Genetic Screening in a Large Cohort of Italian Patients Affected by Primary Lymphedema Using a Next Generation Sequencing (NGS) Approach

Primary lymphedema is a rare inherited condition characterized by swelling of body tissues caused by accumulation of fluid, especially in the lower limbs. In many patients, primary lymphedema has been associated with variations in a number of genes involved in the development and maintenance of the lymphatic system. In this study, we performed a genetic screening in patients affected by primary lymphedema using a next generation sequencing (NGS) approach. With this technology, based on a custom-made oligonucleotide probe library, we were able to analyze simultaneously in each patient all the coding exons of 10 genes (FLT4, FOXC2, CCBE1, GJC2, MET, HGF, GATA2, SOX18, VEGFC, KIF11) associated with primary lymphedema. In the study population, composed of 45 familial and 71 sporadic cases, we identified the presence of rare variants with a potential pathogenic effect in 33% of subjects. Overall, we found a total of 36 different rare nucleotidic alterations, 30 of which had not been previously described. Among these, we identified 23 mutations that we considered most likely to be disease causing. Patients with an FLT4 or FOXC2 alteration accounted for the largest percentage of the sample, followed by MET, HGF, KIK11, GJC2 and GATA2. No alterations were identified in SOX18, VEGFC, and CCBE1 genes. In conclusion, we showed that NGS technology can be successfully applied to perform molecular screening of lymphedema-associated genes in large cohort of patients with a reasonable effort in terms of cost, work, and time

Image-guided Stereotactic Body Radiotherapy in Metastatic Prostate Cancer

BACKGROUND/AIM: In the last years, the use of Image Guided Stereotactic Radiotherapy (IG-SBRT) in patients with metastatic prostate cancer has increased. In this study, we aimed to assess the role of IG-SBRT in terms of local control and safety in patients with metastatic prostate cancer. MATERIALS AND METHODS: Primary and secondary endpoints of this prospective observational study were local control and safety related to IG-SBRT. All lesions were treated with 24 Gy as a single fraction or 27 Gy in 3 fractions. After SBRT, Systemic therapies were administered only after the occurrence of more than three synchronous active lesions in oligometastatic patients (patients with less than 4 active synchronous lesions) or new lesions occurrence in patients with more than 3 synchronous lesions. RESULTS: From April 2011 to June 2017, 78 metastatic lesions (32 bone and 46 node) from 51 patients with prostate cancer were treated. After a median follow-up of 18.5 months (range=3-103 months), only 2 lesions (4%) relapsed inside the radiation field. All local recurrences were located on the bone. Estimated 12 and 24 months local control ratios were 98.7 and 97.4%, respectively. Except for one case, toxicity greater than G2 was not recorded. CONCLUSION: IG-SBRT is safe and can be considered as a valid therapy in patients with metastatic prostate cancer requiring a long-lasting metastases control