Ten-year follow-up of helium ion therapy for uveal melanoma.

PURPOSE: To examine the results of helium ion irradiation in 218 patients with uveal melanoma treated more than 10 years ago. METHOD: A retrospective review was made of 218 patients (218 eyes) treated with helium ion radiation for uveal melanoma between 1978 and 1984. RESULTS: After helium ion irradiation, 208 (95.4%) of 218 eyes had local tumor control. Ten years after irradiation, 46 (22.4%) of 218 eyes had been enucleated; the majority of enucleations (37 of 46) resulted from anterior ocular segment complications. Ten years after radiation, 102 (46.8%) of the 218 patients were dead; 51 had non-melanoma-related deaths and 51 had died of metastatic melanoma. Best-corrected visual acuity after radiation was greater than 20/40 in 21 (23%) of 93 eyes of the patients who were alive and who had retained their eyes 10 or more years after treatment. In patients with tumors less than 6 mm in height and more than 3 mm distant from the nerve or the fovea, 13 (72%) of 18 retained visual acuity greater than 20/40. In contrast, only 11% of the patients with either thicker tumors or those close to the nerve or fovea retained that level of visual acuity. CONCLUSIONS: Helium ion irradiation of uveal melanoma is associated with good local tumor control and reasonable retention of the treated eye 10 years after treatment. In eyes with tumors less than 6 mm in thickness and more than 3 mm distant from the optic nerve and fovea, many retain excellent vision.

Long-term follow-up after uveal melanoma charged particle therapy.

PURPOSE: To examine the results of helium ion irradiation in 218 uveal melanoma patients treated more than 10 years ago. METHODS: Retrospective review of 218 eyes treated with helium ion radiation for uveal melanoma between 1978 and 1984. Several parametric and non-parametric statistical analysis techniques were used. RESULTS: In 218 eyes treated with helium ion radiation for uveal melanoma, the mean dimension for largest basal diameter was 11.9 mm (range 5 mm to 24 mm). The mean tumor thickness was 6.7 mm (range 1.3 mm to 14.2 mm). Following helium ion radiation 208 (95.4%) of 218 eyes had local tumor control. At 10 years after radiation 46 (22.4%) of 218 eyes were enucleated; the majority (37 of 46) of enucleations were due to anterior ocular segment complications. At 10 years after radiation 102 (46.8%) of the 218 patients were dead; half had non-tumor related deaths and 51 died from metastatic melanoma. Best corrected visual acuity after radiation was > or = 20/40 in 21 of 93 eyes of patients that were alive and retained their eyes 10 or more years after treatment. In patients with tumors that were less than 6 mm in height and more than 3 mm away from the nerve or the fovea, 13 of 18 (72%) retained > or = 20/40. In contrast, only 11% of the patients with either thicker tumors or those close to the nerve or fovea retained that level of acuity. The actuarial enucleation rate at 5 years was 17.2% (2.7% S.E.) and at 10 years this was 22.4% (3.1% S.E). The recurrence tumor control rate at both 5 and 10 years was 5.3% (S.E 1.7%). CONCLUSIONS: Helium ion radiation of uveal melanoma is associated with good local tumor control and reasonable retention of the treated eye 10 years after treatment. In tumors that are less than 6 mm in thickness and greater than 3 mm from the optic nerve and fovea, many retain excellent vision. Approximately one-half of the deaths 10 years after treatment were due to non-tumor-related causes.

Irradiated uveal melanomas: cytopathologic correlation with prognosis.

PURPOSE: We analyzed the additional prognostic information from cytopathologic data obtained at the time of uveal melanoma irradiation. METHODS: Fine-needle aspiration biopsies (FNABs) were performed and reviewed in a masked manner. These data and standard prognostic variables were correlated with survival and local tumor recurrence using Kaplan-Meier and Cox model statistical techniques. RESULTS: Cytopathologic assessment of cell type added to prognostic accuracy. In 116 patients, the percentage of epithelioid cells on FNAB and ciliary body involvement were most strongly correlated with melanoma-related mortality. CONCLUSIONS: FNAB data improved our prognostic accuracy in irradiated uveal melanoma patients.

Helium-ion-induced human cataractogenesis.

Retrospective and ongoing analyses of clinical records from 347 primary intraocular melanoma patients treated with helium ions at LBL will allow examination of the exposure-response data for human cataract; which is a complication of the therapy from incidental exposure of the lens. Direct particle beam traversal of at least a portion of the lens usually is unavoidable in treatment of posterior intraocular tumors. The precise treatment planned for each patient permits quantitative assessment of the lenticular dose and its radiation quality. We are reporting our preliminary results on the development of helium-ion-induced lens opacifications and cataracts in 54 of these patients who had 10% or less of their lens in the treatment field. We believe these studies will be relevant to estimating the human risk for cataract in space flight.

High intensity 125-iodine (125I) plaque treatment of uveal melanoma.

PURPOSE: Episcleral 125I plaque therapy of uveal melanoma is an important treatment modality to control tumor, salvage the globe, and potentially preserve vision. We retrospectively analyzed our experience in 239 patients to assess treatment outcome with this technique. METHODS AND MATERIALS: Between 1983 and 1990, 239 uveal melanoma patients were treated with 125I plaques at the University of California, San Francisco. High intensity 125I seeds in the range of 3-20 mCi were used to give a minimum tumor dose of 70 Gy in 4 days. Initial mean tumor size was 10.9 mm x 9.2 mm x 5.5 mm with a range in tumor diameter from 4 to 18 mm and tumor height from 1.9 to 11.1 mm. Best corrected pre-treatment visual acuity was 20/200 or better in 92% of patients. RESULTS: Local tumor control was maintained in 91.7% of patients with a mean follow-up of 35.9 months; 19 patients had local tumor progression; mean time to progression was 27.3 mo (1.8 to 60.1 mo). Actuarial local control is 82% at 5 years. Multivariate analysis demonstrates significant correlation of local failure with larger maximum tumor diameter (p = 0.0008), closer proximity to the fovea (p = 0.0001), lower radiation dose (p = 0.0437), and smaller ultrasound height (p = 0.0034). The actuarial incidence of distant metastases is 12% at 5 years with multivariate analysis showing significant correlation only with maximum tumor diameter (p = 0.0064). Visual outcome is 20/200 or better in 58% of patients. CONCLUSION: While the tumor control rates appear favorable, ocular morbidity is significant. A current randomized trial comparing 125I plaque with Helium ion therapy is in progress with specific comparison of tumor control, survival, and visual outcome.

Cytomorphometry of uveal melanoma. Comparison of fine needle aspiration biopsy samples with histologic sections.

A number of approaches are being investigated to increase the prognostic accuracy for uveal melanoma patients; the standard deviation of nucleolar area measurements and the DNA content appear to correlate better with survival than do classic histologic parameters. The utility of performing cytomorphometric measurements on fine needle aspiration (FNA) biopsy samples was prospectively analyzed for 24 eyes containing uveal melanomas that were examined with both 25-gauge FNA biopsy and standard histologic techniques. "Masked" analysis of the cellular composition of the 24 cases showed the presence or absence of epithelioid cells to be accurately predicted on the FNA samples in all cases. Image analysis cytomorphometric measurements of nucleolar area showed marked variability (with r less than 0.4) when FNA and histologic samples from the same case were compared. The relationship between these measurements was affected by cell type, sampling, specimen processing and investigator experience.

Ki-67 and bromodeoxyuridine labeling of human choroidal melanoma cells.

Understanding tumor growth patterns has implications for prognosis as well as for response and susceptibility to treatment. The antibody Ki-67 was used as a marker of cycling cells and bromodeoxyuridine (BrdUrd) was used as a marker of proliferating cells to characterize the cycling and proliferative rates of cells from human choroidal melanoma. The BrdUrd labeling indices varied from 0-1.1% and the Ki-67 labeling indices ranged from 0-3.0.3%. Linear regression modeling showed good correlation defined by the equation: Ki-67 index = 0.237 + 1.63 x BrdUrd labeling index with r = 0.919. Correlations between these indices and clinical and histologic parameters were not significant.

Retinoblastoma cell cycling.

Techniques for the measurement of bromodeoxyuridine (BrdUrd) positive cells generally include either microscopic evaluation of paraffin embedded sections or measurements on cell suspensions using a fluorescent activated cell sorter. The accuracy of these measurements and their correlations can be affected by a number of technical and intrinsic tumor factors. Extrinsic parameters including degree of necrosis and tumor growth fraction are less easily analyzed in BrdUrd stained material. Retinoblastoma tumor cell cycling was prospectively studied in 11 children using in vivo and one child using in vitro BrdUrd. BrdUrd measurements were made by staining cell suspensions or sections of paraffin embedded tumor and analyzing by microscopy. Approximately 14% of viable cells were in the synthesis-phase of the cell cycle. The correlation between BrdUrd in cell suspensions and BrdUrd in paraffin embedded sections did not reach significance (r = 0.48). DNA analysis of these tumors was also performed using flow cytometry. Nine tumors were found to have a normal diploid DNA content, one had a G1 peak below the diploid control, two had a G1 peak above the diploid control, and one had two G1 peaks (a diploid and a hyperdiploid peak). There was no correlation between abnormal DNA content and the percent of cells in synthesis.

Five-year follow-up of helium ion therapy for uveal melanoma.

One hundred sixty-four patients with uveal melanoma were treated with helium ion irradiation prior to May 1984, and the data were analyzed in June 1989. Most uveal melanomas were large, with a mean tumor thickness of 6.5 mm; approximately 60% of the patients had tumors that extended anterior to the equator. A complete follow-up was obtained for all patients. One hundred twelve patients were alive at the time of this report; 18% of the patients developed clinical and laboratory evidence of metastases and eventually died of widespread tumor. Eighty-four percent of eyes were retained. Data were analyzed with a number of parametric and nonparametric techniques. Larger tumors and those located in close proximity to the optic nerve and fovea had a higher incidence of most complications, especially visual loss.

The effect of silicone nasolacrimal intubation on epiphora after helium ion irradiation of uveal melanomas.

We evaluated prophylactic silicone tube intubation of the nasolacrimal drainage system prior to helium ion irradiation of uveal melanomas located on the nasal side of the globe. Twelve patients received silicone tubes and were compared to a control group of 12 patients with irradiated nasal tumors without silicone tubes. Symptoms of nasolacrimal duct obstruction and epiphora were evaluated by means of a questionnaire. All patients had nasolacrimal duct irrigation. Patients intubated before irradiation maintained patency (11 of 12), whereas those in the control group did not (zero of 12) (P less than .0014); ten of 12 control patients had closure of both superior and inferior puncta. No significant difference in symptoms of epiphora was observed between the two groups.

Coincident systemic malignant disease in uveal melanoma patients.

Differentiation of a primary uveal melanoma from a uveal metastasis can be difficult. Review of the records of 627 patients with choroidal or ciliary body melanoma seen at our institution between September 1977 and November 1987 showed that 53 (8%) had a second, systemic malignant disorder. A complete ophthalmologic evaluation, including indirect ophthalmoscopy, fundus photography, ultrasonography and general medical studies, should minimize incorrect ocular diagnosis and inappropriate therapy.