3D Printing Planning Stereotactic Radiosurgery in Uveal Melanoma Patients

The aim of our work is to use a new modality for visualization of intraocular tumors in three-dimensional space for planning of stereotactic radiosurgery procedure on linear accelerator. Malignant uveal melanoma is the most common malignant tumor of the inner eye structures in adults. Stereotactic radiosurgery on linear accelerator is the method of treatment that requires precise planning. However, in some cases, it is very difficult to imagine the structures based only on fusion of two-dimensional computed tomography (CT) and magnetic resonance imaging (MRI) scans. For the team of specialists planning the procedure, 3D printed models represent the way how to perceive the real shape of the tumor and its location considering the important structures of the eye globe. By using the open-source software for segmentation (3D Slicer), we created a virtual 3D model of the eye globe with a tumor that utilized tissue density information based on CT and/or MRI dataset. By creating and introducing a new imaging modality for tumor visualization, we provided real 3D model of the eye globe for the specialists that enabled them more effective planning of the stereotactic radiosurgery

Secondary Malignancies in Adulthood and after Retinoblastoma Treatment in Childhood

Advances in retinoblastoma treatment in children nowadays and in the last decades lead to success and adulthood life without problems. Treatment modalities used in childhood to cure the retinoblastoma can affect health later. Some secondary malignancies in patients with retinoblastoma may be long-term side effects of radiation and chemotherapy. However, rates of second cancers in people treated for hereditary retinoblastoma are higher than in people who had sporadic retinoblastoma. The survivors of retinoblastoma in whom second malignant neoplasms develop are at a higher risk for the development of additional tumors than they were for the development of a second tumor. The standardized incidence rate of secondary malignancies is about 15% in inherited cases and about 1.5% in nonheritable retinoblastoma. However, today there is no clear consensus on what, if any, screening protocol would be most appropriate and effective

Uveal Melanoma

Currently, melanoma of uvea is the most well-known essential tumor, which is intaocular and malignant. Treatment using radiation has now supplanted enucleation as the therapy of decision. Radioactive eye plaques and treatment using proton are being the two most examined radiotherapeutic modalities. All the more as of late, stereotactic radiosurgery and fractionated stereotactic radiotherapy have risen as promising, non-intrusive medicines for uveal melanoma. Technique called stereotactic radiosurgery might be viewed as like “not surgery” on the grounds no extractions are included. All things being equal, it is a serious strategy for radiation treatment that conveys high dosages of radiation to exceptionally little territories and volumes

Clinical Experience of Stereotactic Radiosurgery at a Linear Accelerator for Intraocular Melanoma Combined with Iridociliary Tumor Resection: A Case Report

Introduction: The treatment of iridociliary and choroidal melanoma relies on the patient’s systemic health, tumor size, location, related features, state of the opposing eye, and personal preferences. The two categories are radiation and surgical techniques. Transpupillary thermotherapy, plaque radiotherapy, charged particle irradiation, local resection, enucleation, orbital exenteration, and experimental nanoparticle therapy are all options for treating choroidal melanoma. Case Presentation: The method that entails creating a partial thickness circular, rectangular, or polyhedral scleral flap in the region covering the tumor after removing a portion of the extraocular muscles is the most popular method for local excision in choroidal or choroidal-ciliary body cancers. We discuss our experience treating iridociliary melanoma using block excision and stereotactic irradiation on a linear accelerator with TD 20.0 Gy. Conclusion: One of the treatment modalities is the combined treatment approach using stereotactic irradiation and tumor resection, and our results 1 year after therapy are comparable to the rates of local control and anatomic eye preservation to those achieved in studies of comparable uveal melanoma treatment modalities

Targeting Epigenetic Modifications in Uveal Melanoma

Uveal melanoma (UM), the most common intraocular malignancy in adults, is a rare subset of melanoma. Despite effective primary therapy, around 50% of patients will develop the metastatic disease. Several clinical trials have been evaluated for patients with advanced UM, though outcomes remain dismal due to the lack of efficient therapies. Epigenetic dysregulation consisting of aberrant DNA methylation, histone modifications, and small non-coding RNA expression, silencing tumor suppressor genes, or activating oncogenes, have been shown to play a significant role in UM initiation and progression. Given that there is no evidence any approach improves results so far, adopting combination therapies, incorporating a new generation of epigenetic drugs targeting these alterations, may pave the way for novel promising therapeutic options. Furthermore, the fusion of effector enzymes with nuclease-deficient Cas9 (dCas9) in clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9) system equips a potent tool for locus-specific erasure or establishment of DNA methylation as well as histone modifications and, therefore, transcriptional regulation of specific genes. Both, CRISPR-dCas9 potential for driver epigenetic alterations discovery, and possibilities for their targeting in UM are highlighted in this review

Periocular basal cell carcinoma - clinical perspectives

Basal cell carcinoma (BCC) as a non-melanoma skin cancer type is the most common malignant tumor throughout the world. The incidence is higher in age over 60. The intense of exposure to ultraviolet radiation is one of the known risk factors. Over 50% of BCC of the periocular region initially occur on the lower lid and inner angle. Literature review of treatment options for basal cell carcinoma, which consist of surgery, or combined techniques plus vismodegib, radiotherapy and imiquimod. The first consideration for treatment of periocular BCC is radical surgical excision using Mohs micrographic technique. Functional and esthetic outcome in patients are important after clear excisions and reconstruction should be carefully considered. Radical exenteration is considered in the case of orbital invasion of high-risk aggressive BCC

Suicide-Gene-Modified Extracellular Vesicles of Human Primary Uveal Melanoma in Future Therapies

Extracellular vesicles secreted from uveal melanoma (UM) cells are involved in the establishment of the premetastatic niche and display transforming potential for the formation of metastases, preferentially in the liver. In this study, we cultivated human primary UM cells and uveal melanoma-associated fibroblasts in vitro to be transduced by infection with a retrovirus containing the suicide gene—fused yeast cytosine deaminase::uracil phospho-ribosyl transferase (yCD::UPRT). A homogenous population of yCD::UPRT-UM cells with the integrated provirus expressed the gene, and we found it to continuously secrete small extracellular vesicles (sEVs) possessing mRNA of the suicide gene. The yCD::UPRT-UM-sEVs were internalized by tumor cells to the intracellular conversion of the prodrug 5-fluorocytosine (5-FC) to the cytotoxic drug 5-fluorouracil (5-FU). The host range of the yCD::UPRT-UM-sEVs was not limited to UMs only. The yCD::UPRT-UM-sEVs inhibited the growth of the human cutaneous melanoma cell line A375 and uveal melanoma cell line MP38, as well as other primary UMs, to various extents in vitro. The yCD::UPRT-UM-sEVs hold the therapeutic and prophylactic potential to become a therapeutic drug for UM. However, the use of yCD::UPRT-UM-sEVs must first be tested in animal preclinical studies

KIT Expression Is Regulated by DNA Methylation in Uveal Melanoma Tumors

Uveal melanoma (UM) is an ocular tumor with a dismal prognosis. Despite the availability of precise molecular and cytogenetic techniques, clinicopathologic features with limited accuracy are widely used to predict metastatic potential. In 51 UM tissues, we assessed a correlation between the expression of nine proteins evaluated by immunohistochemistry (IHC) (Melan-A, S100, HMB45, Cyclin D1, Ki-67, p53, KIT, BCL2, and AIFM1) and the presence of UM-specific chromosomal rearrangements measured by multiplex ligation-dependent probe amplification (MLPA), to find IHC markers with increased prognostic information. Furthermore, mRNA expression and DNA methylation values were extracted from the whole-genome data, achieved by analyzing 22 fresh frozen UM tissues. KIT positivity was associated with monosomy 3, increasing the risk of poor prognosis more than 17-fold (95% CI 1.53–198.69, p = 0.021). A strong negative correlation was identified between mRNA expression and DNA methylation values for 12 of 20 analyzed positions, five located in regulatory regions of the KIT gene (r = −0.658, p = 0.001; r = −0.662, p = 0.001; r = −0.816; p < 0.001; r = −0.689, p = 0.001; r = −0.809, p < 0.001, respectively). DNA methylation β values were also inversely associated with KIT protein expression (p = 0.001; p = 0.001; p = 0.015; p = 0.025; p = 0.002). Our findings, showing epigenetic deregulation of KIT expression, may contribute to understanding the past failure to therapeutically target KIT in UM