Salvage I-125 brachytherapy for locally-recurrent prostate cancer after radiotherapy.

PURPOSE: Retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity in patients treated with salvage I-125 low-dose rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer after radiotherapy. MATERIALS AND METHODS: Between 2008 and 2018, 30 patients with biopsy-confirmed prostate cancer recurrence underwent salvage treatment with I-125 LDR-BT. Of these 30 patients, 14 were previously treated with primary external beam radiotherapy (EBRT; median dose, 73 Gy) and 16 with primary I-125 LDR-BT (145 Gy and 160 Gy in 14 and 2 cases, respectively). At seed implantation, the mean age was 75.8 years, with a median Gleason score of 7 and pre-salvage PSA of <10 ng/mL. Six patients received androgen deprivation therapy for six months after relapse diagnosis. The prescribed salvage I-125 BT dose to the gland was 120-130 Gy, with dose restrictions of Dmax <135% (urethra) and <100% (rectum). Toxicity was evaluated according to the CTCAE scale (v4.0). RESULTS: At a median follow-up of 45 months, the biochemical recurrence-free survival rates at 1, 3 and 5 years were 86.7%, 56.7% and 53.3%, respectively. Overall survival at 5 years was 87%. On the multivariate analysis, two variables were significant predictors of recurrence: PSA at relapse and nadir PSA post-salvage. Grade 3 genitourinary toxicity was observed in 5 patients (radiation-induced cystitis in 3 cases and urethral stenosis in 2) and G3 gastrointestinal toxicity in 3 patients (rectal bleeding). CONCLUSION: Salvage therapy with I-125 brachytherapy is a safe and effective treatment option for locally-recurrent prostate cancer in previously-irradiated patients. High pre-salvage PSA and post-salvage nadir PSA values were significantly associated with a worse disease control after salvage I-125 LDR-BT. In well-selected patients, I-125 LDR-BT is comparable to other salvage therapies in terms of disease control and toxicity. However, more research is needed to determine the optimal management of locally-recurrent prostate cancer.

Inflammatory profile discriminates clinical subtypes in LRRK2-associated Parkinson's disease.

BACKGROUND AND PURPOSE: The presentation of Parkinson's disease patients with mutations in the LRRK2 gene (PDLRRK2 ) is highly variable, suggesting a strong influence of modifying factors. In this context, inflammation is a potential candidate inducing clinical subtypes. METHODS: An extensive battery of peripheral inflammatory markers was measured in human serum in a multicentre cohort of 142 PDLRRK2 patients from the MJFF LRRK2 Consortium, stratified by three different subtypes as recently proposed for idiopathic Parkinson's disease: diffuse/malignant, intermediate and mainly pure motor. RESULTS: Patients classified as diffuse/malignant presented with the highest levels of the pro-inflammatory proteins interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein 1-ß (MIP-1-ß) paralleled by high levels of the neurotrophic protein brain-derived neurotrophic factor (BDNF). It was also possible to distinguish the clinical subtypes based on their inflammatory profile by using discriminant and area under the receiver operating characteristic curve analysis. CONCLUSIONS: Inflammation seems to be associated with the presence of a specific clinical subtype in PDLRRK2 that is characterized by a broad and more severely affected spectrum of motor and non-motor symptoms. The pro-inflammatory metabolites IL-8, MCP-1 and MIP-1-ß as well as BDNF are interesting candidates to be included in biomarker panels that aim to differentiate subtypes in PDLRRK2 and predict progression.

Genes related to iron metabolism and susceptibility to Alzheimer's disease in Basque population.

Alzheimer's disease (AD) is the most common dementing disorder and presents with a progressive and irreversible cognitive decline of gradual onset. To date, several reports have involved iron in AD physiopathology. In this study, we have analysed TFC2 variant and HFE mutations (H63D and C282Y) in 211 AD patients and 167 controls recruited from an area of the Basque Country. Furthermore, we have studied APOE genotype as it is a well-known risk factor for AD. APOE epsilon 4 allele was associated with an increased risk of AD and an earlier age at onset, whereas no association was found between TFC2 or HFE C282Y mutation and disease susceptibility. The frequency of H63D mutation was higher in control population (29.9%) than in AD patients (18%), suggesting a protective role of this allele on AD either due to the presence of the mutation itself or through the effect of other related genes in the ancestral haplotype in which it is included.