scholarly journals Sequential intrahepatic fluorodeoxyuridine and systemic fluorouracil plus leucovorin for the treatment of metastatic colorectal cancer confined to the liver.

1998 ◽  
Vol 16 (7) ◽  
pp. 2528-2533 ◽  
Author(s):  
M J O'Connell ◽  
D M Nagorney ◽  
A M Bernath ◽  
G Schroeder ◽  
R J Fitzgibbons ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Disease Progression ◽  
Residual Disease ◽  
Hepatic Metastases ◽  
Frequent Pattern ◽  
Survival Duration ◽  
Short Term Treatment ◽  
Aggressive Approach ◽  
Arterial Perfusion

PURPOSE Extrahepatic metastasis represents a frequent pattern of disease progression when fluorodeoxyuridine (FUDR) is given by the intraarterial route for the treatment of unresectable colorectal liver metastases. Systemic fluorouracil (5-FU) plus leucovorin was added to intrahepatic FUDR to prolong the duration of disease control. METHODS Only patients with colorectal cancer who had evidence of unresectable metastases confined to the liver were eligible. Laparotomy was performed to establish arterial perfusion of the liver. Cycles of intrahepatic FUDR followed by a 1-week rest period then intravenous chemotherapy with 5-FU plus leucovorin were administered until maximal regression of hepatic metastases. Maintenance chemotherapy with 5-FU plus leucovorin was then given until disease progression. RESULTS Fifty-seven patients entered this trial; four patients (7%) were ineligible and 13 (23%) did not receive any chemotherapy on study because of findings at laparotomy. The 40 eligible patients who began chemotherapy are included in the statistical analyses. Twenty-five patients (62% of those who received chemotherapy) experienced regression of liver metastases. The median time to tumor progression was 9 months, but only 3% remained progression-free at 24 months. The median survival duration was 18 months. Toxicity was tolerable with no cases of biliary sclerosis. One treatment-related fatality due to sepsis was observed. CONCLUSION Although short-term treatment results appear to be somewhat better than we have previously observed with intrahepatic FUDR alone, the sequential regimen did not have an impact on long-term, progression-free survival in patients with unresectable liver metastases. We are now investigating this regimen as surgical adjuvant therapy in selected patients following hepatic metastasectomy where this aggressive approach might have a greater therapeutic effect in the minimal residual disease setting.

A prospective phase II study of neoadjuvant FOLFOX6 plus cetuximab in patients with colorectal cancer and unresectable liver metastasis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14072-e14072
Author(s):  
Jun Ho Ji ◽  
Young Suk Park ◽  
Jeeyun Lee ◽  
Tae Won Kim ◽  
Yong Sang Hong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Liver Metastases ◽  
Disease Progression ◽  
Hepatic Metastases ◽  
Progression Free Survival ◽  
Response Rates ◽  
R0 Resection ◽  
Resection Rate ◽  
Curative Intent

e14072 Background: Colorectal cancer(CRC) with liver-only metastasis is considered potentially curable when liver metastases are completely resectable, while nonresectable liver metastases(NLM) are still incurable. In the latter cases, neoadjuvant chemotherapy could render curability by achieving resectability. We assessed efficacy of neoadjuvant cetuximab combined with FOLFOX6 in colorectal patients with NLM. Methods: Between July 2008 and Dec 2009, 73 patients were enrolled from 11 centers in Korea. Newly diagnosed K-RAS wild type CRC patients with NLM were treated with FOLFOX6 plus cetuximab(provided by Merck Serono) every 2 weeks. Response was evaluated every 3 cycles by CT scan according to RECIST 1.0. Chemotherapy was continued until disease progression or maximum of 12 cycles. Liver metastasectomy was performed at physician’s discretion in patients with enough tumor shrinkage, followed by chemotherapy of same regimen to complete total 12 cycles. The primary endpoint was overall R0 resection rate. The secondary endpoints were the response rates, progression-free survival(PFS), overall survival and toxicity. Results: In total, 73 patients were enrolled and analyzed. The median follow up duration was 28.6 months (range 11.5 to 38.1). Among 53 (72.6%) patients who showed response, surgery with curative intent was attempted in 36 (49.3%) patients. With intention-to-treat analysis, R0 resection rate(RR) was 19.2% (14/73), RFA plus R0, R1 and R2 RR were 8.2% (6/73), 8.2% (6/73), 13.7% (10/73), respectively. Despite neoadjuvant chemotherapy, 37 (50.7%) patients had unresectable hepatic metastases, however. RFA was successfully performed in combination with surgery (n=7) or alone (n=1) in 8 patients of them. Chemotherapy was discontinued in 26 patients due to disease progression (n=13), death (n=2), consent withdrawal (n=10), or protocol violation (n=1). The most common grade 3 and 4 toxicity was neutropenia (10.7%). Median PFS was 14.1 months (range 1.3 - 30.8) in patients received R0 resection and RFA + R0 resection. Conclusions: Neoadjuvant chemotherapy with FOLFOX6 plus cetuximab showed high response rates and increase resection rate in CRC patients with NLM.

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 Clinical and molecular determinants of extrahepatic disease progression in patients with metastatic colorectal cancer with liver-limited metastases deemed initially unresectable

ESMO Open ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. e000496
Author(s):  
Elena Ongaro ◽  
Chiara Cremolini ◽  
Daniele Rossini ◽  
Francesca Corti ◽  
Filippo Pagani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Progression Free Survival ◽  
Extrahepatic Disease ◽  
Nodal Involvement ◽  
Liver Resections ◽  
Multicentre Cohort Study ◽  
Molecular Determinants

BackgroundNo tools to predict the probability of extrahepatic disease progression (ePD) of initially unresectable, liver-limited metastatic colorectal cancer (mCRC) are currently available. To estimate the likelihood to develop ePD and to identify clinical and molecular factors that could predict extrahepatic progression-free survival (ePFS), we conducted an observational, retrospective, multicentre cohort study.MethodsWe retrospectively identified a cohort of 225 patients with initially unresectable liver-limited disease (LLD), treated from January 2004 to December 2017 with first-line doublets or triplet plus a biological agent at two Italian institutions.Results173 (77%) patients experienced ePD which occurred within 1, 2 or 3 years from the diagnosis of mCRC in 15%, 49% and 66% of patients, respectively. Globally, 164 (73%) patients underwent a liver resection at some point of their disease history, and 54 (33%) of them underwent a subsequent locoregional treatment. Age > 70 years, locoregional nodal involvement at diagnosis of colorectal cancer and ≥4 liver metastases were significantly associated with higher risk of ePD while liver resections were associated with reduced risk of ePD. In the multivariable model, number of liver metastases (subdistribution HR, SHR 1.63, 95% CI 1.12 to 2.36; p = 0.01) and liver resections (SHR 0.43, 95% CI 0.29 to 0.63; p = 0.001) were still associated with ePD. Number of liver metastases < 4, no nodal involvement at diagnosis and liver resections were also associated with prolonged ePFS.ConclusionsThe identified clinical factors could help physicians in personalising the intensity and aggressiveness of liver-directed treatments in patients with mCRC with initially unresectable LLD.

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.

scholarly journals Conversion to Resectability Using Hepatic Artery Infusion Plus Systemic Chemotherapy for the Treatment of Unresectable Liver Metastases From Colorectal Carcinoma

2009 ◽  
Vol 27 (21) ◽  
pp. 3465-3471 ◽  
Author(s):  
Nancy E. Kemeny ◽  
Fidel D. Huitzil Melendez ◽  
Marinela Capanu ◽  
Philip B. Paty ◽  
Yuman Fong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Systemic Chemotherapy ◽  
Hepatic Metastases ◽  
Hepatic Arterial Infusion ◽  
Hepatic Artery Infusion ◽  
Baseline Variable ◽  
Unresectable Liver Metastases ◽  
Previously Treated ◽  
Additional Value

Purpose To determine the conversion to resectability in patients with unresectable liver metastases from colorectal cancer treated with hepatic arterial infusion (HAI) plus systemic oxaliplatin and irinotecan (CPT-11). Patients and Methods Forty-nine patients with unresectable liver metastases (53% previously treated with chemotherapy) were enrolled onto a phase I protocol with HAI floxuridine and dexamethasone plus systemic chemotherapy with oxaliplatin and irinotecan. Results Ninety-two percent of the 49 patients had complete (8%) or partial (84%) response, and 23 (47%) of the 49 patients were able to undergo resection in a group of patients with extensive disease (73% with > five liver lesions, 98% with bilobar disease, 86% with ≥ six segments involved). For chemotherapy-naïve and previously treated patients, the median survival from the start of HAI therapy was 50.8 and 35 months, respectively. The only baseline variable significantly associated with a higher resection rate was female sex. Variables reflecting extensive anatomic disease, such as number of lesions or number of vessels involved, were not significantly associated with the probability of resection. Conclusion The combination of regional HAI floxuridine/dexamethasone and systemic oxaliplatin and irinotecan is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, demonstrating a 47% conversion to resection (57% in chemotherapy-naïve patients). Future randomized trials should compare HAI plus systemic chemotherapy with systemic therapy alone to assess the additional value of HAI therapy in converting patients with hepatic metastases to resectability.

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.

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