Markiewicz A

Transplantable Melanomas in Hamsters and Gerbils as Models for Human Melanoma. Sensitization in Melanoma Radiotherapy—From Animal Models to Clinical Trials

The focus of the present review is to investigate the role of melanin in the radioprotection of melanoma and attempts to sensitize tumors to radiation by inhibiting melanogenesis. Early studies showed radical scavenging, oxygen consumption and adsorption as mechanisms of melanin radioprotection. Experimental models of melanoma in hamsters and in gerbils are described as well as their use in biochemical and radiobiological studies, including a spontaneously metastasizing ocular model. Some results from in vitro studies on the inhibition of melanogenesis are presented as well as radio-chelation therapy in experimental and clinical settings. In contrast to cutaneous melanoma, uveal melanoma is very successfully treated with radiation, both using photon and proton beams. We point out that the presence or lack of melanin pigmentation should be considered, when choosing therapeutic options, and that both the experimental and clinical data suggest that melanin could be a target for radiosensitizing melanoma cells to increase efficacy of radiotherapy against melanoma.

The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group

PURPOSE To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. DESIGN Retrospective, multicenter observational study. PARTICIPANTS Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. METHODS Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. MAIN OUTCOME MEASURES Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. RESULTS Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. CONCLUSIONS This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.

Preliminary results of proton radiotherapy for choroidal melanoma - the Kraków experience

Aim of the study The objective of the study was to present the preliminary results of proton radiotherapy as a method for treating 15 patients with choroidal melanoma. Material and methods The proton radiotherapy was administered using beams providing energy levels of 60 MeV, which ensures a clinical range of 28.4 mm. In addition, the beam has a very narrow penumbra of 1.3 mm and a sharp distal dose fall-off. All patients received the dose of 60 CGE (cobalt gray equivalent) given to the PTV (planning target volume). This dose was administered in 4 fractions over 4 successive days of treatment. Results The tumour had regressed in 8 patients (53.3%) and remained stable in 3 patients (20%). The large tumours in another 3 patients (20%) were removed during vitrectomy (endoresection), which increased the number of patients with tumour regression up to 11 (73.3%). In the case of 1 patient, despite intraocular tumour regression occurring the choroidal melanoma had spread multifocally into the orbit, which necessitated orbit exenteration. The results ensured that the eyeballs of 14 patients (93.3%) could be saved. The follow-up period for the 15 patients ranged between 8 and 26 months (average: 17.4 months, median: 19 months). In this period some side effects were noted: an increase in intraocular pressure, retinal detachment, cataract, maculopathy, neuropathy and vitreous haemorrhaging. Conclusions The preliminary results confirm that proton radiotherapy is an effective method for treating patients with choroidal melanoma. This method ensures an eyeball preservation rate of 93%, with the vision function of 80% of the patients being saved.

Characteristic features of choroidal nevus and small choroidal melanoma in Deep Range Imaging Optical Coherence Tomography

Purpose: To determine characteristic features of choroidal nevi and small choroidal melanomas in Deep Range Imaging Optical Coherence Tomography in patients diagnosed and treated at the Department of Ophthalmology and Ocular Oncology of the Jagiellonian University, Medical College in Cracow within 2014 year. Materrial and methods: 71 patients with choroidal nevi or small choroidal melanomas were studied. Choroidal lesions were diagnosed clinically based on measurements of cross-sectional ultrasound images, mostly B-scans, and color fundus photography. The Topcon’s Deep Range Imaging Optical Coherence Tomography was used to enable better visualization of choroidal pathologies. Results: 11 patients were diagnosed with small choroidal nevus (<1.0 mm thickness and < 3.0 mm diameter), 42 – with typical nevus (1.0–2.0 mm thickness and 3.0–5.0 mm diameter), 5 – with atypical nevus (≤ 2.0 mm thickness and > 5.0 mm diameter) and 13 – with small melanoma (according to Shields’ TFSOM rule). Deep Range Imaging Optical Coherence Tomography demonstrated characteristic features of these lesions: compression of choriocapillaris in all atypical nevi and small melanomas, inner and/or outer choroidal changes in all choroidal lesions. Other features, such as subretinal fluid, photoreceptors changes, macrophages with lipofuscin, were mostly present in atypical nevi and small melanomas. Dome tumor shape and wing border shape were found only in small melanomas. Conclusion: Deep Range Imaging Optical Coherence Tomography enables visualization of all choroidal structures and their pathology. It is useful in differential diagnosis of choroidal nevi and small choroidal melanomas.

Preliminary results of proton radiotherapy for choroidal melanoma in Departhment of Ophthalmology Jagiellonian University in Kraków

Purpose Analysis of all cases choroidal melanoma treated with proton beam radiotherapy (PBRT) in 2011‐2013 in Krakow.