Hypofractionated stereotactic radiotherapy and continuous low-dose temozolomide in patients with recurrent or progressive malignant gliomas

To evaluate the efficacy of reirradiation and systemic chemotherapy as salvage treatment in patients with recurrent malignant glioma. Between May 2006 and December 2011, 54 patients with recurrent malignant glioma received hypofractionated stereotactic radiotherapy (HSRT) plus systemic therapy at University of Rome Sapienza, Sant' Andrea Hospital. All patients had Karnofsky performance score ≥60 and were previously treated with standard conformal RT (60 Gy) with concomitant and adjuvant temozolomide (TMZ) up to 12 cycles. Thirty-eight patients had a GBM and 16 patients had a grade 3 glioma. The median time interval between primary RT and reirradiation was 15.5 months. At the time of recurrence all patients received HSRT (30 Gy in 6-Gy fractions) plus concomitant TMZ (75 mg/m2/day) followed by continuous TMZ at 50 mg/m2 everyday up to 1 year or until progression. Median overall survival after HSRT was 12.4 months, and the 12- and 24-month survival rates were 53 and 16 %, respectively. The median progression-free survival (PFS) was 6 months, and the 12- and 24-month PFS rates were 24 and 10 %, respectively. KPS >70 (P = 0.04) and grade 3 glioma were independent favourable prognostic factors for survival. In general chemoradiation regimen was well tolerated with relatively low treatment-related toxicity. HSRT plus concomitant TMZ followed by continuous dose-intense TMZ is a feasible treatment option associated with survival benefits and low risk of complications in selected patients with recurrent malignant glioma. The potential advantages of combined chemoradiation schedules in patients with recurrent malignant gliomas need to be explored in future studies. © 2012 Springer Science+Business Media New York

Microarrays as research tools and diagnostic devices

Molecular diagnostics comprises a main analytical division in clinical laboratory diagnostics. The analysis of RNA or DNA helps to diagnose infectious diseases and identify genetic determined disorders or even cancer. Starting from mono-parametric tests within the last years, technologies have evolved that allow for the detection of many parameters in parallel, e.g., by using multiplex nucleic acid amplification techniques, microarrays, or next-generation sequencing technologies. The introduction of closed-tube systems as well as lab-on-a-chip devices further resulted in a higher automation degree with a reduced contamination risk. These applications complement or even stepwise replace classical methods in clinical microbiology like virus cultures, resistance determination, microscopic and metabolic analyses, as well as biochemical or immunohistochemical assays. In addition, novel diagnostic markers appear, like noncoding RNAs and miRNAs providing additional room for novel biomarkers. This article provides an overview of microarrays as diagnostics devices and research tools. Introduced in 1995 for transcription analysis, microarrays are used today to detect several different biomolecules like DNA, RNA, miRNA, and proteins among others. Mainly used in research, some microarrays also found their way to clinical dia- gnostics. Further, closed lab-on-a-chip devices that use DNA microarrays as detection tools are discussed, and additionally, an outlook toward applications of next-generation sequencing tools in diagnostics will be given