Deterioration of Visual Acuity after Brachytherapy and Proton Therapy of Uveal Melanoma, and Methods of Counteracting This Complication Based on Recent Publications.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. The eyeball is the most common extracutaneous location of melanoma. UM is a huge threat to a patient's life. It metastasizes distantly via blood vessels, but it can also spread locally and infiltrate extraocular structures. The treatment uses surgical methods, which include, among others, enucleation and conservative methods, such as brachytherapy (BT), proton therapy (PT), stereotactic radiotherapy (SRT), stereotactic radiosurgery (SRS), transpupillary thermotherapy (TTT) and photodynamic therapy. The key advantage of radiotherapy, which is currently used in most patients, is the preservation of the eyeball with the risk of metastasis and mortality comparable to that of enucleation. Unfortunately, radiotherapy very often leads to a significant deterioration in visual acuity (VA) as a result of radiation complications. This article is a review of the latest research on ruthenium-106 (Ru-106) brachytherapy, iodine-125 (I-125) brachytherapy and proton therapy of uveal melanoma that took into account the deterioration of eye function after therapy, and also the latest studies presenting the new concepts of modifications to the applied treatments in order to reduce radiation complications and maintain better visual acuity in treated patients.

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.

Recurrence of choroidal melanoma after Ru- 106 brachytherapy.

AIM: The aim of the study was to analyse the recurrence rates of choroidal melanoma treated with Ru-106 brachytherapy with or without adjunctive transpupillary thermotherapy. MATERIAL AND METHODS: We analysed medical records of 97 patients treated with Ru-106 brachytherapy with or without adjunctive transpupillary thermotherapy who subsequently presented with recurrence. All patients were treated at the Department of Ophthalmology and Ocular Oncology in Krak6w between 1995 and 2006. RESULTS: The mean time to recurrence was 29.15 months and tended to be shorter in larger melanomas. The 5-year recurrence rate determined using Kaplan-Meier estimator was 28.69%. Marginal recurrence was the most common type of recurrence, especially in tumors adjacent to the optic disc. The recurrence rates were the highest for all types of recurrence after the use of COB plaque with or without adjunctive transpupillary thermotherapy. CONCLUSION: The highest incidence of recurrence was shown in the second year following the Ru-106 brachytherapy and the time to recurrence tended to be shorter in larger melanomas. Marginal recurrence was the most common type of recurrence, especially in tumors adjacent to the optic disc.

[Available approaches to retinoblastoma therapy--literature review]. / Dostepne metody leczenia siatkówczaka--przeglad pismiennictwa.

Retinoblastoma is a malignant tumor and treatment should be started as soon as possible. Currently, the most common approach combines local therapy with chemotherapy. Chemoreduction represents a significant advance in the treatment of retinoblastoma. This paper presents treatment approaches including local chemotherapy, intraarterial and intravitreous chemiotheraphy. retinoblastoma, chemotherapy chemoreduction, brachytherapy, thermotherapy, laser photocoagulation, proton radiotherapy, teleradiotherapy, intraarterial chemotherapy.

[Risk factors for the recurrence of choroidal melanoma after the Ru-106 brachytherapy]. / Czynniki ryzyka wznowy czerniaka naczyniówki leczonego metoda brachyterapii Ru-106.

PURPOSE: The aim of the study was to determine factors, which are likely to affect local recurrence of choroidal melanoma after ruthenium-106 brachytherapy with or without adjunctive transpupillary thermotherapy. MATERIAL AND METHODS: We analysed 355 cases of patients with choroidal melanoma treated ruthenium-106 brachytherapy with or without adjunctive transpupillary thermotherapy. These were divided into two groups of patients with confirmed recurrence of choroidal melanoma (97 subjects) and patients without recurrence (control group, 258 subjects). RESULTS: We found a significant relationship between tumour recurrence and the presence of retinal detachment at the time of diagnosis, tumor shape, its large size and location with the marginal adjacency to the optic disc and with the anterior margin located 1-2 optic disc diameters from the macula. Among other risk factors, the use of COB plaque with supplementary transpupillary thermotherapy, dose to the tumor base, visibility of tumor base shade during transillumination, and uncertainty regarding precise plaque placement showed a significant correlation with tumour recurrence, just as the presence of metastases did. CONCLUSION: It seems that large tumour size and its location at the proximity of the optic disc are the key factors to affect the failure of brachytherapy and recurrence in patients with choroidal melanoma.

[Transpupillary thermotherapy (TTT) for intraocular metastases in choroid]. / Przezzreniczna termoterapia (TTT) w leczeniu nowotworów przerzutowych rosnacych w naczyniówce.

UNLABELLED: Uveal metastases are the most common intraocular malignant tumors. Most patients who develop metastatic carcinoma to the choroid are managed by radiation or chemotherapy. Since TTT is an optional treatment for choroidal melanomas and hemangiomas, we ought to determine whether TIT is suitable for treatment of solitary choroidal metastasis at the posterior pole. PURPOSE: To evaluate effectivenes of TTT treatment for intraocular metastases. MATERIAL AND METHODS: 45 patients (59 eyes) with intraocular metastases were treated in the Ophthalmological Department of Jagiellonian University in Kraków. There were 30 women and 15 man, at the age 31-84 years (av. 57.5). The primary tumor was a breast cancer in 22 women, lung cancer in 5 men and 2 women, kidney (3), colon (2), uterus (1), larynx (1), testicle (1), esophagus (1). 10 patients had also metastases in other organs. TTT was performed in all treated eyes, in 11 combined with 106Ru brachytherapy (BT). Chemotherapy as adjuvant treatment was performed in 18 patients. The results of treatment were evaluated in mean 14.5 months (1-61) follow-up. RESULTS: After TTT, tumor shrinking was observed in most treated tumors (in 37 eyes, 62.7%), inhibition of tumor growth in 5 (8.4%), and in 4 cases (6.7%) progression of tumor growth. In 3 cases (5.1%) with flat scar and intraocular tumor shrinking, extrascleral extension located close to the tumor base appeared after treatment (TTT in 2 eyes, TTT combined with BT in one case). CONCLUSIONS: TTT is an effective treatment method for small choroidal metastases located in the posterior pole. TTT combined with 106Ru brachytherapy can be useful treatment in medium sized choroidal metastases. Efficient results encourage further application of thermotherapy in the treatment of intraocular metastases. It allows for the conservative treatment of the eyeball and also useful visual acuity. Extraocular extension appearing after TT needs further study.

Microcirculation patterns in indocyanine green angiography and the results of plaque therapy in choroidal melanoma.

PURPOSE: To determine the effect of radioactive plaque therapy on blood vessel behaviour in choroidal melanomas using indocyanine green (ICG) angiography. MATERIAL AND METHODS: Fifty-five patients with choroidal melanoma were studied. Ruthenium-106 plaques were used in 30 eyes, in 11 the "sandwich method" (Ruthenium-106 plaque with transpupillary thermotherapy), was applied and 14 tumours were treated with Iodine-125. In all cases ICG angiography was performed prior to treatment and 12 months after, and at different time afterwards. Baseline tumour microcirculation patterns (MCPs) were studied prior to treatment and post-treatment blood vessels changes were evaluated. Total follow-up period ranged from 14-22 months (mean: 16 months). RESULTS: Pre-treatment ICG angiography revealed complex MCPs, combining parallel with cross-linking, arcs with branching, loops and networks patterns in 23 (41.8%) and non-complex MCPs, including straight, parallel without cross-linking and arcs without branching patterns in 32 (58.2%) melanomas. Twelve months after treatment, 38 tumours (69.1%) showed a significant changes in their MCPs. The mean ultrasonographic regression rate in tumours with complex MCPs was 57.4% as opposed to 36.2% in the group with non-complex MCPs (p = 0.01). No statistically significant correlation in the height regression rate was found among the various methods of therapy, however a significant difference between the type of therapy and MCPs changes was observed (p < 0.001). Melanomas treated with Ruthenium-106 and TTT demonstrated slight or no MCPs changes, while tumours treated with Ruthenium-106 and Iodine-125 plaques alone showed a significant MCPs changes (p < 0.001). The statistical analysis showed the correlation between the type of baseline MCPs and the degree of their changes after treatment (p < 0.001). Tumours with networks, loops, arcs with branching and parallel with crossing showed an increased regression as compared to other MCPs. Twelve patients whose tumours contained complex MCPs developed metastatic disease. CONCLUSIONS: This study suggests that the response of choroidal melanoma to irradiation is related to MCPs as identified by ICG angiography; the presence of complex MCPs is associated with a high regression rate after plaque therapy and a high risk of development of systemic metastatic disease.

[Photothrombosis in choroidal melanoma mediated by indocyanine green]. / Fototromboza indukowana zielenia indocyjaninowa (iMP) w leczeniu czerniaka naczyniówki.

PURPOSE: To assess the distant results of choroidal melanoma treatment with indocyanine green induced photothrombosis (iMP). MATERIAL AND METHODS: The study comprised 57 patients (57 eyes) at the age 39 to 68 yrs (mean age: 57.4 yrs), with choroidal melanoma. In all cases basic ophthalmic examination with ultrasonography and indocyanine green angiography (ICGA) were performed. IMP was performed with diode laser at 810 nm wave length 15 minutes after intravenous indocyanine dye injection as a bolus (50 mg/5 ml). The main criteria for assessment of treatment efficacy included changes in tumor thickness measured by ultrasonography and microcirculation changes in ICGA. The follow-up period ranged from 37 to 59 months (mean: 45.5 month). RESULTS: Before iMP plaque therapy with 106Ru was performed in 18 eyes, and with 125l in 5, transpupillary thermotherapy (TTT) or xenon arc photocoagulation was used in 5 eyes and "sandwich method" (106Ru + TTT) in 16 eyes. Only in 13 eyes the primary treatment consisted of iMP. IMP was performed twice in 4 patients and three times in 2. After iMP the total regression of tumor microcirculation was observed in 36 cases, in 14 the partial regression was noted and in 7 the inner microcirculation remained unchanged. Ultrasonography showed the mean reduction of tumor thickness by 47.3% in 37 eyes, among which the flat scar was present in 12. Stabilization was observed in 15 cases while in 5 the further progression of the tumor was detected in spite of performed therapies. The additional treatment was performed in 20 cases. Six eyes was enucleated; in one case because of neovascular glaucoma, and in 5 because of no positive reaction to performed conservative treatment. CONCLUSIONS: IMP can be an effective method of therapy in some cases of small choroidal melanoma. In medium size and in large melanomas iMP can serve only as the additional method adjunctive to plaque therapy and TTT.

[Bronchial carcinoid--a rare neoplasm metastasis to choroid]. / Rakowiak pluca--rzadki nowotwór przerzutujacy do naczyniówki.

PURPOSE: To present a clinical picture and results of treatment in two patients with bronchial carcinoid metastases to choroid. MATERIAL AND METHODS: Two females aged 47 and 56 with bilateral and multiple metastases of bronchial carcinoid were enrolled in this study. Choroidal metastases occurred 6-7 years after primary tumors had been diagnosed. The follow-up period ranged from 2.5 to 5 years. In one patient teleradiotherapy of choroidal metastases was performed, while in a second case plaque therapy with 106 Ru and 125 I and a diode laser therapy were used. RESULTS: After therapy, one patient demonstrated partial regression of two choroidal metastases and total regression of one tumor, while the second one, showed total regression of all intraocular tumors. One patient developed irradiation neuropathy and retinopathy as a result of teleradiotherapy, which were the main cause of decreased visual acuity in her one eye. CONCLUSIONS: Regarding the good prognosis and potentially long survival of patients with bronchial carcinoid, prompt treatment of choroidal metastases is recommended. Applied method of therapy depends on tumor size, its localization and patient's general condition.

[Retinoblastoma update--therapy (Part II)]. / Siatkówczak--aktualne zalecenia dotyczace leczenia (Czesc II).

The aim of this paper is to present updated data on the treatment of retinoblastoma. The authors describe current management based on the International Intraocular Retinoblastoma Classification (IIRC). They discuss the different methods of treatment, including chemoreduction, subconjunctival carboplatin, transpupillar thermotherapy, cryotherapy, laser photocoagulation, episcleral plaque radiotherapy, external-beem radiotherapy and enucleation.

[Choroidal metastases from breast cancer--clinical observations of 18 cases]. / Przerzuty raka gruczolu piersiowego do naczyniówki--obserwacje kliniczne 18 przypadków.

PURPOSE: To present clinical picture and results of treatment of breast carcinoma metastases to choroid. MATERIAL AND METHODS: Eighteen females (26 eyes), age: 31-70 years old; mean age: 50.5 +/-14.5 years with breast carcinoma choroidal metastases were enrolled in this study. Choroidal metastases occurred 1 month to 288 months, mean: 64 +/- 33 months, after primary tumors had been diagnosed. In all cases basic eye examination with ultrasonography as well as fluorescein and indocyanine green angiography in some patients, were performed. Method of treatment was applied according to tumor size and its localization; 106Ru plaque therapy was used in 8 cases, I25I in 2, transpupillary therapy (TTT) in 8, 106Ru + TTT ("sandwich method") in 4, teleradiotherapy in 3 and enucleation was performed in one case. The follow-up period ranged from 6 months to 5 years, mean 15.3 +/- 7.7 months. RESULTS: Unilateral choroidal metastases were present in 10 patients and bilateral in 8. Single metastatic lesions were detected in 15 patients and multiple in 3. Tumors thickness measured by ultrasonography ranged from 1.2 to 16.2 mm. After therapy regression of tumors was noted in 7 eyes (10 tumors), among which in four eyes (7 tumors) total regression was observed. Stabilization was found in 4 eyes (4 tumors) and progression in other 4 eyes (4 lesions). CONCLUSIONS: Tumor size, its localization and general patient condition are the main factors deciding about the method in treatment of choroidal metastases. Plaque therapy and transpupillary thermotherapy are effective methods of treatment in majority of metastatic tumors. They induce tumor regression and in some cases they may provide improvement in visual acuity.

[Surgical management of choroidal melanoma]. / Leczenie chirurgiczne czerniaka naczyniówki.

The aim of this paper, was to report my own experiences of the surgical treatment of choroidal melanoma. 10 patients treated by transscleral resection with additional rutenium brachytherapy between January 1995 and June 2001, were evaluated in the study. Intraoperative complications included bleeding (3 cases), vitreous loss (3) and residual tumor successfully treated with iodine brachytherapy in one case. Postoperative retinal detachment with painful hypotony in one case was the reason of enucleation. The evaluation of functional results has shown no impairment of visual acuity in 20% of cases and did not change during follow up. These observations encouraged us in our belief that transscleral resection is an alternative method of treatment of choroidal melanoma.

[Use of indocyanine green for photodynamic therapy of choroidal melanoma--preliminary report]. / Zastosowanie zieleni indocyjaninowej w leczeniu fotodynamicznym czerniaka naczyniówki--doniesienie wstepne.

PURPOSE: To evaluate the usefulness of indocyanine green (ICG) in the photodynamic therapy (iPDT) of choroidal melanoma. MATERIAL AND METHODS: Thirty eight patients with choroidal melanoma were treated with iPDT. Tumor thickness ranged from 2.6 to 4.1 mm in ultrasonography. Before iPDT Ruthenium-106 plaques were used in 18 cases, in 6 cases with additional transpupillary thermotherapy ("sandwich method"), and Iodine-125 plaques in 3 cases. In 11 eyes the iPDT was the only performed treatment. Therapy was performed with 810 nm diode laser after intravenous injection of 25 mg solution of indocyanine green. Six months after iPDT ophthalmological examination was performed with ultrasonography and ICGA images evaluation. RESULTS: The baseline ICG study showed pathological intrinsic vasculature in all examined cases. Six months after iPDT changes in microcirculation, as well as significant decrease of tumors thickness in ultrasonography (mean 38%), were detected in all cases. Complete regression of intrinsic vessels was demonstrated by ICGA in 26 cases, and partial regression of pathological vascularization was found in 12 patients. CONCLUSIONS: Our preliminary study suggests, that ICG mediated iPDT can be a new and promising way, to treat choroidal melanoma.

[Treatment of intraocular metastatic tumors]. / Leczenie wewnatrzgalkowych guzów przerzutowych.

PURPOSE: Analysis of the clinical picture of intraocular metastatic tumors and the results of the treatment with various methods. MATERIAL AND METHODS: Between 1994-1997 intraocular metastatic tumors were diagnosed in 14 patients (19 eyes). There were 13 females and 1 male, aged 28 to 69 years (average 50). The primary tumor in 8 patients developed in the breast, in 4 cases in the lungs, 1 in the brain, and 1 in the kidney. In all patients the primary tumor was excised, then chemotherapy was applied in 9 cases, radiotherapy in 3 cases, and hormonal treatment in 2 cases. In 7 patients the metastatic process concerned also other organs: bones, liver, lungs, hypophysis, and lymphatic glands. Metastases developed in 10 months to 11 years since the diagnosis and treatment of the primary tumor. Intraocular tumors were the most often located near the optic disc (8 cases), or near the macula (4 cases). There were usually flat tumors (in 12 cases < 5 mm in thickness), creamy white, sometimes with pigment clamping. In order, to confirm the diagnosis of the tumor, USG was always performed and in 8 cases fluorescein angiography. In all cases topical treatment was applied, which consisted of irradiation with ruthenium (106Ru) in 6 eyes (in 1 case two times), laser coagulation in 3 eyes, and thermotherapy (TTT) with diode laser in 4 eyes, combined treatment (106Ru + TTT) in 2 eyes, 106Ru and 125I brachytherapy in one eye. The dose of radiation for the apex of the tumor was 60-90 Gy (av. 65). The eyeball was enucleated in 3 patients, 4 patients received chemotherapy. 2 patients received hormonal therapy, applied together with the topical treatment. RESULTS: In the majority of cases (14 eyes), a flat scar or the significant decrease of the volume of the tumor was obtained. 8 patients died, two are currently observed, the remaining 4 do not come to the control examination, and there is no information as to their fate. CONCLUSIONS: Good results of the treatment encourage further application of brachy and thermotherapy in the treatment of intraocular metastatic tumors. It allows for the conservative treatment of the eyeball, and also useful visual acuity is retained often.