Long-term biochemical results after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy for high risk prostate cancer

Abstract Background Biochemical control from series in which radical prostatectomy is performed for patients with unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal. The treatment regimen of HDR brachytherapy and external beam radiotherapy is a safe and very effective treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity.</p

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Meta-Analysis of Modulated Electro-Hyperthermia and Tumor Treating Fields in the Treatment of Glioblastomas

Background: Glioblastoma is one of the most difficult to treat and most aggressive brain tumors, having a poor survival rate. The use of non-invasive modulated electro-hyperthermia (mEHT) and Tumor Treating Fields (TTF) devices has been introduced in the last few decades, both of which having proven anti-tumor effects. Methods: A meta-analysis of randomized and observational studies about mEHT and TTF was conducted. Results: A total of seven and fourteen studies about mEHT and TTF were included, with a total number of 450 and 1309 cases, respectively. A 42% [95% confidence interval (95% CI): 25–59%] 1-year survival rate was found for mEHT, which was raised to 61% (95% CI: 32–89%) if only the studies conducted after 2008 were investigated. In the case of TTF, 1-year survival was 67% (95% CI: 53–81%). Subgroup analyses revealed that newly diagnosed patients might get extra benefits from the early introduction of the devices (mEHT all studies: 73% vs. 37%, p = 0.0021; mEHT studies after 2008: 73% vs. 54%, p = 0.4214; TTF studies: 83% vs. 52%, p = 0.0083), compared with recurrent glioblastoma. Conclusions: Our meta-analysis showed that both mEHT and TTF can improve glioblastoma survival, and the most benefit may be achieved in newly diagnosed cases

Meta-Analysis of Modulated Electro-Hyperthermia and Tumor Treating Fields in the Treatment of Glioblastomas

Background: Glioblastoma is one of the most difficult to treat and most aggressive brain tumors, having a poor survival rate. The use of non-invasive modulated electro-hyperthermia (mEHT) and Tumor Treating Fields (TTF) devices has been introduced in the last few decades, both of which having proven anti-tumor effects. Methods: A meta-analysis of randomized and observational studies about mEHT and TTF was conducted. Results: A total of seven and fourteen studies about mEHT and TTF were included, with a total number of 450 and 1309 cases, respectively. A 42% [95% confidence interval (95% CI): 25&ndash;59%] 1-year survival rate was found for mEHT, which was raised to 61% (95% CI: 32&ndash;89%) if only the studies conducted after 2008 were investigated. In the case of TTF, 1-year survival was 67% (95% CI: 53&ndash;81%). Subgroup analyses revealed that newly diagnosed patients might get extra benefits from the early introduction of the devices (mEHT all studies: 73% vs. 37%, p = 0.0021; mEHT studies after 2008: 73% vs. 54%, p = 0.4214; TTF studies: 83% vs. 52%, p = 0.0083), compared with recurrent glioblastoma. Conclusions: Our meta-analysis showed that both mEHT and TTF can improve glioblastoma survival, and the most benefit may be achieved in newly diagnosed cases

Intraoperative Neurovascular Bundle Preservation with Hyaluronic Acid during Radical Brachytherapy for Localized Prostate Cancer: Technique and MicroMosfet In Vivo Dosimetry

Purpose: To evaluate the reduction in the absorbed dose delivered to the neurovascular bundle (NB) in patients with localized prostate cancer treated with only HDR brachytherapy and NB protection with hyaluronic acid (HA) on the side of the prostate to increase the distance from NB to the radioactive sources. Methods: This is the first published report in the medical literature that studies a new approach to decrease neurovascular bundle toxicity and improve quality of life for patients with prostate cancer treated with radical brachytherapy as monotherapy. Transperineal HA injection on the side of the prostate into the lateral aspect of the prostate fat was used to consistently displace several autonomic fibers and vessels on the lateral wall of the prostate away from radiation sources. Results: When a protection in the form of an HA layer is placed, the reduction effect at the maximum dose is between 46% and 54% (calculated values), which means that the method for protection is highly recommended. The values of the absorbed dose calculated in this project have been compared with the ones given by the treatment planning system. Conclusions: This newly created space decreases absorbed dose in the NB, calculated with the TPS and measured by microMOSFET due to the thickness of HA