Prognostic value of c-MET in head and neck cancer: A systematic review and meta-analysis of aggregate data.

OBJECTIVES: The hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (c-MET) ligand/receptor axis has been implicated in pathogenesis of malignant diseases including squamous cell carcinoma of the head and neck (SCCHN). Overexpression of c-MET has been reported as a common molecular abnormality in SCCHN, although its prognostic and predictive value remains to be validated. METHODS: We systematically searched literature for studies evaluating c-MET expression on immunohistochemistry in newly diagnosed, non-metastatic SCCHN. The c-MET expressing cases were classified into three categories according to predefined cut-off values for positivity. Our aim was to assess the prevalence of c-MET expression and its relationship with selected clinicopathological variables. RESULTS: Twenty-eight studies with 2019 cases were included. Relative frequencies of c-MET expression above cut-off levels I, II, and III were 81.8%, 63.8%, and 46.2%, respectively. Differences between these three values were statistically significant (p<1.0×10-6). Above cut-off level II, c-MET positivity was associated with worse overall survival (p=4.0×10-6), positive nodal status (p=1.0×10-4), higher disease stage (p=7.0×10-4), older age (p=2.1×10-3), disease recurrence (p=2.0×10-2), and primary tumour localization in the oral cavity (p=2.3×10-2). Above cut-off level III, c-MET positivity was associated with worse disease-free or progression-free survival (p=9.0×10-6), p16 negativity (p=2.4×10-4), worse overall survival (p=4.0×10-4), positive epidermal growth factor receptor (EGFR) status (p=7.2×10-4), and larger primary tumours (p=4.6×10-3). CONCLUSION: In SCCHN, immunohistochemical overexpression of c-MET above cut-off levels III and particularly II was associated with inferior survival outcomes and advanced disease. Moreover, it represents a promising predictive biomarker for c-MET targeting, yet the optimal scoring method remains to be defined.

Hazard function for cancer patients and cancer cell dynamics.

The aim of the paper is to develop a procedure for an estimate of an analytical form of a hazard function for cancer patients. Although a deterministic approach based on cancer cell population dynamics yields the analytical expression, it depends on several parameters which should be estimated. On the other hand, a kernel estimate is an effective nonparametric method for estimating hazard functions. This method provides the pointwise estimate of the hazard function. Our procedure consists of two steps: in the first step we find the kernel estimate of the hazard function and in the second step the parameters in the deterministic model are obtained by the least squares method. A simulation study with different types of censorship is carried out and the developed procedure is applied to real data.

Current status of Japanese HIV-infected patients with coagulation disorders: coinfection with both HIV and HCV.

We herein report on the current status of Japanese HIV-positive patients with coagulation disorders, primarily hemophilia, based on the national survey of 31 May 2006. The total number of registered patients was 1,431 (Hemophilia A 1,086; Hemophilia B 325; von Willebrand disease 8; others 12), and 604 of these patients were deceased by 31 May 2006. The survival rate after the beginning of 1983 was evaluated by the Kaplan-Meier method. The total number of surviving patients was 827, and the survival rate on 31 May 2006 was 55.7 +/- 1.4%. Among the 827 surviving patients, HCV antibody was observed in 740, was negative in 16, and was not reported in 71 patients. Thus, the prevalence of HCV infection was 98% in the surviving patients based on the presence of HCV antibody. Among the 604 deceased patients, liver disease was reported as a cause of death in 149 cases (25%), and infection with HCV was reported as the possible cause of liver disease in 120 cases (20%). After 1997, 63 cases among the subtotal of 148 deaths had critical hepatic disease that originated from HCV infection, which accounted for 43% of the subtotal. The cumulative rate of patients who received interferon therapy was 32%. Interferon therapy should be prescribed more frequently to HIV-positive patients with coagulation disorders in order to realize the survival benefits, although clinicians should be aware of side effects and toxicities.

Retrospective analysis of 25 women with malignant cystosarcoma phyllodes--treatment results.

PURPOSE: Mastectomy without axillary dissection should be the standard treatment in patients with malignant form of cystosarcoma phyllodes. The role of postoperative radiotherapy and chemotherapy remains to be fully established. We evaluate treatment results in a group of patients with cystosarcoma phyllodes (CP) treated at our Institute. PATIENTS AND METHODS: In this report we analyze treatment outcome in 25 patients with malignant cystosarcoma phyllodes treated at Masaryk Memorial Cancer Institute between 1970 and 1995. Mean tumor size was 10 cm in diameter. All patients underwent surgery. Subsequently, 17 patients (68%) received radiotherapy on the breast or chest wall. RESULTS: Median follow-up was 139.5 months. Local recurrence was observed in 16% of all patients and all patients with local recurrence died. Time to local relapse after surgery was 4-11 months. Distant metastases occurred in 5 patients. All patients with local recurrence had distant metastases. Dissemination occurred 3-19 months after local recurrence. Five-year survival of all patients was 80%. CONCLUSION: A specific protocol for the treatment of cystosarcoma phyllodes is missing, probably due to rarity of the disease. The treatment of local recurrent disease remains unsuccessful in most CP patients. We recommend postoperative irradiation on the chest wall in patients with malignant form of CP, because adjuvant radiotherapy decreased the incidence of local relapse in our group of patients.