Cancer‐associated stroma reveals prognostic biomarkers and novel insights into the tumour microenvironment of colorectal cancer and colorectal liver metastases

Background : Liver metastases of colorectal cancer are frequent and potentially fatal event in the evolution of patients with these tumors. Aim : In this module, was contextualized the clinical situations and parameterized epidemiological data and results of the various treatment modalities established. Method: Was realized deep discussion on detecting and staging metastatic colorectal cancer, as well as employment of imaging methods in the evaluation of response to instituted systemic therapy. Results : The next step was based on the definition of which patients would have their metastases considered resectable and how to expand the amount of patients elegible for modalities with curative intent. Conclusion : Were presented clinical, pathological and molecular prognostic factors, validated to be taken into account in clinical practice.

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Abstract 3419: VEGFA and SLC2A1 are prognostic biomarkers for patients with resectable colorectal cancer liver metastases

10.1158/1538-7445.am2015-3419 ◽

2015 ◽

Author(s):

Jeroen A.C.M. Goos ◽

Erienne M.V. de Cuba ◽

Veerle M.H. Coupe ◽

Begona Diosdado ◽

Pien M. Delis-van Diemen ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Prognostic Biomarkers ◽

Colorectal Cancer Liver Metastases

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METACHRONOUS COLORECTAL LIVER METASTASES HAS BETTER PROGNOSIS - IS IT TRUE?

Arquivos de Gastroenterologia ◽

10.1590/s0004-2803.201800000-64 ◽

2018 ◽

Vol 55 (3) ◽

pp. 258-263 ◽

Cited By ~ 1

Author(s):

Claudemiro QUIREZE JUNIOR ◽

Andressa Machado Santana BRASIL ◽

Lúcio Kenny MORAIS ◽

Edmond Raymond Le CAMPION ◽

Eliseu José Fleury TAVEIRA ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Liver Metastases ◽

Hepatic Metastasis ◽

Colorectal Liver Metastases ◽

Public Health Problem ◽

Recurrence Free Survival ◽

Free Survival ◽

The Mean ◽

Colorectal Hepatic Metastasis

ABSTRACT BACKGROUND: Liver metastases from colorectal cancer are an important public health problem due to the increasing incidence of colorectal cancer worldwide. Synchronous colorectal liver metastasis has been associated with worse survival, but this prognosis is controversial. OBJECTIVE: The objective of this study was to evaluate the recurrence-free survival and overall survival between groups of patients with metachronous and synchronous colorectal hepatic metastasis. METHODS: This was a retrospective analysis of medical records of patients with colorectal liver metastases seen from 2013 to 2016, divided into a metachronous and a synchronous group. The Cox regression model and the Kaplan-Meier method with log-rank test were used to compare survival between groups. RESULTS: The mean recurrence-free survival was 9.75 months and 50% at 1 year in the metachronous group and 19.73 months and 63.3% at 1 year in the synchronous group. The mean overall survival was 20.00 months and 6.2% at 3 years in the metachronous group and 30.39 months and 31.6% at 3 years in the synchronous group. Patients with metachronous hepatic metastasis presented worse overall survival in multivariate analysis. The use of biological drugs combined with chemotherapy was related to the best overall survival prognosis. CONCLUSION: Metachronous colorectal hepatic metastasis was associated with a worse prognosis for overall survival. There was no difference in recurrence-free survival between metachronous and synchronous metastases.

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HCT116 colorectal liver metastases exacerbate muscle wasting in a mouse model for the study of colorectal cancer cachexia

Disease Models & Mechanisms ◽

10.1242/dmm.043166 ◽

2020 ◽

Vol 13 (1) ◽

pp. dmm043166 ◽

Cited By ~ 3

Author(s):

Joshua R. Huot ◽

Leah J. Novinger ◽

Fabrizio Pin ◽

Andrea Bonetto

Keyword(s):

Colorectal Cancer ◽

Mouse Model ◽

Liver Metastases ◽

Colorectal Liver Metastases ◽

Cancer Cachexia ◽

Muscle Wasting

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Extending the Limits of Resection for Colorectal Liver Metastases: Positive Resection Margin and Outcome After Resection of Colorectal Cancer Liver Metastases

Journal of Gastrointestinal Surgery ◽

10.1007/s11605-016-3253-5 ◽

2016 ◽

Vol 21 (1) ◽

pp. 196-198 ◽

Cited By ~ 2

Author(s):

Motaz Qadan ◽

Michael I. D’Angelica

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Colorectal Liver Metastases ◽

Resection Margin ◽

Positive Resection Margin ◽

Colorectal Cancer Liver Metastases

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Stereotactic body radiation therapy for local control of liver metastases from colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.662 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 662-662

Author(s):

Ji Hyeon Joo ◽

Jong Hoon Kim

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Local Control ◽

Colorectal Liver Metastases ◽

Lesion Size ◽

Dose Fractionation ◽

Pattern Of Failure ◽

N Stage ◽

Hepatic Lesions ◽

Significant Factors

662 Background: Although possible candidates for surgical treatment are increasing, majority of colorectal cancer patients with liver metastases are ineligible for surgery. In our institution, SBRT for liver metastatic colorectal carcinoma has been adopted since 2005. By reviewing the treatment outcomes of relatively large cohorts treated with homogeneous technique, we aimed to report patterns of recurrence and the most effective dose fractionation schedule. Methods: Seventy patients with colorectal liver metastases were treated with SBRT from 2005 to 2014. Total number of treated lesions was 103. Median tumor size was 2.5 cm, with ≥ 3 cm in 42 (41%) lesions. Prescribed doses were biologically equivalent dose (BED) ≥ 112 Gy10, but, if small bowel is adjacent to target volume, dose was decreased according to the normal tissue tolerance dose. Prescription doses relevant to BED ≥ 112 Gy10 were ≥ 45 Gy in 3 fractions or ≥ 60 Gy in 5 fractions, in this study. Results: Median follow-up period was 34.2 months (range, 5.3-121.8). The 2-year local control rate was 92% when full prescription dose was delivered, and 73% if compromised dose group was included. On prognostic factor analysis for local control, N-stage (P= 0.008), and BED (P= 0.001) were significant factors. Overall survival rate was 86% for BED ≥ 112 Gy10 group, and 73% for total cohort. The major pattern of failure was out-of-field intrahepatic progression. On multivariate analysis, N stage (P= 0.001), lesion size (P= 0.010) and number of treated hepatic lesions (P< 0.001) were significant factors for intrahepatic control. Conclusions: Liver SBRT was an effective treatment option for colorectal liver metastases. If BED ≥ 112 Gy10 was delivered, we could expect long-term survival in substantial portion of patients. Major pattern of failure was out-of-field intrahepatic progression, which was related to number of treated hepatic lesions, lesion size and N-stage.

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Prognostic impact of mutation profiling in Chinese patients with colorectal liver metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15157 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15157-e15157

Author(s):

Kun Wang ◽

Yadong Yang ◽

Xiaoyu Zhang ◽

Juan Li ◽

Quan Bao ◽

...

Keyword(s):

Liver Metastases ◽

Colorectal Liver Metastases ◽

Disease Free Survival ◽

Copy Number Variations ◽

Prognostic Biomarkers ◽

Chinese Patients ◽

Driver Gene ◽

Prognostic Impact ◽

Synonymous Mutations ◽

Mutation Profiling

e15157 Background: To investigate mutation profiling in Chinese patients with colorectal liver metastases and explore new prognostic biomarkers. Methods: We investigated 197 patients who underwent surgery for colorectal liver metastases at Beijing Cancer Hospital between January 2015 and February 2017. Tumor DNA was isolated from FFPE tissues from liver metastatic lesions. Mutation spectrum was obtained by targeted deep sequencing of 620 selected genes. Tumor mutational burden (TMB) was defined as the number of non-synonymous mutations per 1Mbp and divided into quartiles. MSI status was tested with next-generation sequencing. Studies of impacts of mutation status on disease-free survival (DFS) and overall survival (OS) were performed with Kaplan-Meier analysis. Results: Mutation significance analysis confirmed enrichment in colorectal cancer driver gene mutations of TP53, APC, KRAS, SMAD4, SOX9, FBXW7 and PIK3CA in 72%, 61%, 29%, 14%, 10%, 10% and 9% of liver metastases, with no BRAF mutation found in any of these patients. Additionally, we observed frequent gene-level copy number variations, including amplifications of MYC, BRCA2, ERBB2, CCND2 and deletion of APC. Among 197 patients, only three showed MSI-high, who also exhibited high TMBs. Moreover, KRAS, MXRA5, and SETD2 mutations were significantly associated with shorter DFS ( KRAS mt vs wt: 8 months vs 11 months, p = 0.0086; MXRA5 mt vs wt: 6 months vs 11 months, p = 0.0178; SETD2 mt vs wt: 8 months vs 11 months, p = 0.0381), but KMT2A mutation associated with longer DFS (mt vs wt: 31.5 months vs 10 months, p = 0.0409). SPEN, GNAS, CTNNB1, SETD2 and FANCM mutations were significantly associated with poor OS ( SPEN mt vs wt: 23 months vs 30 months, p = 0.0047; GNAS mt vs wt: 24.5 months vs 30 months, p = 0.0386; CTNNB1 mt vs wt: 20 months vs 30 months, p = 0.0001; SETD2 mt vs wt: 20 months vs 30 months, p = 0.0026; FANCM mt vs wt: 13 months vs 30 months, p = 0.0007). Conclusions: Our study has found a novel panel of prognostic biomarkers in colorectal liver metastases. The clinical significance of mutations of MXRA5, SETD2, KMT2A, SPEN, GNAS, CTNNB1, FANCM needs to be confirmed on a larger scale.

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