The purpose of this study was to evaluate the added role of a chemotherapeutic in transarterial chemoembolization (TACE) of intermediate-stage hepatocellular carcinoma (HCC). The issue is of major importance since, as suggested by recent evidence, hypoxia or incomplete devascularization of the tumor is a potent stimulator of angiogenesis, and there are not many papers supplying level one evidence confirming the value of a chemotherapeutic. The hypothesis was that since drug-eluting bead (DEB)-TACE is standardized and reproducible, a comparison with bland TACE can readily reveal the potential value of the chemotherapeutic. Two groups were randomized in this prospective study: group A (n = 41) was treated with doxorubicin DEB-TACE, and group B (n = 43) with bland embolization. Patients were randomized for tumor diameter. Patients were embolized at set time intervals (2 months), with a maximum of three embolizations. Tumor response was evaluated using the EASL criteria and alpha-fetoprotein levels. At 6 months a complete response was seen in 11 patients (26.8%) in the DEB-TACE group and in 6 patients (14%) in the bland embolization group; a partial response was achieved in 19 patients (46.3%) and 18 (41.9%) patients in the DEB-TACE and bland embolization groups, respectively. Recurrences at 9 and 12 months were higher for bland embolization (78.3% vs. 45.7%) at 12 months. Time to progression (TTP) was longer for the DEB-TACE group (42.4 +/- 9.5 and 36.2 +/- 9.0 weeks), at a statistically significant level (p = 0.008). In conclusion, DEB-TACE presents a better local response, fewer recurrences, and a longer TTP than bland embolization with BeadBlock. However, survival benefit and bland embolization with smaller particles must be addressed in future papers to better assess the clinical value.
DEB-DOX results, with high rates of 5-year survival for patients, not amenable to curative treatments. Number of lesions, lesion vascularity, and local response were significant independent determinants of 5-year survival.
DEBDOX chemoembolization is safe and small calibres do not result in increased complication rates compared with results of series using larger diameters of beads.
Angiogenesis plays an important role in growth, progression, and metastasis of tumors. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF). VEGF expression has been associated with advance stage and poor survival of several cancers. In the present study we evaluated the association of functional polymorphisms in the VEGF gene with colorectal cancer development, prognosis, and survival. Three hundred twelve consecutive patients with surgically treated colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and five VEGF (-2578C>A, -1154G>A, -634G>C, -460T>C, and +936C>T) gene polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. VEGF -2578C>A, -1154G>A, -634G>C, -460T>C, and +936C>T genotype and allele frequencies were similar among patients and controls. There was a trend showing carriers of the -2578A and +936T alleles more frequent among patients with CRC, but these differences did not reach statistical significance. Furthermore, no correlation was found between all these variants and tumor characteristics like size, histological grading, positive regional lymph node metastases or tumor stage. However, the -2578AA, -634CC, and +936TT genotypes found to be related with a significantly lower overall survival in our study. In conclusion, VEGF gene polymorphisms were found to be an independent prognostic marker for Greek CRC patients.
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