Management of choroidal melanomas less than 10 mm in largest basal diameter with a 10-mm ruthenium plaque.

PURPOSE: To assess tumor control, complications, and vision after brachytherapy for posterior choroidal melanoma <10 mm in largest basal diameter with the 10-mm ruthenium plaque. METHODS: This was a retrospective cohort study of consecutive choroidal melanomas <10 mm by largest basal diameter in a national ocular oncology service in 1998 to 2010. The median dose was 116 Gy (range, 80-194 Gy) to the apex and 327 Gy (range, 201-824 Gy) to the sclera. The median tumor height and largest basal diameter were 1.9 mm (range, 0.4-5.2 mm) and 7.0 mm (range, 3.3-9.6 mm), respectively. The median distance to disk and foveola was 3.0 mm (range, 0-7.5 mm) and 2.0 mm (range, 0-8.5 mm), respectively. RESULTS: Four recurrences occurred at a median of 1.4 years (range, 0.6-3.1 years) after irradiation. Five-year cumulative incidence of local recurrence was 9% (95% confidence interval [CI], 3-20). Six patients died at a median of 4.2 years (range, 0.28-8.6 years) after treatment, one with evidence of metastases. At 5 years, 57% (95% CI, 31-79), 72% (95% CI, 58-85), and 97% (95% CI, 88-100) of eyes were free of any maculopathy, radiation maculopathy, and optic neuropathy, respectively. Cumulative incidence of developing low vision and blindness were 17% (95% CI, 7-31) and 3% (95% CI, 2-12) at 5 years, respectively. Thickness >3.0 mm, largest basal diameter >7.0 mm, and location ≤ 1.5 mm of foveola were associated with visual loss. CONCLUSION: Local tumor control and vision outcomes support the use of 10-mm ruthenium plaques in managing smallest choroidal melanomas.

Presumed incipient choroidal melanoma: proposed diagnostic criteria and management.

AIMS: To propose diagnostic criteria for a presumed incipient choroidal melanoma based on tumour growth rate and tumour doubling time (TDT) and to describe management of such tumours with transpupillary thermotherapy (TTT). METHODS: Retrospective interventional case series of nine consecutive presumed incipient uveal melanomas diagnosed and treated with TTT in 2010-2017. Growth rate in mm/year and per cent/year in largest basal diameter (LBD) and TDT were compared with published data for uveal melanomas and growing naevi that did not transform to melanoma under long-term follow-up. RESULTS: The median LBD and thickness were 1.6 mm (range 0.9-2.3) and 0.20 mm (range 0.15-0.29), respectively. The median age was 57 years (range 47-78). Seven tumours were classified as de novo melanomas and two as transformed naevi. The median time from first observation to diagnosis was 3.3 years (range 2.2-7.3), LBD growth rate 0.25 mm/year (range 0.11-0.72) and 34 per cent/year (range 10-1437), and TDT 609 days (range 97-1612). The estimates matched those reported for uveal melanoma (median TDT 521 days, 90th percentile 2192) and exceeded those for growing naevi (median growth rate 0.04 mm/year, 90th percentile 0.12; 1.1 per cent/year, 90th percentile 2.6). The predicted median age at de novo appearance was 51 years (range 32-63). No tumour grew after TTT during a median follow-up of 2.1 years (range 0.6-8.7). CONCLUSIONS: In this series, relative growth rate and TDT best qualified as diagnostic criteria for an incipient choroidal melanoma. Too small for brachytherapy, they could be managed with TTT.

Validation of a Prognostic Staging for Metastatic Uveal Melanoma: A Collaborative Study of the European Ophthalmic Oncology Group.

PURPOSE: To validate a staging system for metastatic uveal melanoma that will facilitate planning, reporting, and interpreting the results of clinical trials. DESIGN: Reliability and validity study. METHODS: The performance index, the largest diameter of the largest metastasis and alkaline phosphatase level at the time of diagnosis of metastases, and overall survival of 249 patients from 7 ocular oncology centers who died of dissemination were analyzed. Predicted median survival time calculated according to the Helsinki University Hospital Working Formulation was used to assign patients to stages IVa, IVb, and IVc, which correspond to predicted survival times of ≥12, <12-6, and <6 months, respectively. The predictions were compared against observed survival. RESULTS: The 3 variables used to assign stage were independent predictors of survival in the validation dataset. Of the 249 patients, 110 (44%), 109 (44%), and 30 (12%) were classified to Working Formulation stages IVa, IVb, and IVc, respectively. Corresponding median observed survival times were 18.6, 10.7, and 4.6 months and worsened by increasing stage (P < .001). Of 201 patients managed without surgical resection of metastases, 83 (41%), 89 (44%), and 29 (15%) were classified to stages IVa, IVb, and IVc, respectively, and their median observed survival times were 17.2, 10.0, and 4.6 months (P < .001). Survival of 47 patients who underwent resection did not differ by working formulation stage (P = .69). CONCLUSIONS: This multicenter study confirms that the Working Formulation is a reliable and valid, repeatable system for dividing metastatic uveal melanoma into distinct prognostic subgroups, especially for stage-specific reporting of survival in prospective clinical trials.

Population-based assessment of clinical characteristics predicting outcome of conjunctival melanoma in whites.

PURPOSE: To identify the clinical determinants of prognosis and the incidence of malignant conjunctival melanoma in whites. METHODS: A nationwide search identified 85 patients in whom primary conjunctival melanoma was diagnosed in Finland between 1967 and 2000, all of whom were enrolled. Data were collected from the Finnish Cancer and Population Registries and from patients' charts in all involved hospitals. The age-specific and age-adjusted incidences were calculated. Clinical characteristics of the tumors were recorded and time to local recurrence and melanoma-specific survival were analyzed by Kaplan-Meier analysis and univariate and multivariate extended Cox regression. RESULTS: The annual crude incidence of conjunctival melanoma in Finland was 0.51 per million inhabitants, and the age-adjusted incidence (mean, 0.54) increased from 0.4 to 0.8 during the 34-year study period. The median age at diagnosis was 60 years (range, 20-90). Clinically detectable primary acquired melanosis preceded or accompanied the primary tumor in 61% of patients. The 5-year cumulative proportion of cases with local recurrence was 0.36 (95% confidence interval [CI], 0.25-0.48). The melanoma-specific 5-and 10-year mortalities were 0.20 (95% CI, 0.12-0.32) and 0.38 (95% CI, 0.26-0.53), respectively. By multiple-event Cox regression, nonlimbal location of the primary tumor predicted a short time to local recurrence (hazard ratio [HR] 1.81, P = 0.024). Nonlimbal location of the primary tumor (HR 4.08, P = 0.023) and increasing tumor thickness (HR 1.19 for each millimeter change, P=0.063) were associated with increased mortality. Local recurrence, analyzed as a time-dependent covariate, also increased mortality (HR 1.39 for each recurrence, P = 0.014). CONCLUSIONS: The incidence of conjunctival melanoma in the white population of Finland increased analogous to cutaneous melanoma. Nonlimbal tumors recur more often and are associated with decreased survival, independent of their greater thickness. Local recurrence contributes to mortality, whereas primary acquired melanosis was not associated with either outcome.

Mortality after uveal and conjunctival melanoma: which tumour is more deadly?

PURPOSE: We aimed to model and compare mortality rates for uveal melanoma (UM) and conjunctival melanoma (CM) by adjusting for differences in tumour size and local recurrence. METHODS: Population-based mortality data for 240 and 85 patients with primary UM and CM and 91 and 23 patients with disseminated UM and CM, respectively, were compared with cumulative incidence analysis. Cox proportional hazards multivariate regression with time-dependent variables was used to adjust for differences in tumour diameter, thickness and recurrence rates. RESULTS: The 10-year cumulative incidences of metastatic death from UM and CM were 39% (95% confidence interval [CI] 33-45) and 32% (95% CI 21-44), respectively. After adjusting for tumour size, risk of death from CM was higher than from UM (hazard ratio [HR] 1.9; p = 0.039). Additional adjustment for more frequent local recurrence of CM diminished the difference (HR 1.5; p = 0.25). Survival periods after systemic metastasis of UM and CM were comparable (median 8 months). CONCLUSIONS: Clinical observations show longer survival after primary CM than after primary UM. This reflects the smaller average size of CM. However, a primary CM of a given size is more deadly than a UM of equivalent size because primary CM tends to recur after treatment and, possibly, because additional lymphatic dissemination occurs with CM.

Photodynamic therapy with verteporfin to induce regression of aggressive retinal astrocytomas.

PURPOSE: To evaluate the effect of photodynamic therapy (PDT) with verteporfin on symptomatic, aggressive retinal astrocytomas. METHODS: A prospective, interventional study in a tertiary referral centre. Two patients were treated with a single session of PDT using the standard parameters of the Verteporfin in Photodynamic Therapy (VIP) study: a 34-year-old man whose previously stationary juxtapapillary retinal astrocytoma, secondary to tuberous sclerosis, progressed within 7 months to involve the foveola; and a 68-year-old man whose acquired retinal astrocytoma progressed over 18 months in spite of standard photocoagulation. Both tumours were vascularized and had caused secondary lipid exudation and an exudative retinal detachment. Outcome measures were visual acuity, resorption of subretinal fluid, tumour height and fluorescein angiography. RESULTS: The progressing, vascularized part of both retinal astrocytomas regressed, with little change in the poorly vascularized, stationary part of the congenital hamartoma. Visual acuity improved in the first patient and was unchanged in the second by 3 months, with stable vision in both and no sign of recurrence at 2 years. The exudative retinal detachments resolved completely. Tumour height reduced a median of 30%. Regression was associated with obliteration of tumour vessels within the progressing part of the lesion, with closure of some of the dilated retinal capillaries over the tumour. Intraretinal microvascular abnormalities and scattered haemorrhages appeared outside the treated area in the first patient. CONCLUSION: PDT with verteporfin can induce regression of progressive, vascularized, aggressive retinal astrocytomas and may prevent typical progression to total retinal detachment and enucleation, whether the astrocytoma is associated with tuberous sclerosis or not. PDT may be considered a first-line treatment for aggressive retinal astrocytomas.

A prognostic model and staging for metastatic uveal melanoma.

BACKGROUND: To identify factors that independently contribute to overall survival in Stage IVB uveal melanoma and to subcategorize by prognosis. METHODS: Data of 91 consecutive patients who died of metastatic uveal melanoma in 1985-2000 were analyzed by Kaplan-Meier and Cox regression analysis. Main covariates were participation in annual review, symptoms, Karnofsky index, metastatic burden, liver function tests, and age. Time on chemotherapy was modeled as a confounder. A working formulation for staging patients according to predicted survival was designed. RESULTS: Of the 91 patients, 85% underwent annual liver imaging and function tests, 63% were asymptomatic, and 73% received chemotherapy. The median survival period was 8.4 months (95% confidence interval [CI], 6.3-11.8). Karnofsky index, largest dimension of the largest metastasis, metastatic burden, serum transaminase, lactate dehydrogenase, and alkaline phosphatase (AP) levels, and time on chemotherapy were strongly (P < 0.001) associated with survival. Symptoms (P = 0.031) and regular review (P = 0.081) were weakly associated with survival. Karnofsky index (P = 0.013), the largest dimension of the largest metastasis (P = 0.003), and serum AP level (P = 0.042) retained independent significance, adjusting for time on chemotherapy. Predicted median survival calculated for relevant covariate combinations was divided into three periods (> or =12 months vs. 6-11 months vs. < 6 months). Observed median survival for Stage IVBa was 14.9 months (95% CI, 11.7-21.3), for Stage IVBb 8.9 months (95% CI, 2.7-13.7), and for Stage IVBc 2.0 months (95% CI, 1.0-3.7). CONCLUSION: The model and working formulation for categorization can be tested as an aid in patient counseling and as a tool in design and analysis of clinical trials.

Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD), and human leukocyte interferon for metastatic uveal melanoma.

BACKGROUND: A Phase II trial comprising patients with metastatic uveal melanoma (Stage IVB) was undertaken to determine the activity of bleomycin, vincristine, lomustine, and dacarbazine (BOLD) chemotherapy with human leukocyte interferon, as well as the progression-free and overall survival of the patients according to the substage before treatment. METHODS: Twenty-two patients with histologically proven metastatic uveal melanoma received 15 mg of bleomycin (Days 2 and 5), 1 mg/m(2) vincristine (Days 1 and 4), 200 mg/m(2) dacarbazine (Days 1 to 5), and 80 mg lomustine (Day 1) every 4 weeks together with a leukocyte interferon preparation (3 x 10(6) IU daily for 6 weeks followed by 6 x 10(6) IU three times per week). RESULTS: Of 20 evaluable patients, 3 (15%; 95% confidence interval [CI] 0-38) obtained a partial objective response in hepatic and extrahepatic sites and 11 (55%; 95% CI 32-77) showed stable disease after receiving more than two cycles. The median progression-free survival was 4 months (95% CI 2-10) and the median overall survival was 12 months (95% CI 8-22). Eleven patients who had favorable pretreatment characteristics (Stage IVBa) survived a median of 17 months (95% CI 4-37) whereas 10 patients with less favorable characteristics (Stage IVBb) survived a median of 11 months (95% CI 1-23). Moderate toxicity occurred with this outpatient regimen. CONCLUSIONS: The BOLD/human leukocyte interferon regimen had modest activity against metastatic uveal melanoma in hepatic and extrahepatic sites. The median overall survival approached that reported for more aggressive intrahepatic therapy regimens. Substage differences can significantly impact study outcomes. Therefore, substage information should be reported to facilitate comparisons between studies.