Intraoperative sonographically assisted radioactive iodine 125 plaque brachytherapy for choroidal melanoma: visual acuity outcome.

OBJECTIVES: The purpose of this study was to present a retrospective series of cases from a single Canadian academic center assessing visual acuity outcomes after intraoperative sonographically assisted iodine 125 ((125)I) plaque brachytherapy treatment. METHODS: The cases of 28 patients (16 male and 12 female; mean age ± SD diagnosis, 62.3 ± 15 years) with choroidal melanoma treated with (125)I plaque brachytherapy using intraoperative sonography between 1997 and 2002 were reviewed. RESULTS: The mean longitudinal, transverse, and depth dimensions were 11.4, 10.6, and 4.7, respectively. The median follow-up was 48 months (range, 3-102 months) for our cohort of patients. The prescribed dose was 85 Gy to a height of 5 mm (for an apex height ≤5 mm) or to the tumor apex (for an apex height >5 mm). Five years after (125)I plaque brachytherapy, all tumors had regressed in their longitudinal, transverse, and depth dimensions. The prebrachytherapy tumor depth (P = .023) and sclera dose (P = .036) were found to significantly affect visual acuity after plaque brachytherapy at 24 months. One recurrence was recorded 6 years after plaque brachytherapy. CONCLUSIONS: This study supports (125)I plaque brachytherapy as an efficacious treatment for patients with choroidal melanoma, and intraoperative sonography may help with optimizing tumor control. In addition, to our knowledge, this study is the first to report the sclera dose as a significant predictor of visual acuity.

Stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma: the McGill University experience.

PURPOSE: To report our experience with linear accelerator-based stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma. METHODS AND MATERIALS: We performed a retrospective review of 50 consecutive patients diagnosed with juxtapapillary choroidal melanoma and treated with linear accelerator-based stereotactic fractionated radiotherapy between April 2003 and December 2009. Patients with small to medium sized lesions (Collaborative Ocular Melanoma Study classification) located within 2 mm of the optic disc were included. The prescribed radiation dose was 60 Gy in 10 fractions. The primary endpoints included local control, enucleation-free survival, and complication rates. RESULTS: The median follow-up was 29 months (range, 1-77 months). There were 31 males and 29 females, with a median age of 69 years (range, 30-92 years). Eighty-four percent of the patients had medium sized lesions, and 16% of patients had small sized lesions. There were four cases of local progression (8%) and three enucleations (6%). Actuarial local control rates at 2 and 5 years were 93% and 86%, respectively. Actuarial enucleation-free survival rates at 2 and 5 years were 94% and 84%, respectively. Actuarial complication rates at 2 and 5 years were 33% and 88%, respectively, for radiation-induced retinopathy; 9.3% and 46.9%, respectively, for dry eye; 12% and 53%, respectively, for cataract; 30% and 90%, respectively, for visual loss [Snellen acuity (decimal equivalent), <0.1]; 11% and 54%, respectively, for optic neuropathy; and 18% and 38%, respectively, for neovascular glaucoma. CONCLUSIONS: Linear accelerator-based stereotactic fractionated radiotherapy using 60 Gy in 10 fractions is safe and has an acceptable toxicity profile. It has been shown to be an effective noninvasive treatment for juxtapapillary choroidal melanomas.

Intra-operative echographic localization for radioactive ophthalmic plaques in choroidal melanoma.

The objectives were to evaluate the beneficial effect of intra-operative echographic plaque site localization and to assess the rate of complications of postplaque insertion. This paper is a descriptive study of 48 patients with choroidal melanoma who underwent iodine-125 (I(125)) or ruthenium-106 (Ru(106)) plaque radiotherapy with intra-operative echographic confirmation of plaque placement with the aid of a nonradioactive plaque (dummy) at McGill University Health Centre from 1997 to 2003. Patients' mean age was 63.7 years; 52% (25/48) male, 48% (23/48) female. Twenty-seven percent (13/48) of the tumors were confined to the right eye and 73% (35/48) to the left eye. Forty-eight percent (23/48) of the tumors were located posterior to the equator, 14.6% (7/48) were anterior to the equator, 18.7% (9/48) in posterior pole, and 18.7% (9/48) at equator. Sixty-nine percent (33/48) received I(125) and 31% (15/48) had Ru(106) treatment. Ninety percent of the dummy plaques were initially positioned suboptimally and required repositioning under echographic guidance. At mean follow-up of 18.8 months, there was no tumor-related death or metastasis, but one patient required enucleation. The dummy plaque technique under echographic visualization resulted in reduction of radioactive exposure time during surgery of up to 50%. Intra-operative echographic utilization has the ability to localize precisely the tumor-plaque relationship, thereby optimizing the radiation delivered to the choroidal melanoma, while minimizing the surgeon's exposure time.

Iodine-125 radiotherapy for choroidal melanoma.

The objective was to evaluate the effect of the gender, size, and tumor location at the time of the diagnosis on the regression response of choroidal melanoma following plaque radiotherapy treatment. The paper is a longitudinal prospective study of 28 patients diagnosed with choroidal melanoma at McGill University Health Centre from 1997 to 2002. All patients were treated with episcleral iodine-125 (I(125)) plaque radiotherapy. Plaques were inserted at the tumor site under echographic visualization. All patients had medium-size tumors, except for three. Patients had periodic ophthalmic evaluation at 3 and 6 months post radiation treatment, followed by 6-month intervals thereafter. Patients' mean age was 62 +/- 15 years, 16 males and 12 females. Fifty percent of the tumors were located posterior to the equator with significant reduction in size at 12 months post plaque radiotherapy treatment. Significant regression was observed in all the tumor diameters at 5 years post treatment follow-up. Reduction in the depth diameter was significant (P < 0.01) in both male and female groups post treatment. There was a 25% (P < 0.001) reduction in the medium size of tumors at 5-year follow-up. Tumors located posterior to the equator responded best to I(125) plaque radiotherapy. Male patients responded better than females to treatment. Medium-size melanoma responded well to plaque radiotherapy.

Cyclooxygenase-2 expression in human irradiated uveal melanomas.

AIM: Previous studies have shown that radiotherapy is a stimulus for cyclooxygenase-2 (COX-2) expression and that use of COX-2 inhibitors enhances the radio sensitivity of tumor cells. The objective of this study was to evaluate COX-2 expression, and its correlation with tumor regrowth after irradiation, in enucleated eyes with uveal melanomas. METHODS: Fifteen tissue samples from patients who underwent enucleation after radiotherapy between 1988 and 2001 were used. Nine cases (60%) were enucleated because of tumor regrowth and six (40%) because of severe complications of radiotherapy. Specimens were immunostained for COX-2, and tumor cells were evaluated for specific cytoplasmic and granular immunostaining. COX-2 expression for these cases was compared with that in the previous study including 40 non-irradiated uveal melanoma cases. COX-2 expression was also correlated with tumor regrowth after radiotherapy. RESULTS: Two cases (13.3%) were positive and thirteen (86.7%) were negative for COX-2 expression. One of the positive cases had been enucleated because of tumor regrowth and one because of radiotherapy complications. There was no relationship between tumor regrowth and COX-2 expression. COX-2 expression was significantly lower in irradiated cases than in non-irradiated cases in the previous study (p<0.001). CONCLUSIONS: In contrast with studies showing an increase of COX-2 expression in other irradiated malignancies, irradiation was not a factor inducing COX-2 in uveal melanomas. Radiotherapy may, moreover, be a factor that reduces COX-2 expression in uveal melanomas.

Immunohistochemical expression of phospho-Akt in uveal melanoma.

The aim of this study was to evaluate the immunohistochemical expression of phospho-Akt and its possible association with clinicopathological features in uveal melanoma. Thirty-four enucleated eyes from 34 patients with choroidal melanoma were included in the study. Patients were divided into two groups based on the treatment received: (1) primary enucleation (n=18); (2) radiotherapy, either external beam or brachytherapy, and enucleation (n=16). Clinicopathological data were obtained. The minimum follow-up time was 72 months. Immunohistochemistry for phospho-Akt was performed using an anti-phospho-Akt (Ser 473) rabbit antibody. The association of phospho-Akt with clinicopathological parameters was investigated in each patient group separately. Phospho-Akt immunostaining was cytoplasmic in both groups. In the primary enucleation group, 10 tumours were phospho-Akt positive (55.5%). Patients with phospho-Akt-positive tumours were older (average 70.8 years versus 59 years, P=0.01) and phospho-Akt immunoreactivity was significantly associated with a higher risk of metastatic disease (Kaplan-Meier analysis, P=0.02). In the radiotherapy and enucleation group, nine tumours were phospho-Akt positive (56.2%). The absence of phospho-Akt expression was correlated with male gender (P=0.02). The following conclusions can be drawn from this study: (1) phospho-Akt immunoexpression was detected in 55.5% of uveal melanomas treated with primary enucleation and in 56.2% of uveal melanomas treated with radiotherapy and enucleation; (2) the association of phospho-Akt immunoexpression with clinicopathological features, including prognosis, merits further study.

Choroidal melanoma: clinical presentation and differential diagnosis.

Choroidal melanoma represents a diagnostic challenge in ophthalmology owing to the varied presenting symptoms and signs coupled with a wide variety of masquerading lesions. In this article the authors review the clinical presentation and differential diagnosis of this malignant neoplasm.

The risk of other primary cancer in patients with uveal melanoma: a retrospective cohort study of a Canadian population.

BACKGROUND: The incidence of second primary malignant tumours has doubled during the last 2 decades. These tumours now represent the sixth most common group of cancers. Many authors have described the presence of multiple primary cancers in patients with uveal melanoma. However, no studies have been performed using Canadian data. The purpose of this study was to describe the occurrence of other primary cancers diagnosed before or after uveal melanoma and to calculate the incidence of subsequent primary cancer in a Canadian cohort with uveal melanoma. METHODS: We conducted a retrospective study of a cohort of patients with uveal melanoma diagnosed between 1990 and 2002 at a university-affiliated centre in Montreal. We reviewed medical records to identify patients in whom other, unrelated primary malignant disease had been diagnosed. We used the standardized incidence ratio to calculate the risk of development of a second, unrelated cancer following the diagnosis of uveal melanoma. RESULTS: A total of 129 cases of uveal melanoma were diagnosed. Eighteen patients (14%) also had a diagnosis of an unrelated primary cancer. In nine patients the other cancer had been diagnosed first, and in nine patients the other tumour had been diagnosed after the uveal melanoma. There was no increased risk of development of any particular form of cancer studied for females or males. INTERPRETATION: In our Canadian cohort, statistical analysis showed no increased risk of a second cancer, overall or by organ site, in male or female patients with uveal melanoma. As uveal melanoma is a rare type of cancer, analyses of a much larger cohort may be needed to accurately estimate the risk of development of a second primary cancer in patients with uveal melanoma.

New prognostic factors in uveal melanomas: potential molecular targets for therapy.

Even with advances in the diagnosis and local treatment of uveal melanoma, there has been no significant change in the survival rates of these patients in the last decades. Metastatic disease still occurs at the same frequency, and no systemic therapy is currently offered to patients after local eye treatment. Therefore, experimental and clinical research has been focused on the metastatic cascade in order to elucidate its underlying mechanisms at the molecular level. As a result, new prognostic factors in uveal melanoma have been described that also serve as molecular targets for the development of novel treatments. These prognostic factors/molecular targets, such as membrane receptors, enzymes, cytokines, cytoskeleton components, oncogenes, tumour suppressor genes, cell-cycle proteins and nuclear antigens, are reviewed in this article.