Pilar Baca García

Deletions Affecting Codons 557-558 of the c-KIT Gene Indicate a Poor Prognosis in Patients With Completely Resected Gastrointestinal Stromal Tumors: A Study by the Spanish Group for Sarcoma Research (GEIS)

PURPOSE To explore the prognostic value of mutations in c-KIT and PDGFR-alpha genes with respect to relapse-free survival (RFS) in patients with gastrointestinal stromal tumors (GIST). We have investigated the prognostic relevance of the type and position of the mutations, in addition to other clinicopathologic factors, in a large series of patients with GIST. METHODS For this study, 162 patients were selected according to the following criteria: completely resected tumors with negative margins attended between 1994 and 2001; no metastasis at diagnosis; tumor larger than 2 cm, c-KIT-positive immunostaining; and no other primary tumors. RESULTS The median follow-up was 42 months for patients free of recurrence. Mutations were detected in 96 tumors (60%): 82 cases involving c-KIT and 14 cases involving PDFGR-alpha. Univariate analysis demonstrated the following as poor prognostic factors for RFS: tumors larger than 10 cm (P < .0001); mitotic count higher than 10 mitoses per 50 high-power fields (P < .0001); high risk index (P < .0001); intestinal GIST location (P = .0041); high cellularity (P < .0001); tumor necrosis (P < .0001); deletions affecting exon 11 (P = .0007); and deletions affecting codons 557 to 558 (P < .0001). After the multivariate analysis, only the high risk index (relative risk [RR], 12.36), high cellularity (RR, 3.97), and deletions affecting codons 557 to 558 of c-KIT (RR, 2.57) corresponded to independent prognostic factors for RFS in GIST patients. CONCLUSION Deletions affecting codons 557 to 558 are relevant for the prognosis of RFS in GIST patients. This critical genetic alteration should be considered to be a new prognostic stratification variable for randomized trials exploring imatinib mesylate in the adjuvant setting in GIST patients.

Cetuximab Given Every 2 Weeks plus Irinotecan Is an Active and Safe Option for Previously Treated Patients with Metastatic Colorectal Cancer

Background: We gathered data from multiple institutions on the cetuximab regimen of patients with metastatic colorectal cancer. Methods: 126 patients from 19 centers were included from July 2006 to July 2007 in this prospective non-controlled study. Irinotecan-refractory metastatic colorectal cancer patients with Karnofsky ≧70 received cetuximab 500 mg/m2 every 2 weeks (q2w) in combination with irinotecan 180 mg/m2 q2w until disease progression or unacceptable toxicity. The primary endpoint was the progression-free rate at 12 weeks. Results: Median age was 65 years; 65.9% male; colon/rectum 64.3/34.1%; Karnofsky status ≤80/≧90% in 45.3/54.7% of the patients. The progression-free rate was 42.7 (95% CI 32.8–52.6) and 22.4% (95% CI 14.2–30.7) at 12 and 24 weeks, respectively. The main grade 3 or 4 toxicities were: diarrhea 13.5% and acne-like rash 10.3%. No grade 3 or 4 infusional or allergic reactions were reported. Conclusions: The progression-free rates confirm that cetuximab q2w in combination with irinotecan is an option, and is as active and safe as the standard weekly regimen.

Sliding mode control of a m-phase DC/DC buck converter with chattering reduction and switching frequency regulation

This paper presents a sliding mode control for a multiphase synchronous buck converter with chattering reduction, which is capable to operate with fixed switching frequency at steady state. The system works with a Master-Slave configuration. The chattering reduction is achieved using interleaved control action, while the switching frequency is regulated using a variable hysteresis band comparator for the Master phase. Experimental results show that interleaving operation, robust output regulation and fixed switching frequency at steady state are properly achieved.