Exploring Gene Expression Signatures for Predicting Disease Free Survival after Resection of Colorectal Cancer Liver Metastases

Background and Aims: The impact of biliary invasion on recurrence and survival, after resection of colorectal cancer liver metastases, is not well known as publications are limited to small patient series. The aim was to investigate if biliary invasion in liver resected patients associated with liver relapses and recurrence-free survival. Secondary endpoints included association with other prognostic factors, disease-free survival and overall survival. Materials and Methods: All patients with histologically verified biliary invasion (n = 31, 9%) were identified among 344 patients with liver resection between January 2009 and March 2015. Controls (n = 78) were selected from the same time period and matched for, among others, size and number of colorectal cancer liver metastasis. Results: Median liver recurrence-free survival was significantly shorter in patients with biliary invasion than in controls (15.3 months versus not reached; p = 0.031) and more relapses were noted in the liver (61.3% versus 33.3%; p = 0.010), respectively. In univariate analyses for liver recurrence-free survival, biliary invasion was the only significant prognostic factor; p = 0.034. There were no statistical differences in disease-free and overall survival between the groups. Conclusion: Biliary invasion was associated with higher liver recurrence rates and shorter liver recurrence-free survival in patients with resected colorectal cancer liver metastasis.

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Liver Transplantation for Non-Resectable Liver Metastases from Colorectal Cancer: A Systematic Review and Meta-Analysis

World Journal of Surgery ◽

10.1007/s00268-021-06248-4 ◽

2021 ◽

Author(s):

Rebecca Varley ◽

Munir Tarazi ◽

Madhav Davé ◽

Shahd Mobarak ◽

Martyn C. Stott ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Transplantation ◽

Liver Metastases ◽

Colorectal Liver Metastases ◽

Palliative Chemotherapy ◽

Meta Analysis ◽

Disease Free Survival ◽

Current Evidence ◽

Free Survival ◽

Disease Free

Abstract Backgrounds Colorectal liver metastases were historically considered a contraindication to liver transplantation, but dismal outcomes for those with metastatic colorectal cancer and advancements in liver transplantation (LT) have led to a renewed interest in the topic. We aim to compare the current evidence for liver transplantation for non-resectable colorectal liver metastases (NRCLM) with the current standard treatment of palliative chemotherapy. Methods A systematic review and meta-analysis of proportions was conducted following screening of MEDLINE, EMBASE, SCOPUS and CENTRAL for studies reporting liver transplantation for colorectal liver metastases. Post-operative outcomes measured included one-, three- and five-year survival, overall survival, disease-free survival and complication rate. Results Three non-randomised studies met the inclusion criteria, reporting a total of 48 patients receiving LT for NRCLM. Survival at one-, three- and five-years was 83.3–100%, 58.3–80% and 50–80%, respectively, with no significant difference detected (p = 0.22, p = 0.48, p = 0.26). Disease-free survival was 35–56% with the most common site of recurrence being lung. Thirteen out of fourteen deaths were due to disease recurrence. Conclusion Although current evidence suggests a survival benefit conferred by LT in NRCLM compared to palliative chemotherapy, the ethical implications of organ availability and allocation demand rigorous justification. Concomitant improvements in the management of patients following liver resection and of palliative chemotherapy regimens is paramount.

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Multicenter Randomized Trial of Adjuvant Fluorouracil and Folinic Acid Compared With Surgery Alone After Resection of Colorectal Liver Metastases: FFCD ACHBTH AURC 9002 Trial

Journal of Clinical Oncology ◽

10.1200/jco.2006.06.8353 ◽

2006 ◽

Vol 24 (31) ◽

pp. 4976-4982 ◽

Cited By ~ 376

Author(s):

Guillaume Portier ◽

Dominique Elias ◽

Olivier Bouche ◽

Philippe Rougier ◽

Jean-François Bosset ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Liver Metastases ◽

Odds Ratio ◽

Systemic Chemotherapy ◽

Disease Free Survival ◽

Secondary Outcome ◽

Control Group ◽

Free Survival ◽

Disease Free

Purpose Complete resection of liver metastases of colorectal origin is the only potentially curative treatment. In order to decrease recurrences, the use of adjuvant systemic chemotherapy after liver resection is controversial because no randomized study demonstrated its benefit. Patients and Methods In a multicenter trial, we randomly assigned 173 patients with completely resected (R0) hepatic metastases from colorectal cancer to surgery alone and observation (87 patients) or to surgery followed by 6 months of systemic adjuvant chemotherapy with a fluorouracil and folinic acid monthly regimen (86 patients). The main outcome criterion was disease-free survival. Secondary outcome measures were overall survival and treatment-related toxicity. Results The intention-to-treat analysis was based on 171 patients, after a median follow-up of 87 months (SE = 5.8). The 5-year disease-free survival rate, after adjustment for major prognostic factors, was 33.5% for patients in the chemotherapy group and 26.7% for patients in the control group (Cox multivariate analysis: odds ratio for recurrence or death = 0.66; 95% CI, 0.46 to 0.96; P = .028). With regard to secondary outcome measures, a trend towards increased overall survival was observed but did not reach statistical significance (5-year overall survival: chemotherapy group, 51.1% v control group, 41.1%; odds ratio for death, 0.73; 95% CI, 0.48 to 1.10; P = .13). Conclusion Despite a suboptimal regimen, which was the standard at the beginning of the study, adjuvant intravenous systemic chemotherapy provided a significant disease-free survival benefit for patients with resected liver metastases from colorectal cancer.

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Generation and application of a colorectal cancer microarray library to identify a novel prognostic biomarker, adipose differentiation related protein (adipophilin).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.508 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 508-508

Author(s):

John Hogan ◽

Laura O Byrne ◽

Michael O Callaghan ◽

Matthew F. Kalady ◽

John C. Coffey

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Gene Expression Data ◽

Late Stage ◽

Disease Free Survival ◽

Adverse Outcomes ◽

Expression Data ◽

Related Protein ◽

Free Survival ◽

Disease Free

508 Background: Substantial volumes of genetic expression data are archived within public gene expression repositories (PGER). Although the data contained is reported according to particular standards, it is not feasible to search the data using clinically relevant search terms (i.e., oncologic outcome). This study aimed to generate an archive of microarray expression data that could be searched using oncologically-relevant terminology, and then to test this facility. Methods: A UL Colorectal Cancer Archive was established based on data derived from the Gene Expression Omnibus (GEO). A software (Rover) was developed to permit clinically relevant searches using terminology such as stage and disease-free survival. As a first test, experiments were identified that compared early and late stage colorectal cancer. From these, consensus profiles were developed and adipocyte differentiation related protein identified as the top-most frequently dysregulated gene. As a second test, the cancer archive was again challenged to identify data sets annotated with outcome data. The association between ADFP and outcome was assessed using a regression-tree (CRT) based approach and Kaplan-Meier estimates. Results: The UL Colorectal cancer archive was constructed so as to permit the novice-user to search for gene expression data associated with particular clinical parameters. Rover was a graphic user interface that permitted these searches. ADFP was identified as dysregulated across the majority of experiments comparing early and late stage colorectal cancer. CRT-analyses identified levels of ADFP above which adverse outcomes were identified. In general, increasing ADFP was independently associated with adverse disease-free outcomes in stage II and III cancer. Conclusions: A novel archive of gene expression data was generated that (a) related to colorectal cancer and (b) could be searched using clinically-relevant terms. Using this archive ADFP was identified as dysregulated between early and late stage colorectal cancer. Increasing ADFP expression levels were associated with adverse disease-free survival in stages II and III colorectal cancer.

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Abstract GS3-02: Invasive disease-free survival and gene expression signatures in CALGB (Alliance) 40601, a randomized phase III neoadjuvant trial of dual HER2-targeting with lapatinib added to chemotherapy plus trastuzumab

10.1158/1538-7445.sabcs17-gs3-02 ◽

2018 ◽

Cited By ~ 1

Author(s):

IE Krop ◽

D Hillman ◽

M-Y Polley ◽

M Tanioka ◽

J Parker ◽

...

Keyword(s):

Gene Expression ◽

Disease Free Survival ◽

Invasive Disease ◽

Phase Iii ◽

Free Survival ◽

Gene Expression Signatures ◽

Disease Free

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SURGICAL OUTCOMES AND PROGNOSTIC FACTORS IN PATIENTS WITH SYNCHRONOUS COLORECTAL LIVER METASTASES

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032014000100002 ◽

2014 ◽

Vol 51 (1) ◽

pp. 4-9 ◽

Cited By ~ 1

Author(s):

Rafael FONTANA ◽

Paulo HERMAN ◽

Vincenzo PUGLIESE ◽

Marcos Vinicius PERINI ◽

Fabricio Ferreira COELHO ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Liver Metastasis ◽

Liver Metastases ◽

Colorectal Liver Metastases ◽

Disease Free Survival ◽

Term Survival ◽

Free Survival ◽

Disease Free

Context Colorectal cancer is the second most prevalent cancer worldwide, and the liver is the most common site of metastases. Surgical resection of colorectal liver metastases provides the sole possibility of cure and the best odds of long-term survival. Objectives To describe surgical outcomes and identify features associated with disease prognosis in patients submitted to synchronous colorectal cancer liver metastasis resection. Methods Retrospective study of 59 patients who underwent surgery for synchronous colorectal cancer liver metastasis. Actuarial survival and disease-free survival were assessed, depending on the prognostic variable of interest. Results Postoperative mortality and morbidity rates were 3.38% and 30.50% respectively. Five-year disease-free survival was estimated at 23.96%, and 5-year overall survival, at 38.45%. Carcinoembryonic antigen levels ≥50 ng/mL and presence of three or more liver metastasis were limiting factors for disease-free survival, but did not affect late survival. No patient with liver metastases and extrahepatic disease had disease-free interval longer than 20 months, but this had no significance or impact on long-term survival. None of the prognostic factors assessed had an impact on late survival, although no patients with more than three liver metastases survived beyond 40 months. Conclusions Although Carcinoembryonic antigen levels and number of metastases are prognostic factors that limit disease-free survival, they had no impact on 5-year survival and, therefore, should not determine exclusion from surgical treatment. Resection is the best treatment option for synchronous colorectal liver metastases, and even for patients with multiple metastases, large tumors and extrahepatic disease, it can provide long-term survival rates over 38%.

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TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

Cell Death and Disease ◽

10.1038/s41419-021-03734-4 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Sha Zhou ◽

Jianhong Peng ◽

Liuniu Xiao ◽

Caixia Zhou ◽

Yujing Fang ◽

...

Keyword(s):

Colorectal Cancer ◽

Disease Free Survival ◽

Free Survival ◽

Epigenetic Regulator ◽

Crc Management ◽

Disease Free ◽

Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

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Thymidylate synthase expression pattern, expression level and single nucleotide polymorphism are predictors for disease-free survival in patients of colorectal cancer treated with 5-fluorouracil

International Journal of Oncology ◽

10.3892/ijo.28.5.1303 ◽

2006 ◽

Author(s):

María-Encarnación Fernández-Contreras ◽

Sandra Sánchez-Prudencio ◽

José-Javier Sánchez-Hernández ◽

María-Luisa García de Paredes ◽

Javier Gisbert ◽

...

Keyword(s):

Colorectal Cancer ◽

Single Nucleotide Polymorphism ◽

Expression Pattern ◽

Thymidylate Synthase ◽

Disease Free Survival ◽

Expression Level ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Free Survival ◽

Disease Free

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Radiofrequency Ablation of Hepatic Metastases from Colorectal Cancer: Are Newer Generation Probes Better?

The American Surgeon ◽

10.1177/000313480607201007 ◽

2006 ◽

Vol 72 (10) ◽

pp. 875-879 ◽

Cited By ~ 8

Author(s):

Aziz Ahmad ◽

Steven L. Chen ◽

Maihgan A. Kavanagh ◽

David P. Allegra ◽

Anton J. Bilchik

Keyword(s):

Colorectal Cancer ◽

Radiofrequency Ablation ◽

First Generation ◽

Hepatic Metastases ◽

Disease Free Survival ◽

Cancer Center ◽

Free Survival ◽

Alive With Disease ◽

Disease Free

Second-generation radiofrequency ablation (RFA) probes and their successors have more power, shorter ablation times, and an increased area of ablation compared with the first-generation probes used before 2000. We examined whether the use of the newer probes has improved the clinical outcome of RFA for hepatic metastases of colorectal cancer at our tertiary cancer center. Of 160 patients who underwent RFA between 1997 and 2003, 52 had metastases confined to the liver: 21 patients underwent 46 ablations with the first-generation probes and 31 patients underwent 58 ablations with the newer probes. The two groups had similar demographic characteristics. At a median follow-up of 26.2 months, patients treated with the newer probes had a longer median disease-free survival (16 months vs 8 months, P < 0.01) and a lower rate of margin recurrence (5.2% vs 17.4%); eight patients had no evidence of disease and one patient was alive with disease. By contrast, of the 46 patients treated with the first-generation probes, 2 patients had no evidence of disease and 1 patient was alive with disease. Newer-generation probes are associated with lower rates of margin recurrence and higher rates of disease-free survival after RFA of hepatic metastases from colorectal cancer.

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