Adjuvant therapy after resection of colorectal liver metastases: the predictive value of the MSKCC clinical risk score in the era of modern chemotherapy.

BACKGROUND: Despite introduction of effective chemotherapy protocols, it has remained uncertain, if patients with colorectal cancer (CRC) liver metastases should receive adjuvant therapy. Clinical or molecular predictors may help to select patients at high risk for disease recurrence and death who obtain a survival advantage by adjuvant chemotherapy. METHODS: A total of 297 patients with potentially curative resection of CRC liver metastases were analyzed. These patients had no neoadjuvant therapy, no extrahepatic disease and negative resection margins. The primary endpoint was overall survival. Patients' risk status was evaluated using the Memorial Sloan-Kettering Cancer Center clinical risk score (MSKCC-CRS). Multivariable analyses were performed using Cox proportional hazard models. RESULTS: A total of 137 (43%) patients had a MSKCC-CRS > 2. Adjuvant chemotherapy was administered to 116 (37%) patients. Patients who received adjuvant chemotherapy were of younger age (p = 0.03) with no significant difference in the presence of multiple metastases (p = 0.72) or bilobar metastases (p = 0.08). On multivariate analysis adjuvant chemotherapy was associated with improved survival in the entire cohort (Hazard ratio 0.69; 95% confidence interval 0.69-0.98). It improved survival markedly in high-risk patients with a MSKCC-CRS > 2 (HR 0.40; 95% CI 0.23-0.69), whereas it was of no benefit in patients with a MSKCC-CRS ≤ 2 (HR 0.90; 95% CI 0.57-1.43). CONCLUSIONS: The MSKCC-CRS offers a tool to select patients for adjuvant therapy after resection of CRC liver metastases. Validation in independent patient cohorts is required.

The impact of patient and tumour baseline characteristics on the overall survival of patients with advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND: Impact of patient and tumour baseline characteristics on the overall survival is not well characterized in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. AIMS/METHODS: Univariate/multivariate analyses were conducted to identify retrospectively the impact of baseline characteristics on the survival of 110 patients with advanced HCC treated with sorafenib. RESULTS: Median survival of the whole cohort was 6.7 months, median survival in Child-Pugh A, B, C patients was 10.5, 6.1 and 3.0 months and median survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage C/D was 6.8/2.6 months. Presence of ascites, presence of macrovascular invasion and BCLC stage D (mainly determined by Child-Pugh C status and Eastern Cooperative Oncology Group Performance Status>2) remained independent prognostic factors for the survival on multivariate analysis. Particularly, the presence of macrovascular invasion significantly influenced survival both in patients with liver cirrhosis Child-Pugh A and Child-Pugh B. CONCLUSION: Well maintained liver function and performance status are prerequisites for sorafenib treatment in patients with advanced HCC. Our findings do not support routine clinical use of sorafenib in Child-Pugh B patients. Evaluation of ascites and particularly macrovascular invasion might help to identify patients more likely to benefit from sorafenib treatment.

Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma in consideration of concomitant stage of liver cirrhosis.

GOALS AND BACKGROUND: The multikinase inhibitor sorafenib provides survival benefit for patients with advanced hepatocellular carcinoma (HCC) and liver cirrhosis (LCI) Child-Pugh A. We report our experiences with sorafenib in advanced HCC, particularly in patients with LCI Child-Pugh B/C, where only limited data are available in regard to safety and efficacy of sorafenib. METHODS: Thirty-four patients with advanced HCC were treated with sorafenib regardless of liver function and prior anticancer therapy. Adverse events (AEs) were graded using Common Toxicity Criteria version 3.0, tumor response was assessed according to Response Evaluation Criteria in Solid Tumors. RESULTS: Fifteen patients presented without LCI or with LCI Child- Pugh A, 15/4 patients had LCI Child-Pugh B/C. Barcelona Clinic Liver Cancer stage was B/C/D in 4/22/8 patients. During treatment period (median 2.2 mo), therapy was discontinued in 61.8% of patients due to tumor progression (32.3%), death (17.6%), AEs (8.8%), or noncompliance (2.9%). Most common grade 3/4 AEs included liver dysfunction (23.5%), diarrhea (14.7%), increased lipase (8.8%), fatigue (8.8%), and hand-foot skin reaction (5.9%). Worsening liver dysfunction/failure was more frequent (P=0.036) in patients with LCI Child-Pugh B/C compared with patients with maintained liver function (no LCI/LCI Child-Pugh A). Median overall survival was 7.2 months for patients with maintained liver function versus 3.3/3.4 months for patients with LCI Child-Pugh B/C. CONCLUSIONS: These data do not support the use of sorafenib in patients with LCI Child-Pugh C, and patients with LCI Child-Pugh B should be treated with caution until larger trials provide more safety data and a clinically relevant survival benefit under sorafenib therapy.