also challenging for stereotactic radiosurgery (SRS). We describe the case of a 3.1-cm BM from CAC in the left parasagittal para-central sulcus region, which was treated using five-fraction SRS with a biologically effective dose (BED) of 81.6 Gy. In the SRS, the gross tumor volume (GTV, 7.14 cm 3 ) was defined based on computed tomography (CT)/T1/T2 matching (enhancing lesion 11.66 cm 3 ), and 98.7% of the GTV (CT/T2 mass) was covered with 43.6 Gy (58% isodose) using volumetric-modulated arcs. The maximum tumor response was partial (19.7% of the prior GTV) and sustained for 15.2 months, leaving minor neurological symptoms. However, the patient developed neurological worsening at six months, attributed to adverse radiation effects with a CT/T1/T2 mismatch, for which medical management, including the addition of bevacizumab (BEV), was effective for one year. Multi-fraction SRS with a high marginal and internal BED and sequential systemic therapy, including BEV, can be a minimally invasive, efficacious, and durable treatment option for a large CAC-BM involving the central sulcus. Early co-administration of BEV following SRS, dose escalation to the GTV boundary, and more than five fractions of SRS may be considered to improve the efficacy and safety further.

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“…In addition, studies have revealed the genetic heterogenicity of colorectal cancers, as evidenced by concurrent high-and lowfrequency mutations and transcription profile drift (10, [14][15][16]). These factors affect the susceptibility of colorectal cancer to pharmaceutical chemicals and prognosis of the patients (12,(17)(18)(19)(20). With respect to anatomical heterogeneity, the right-sided intestine originates from embryonic midgut, while the leftsided large intestine originates from embryonic hindgut.…”

Section: Introductionmentioning

confidence: 99%

Integrated single-cell RNA-seq analysis identifies immune heterogeneity associated with KRAS/TP53 mutation status and tumor-sideness in colorectal cancers

Liu

et al. 2022

Front. Immunol.

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BackgroundThe main objective of this study was to analyze the effects of KRAS/TP53 mutation status and tumor sideness on the immune microenvironment of colorectal cancer using integrated scRNA-seq data.MethodsA total of 78 scRNA-seq datasets, comprising 42 treatment-naive colorectal tumors, 13 tumor adjacent tissues and 23 normal mucosa tissues were included. Standardized Seurat procedures were applied to identify cellular components with canonical cell marks. The batch-effect was assessed and corrected using harmony algorithm. The scMetabolism algorithm was used for single-cell metabolic analysis. The results and clinical significance were further validated using immunofluorescent-staining and TCGA-COAD datasets. Immune-infiltration scores of bulk-RNA-seq data were estimated using ssGSEA. The presto-wilcoxauc algorithm was used to identify differentially enriched genes or pathways across different subgroups. Two-sided p-value less than 0.05 was considered statistically significant.ResultsWe refined the landscape of functional immune cell subtypes, especially T cells and myeloid cells, across normal mucosa, tumor adjacent and tumor tissue. The existence and function of two states of exhausted CD8+ T (Tex) subtypes in colorectal cancer, and FOLR2+ LYVE1+ macrophages indicating unfavorable prognosis in colorectal cancer were identified and validated. The diverse tumor mutation status reshaped the immune cell function and immune checkpoint ligands/receptors (ICLs/ICRs) expression pattern. Importantly, the KRAS/TP53 dual mutations significantly reduced the major energy metabolic functions in immune cells, and promoted the cell-to-cell communications towards immunosuppression in colorectal cancers. The results revealed LAG3, CD24-SIGLEC10 and HBEGF-CD9 pathways as potential therapeutic targets for dual mutant colorectal cancers.ConclusionsWe revealed that the immune microenvironment underwent a gradual remodeling with an enrichment of immunosuppressive myeloid cells from normal mucosa to tumor regions in colorectal cancers. Moreover, we revealed the metabolic heterogeneity of tumor-infiltrating immune cells and suggested that the KRAS/TP53 dual mutation may impair antitumor immunity by reducing T and myeloid cell energy metabolism and reshaping cellular interactions toward immunosuppression.

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Primary tumor side is associated with prognosis of colorectal cancer patients with brain metastases

Cited by 8 publications

References 31 publications

Primary Tumor Resection Provides Survival Benefits for Patients with Synchronous Brain Metastases from Colorectal Cancer

Primary Tumor Resection Provides Survival Benefits for Patients with Synchronous Brain Metastases from Colorectal Cancer

Five-Fraction Radiosurgery Using a Biologically Equivalent Dose of a Single Fraction of 24 Gy for a 3-cm Parasagittal Para-Central Sulcus Brain Metastasis From Adenocarcinoma of the Cecum

Integrated single-cell RNA-seq analysis identifies immune heterogeneity associated with KRAS/TP53 mutation status and tumor-sideness in colorectal cancers

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