Nordlinger, B. et al. Does chemotherapy prior to liver resection increase the potential for cure in patients with metastatic colorectal cancer? A report from the European Colorectal Metastases Treatment Group. Eur. J. Cancer 43, 2037-2045
Liver resection offers the only chance of cure for patients with advanced colorectal cancer (CRC). Typically, the 5-year survival rates following liver resection range from 25% to 40%. Unfortunately, approximately 85% of patients with stage IV CRC have liver disease which is considered unresectable at presentation. However, the rapid expansion in the use of improved combination therapy regimens has increased the percentage of patients eligible for potentially curative surgery. Despite this, the selection criteria for patients potentially suitable for resection are not well documented and patient management by multidisciplinary teams, although essential, is still evolving. The goal of the European Colorectal Metastases Treatment Group is to establish pan-European guidelines for the treatment of patients with CRC liver metastases that can be adopted more widely by established treatment centres and to develop more accurate staging systems and evaluation criteria.
"Newly developed, expensive, biologically targeted agents have had marginal effects in improving survival and have not significantly affected the chances of cure . It is notable that in a subset of patients with liver-only mCRC, in whom surgical resection of disease can be achieved, the 5-year survival probability is 27-39%, with 20% of patients achieving long-term cure [3-6]. "
[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer (CRC) is the second most common malignancy in Europe and a leading cause of cancer-related death. Almost 50% of patients with CRC develop liver metastases, which heralds a poor prognosis unless metastases can be downsized to surgical resection or ablation. The FOXFIRE trial examines the hypothesis that combining radiosensitising chemotherapy (OxMdG: oxaliplatin, 5-fluorouracil and folic acid) with Selective Internal Radiation Therapy (SIRT or radioembolisation) using yttrium-90 resin microspheres (SIR-Spheres®; Sirtex Medical Limited, North Sydney, Australia) as a first-line treatment for liver-dominant metastatic CRC will improve clinical outcomes when compared to OxMdG chemotherapy alone.
FOXFIRE is an open-label, multicentre, randomised controlled trial of OxMdG with or without the addition of SIRT (1:1 randomisation). Eligible adult patients have histologically confirmed colorectal adenocarcinoma, liver metastases measurable on computed tomography scan and untreatable by either surgical resection or local ablation, and they may have limited extra-hepatic disease, defined as ≤5 nodules in the lung and/or one other metastatic site which is amenable to future definitive treatment. Eligible patients may have received adjuvant chemotherapy following resection of the primary tumour, but are not permitted to have previously received chemotherapy for metastatic disease, and must have a life expectancy of ≥3 months and a WHO performance status of 0–1. The primary outcome is overall survival. Secondary outcomes include progression free survival (PFS), liver-specific PFS, patient-reported outcomes, safety, response rate, resection rate and cost-effectiveness. FOXFIRE shares a combined statistical analysis plan with an international sister trial called SIRFLOX.
This trial is establishing a network of SIRT centres and ‘feeder’ chemotherapy-only centres to standardise the delivery of SIRT across the whole of the UK and to provide greater equity of access to this highly specialised liver-directed therapy. The FOXFIRE trial will establish the potential role of adding SIRT to first-line chemotherapy for unresectable liver metastatic colorectal cancer, and the impact on current treatment paradigms for metastatic CRC.
BMC Cancer 07/2014; 14(1):497. DOI:10.1186/1471-2407-14-497 · 3.36 Impact Factor
"Neoadjuvant chemotherapy was given in patients with high preoperative CEA levels or stage M1b, M1c according to European Colorectal Metastases Treatment Group . All patients underwent adjuvant chemotherapy. "
[Show abstract][Hide abstract] ABSTRACT: Purpose
Hepatic resection is a standard method of treatment for colorectal liver metastases (CRLM). However, the pathologic factors of metastatic lesions that affect tumor recurrence are less well defined in CRLM. The aim of this study was to evaluate the risk factors for recurrence of CRLM, focusing on histopathologic factors of metastatic lesions of the liver.
From January 2003 to December 2008, 117 patients underwent curative hepatic resection for CRLM were reviewed. Tumor size and number, differentiation, tumor budding, angio-invasion, dedifferentiation and tumor infiltrating inflammation of metastatic lesions were investigated.
The mean number of hepatic tumors was 2 (range, 1-8). The mean size of the largest tumor was 2.9 cm (range, 0.3-18.5 cm) in diameter. The moderate differentiation of the hepatic tumor was the most common in 86.3% of the patients. Tumor budding, angio-invasion, and dedifferentiation were observed in 81%, 34%, and 12.8% of patients. Inflammation infiltrating tumor was detected in 6.8% of patients. Recurrence after hepatic resection appeared in 69 out of 117 cases (58.9%). Recurrence-free survival at 1, 2 and 5 years were 62.4%, 43.6%, and 34.3%. The multivariate analysis showed the number of metastases ≥3 (P = 0.007), the tumor infiltrating inflammation (P = 0.047), and presence of dedifferentiation (P = 0.020) to be independent risk factors for tumor recurrence.
Histopathological factors, i.e., dedifferentiation and tumor infiltrating inflammation of the metastatic lesion, could be one of the risk factors of aggressive behavior as well as the number of metastases even after curative resection for CRLM.
Annals of Surgical Treatment and Research 07/2014; 87(1):14-21. DOI:10.4174/astr.2014.87.1.14
"Despite surgical advances, only 10% to 15% of patients have resectable liver disease at presentation [9, 10]. Preoperative chemotherapy has been introduced to increase the number of patients that may be eligible for liver resection by downsizing liver metastases . Unfortunately, a large proportion of patients with unresectable CLM will experience disease progression during the course of neoadjuvant chemotherapy. "
[Show abstract][Hide abstract] ABSTRACT: Surgical resection is the only potentially curative strategy in the treatment of patients with colorectal liver metastases (CLM). Unfortunately, only about 10%-15% of patients are candidates for resection. Preoperative chemotherapy aims to increase the number of patients that may be eligible for liver resection by downsizing liver metastases. For patients with unresectable, chemotherapy refractory CLM the available treatment options are limited. Selective interarterial radiation therapy (SIRT) is one of the most promising treatment options for this group of patients. Although only a small number of these patients have been reported as becoming candidates for potentially curative hepatic resection following sufficient reduction in the volume of liver metastases, the question arises regarding the safety of liver resection in these patients. We report a case of a patient who presented unresectable liver relapse of CLM after previous right hepatectomy. He underwent SIRT which resulted in downsizing of the liver metastases making the patient candidate for left lateral sectionectomy. He underwent the redo hepatectomy without any complications. To the best of our knowledge, this is the first reported case of redo hepatectomy after SIRT for CLM.
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