Treatment of liver metastases from colorectal cancer: what is the best approach today?

doi:10.1016/S1590-8658(01)80018-9

Digestive and Liver Disease

Volume 33, Issue 5, June–July 2001, Pages 438-444

https://doi.org/10.1016/S1590-8658(01)80018-9 Get rights and content

Abstract

Liver is the common site for metastases from colorectal cancer. The 5-year overall survival rate of patients following radical operations is 25%. Surgery can be carried out in only 10–15% of the patients, yet it remains the potential curative treatment for resectable lesions. For the unresectable cancers, only chemotherapy is recommended. New drugs such as Irinotecan prolongs the overall survival of patients affected by advanced disease. In patients with unresectable metastases at diagnosis, pre-surgical treatment with Oxaliplatin leads to reduction of the lesions, allowing resection in 16% of cases. Chemotherapy may be delivered directly into the liver via the hepatic artery. No, clinical trials, to date, have shown convincing survival results in patients treated with this procedure. Combined hepatic artery and systemic treatment may provide a new strategy as adjuvant therapy for patients undergoing resections.

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Cited by (23)

The pre-operative rate of growth of colorectal metastases in patients selected for liver resection does not influence post-operative disease-free survival
2016, European Journal of Surgical Oncology
Citation Excerpt :
The main finding of clinical significance from this study is that, in contrast to the treatment of many other solid tumours, and colorectal metastases in the lung, the rate of growth of CRLM has no influence on survival after resection. The proportion of patients with CRLM who are offered liver resection is small (10–20%)32,33 and patients undergo a selection process before being offered liver resection. In the majority of cases this involves exclusion of patients with extra-hepatic disease, rapidly progressive disease and where there is extensive replacement of the liver with tumour.
To assess the potential association between the change in diameter of colorectal liver metastases between pre-operative imaging and liver resection and disease-free survival in patients who do not receive pre-operative liver-directed chemotherapy.
Analysis of a prospectively maintained database of patients undergoing liver resection for colorectal liver metastases between 2005 and 2012 was undertaken. Change in tumour size was assessed by comparing the maximum tumour diameter at radiological diagnosis determined by imaging and the maximum tumour diameter measured at examination of the resected specimen in 157 patients.
The median interval from first scan to surgery was 99 days and the median increase in tumour diameter in this interval was 38%, equivalent to a tumour doubling time (DT) of 47 days. Tumour DT prior to liver resection was longer in patients with T1 primary tumours (119 days) than T2-4 tumours (44 days) and shorter in patients undergoing repeat surgery for intra-hepatic recurrence (33 days) than before primary resection (49 days). The median disease-free survival of the whole cohort was 1.57 years (0.2–7.3) and multivariate analysis revealed no association between tumour DT prior to surgery and disease-free survival.
The rate of growth of colorectal liver metastases prior to surgery should not be used as a prognostic factor when considering the role of resection.
Socioeconomic status influences the likelihood but not the outcome of liver resection for colorectal liver metastasis
2015, HPB
Citation Excerpt :
Patients with primary colorectal cancer often present symptomatically and are at risk of colonic obstruction, and population studies have shown that 60–80% of patients with primary colorectal cancer will be offered surgery.9 However, the proportion of patients with CLM who are offered surgery is far lower, at 10–20%.10,11 Patients who develop CLM must overcome a number of potential obstacles before undergoing liver surgery.
The aim of this study was to compare the socioeconomic profile of patients undergoing liver resection for colorectal liver metastasis (CLM) in a regional hepatopancreatobiliary unit with that of the local population. A further aim was to determine if degree of deprivation is associated with tumour recurrence after resection.
A retrospective analysis of patients undergoing liver resection for CLM was performed. Geodemographic segmentation was used to divide the population into five categories of socioeconomic status (SES).
During a 7‐year period, 303 patients underwent resection for CLM. The proportion of these patients in the two least deprived categories of SES was greater than that of the local population (50.2% versus 40.2%) and the proportion in the two most deprived categories was lower (18.3% versus 30.1%) (P < 0.001). There was no difference in recurrence rate (P = 0.867) or disease‐free survival among categories of SES (P = 0.913). Multivariate analysis demonstrated no association between SES and tumour recurrence (P = 0.700).
Liver resection for CLM is performed more commonly among the least socioeconomically deprived population than among the most deprived. However, degree of deprivation was not associated with tumour recurrence after resection.
Vaccination with in vitro grown whole tumor cells induces strong immune responses and retards tumor growth in a murine model of colorectal liver metastases
2008, Vaccine
Citation Excerpt :
The remaining >75% can be treated by systemic chemotherapy, which is regarded as only palliative [4,5]. Patients treated with surgical resection in combination with adjuvant treatment have significantly better tumor free survival rates compared to either modality alone [6–8]. However even the best combination treatment at this stage only offers a 20–40% 5-year survival [9], thus additional treatments are being sought.
In vitro adaptation of a murine colorectal cell line (MoCR) rendered it less aggressive and more immunogenic than the in vivo passaged parent tumor. Vaccination of syngeneic mice with the in vitro cultured tumor cells was shown to induce immune responses and protection against tumor challenge, thus overcoming the need for antigen selection and adjuvants. A syngeneic murine model of colorectal cancer (CRC) liver metastasis was used. In a prophylactic setting mice vaccinated with in vitro cultured tumor cells produced strong cellular immune responses and significant inhibition of tumor growth, compared to sham vaccinated controls. In a therapeutic setting however, vaccination exacerbated tumor growth, suggesting that the presence of tumor subverts the course of the immune response. The mechanisms of this subversion need to be investigated and counteracted for successful immunotherapy.
Long-term follow-up of patients of intrahepatic malignancies treated with iodine-125 brachytherapy
2006, International Journal of Radiation Oncology Biology Physics
Purpose: We investigated the role of intraoperative iodine-125 (¹²⁵I) brachytherapy as a treatment option for unresectable primary and metastatic liver tumors.
Methods and Materials: Between 1989 and 2002, 64 patients with unresectable or residual disease after surgical resection for intrahepatic malignancies underwent 160-Gy permanent ¹²⁵I brachytherapy.
Results: The median length of follow-up was 13.2 years. The overall 1-year, 3-year, and 5-year actuarial intrahepatic local control rates were 44%, 22%, and 22%, respectively, with a median time to liver recurrence of 9 months (95% CI, 6–12 months). The 5-year actuarial intrahepatic control was higher for patients with solitary metastasis (38%) than for those with multiple metastases (6%, p = 0.04). The 1-year, 3-year, and 5-year actuarial overall survival rates were 73%, 23%, and 5%, respectively (median, 20 months; 95% CI, 16–24; longest survival, 7.5 years). Overall survival was higher for patients with smaller-volume implants (p = 0.003) and for patients without prior liver resection (p = 0.002). No mortality occurred. Radiation-related complications were minimal.
Conclusions: For select patients with unresectable primary and metastatic liver tumors for whom curative surgical resection is not an option, ¹²⁵I brachytherapy is a safe and effective alternative to other locally ablative techniques and can provide long-term local control and increased survival.
Tumour angiogenesis and mast cell density in the prognostic assessment of colorectal carcinomas
2005, Digestive and Liver Disease
Tumour angiogenesis is essential for the growth, invasion and metastasis of solid tumours. There are several lines of evidence that the mast cells play an important role in tumour angiogenesis.
The study focused to determine the correlation between the microvessel and mast cell densities, and to evaluate whether tumour angiogenesis and mast cell density could predict recurrence following curative surgery in patients with colorectal carcinomas.
Microvessel and mast cell densities were investigated in tumour specimens from 60 patients with colorectal carcinoma.
Microvessels were stained by immunohistochemical method using a monoclonal antibody anti-CD34. The routine Giemsa blue staining method was used to assess the mast cells. Microvessels and mast cells were counted in a ×400 field.
The mean microvessel and mast cell counts were higher in patients with recurrence compared with those patients who were disease-free for at least 24 months (p < 0.001). The Spearman's correlation coefficient revealed a significant correlation between mast cell and microvessel counts in colorectal carcinomas (r = 0.684; p < 0.001). Kaplan–Meier plots of survival showed that the high microvessel (>28) and mast cell (>6) counts correlated with a shorter disease-free survival (p = 0.0003 and p = 0.0013, respectively). Multivariate analysis showed that the depth of penetration (T4 versus T2) (p = 0.004), liver metastasis (p = 0.04) and microvessel density (p = 0.003) were independent predictors of recurrence. In multivariate analysis, mast cell density did not reach significance.
Our results suggest that the microvessel density of the primary tumour may be an important independent predictor of tumour recurrence and time to recurrence in colorectal carcinomas. The significant correlation between mast cell and microvessel counts suggest that the mast cells may have a role in tumour progression via promoting angiogenesis.
Percutaneous portal vein embolisation in preparation for extended hepatic resection of primary nonresectable liver tumours
2003, Digestive and Liver Disease
Background. In patients with malignant primary and secondary liver tumours or proximal bile duct carcinoma radical surgery is superior to all other therapeutic modalities in terms of survival and quality of life. Radical resection, however, often requires the removal of a large amount of liver parenchyma, resulting in a marked reduction of functional liver tissue with the risk of liver failure.
Aim. Preoperative partial portal vein embolisation induces hypertrophy of the controlateral liver and thereby increases the safety of extended liver resections.
Patients and methods. Between January 1997 and February 2001 we applied this strategy in 19 patients with primary and secondary nonresectable hepatobiliary malignancies, in whom the estimated amount of the remnant liver was ≤25% of the liver volume.
Results. The increase in volume ranged between 7 and 245%. Radical extended liver resection was performed in 13 patients (68%) without mortality. After a mean observation time of 22 months patient survival was 19 months with six tumour-related deaths during the second year after surgery. The remaining seven patients are alive and well with tumour recurrence in one.
Conclusion. Preoperative partial portal vein embolisation allows more patients with previously unresectable liver tumours to benefit from a potentially curative resection.

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Progress reportTreatment of liver metastases from colorectal cancer: what is the best approach today?

Abstract

Ann Oncol

Lancet

Lancet

The Lancet

Ann Oncol

Expectancy or primary chemotherapy in patients with advanced asymptomatic colon cancer: a randomized trial

J Clin Oncol

Biochemical modulation of FU: evidence of significant improvement of survival and quality of life in patients with advanced colorectal cancer

J Clin Oncol

Randomised trial comparing monthly low dose LV and FU bolus with bimonthly high dose LV and FU bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study

J Clin Oncol

Oxaliplatin plus 5-fluorouracil: clinical experience in patients with advanced colorectal cancer

Semin Oncol

Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer

J Clin Oncol

Phase I trial of 5-day continuous venous infusion of oxaliplatin at circadian rhythm-modulated rate compared with constant-rate

J Natl Cancer Inst

Weekly irinotecan (CPT-11), leucovorin (LV), and flurouracil (FU) is superior to daily x5 LV/FU in patients with previously untreated metastatic colorectal cancer

Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicenter randomized trial

Lancet

Treatment of colorectal liver metastases

Br J Surg

Portal triad clamping or hepatic vascular exclusion for major liver resection. A controlled study

Ann Surg

The role of surgical resection of liver metastases in colorectal carcinoma

Semin Oncol

Progress report
Treatment of liver metastases from colorectal cancer: what is the best approach today?