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IntroductionMicroarray analysis has revolutionized the role of genomic prognostication in breast cancer. However, most studies are single series studies, and suffer from methodological problems. We sought to use a meta-analytic approach in combining multiple publicly available datasets, while correcting for batch effects, to reach a more robust oncogenomic analysis.AimThe aim of the present study was to find gene sets associated with distant metastasis free survival (DMFS) in systemically untreated, node-negative breast cancer patients, from publicly available genomic microarray datasets.MethodsFour microarray series (having 742 patients) were selected after a systematic search and combined. Cox regression for each gene was done for the combined dataset (univariate, as well as multivariate - adjusted for expression of Cell cycle related genes) and for the 4 major molecular subtypes. The centre and microarray batch effects were adjusted by including them as random effects variables. The Cox regression coefficients for each analysis were then ranked and subjected to a Gene Set Enrichment Analysis (GSEA).ResultsGene sets representing protein translation were independently negatively associated with metastasis in the Luminal A and Luminal B subtypes, but positively associated with metastasis in Basal tumors. Proteinaceous extracellular matrix (ECM) gene set expression was positively associated with metastasis, after adjustment for expression of cell cycle related genes on the combined dataset. Finally, the positive association of the proliferation-related genes with metastases was confirmed.ConclusionTo the best of our knowledge, the results depicting mixed prognostic significance of protein translation in breast cancer subtypes are being reported for the first time. We attribute this to our study combining multiple series and performing a more robust meta-analytic Cox regression modeling on the combined dataset, thus discovering 'hidden' associations. This methodology seems to yield new and interesting results and may be used as a tool to guide new research.

BACKGROUND AND PURPOSE: This study evaluates the impact of MRI guided adaptive brachytherapy (BT) on uterine corpus dose.MATERIAL AND METHODS: 84 patients with median follow-up of 18 months were analysed. MRI based BT was done according to GEC-ESTRO guidelines. Non-involved uterine corpus at the time of BT was contoured and the uterine corpus dose (D90 and D98) was evaluated for (1) standard loading pattern with source loading to the tip of the tandem and (2) optimised dose plan. Tandem lengths and heights of the 85 Gy isodose were recorded.RESULTS: Dose optimisation resulted in a reduction of active tandem length of 0.4±0.4 cm leading to lowering the D90 to the non-involved uterine corpus from 63.8±9.5 Gy to 56.7±7.5 Gy EQD2 (pCONCLUSIONS: MRI guided dose optimisation lowered the dose to the uterine corpus. However, a total EBRT+BT dose larger than 50 Gy was obtained in 99% of patients. Assuming that 45-50 Gy is sufficient to eradicate microscopic disease, the lowering of uterus corpus dose is not expected to induce additional uterine corpus recurrences in the setting of MRI guided adaptive BT. This hypothesis should be tested in a larger number of patients as e.g. the EMBRACE study.

The aim of this study was to ascertain whether diffusion tensor imaging (DTI) metrics fractional anisotropy (FA), mean diffusivity (MD), linear case (CL), planar case (CP), spherical case (CS)-can characterize a threshold dose and temporal evolution of changes in normal-appearing white matter (NAWM) of adults with low-grade gliomas (LGGs) treated with radiation therapy (RT).Conventional and DTI imaging were performed before RT in 5 patients and subsequently, on average, at 3 months (n = 5), 8 months (n = 3), and 14 months (n = 5) following RT for a total of 18 examinations. Isodose distribution at 5-Gy intervals were visualized in all the slices of fluid attenuated inversion recovery (FLAIR) and the corresponding DTI images without diffusion sensitization (b0DTI). The latter were exported for relative quantitative analysis.Compared to pre-RT values, FA and CL decreased, whereas CS increased at 3 and 8 months and recovered partially at 14 months for the dose bins55 Gy and 50-55 Gy. For the 45 50 Gy bin, the FA and CL decreased with an increase in CS at 3 months; no further change was seen at 8 or 14 months. For the55 Gy and 50-55 Gy bins, CP decreased and MD increased at 3 months and returned to baseline at 8 months following RT.Radiation-induced changes in NAWM can be detected at 3 months after RT, with changes in FA, CL, and CS (but not CP or MD) values seen at a threshold dose of 45-50 Gy. A partial recovery was evident by 14 months to regions that received doses of 50-55 Gy and55 Gy, thus providing an objective measure of radiation effect on NAWM.