RESUMEN
Purpose: The aim of this study was to compare a surgical with a Phoenix-derived definition of cure at 4 years after treatment by 125J low-dose-rate brachytherapy (LDR-BT) in patients with low- and intermediate-risk prostate cancer. Methods and Materials: A total of 427 evaluable men with low-risk (62.8%) and intermediate-risk (37.2%) prostate cancer were treated with LDR-BT (160 Gy). Cure was defined at 4 years either as not having experienced a biochemical recurrence by the Phoenix definition, or by a surgical definition, using a posttreatment prostate-specific antigen of ≤0.2 ng/mL. Biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS), and cancer-specific survival were calculated at 5 and 10 years using the Kaplan-Meier method. Standard diagnostic test evaluations were used to compare both definitions with regard to later metastatic failure or cancer-specific death. Results: At 48 months, 427 patients were evaluable with a Phoenix-defined and 327 with a surgical-defined cure. At 5 and 10 years BRFS was 97.4% and 89% and MFS was 99.5% and 96.3% in the Phoenix-defined cure cohort, and BRFS was 98.2% and 92.7% and MFS was 100% and 99.4% in the surgical-defined cure cohort. Specificity for cure was 100% for both definitions. Sensitivity was 97.4% for the Phoenix and 96.3% for the surgical definition. The positive predictive value was 100% for both, whereas the negative predictive value was 29% for the Phoenix and 7.7% for the surgical definition. Accuracies of a correct prediction of cure were 94.8% and 96.3% for the Phoenix and the surgical definition, respectively. Conclusions: Both definitions are useful for a reliable assessment of cure after LDR-BT in patients with low-risk and intermediate-risk prostate cancer. Cured patients might follow a less stringent follow-up schedule from 4 years onward, whereas patients not achieving cure at 4 years should be monitored for an extended time.
RESUMEN
BACKGROUND: Chronic hypoxia influences gene expression in the lung resulting in pulmonary hypertension and vascular remodelling. For specific investigation of the vascular compartment, laser-microdissection of intrapulmonary arteries was combined with array profiling. METHODS AND RESULTS: Analysis was performed on mice subjected to 1, 7 and 21 days of hypoxia (FiO2 = 0.1) using nylon filters (1176 spots). Changes in the expression of 29, 38, and 42 genes were observed at day 1, 7, and 21, respectively. Genes were grouped into 5 different classes based on their time course of response. Gene regulation obtained by array analysis was confirmed by real-time PCR. Additionally, the expression of the growth mediators PDGF-B, TGF-beta, TSP-1, SRF, FGF-2, TIE-2 receptor, and VEGF-R1 were determined by real-time PCR. At day 1, transcription modulators and ion-related proteins were predominantly regulated. However, at day 7 and 21 differential expression of matrix producing and degrading genes was observed, indicating ongoing structural alterations. Among the 21 genes upregulated at day 1, 15 genes were identified carrying potential hypoxia response elements (HREs) for hypoxia-induced transcription factors. Three differentially expressed genes (S100A4, CD36 and FKBP1a) were examined by immunohistochemistry confirming the regulation on protein level. While FKBP1a was restricted to the vessel adventitia, S100A4 and CD36 were localised in the vascular tunica media. CONCLUSION: Laser-microdissection and array profiling has revealed several new genes involved in lung vascular remodelling in response to hypoxia. Immunohistochemistry confirmed regulation of three proteins and specified their localisation in vascular smooth muscle cells and fibroblasts indicating involvement of different cells types in the remodelling process. The approach allows deeper insight into hypoxic regulatory pathways specifically in the vascular compartment of this complex organ.
