Predictive Factors for the Benefit of Perioperative FOLFOX for Resectable Liver Metastasis in Colorectal Cancer Patients (EORTC Intergroup Trial 40983)

Haukeland University Hospital, Bergen, Norway.
Annals of surgery (Impact Factor: 8.33). 03/2012; 255(3):534-9. DOI: 10.1097/SLA.0b013e3182456aa2
Source: PubMed


In EORTC study 40983, perioperative FOLFOX increased progression-free survival (PFS) compared with surgery alone for patients with initially 1 to 4 resectable liver metastases from colorectal cancer (CRC). We conducted an exploratory retrospective analysis to identify baseline factors possibly predictive for a benefit of perioperative FOLFOX on PFS.
The analysis was based on 237 events from 342 eligible patients. Cox proportional hazards regression models with a significance level of 0.1 were used to build up univariate and multivariate models.
After adjustment for identified prognostic factors, moderately (5.1-30 ng/mL) and highly (>30 ng/mL) elevated carcinoembryonic antigen (CEA) serum levels were both predictive for the benefit of perioperative chemotherapy (interaction P = 0.07; hazard ratio [HR] = 0.58 and HR = 0.52 for treatment benefit). For patients with moderately or highly elevated CEA (>5 ng/mL), the 3-year PFS was 35% with perioperative chemotherapy compared to 20% with surgery alone. Performance status (PS) 0 and BMI lower than 30 were also predictive for the benefit of perioperative chemotherapy (interaction P = 0.04 and P = 0.02). However, the number of patients with PS 1 and BMI 30 or higher were limited. The benefit of perioperative therapy was not influenced by the number of metastatic lesions (1 vs 2-4, interaction HR = 0.98).
Perioperative FOLFOX seems to benefit in particular patients with resectable liver metastases from CRC when CEA is elevated and when PS is unaffected, regardless of the number of metastatic number NCT00006479.

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    • "Numerous studies have investigated the factor associated with recurrence after hepatectomy in CRLM. Several clinical factors such as preoperative CEA level, primary colorectal tumor stage, differentiation and lymph node (LN) metastasis of primary colorectal tumor, metastatic tumor burden, time interval to the metastasis, and neoadjuvant/adjuvant chemotherapy have been established as important determinants of tumor recurrence in CRLM [6,7,8]. However, early recurrence sometimes was developed in patients with known good prognostic factors. "
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    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. Methods 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. Results 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. Conclusion 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.
    Full-text · Article · Jul 2014 · Annals of Surgical Treatment and Research
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    • "However, a subsequent analysis suggested that this did not translate into an improved overall survival benefit, but it must be noted that this study was never powered to test for such an improvement in overall survival, which remains a secondary end point of the study [12]. Aiming to identify baseline factors that may predict a survival benefit, a further exploratory retrospective analysis showes that perioperative FOLFOX seems to particularly benefit patients with resectable CRLM when CEA is elevated and performance status is unaffected, regardless of the number of metastatic lesions [13]. However, whether those patients receive a survival benefit from preoperative neoadjuvant chemotherapy remains unknown. "
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    ABSTRACT: Whether patients with resectable colorectal liver metastases (CRLM) receive survival benefit from neoadjuvant chemotherapy remains controversial. We retrospectively analyzed 466 patients with resectable CRLM between 2000 and 2010. Patient characteristics and survival data were recorded. The patients were divided into one group with neoadjuvant chemotherapy (group NC, n = 121) and another without (group WN, n = 345). There was no difference in 5-year survival (52% vs. 48%) between the two groups. No significant differences were identified between the two groups in terms of 30-day mortality (1.7% vs. 1.2%) or morbidity (33.9% vs. 25.8%). A primary tumor at stage T4, ≥4 liver metastases, the largest liver metastasis ≥5 cm in diameter, and a serum CEA level ≥5 ng/ml were independent prognostic factors. By assigning one point to each, the patients were divided into a low-risk group (0-2) and a high-risk (3-4). The patients in the low-risk group received no survival benefit from neoadjuvant chemotherapy, whereas those in the high-risk group received survival benefit (5-year survival, 39% vs. 33%, P = 0.028). Preoperative neoadjuvant chemotherapy did not increase mortality or complications. Not all resectable patients, only those with >2 independent risk factors, received survival benefit from neoadjuvant chemotherapy.
    Full-text · Article · Jan 2014 · PLoS ONE
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    ABSTRACT: Metastatic colorectal cancer is the third most common cancer in the United States with 20 % of the patients presenting with metastatic disease on initial presentation. Sites of metastases are usually to the liver and lung, and less commonly to the peritoneum. Oligometastatic disease may be treated with the combination of systemic chemotherapy, locoregional chemotherapy and surgery to improve survival rates. Thus, the unique setting of adjuvant chemotherapy in metastatic colorectal cancer will be reviewed in this paper.
    No preview · Article · Sep 2012 · Current Colorectal Cancer Reports
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