Visual Results Following Cobalt Plaque Radiotherapy for Posterior Uveal Melanomas

Visual results of cobalt plaque radiotherapy on the eyes of 77 patients with posterior uveal melanoma in one eye and pretreatment visual acuity of 20/25 or better in both eyes were analyzed using actuarial methods. The study demonstrated that eyes receiving a radiation dose in excess of 5,000 rad to the fovea and/or optic disc commonly lose a substantial amount of vision within 2 to 3 years. It also showed that eyes treated by cobalt plaque radiotherapy for a large posterior uveal melanoma are more likely to suffer profound visual loss than those treated for a medium or small melanoma. The predominant cause of severe visual loss in these patients appeared to be foveal radiation retinopathy.     

Cobalt Plaque Therapy of Posterior Uveal Melanomas

One hundred patients with choroidal melanomas who were treated by the authors with cobalt plaque radiotherapy were analyzed with regard to tumor regression, visual results, complications, and mortality rate. The follow-up period at the time of this writing ranged from one to five years. These preliminary observations indicate that cobalt plaque radiotherapy induces tumor regression in 96% of cases, preserves useful vision in many cases and has fewer complications during the one- to five-year follow-up period than previously believed.     

Growth Rates and Doubling Times of Posterior Uveal Melanomas

Seventeen patients having a posterior uveal melanoma underwent enucleation following documentation of tumor growth. Duration of follow-up from diagnosis to enucleation ranged from 3 weeks to 30 months. The mean rate of enlargement in cubic tumor volume was 56.3 mm³/mo for eight spindle cell melanomas and 270.3 mm³/mo for nine mixed cell melanoma. The mean tumor doubling time calculated according to the exponential growth equation was 291.6 days for the eight spindle cell melanomas and 128.2 days for the nine mixed cell melanomas. The mean mitotic activity was 3.5 mf/40 hpf for the eight spindle cell melanomas and 5.4 mf/40 hpf for the nine mixed cell melanomas. These results suggest that mixed cell posterior uveal melanomas generally grow faster and have shorter doubling times than do spindle cell melanomas.     

Radiotherapy of Choroidal Melanoma with Iodine-125

The low-energy radioactive source iodine-125 is ideal for the irradiation of an intraocular tumor such as a choroidal melanoma. The energy (28 kev) of iodine-125 should be sufficient to allow sterilization of tumors as high as 10 mm. However, shielding of 28-kev photons can be achieved with thin metal (eg, gold) plaques. These eye plaques can be individually designed for each eye tumor, depending on its size, shape, and location. This paper deals with the basic considerations and preliminary observations that have lead us to the adoption of iodine-125 as the sole source for the radiation treatment of all intraocular tumors.     

Cataract surgery following cobalt-60 plaque radiotherapy for posterior uveal malignant melanoma

We reviewed the records of thirteen patients with posterior uveal malignant melanoma who had developed a mature radiation cataract following cobalt-60 plaque radiotherapy. Cataract extraction had been performed in seven of these patients as of the survey date of this investigation. We attempted to determine if cataract extraction increased the risk of metastatic melanoma, improved or worsened visual function, or resulted in any consistent intraoperative or postoperative complications that did not occur if the cataract was retained. Our analysis showed that removing the cataract did not appear to increase the risk of death from metastatic melanoma, but it also indicated that cataract extraction did not seem to improve the visual function of the irradiated eye. On the basis of our experience to date, we offer suggested guidelines for the management of patients who develop a mature cataract following cobalt-60 plaque radiotherapy of a posterior uveal malignant melanoma.     

Prognostic Value of 32P Uptake in Posterior Uveal Melanomas

Current follow-up information was obtained for 91 of 100 patients with tumors of the uveal tract for whom transscleral ³²P tests had been performed and the eye had been enucleated because of malignant melanoma. The ³²P uptake test was found to correlate better with outcome than either mitotic activity or invasion of the sclera. However, the correlation was not as good as that observed for tumor size and cell type. While most of the prognostic information in the ³²P uptake value could be determined from the size of the tumor, none of the 13 tumors with ³²P uptake less than 100% developed metastatic melanoma. The amount of necrosis within the tumor correlated with a bad prognosis and lower ³²P uptake. There were three cases of spindle-cell nevi, all with positive ³²P uptake values and none with metastasis.     

Iodine-125 Irradiation of Choroidal Melanoma: Clinical Experience

Twenty-nine patients with choroidal melanomas were treated with iodine-125 seeds in gold scleral plaques. Iodine-125 emits low energy 25 KeV photons which are attenuated by the side and back of the plaques so that the radiation is "directed" towards the choroidal tumor. The anticipated therapeutic benefits of using a low energy isotope and directional applicators have been realized. There has been a marked reduction in ocular complications in the nine medium and 20 large melanomas so treated. Our complication rate was 34% with a mean follow-up of 38 months. This is a lower complication rate, with longer follow-up, and in larger tumors than that reported with the use of cobalt-60, ruthenium-106 or ion beam. Three patients with large tumors and two patients with medium tumors died of metastasis. This compares favorably to results of similarly sized melanomas treated by enucleation.     

Plaque brachytherapy for the management of ocular surface malignancies with corneoscleral invasion

Purpose:  To describe the outcome of patients treated by surgical excision followed by plaque brachytherapy for primary or recurrent ocular surface malignancies with evidence of deep margin (corneoscleral) invasion.
Methods:  Retrospective, non-comparative, interventional case series. Eleven consecutive patients presenting with biopsy-proven scleral and/or corneal stromal involvement from either conjunctival melanoma (CM) or squamous cell carcinoma (SCC) of the conjunctiva were reviewed.
Results:  Five patients had CM (pT3 N0 M0 [ n  = 3], pT4 N0 M0 [ n  = 2]) and six patients had SCC (T3 N0 M0 [ n  = 6]). Mean age was 60.8 years and male : female (3 : 8). Mean follow up was 23.4 months (range 12–36 months). All patients were treated with Iodine-125 plaque following biopsy-proven corneoscleral invasion on histopathology. The treatment dose was 100 Gy to a depth of 1.5–2.5 mm. Outcomes: Median visual acuity and intraocular pressure were unchanged after surgery. Five patients experienced corneal ulceration in the immediate postoperative period. None experienced recurrence at the treatment site. One SCC patient and two CM patients experienced new lesions distant from the treatment site. No sight-threatening complications were observed. No patients developed distant metastases.
Conclusion:  Plaque brachytherapy is an effective and well-tolerated modality for the management of patients with ocular surface malignancy with evidence of localized corneoscleral invasion.     

巩膜敷贴放射治疗后葡萄膜黑色素瘤的退行及其与预后的关系

葡萄膜黑色素瘤是成年人眼内最常见的恶性肿瘤.巩膜敷贴放射治疗是葡萄膜黑色素瘤临床保留眼球的主要治疗方式,能有效控制肿瘤生长,但放疗后肿瘤退行反应异质性明显.有研究提出巩膜敷贴放疗后肿瘤退行速度可作为巩膜敷贴放射治疗预后因素,退行速度越快预后越差.一些学者研究发现,肿瘤初始高度、3号染色体单体化、GEP分型与巩膜敷贴放疗...     

Expression of Vascular Endothelial Growth Factor-A,Matrix Metalloproteinase-9, and Extravascular Matrix Patterns and Their Correlations with Clinicopathologic Parameters in Posterior Uveal Melanomas

Purpose

To assess extravascular matrix patterns (EMP) and expression of vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) in posterior uveal melanomas and their correlations with histopathologic parameters and metastasis.

Methods

This study was conducted on 100 consecutive eyes enucleated for posterior uveal melanomas. All tumors were examined by immunohistochemical techniques for VEGF-A and MMP-9 expression, and the presence of EMPs was assessed on routine paraffin sections stained with reticulin. Cell type, tumor localization, degree of pigmentation, necrosis, mitotic index, lymphocytic infiltration, and scleral and optic nerve invasion were analyzed by using light microscopy. No eyes had received prior treatment such as radiotherapy or transpupillary thermotherapy.

Results

Identified histopathologically, cell types were spindle cells in 60% of the cases, mixed cells in 14%, and epithelioid cells in 26% of tumors. Positive reaction for VEGF-A and MMP-9 was present in 84% and 72% of the tumors, respectively. Microvascular loops and/or networks were seen in 34% of the tumors, with the remaining 16% of the tumors displaying an arc pattern, 21% displaying a parallel pattern, and 29% displaying the normal pattern. The relationships between VEGF-A and MMP-9 expression and necrosis, the degree of lymphocyte infiltration, mitotic rate, and the formation of loop and network patterns were found to be statistically significant (P < 0.05). Metastatic disease developed in 14 patients during follow up.

Conclusions

The incidence of metastatic melanoma increased with the increasing expression of VEGF-A and MMP-9. Our data suggest that increasing VEGF-A and MMP-9 expression and the EMP can be used as independent prognostic factors in the management of posterior uveal melanoma following enucleation.?Jpn J Ophthalmol 2007;51:325–331 © Japanese Ophthalmological Society 2007

     

Effects of radiotherapy on uveal melanomas and adjacent tissues

Most uveal melanomas are treated with radiotherapy. An adequate understanding of the effects of radiation on the tumour and the healthy ocular tissues is necessary. Ionizing radiation damages cell membranes, organelles, and DNA. Irradiated cells are lysed or undergo apoptosis, necrosis, and senescence. These effects occur in tumour cells and vascular endothelial cells, resulting in tumour shrinkage, ischaemia, infarction, exudation, and fibrosis, which can cause exudative maculopathy, serous retinal detachment, rubeosis, and neovascular glaucoma (ie, ‘toxic tumour syndrome''). Such abnormalities must be distinguished from collateral damage to healthy ocular tissues that receive high doses of radiation, and these include radiation-induced retinopathy, optic neuropathy, choroidopathy, cataract, and scleral necrosis. Radiation retinopathy can be treated effectively with photodynamic therapy, anti-angiogenic agents, and intravitreal steroid injections. In some patients, optic neuropathy may improve with intravitreal steroids or anti-angiogenic agents. Neovascular glaucoma resolves with intra-cameral bevacizumab. Exudative retinal detachment can regress with intra-vitreal steroid injections. Cataract is treated in the usual manner. Scleral necrosis, if severe, may require grafting, possibly using a lamellar flap from the same eye. Depending on the bulk of the residual toxic tumour, treatment can consist of intra-vitreal steroids and/or anti-angiogenic agents, transpupillary thermotherapy or photodynamic therapy to the tumour, or surgical removal of the tumour by endo- or exo-resection. Measures aimed at preventing collateral damage include eccentric placement of ruthenium plaques or iodine seeds and delivery of a notched proton beam. The decision to treat a uveal melanoma with radiotherapy requires the ability to manage iatrogenic side effects and complications.