Growth patterns of liver metastases as compared to resected tumors of the same colorectal cancer patients.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 519-519
Author(s):  
Rikke Loevendahl Eefsen ◽  
Gert G. Van den Eynden ◽  
Pnina Brodt ◽  
Julia V. Burnier ◽  
Gunilla Hoyer-Hansen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Metastatic Disease ◽  
Growth Pattern ◽  
Biological Diversity ◽  
Hepatic Metastases ◽  
Tnm Staging ◽  
Growth Patterns ◽  
Laboratory Evaluation ◽  
Metastatic Tumour

519 Background: Colorectal cancer (CRC) affects one million people a year. 25% of the patients have metastatic disease at the time of diagnosis. Metastatic disease is one of the major challenges in the treatment of cancer. Even though the TNM staging system is a good prognostic marker, tumours have a biological diversity that cannot be evaluated by the TNM system. Recently three different growth patterns of CRC liver metastases were identified. The aim of this study was to determine the growth patterns of CRC liver metastases from patients with more than one metastasis. Methods: A pilot study was conducted including 34 patients resected for CRC liver metastases, 28 patients selected from a database of 200 patients, operated in Copenhagen between 2007-2010 and 6 patients, operated in Montreal. From these 34 patients, 15 patients were resected for two or more liver metastases. All paraffin embedded tissue sections were stained for reticulin and haematoxylin and eosin at the Finsen Laboratory. Evaluation of the growth pattern was done by three different observers from Antwerp and Copenhagen. Reproducibility was >90%. Results: In the fifteen patients, 9 from Copenhagen and 6 from Montreal, that had multiple hepatic metastases, there was uniformity in the growth pattern of the individual metastases. 40% had a desmoplastic, 33% a pushing and 20% a replacement growth pattern and 7% had a mix pattern. Of the 9 patients from Copenhagen 33% were synchronous and 67% metachronous metastases. Within patients, all patterns were identical. Conclusions: The uniformity of growth patterns seen in each patient suggests that these patterns are not random. The identical growth pattern may be determined by specific interactions between the tumor and the host microenvironment, as postulated by Paget’s seed and soil theory. This could represent three different stromal and cytokine responses or oncogenic pathway responses and could represent metastatic tumour growth in different microenvironments.

Radioembolization of unresectable hepatic metastases using yttrium-90 microspheres in heavily pretreated colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 559-559
Author(s):  
M. E. Hill ◽  
M. F. Mulcahy ◽  
R. Lewandowski ◽  
A. Rademaker ◽  
R. Salem
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Metastatic Colorectal Cancer ◽  
Metastatic Disease ◽  
Hepatic Metastases ◽  
Extrahepatic Disease ◽  
Disease Stabilization ◽  
Heavily Pretreated ◽  
One Year ◽  
Yttrium 90

559 Background: Yttrium-90 (Y90) microsphere liver-directed treatment has previously demonstrated the ability to provide disease stabilization to patients with liver-dominant metastatic colorectal cancer. Methods: We conducted a retrospective analysis of 36 patients with metastatic colorectal cancer who had undergone Y90 liver-directed therapy between November 2001 and March 2009. All patients had previously received 5-fluorouracil, irinotecan, and oxaliplatin and had unresectable hepatic metastases, with or without extrahepatic metastases. Results: Thirty-six patients with a mean age of 58 were included in the analysis. Twenty patients had both hepatic and extrahepatic metastatic disease and 16 had liver-confined metastatic disease at the time of first Y90 treatment. Radiologic response rate with stabilization of liver metastases was 72%. Median survival from time of diagnosis of liver metastases and from time of first Y90 treatment was 31.7 months and 9.4 months, respectively. One patient is still alive. Nine patients received only one Y90 treatment, 20 patients received two treatments, and 7 patients received three treatments. One-year survival from first Y90 treatment was 47%, and 53% of these patients had no extrahepatic metastatic disease prior to therapy, 41% had minimal extrahepatic disease, and 6% had significant extrahepatic disease. Fifty-three percent of patients survived less than one year after the first Y90 treatment. Of these, 36.8% had no evidence of extrahepatic metastatic disease prior to first Y90 therapy, 31.6% had a small volume of extrahepatic disease, and 31.6% had extensive extrahepatic disease. Conclusions: Liver-directed therapy with Y90 was observed to control the growth of unresectable metastatic liver disease in the majority of patients with heavily-pretreated colorectal cancer. A significantly smaller proportion of patients who survived a year or more had extensive extrahepatic mestastatic disease at the time of first Y90 treatment than those who survived less than a year. This suggests a potential survival advantage of Y90 liver-directed treatment in patients with primary liver metastatic disease and minimal extrahepatic disease. [Table: see text]

RAS mutational status and CEA production at initial presentation in metastatic colorectal cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 542-542
Author(s):  
May Thet Cho ◽  
Leanne Goldstein ◽  
Chie Akiba ◽  
S. Cecilia Lau ◽  
Milhan Telatar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Metastatic Colorectal Cancer ◽  
Metastatic Disease ◽  
Hepatic Metastases ◽  
Small Sample ◽  
Eligibility Criteria ◽  
Mutational Status ◽  
Ras Status ◽  
The Impact

542 Background: Serial CEA testing is recommended in the surveillance of patients with resected stage II-IV colorectal cancer. However, the sensitivity of CEA in identifying metastatic disease has not been evaluated in the settings of RAS mutant (MT) and RAS/BRAF wild-type tumors (WT). In order to evaluate the impact of RAS mutational status on CEA production, we retrospectively evaluated a single-institute metastatic colorectal cancer (mCRC) population. Methods: We retrospectively reviewed, in a single center, all cases with mCRC with known RAS mutational status based on next generation sequencing (ONCO44 and ONCO48). These assays identify clinically relevant mutations in BRAF, KRAS, and NRAS. Additional eligibility criteria included the availability of CEA levels and imaging studies at first diagnosis of mCRC. Patient demographics, primary tumor location and sites of metastatic disease at 1st diagnosis were captured. CEA levels were stratified as normal or elevated based on a cut point of 5ng/ml. Results: 139 mCRC patients satisfied the eligibility criteria (75 RAS-MT, 59 RAS/BRAF-WT, and 5 BRAF-MT). BRAF-MT patients were excluded from the analysis due to their small sample size. Patients with RAS/BRAF-WT tumors were more likely to present with metastatic disease to the liver, but this did not reach statistical significance (p = 0.056). There was no difference in the incidence of normal CEA at presentation in RAS-MT (30%) and RAS/BRAF-WT (28%) cohorts. CEA production was dependent on the pattern of metastatic disease. Elevated CEA was associated with the presence of liver metastases versus no metastases among RAS-MT (92% vs 47% p <.0001) and RAS/BRAF-WT patients (82% vs 50% p = 0.0101). RAS status did not impact the likelihood of CEA production within the hepatic metastases and non-hepatic metastases groups. Conclusions: RAS status does not appear to influence CEA production in patients with mCRC. CEA elevations are highly associated with liver metastases and are less prevalent in patients without hepatic involvement. These findings confirm the limited predictive value of CEA for non-hepatic recurrence, irrespective of RAS status.

scholarly journals Bevacizumab in neoadjuvant treatment of patients with liver metastases from colorectal carcinoma

2010 ◽  
Vol 18 (3) ◽  
pp. 75-78
Author(s):  
Ivan Nikolic ◽  
Svetlana Pavin ◽  
Biljana Kukic ◽  
Bogdan Bogdanovic ◽  
Miroslav Ilic ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Neoadjuvant Treatment ◽  
Hepatic Metastases ◽  
Response Rates ◽  
Control Group ◽  
Significant Difference ◽  
Experimental Group ◽  
Selection Of Patients ◽  
Selection Of

Background: Liver metastases are the leading cause of death in patients with colorectal cancer. Despite advances in chemotherapy, surgical resection of hepatic metastases is still considered the only curative options. However, the majority of patients have inoperable disease at presentation. Perioperative chemotherapy is the most successful way for improved selection of patients for resection. The aim of the study was to demonstrate if and to what extent does bevacizumab, introduced in chemotherapy, increase response rates, and development of liver metastases. Methods: Our study included 50 patients who were divided in two groups. The experimental group included patients who were treated with bevacizumab plus chemotherapy, and the control group included patients who were treated with chemotherapy only. Results: The comparison showed that the patients who were treated with bevacizumab became candidates for resection of liver metastases in higher percentage (85%:52%). In addition, distribution of patients regarding the development of metastases resulted in statistically significant difference. Ratio between the patients with good response from the experimental and the control group was 67%:39%. Ratio of patients with stable disease was 26%:48%, and of patients with progressive disease, it was 7%:3%. The estimate of margin after resection was statistically insignificant. Conclusion: Bevacizumab in combination with chemotherapy in therapy of liver metastases from primary colorectal cancer improves and increases response rates and development of liver metastases.

scholarly journals Primary Tumor Location Is a Prognostic Factor for Intrahepatic Progression-Free Survival in Patients with Colorectal Liver Metastases Undergoing Portal Vein Embolization as Preparation for Major Hepatic Surgery

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1638
Author(s):  
Lea Hitpass ◽  
Daniel Heise ◽  
Maximilian Schulze-Hagen ◽  
Federico Pedersoli ◽  
Florian Ulmer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Confidence Interval ◽  
Portal Vein ◽  
Liver Metastases ◽  
Portal Vein Embolization ◽  
Hepatic Metastases ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Free Survival ◽  
Right Hemihepatectomy

The aim of this study was to identify prognostic factors affecting intrahepatic progression-free survival (ihPFS) and overall survival (OS) in patients with colorectal cancer liver metastases (CRCLM) undergoing portal vein embolization (PVE) and subsequent (extended) right hemihepatectomy. A total of 59 patients (mean age: 60.8 ± 9.3 years) with CRCLM who underwent PVE in preparation for right hemihepatectomy were included. IhPFS and OS after PVE were calculated using the Kaplan–Meier method. Cox regression analyses were conducted to investigate the association between the following factors and survival: patient age, laterality of the colorectal cancer (right- versus left-sided), tumor location (colon versus rectal cancer), time of occurrence of hepatic metastases (synchronous versus metachronous), baseline number and size of hepatic metastases, presence or absence of metastases in the future liver remnant (FLR) before PVE, preoperative carcinoembryogenic antigen (CEA) levels, time between PVE and surgery, history of neoadjuvant or adjuvant chemotherapy, and the presence or absence of extrahepatic disease before PVE. Median follow up was 18 months. The median ihPFS was 8.2 months (95% confidence interval: 6.2–10.2 months), and median OS was 34.1 months (95% confidence interval: 27.3–40.9 months). Laterality of the primary colorectal cancer was the only statistically significant predictor of ihPFS after PVE (hazard ratio (HR) = 2.242; 95% confidence interval: 1.125, 4.465; p = 0.022), with patients with right-sided colorectal cancer having significantly shorter median ihPFS than patients with left-sided cancer (4.0 ± 1.9 months versus 10.2 ± 1.5 months; log rank test: p = 0.018). Other factors, in particular also the presence or absence of additional metastases in the FLR, were not associated with intrahepatic progression-free survival. The presence of extrahepatic disease was associated with worse OS (HR = 3.050, 95% confidence interval: 1.247, 7.459; p = 0.015).

scholarly journals Angiopoietin1 Deficiency in Hepatocytes Affects the Growth of Colorectal Cancer Liver Metastases (CRCLM)

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 35
Author(s):  
Nisreen S. Ibrahim ◽  
Anthoula Lazaris ◽  
Miran Rada ◽  
Stephanie K. Petrillo ◽  
Laurent Huck ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Liver Metastases ◽  
Poor Response ◽  
Growth Patterns ◽  
Migration And Invasion ◽  
Colorectal Cancer Liver Metastases ◽  
Angiogenic Therapy ◽  
Tumor Region

Colorectal cancer liver metastases (CRCLM) that receive their blood supply via vessel co-option are associated with a poor response to anti-angiogenic therapy. Angiopoietins (Ang1 and Ang2) with their Tyrosine-protein kinase receptor (Tie2) have been shown to support vessel co-option. We demonstrate significantly higher expression of Ang1 in hepatocytes adjacent to the tumor region of human chemonaïve and treated co-opting (replacement histopathological growth patterns: RHGP) tumors. To investigate the role of the host Ang1 expression, Ang1 knockout (KO) mice were injected intra-splenically with metastatic MC-38 colon cancer cells that develop co-opting liver metastases. We observed a reduction in the number of liver metastases and interestingly, for the first time, the development of angiogenic driven desmoplastic (DHGP) liver metastases. In addition, in-vitro, knockout of Ang1 in primary hepatocytes inhibited viability, migration and invasion ability of MC-38 cells. We also demonstrate that Ang 1 alone promotes the migration and growth of both human and mouse colon cancer cell lines These results provide evidence that high expression of Ang1 in the host liver is important to support vessel co-option (RHGP lesions) and when inhibited, favours the formation of angiogenic driven liver metastases (DHGP lesions).

The Role of Big Endothelin-1 in Colorectal Cancer

2002 ◽  
Vol 17 (4) ◽  
pp. 268-274 ◽  
Author(s):  
C. Arun ◽  
B. Swift ◽  
K.E. Porter ◽  
K.P. West ◽  
N.J.M. London ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Concentration ◽  
Liver Metastases ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Hepatic Metastases ◽  
Plasma Samples ◽  
Median Score ◽  
Endothelin 1 ◽  
Colorectal Cancer Patients

Introduction Changes in liver blood flow caused by an unknown splanchnic vasoconstrictor have been noted in colorectal cancer patients with liver metastases. This prospective study was performed to assess whether plasma levels of big endothelin-1 (big ET-1) were raised in patients with colorectal cancer. Methods Plasma samples from peripheral vein of patients who underwent surgery for primary colorectal cancer (n=60) and those with known colorectal liver metastases (n=45) for a period of 15 months were taken prior to treatment and compared to age- and sex-matched controls (n=20). Plasma samples were analysed by using a single-step sandwich enzyme immunoassay. Immunohistochemistry and in situ hybridisation were also performed on tumour sections to investigate the expression of ET-1 by cancer cells. Results The median (range) plasma concentration of big ET-1 in controls was 2.1 pg/mL (1.2–13.4 pg/mL). The median (range) plasma concentration of big ET-1 in colorectal cancer patients with no overt hepatic metastases was 3.8 pg/mL (1.2–15.8 pg/mL), p=0.002, and the median (range) plasma concentration of big ET-1 in colorectal cancer patients with hepatic metastases was 5.2 pg/mL (1.7–30 pg/mL), p=0.0001; both were significantly elevated compared to the control group. A significant difference in immunostaining for big ET-1 was noted between paired normal colonic mucosa (median score-1) and tumour sections (median score-3), p=0.01. Conclusion This study has demonstrated elevated concentrations of big ET-1 in colorectal cancer patients, especially in those with hepatic metastases. Upregulation of ET activity in colorectal cancer could be inferred by the increased immunostaining of big ET-1 in cancer cells. Therefore, plasma big ET-1 levels should be evaluated as a potential tumour marker for the identification of hepatic metastases at an earlier stage.

Retrospective analysis of pathologic response in colorectal cancer liver-only metastases following treatment with bevacizumab.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 674-674
Author(s):  
Ruth Vera ◽  
Joan Figueras ◽  
Maria Luisa Gomez Dorronsoro ◽  
S. Lopez-Ben ◽  
Antonio Viúdez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Retrospective Analysis ◽  
Hepatic Metastases ◽  
Stage Iv ◽  
Poor Response ◽  
Pathological Response ◽  
Residual Tumour ◽  
Tumour Location ◽  
Baseline Characteristics

674 Background: Recent reports have shown that pathological response predicts for better outcome (overall survival) following preoperative chemotherapy and surgical resection of colorectal cancer (CRC) liver-only metastases. The aim of this retrospective analysis was to evaluate the effect of adding bevacizumab to standard chemotherapy on pathological response in patients with CRC liver only metastases. Methods: Patients with stage IV CRC with liver metastases who received neoadjuvant chemotherapy (oxaliplatin-or irinotecan-based) at two Spanish centres were analysed retrospectively. Pathological response was evaluated as follows: complete pathological response (cPR), PR1 (25% of residual tumour), PR2 (25–50% of residual tumour), PR3 (>50% of residual tumour). cPR or PR1 was considered to be a good response, and PR2 or PR3 a poor response. Results: A total of 81 patients were evaluated. Of these, 43 received chemotherapy alone and 38 received chemotherapy plus bevacizumab. Baseline characteristics were as follows: median age 61.0 years (range 43.0–80.0 years); male/female (67%/33%); tumour location – colon (69%) / rectum (31%); hepatic metastases – synchronous (74%) / metachronous (26%); In terms of pathological response, 58% of patients receiving bevacizumab had a good response (cPR + PR1) compared with 28% of those receiving chemotherapy alone. At the end of the analysis, 68% of patients were still alive. Conclusions: Adding bevacizumab to oxaliplatin-based chemotherapy in the neoadjuvant setting improves the pathological response of liver metastases in patients with stage IV CRC. These findings indicate that pathological response might be a good indicator of outcome for patients receiving bevacizumab in the neoadjuvant setting.

Surgical management of synchronous colorectal liver metastases: Simultaneous versus staged resections.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 616-616
Author(s):  
Igor Shchepotin ◽  
Andrii Lukashenko ◽  
Olena Kolesnik ◽  
Anton Burlaka
Keyword(s):  
Colorectal Cancer ◽  
Surgical Treatment ◽  
Postoperative Complications ◽  
Liver Metastases ◽  
Metastatic Cancer ◽  
Economic Effect ◽  
Hepatic Metastases ◽  
Group A ◽  
Bed Days ◽  
Group B

616 Background: Surgical treatment of metastatic colorectal cancer remains the only method that improves overall 5-year survival. This study aimed to compare the surgical outcome and survival benefit between synchronous and staged resection of liver metastases from colorectal cancer. Methods: Clinicopathologic data, treatments, and postoperative outcomes from 110 patients who underwent simultaneous (48 patients, group A) or staged (62 patients, group B) colorectal and hepatic resections at clinic of National cancer institute in period of 2008-2013 were reviewed. Results: Postoperative complications in patients with simultaneous resections (group A) were observed in 13 cases (27.1%), including 5, 1, 4, 2, 0, and 1 of grades I, II, IIIa, IIIb, IV, and V, respectively. Similar results have been reported in group B after staged resections, where overall postoperative complications registered in 16 patients (25.8 %), including 4, 3, 6, 3, 0 of grades I, II, IIIa, IIIb, and IV respectively. Overall level of post-operative complications in the groups A and B after surgical stages finishing did not differ statistically (p=0.96). Shorter operative intervention duration was registered in the group A – (311±10.1) min, whereas in the group B it was (496.6±16.2) min (р<0.001). Patients after staged resection stayed in clinic for a longer time – 23.9±0.8 bed-days, when simultaneous resections provided with shorter recovery terms in post-operative period – 9.8±0.5 bed-days (p<0.001). Overall 3-year survival in the group of patients with simultaneous resections (group А) was 42 % and in the group B 55 % (р=0.22). Conclusions: Analysis of our research indicated necessity of the development of differentiated approach in management of synchronous colorectal liver metastatic cancer. Simultaneous resections of colorectal cancer primary lesions and hepatic metastases were safe and could serve as a primary option for selected patients. Subsequent research should be directed towards study of prognosis factors and criteria for patients’ selection for surgical treatment groups, assessment of economic effect, and patients life quality.

Overall survival analysis of the FOXFIRE prospective randomized studies of first-line selective internal radiotherapy (SIRT) in patients with liver metastases from colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3507-3507 ◽  
Author(s):  
Ricky A. Sharma ◽  
Harpreet Singh Wasan ◽  
Guy A. Van Hazel ◽  
Volker Heinemann ◽  
Navesh K. Sharma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Liver Metastases ◽  
Response Rate ◽  
Objective Response ◽  
Hepatic Metastases ◽  
First Line ◽  
Selective Internal Radiotherapy ◽  
Internal Radiotherapy ◽  
Randomized Studies

3507 Background: The FOXFIRE, SIRFLOX and FOXFIRE-Global (FF-SF-FFG) randomized studies evaluated the efficacy of combining first-line chemotherapy for metastatic colorectal cancer (mCRC) with selective internal radiotherapy (SIRT) using yttrium-90 resin microspheres in patients with liver metastases. The studies were designed for prospective, combined analysis of overall survival (OS). Methods: FF-SF-FFG randomized (1:1) chemotherapy-naïve mCRC patients (performance status 0/1) with liver metastases not suitable for curative resection/ablation. Arm A was oxaliplatin-based chemotherapy (mFOLFOX6/ OxMdG) ± investigator-chosen biologically targeted agent. Arm B was the same systemic therapy (oxaliplatin dose modification) + single treatment SIRT with cycle 1/2 of chemotherapy. Primary tumor in situ and/or limited extra-hepatic metastases were permitted. Minimum sample size was 1075 patients (HR 0.8, 80% power, two-sided 5% significance). Secondary outcomes included PFS, liver-specific PFS and response rate. Apart from safety, outcomes were analysed on intention-to-treat population using meta-analytic methods of pooled individual patient data. Results: Between 2006 and 2014, 1103 patients were randomized in 14 countries. Median age was 63 years (range 23-89); median follow-up 43.3 months. There were 844 deaths. There was no difference in OS (HR 1.04; 95% CI 0.90-1.19, p= 0.609) or PFS (HR 0.90, CI 0.79-1.02, p= 0.108) between Arms. Objective response rate ( p= 0.001) and liver-specific progression (HR 0.51, CI 0.43-0.62, p< 0.001) were significantly more favorable in Arm B. Patients in Arm B had higher risk of non-liver progression as first event (HR 1.98, CI 1.53-2.58, p< 0.001). Grade 3-5 adverse events were more common in Arm B (74.0%) than A (66.5%), p= 0.009. In health status questionnaires, EQ-5D utility scores were not significantly different between Arms at 6, 12 or 24 months. Conclusion: Despite higher response rates and improved liver-specific PFS, the addition of SIRT to first-line oxaliplatin-fluorouracil chemotherapy for patients with liver-only and liver-dominant mCRC did not improve OS or PFS. Clinical trial information: 83867919.

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