Metastasis-free survival following treatment for uveal melanoma with either stereotactic radiosurgery or enucleation

PURPOSE: To determine whether metastasis-free survival following stereotactic radiosurgery is comparable with that following enucleation in a cohort of patients with choroidal and ciliary body melanoma. METHODS: This was a non-randomized, retrospective study of 196 patients with uveal melanoma treated between 1990 and 2000. A total of 118 eyes were enucleated and 78 eyes were treated with stereotactic radiosurgery. The following variables were recorded: age and sex of patient; tumour location, volume and height; the presence of retinal detachment, and extrascleral extension. Tumour location was divided into three categories: within the posterior pole; beyond the limits of the posterior pole but not including the ciliary body, and ciliary body location. Analysis of survival time was performed using Kaplan-Meier estimation of survival curves and Cox's proportional hazards regression modelling. RESULTS: The 5-year cumulative metastasis-free survival rate was 51% in the enucleation treatment group compared to 74% in the stereotactic treatment group. However, in the multivariate analysis there was no statistical difference in survival rates between the two treatment groups. The only variables that influenced survival rates were tumour location (p = 0.002), ciliary body tumours with the worst prognosis, and tumour volume (p = 0.001). CONCLUSIONS: Tumour size and location at presentation determined metastasis-free survival. Large ciliary body tumours had the highest risk of metastasis. Metastasis-free survival after stereotactic radiosurgery was comparable to that after enucleation.     

Survival after primary enucleation for choroidal melanoma: changes induced by the introduction of conservative therapies

BACKGROUND: Most uveal melanomas are currently treated by eye-preserving radiotherapies. However, for melanomas of the largest size or with initial complications, enucleation remains the reference treatment. Enucleation is called primary when it is proposed as the only local treatment option for a melanoma. There is very little literature on the use of primary enucleation after the introduction of conservative treatments. Our main goal was to evaluate the survival of melanoma patients treated by primary enucleation since the introduction of proton-beam therapy in France in 1991. METHODS: All melanoma patients undergoing primary enucleation in our department between 1991 and 2002 were included in this retrospective study. The 5-year melanoma-specific survival rate was calculated using the Kaplan-Meier method. The multivariate prognostic analysis was performed using the Cox proportional hazards model. RESULTS: Forty patients, representing 8% of all patients with choroidal uveal melanoma diagnosed and followed up in our department during an 11-year period, were included in the study. No patient was lost to follow-up. The 5-year melanoma-specific survival rate was 31.45% (SE: 7.8) after primary enucleation. Significant prognosis factors in the multivariate analysis were: tumor thickness > 12 mm (p = 0.03), anterior margin of the tumor involving the iris (p = 0.018), and presence of epithelioid cells (p = 0.02). CONCLUSIONS: The very low survival rate reported reflects the evolution of primary enucleation, which is currently indicated only for melanomas with the worst prognosis. The knowledge of current post-enucleation survival rates represents an essential achievement for both correct assessment of conservative therapies and patient counseling.     

Survival, anatomic, and functional long-term results in choroidal and ciliary body melanoma after ruthenium brachytherapy (15 years' experience with beta-rays)

PURPOSE: To analyze survival, radiation-related complications, local recurrence, enucleation, and visual acuity after ruthenium-106 irradiation of malignant uveal melanoma. DESIGN: Retrospective study. METHODS: A total of 213 patients treated with ruthenium-106 brachytherapy between 1983 and 1995. End point rates were estimated by life tables, and prognostic factors by Cox proportional hazards regression. Main outcome measures were survival rate, radiation-related maculopathy, radiation-related vascular occlusion, local tumor recurrence, enucleation, and visual acuity (<20/100 at 3 years). RESULTS: At 5 and 10 years, survival was 82% (standard error [SE] 2.7%) and 72% (SE 3.4%), local recurrence 21.7% (SE 3.0%) and 24.3% (SE 3.2%), and enucleation 18.0% (SE 2.7%) and 19.2% (SE 2.8%), respectively. Sixty-one patients showed maculopathy (29%), 36 retinal vascular occlusion (17%), in 33 local recurrence (16%), and 38 enucleation (18%). Age and large tumor diameter were independently associated with survival (P <.0001 and P <.0075, respectively). Age below 40 and melanoma located posteriorly were significant risk factors for maculopathy (P <.0085 and P <.0004, respectively) and vascular occlusion (P <.0415 and P <.0114, respectively). Diameter and Bruch membrane rupture were significant predictors (P <.0032 and P <.0390, respectively) of local recurrence. Visual acuity <20/100 was observed in only 26 of 97 (27%) cases of anterior but 34 of 42 (81%) of posterior tumor (P <.001). CONCLUSION: Although percentage tumor recurrence was high, survival was comparable to series using other treatments. Radiation-related complication rates were acceptable, especially for anterior tumors. Ruthenium therapy can, therefore, be recommended for small and medium-sized tumors with anterior location.     

眼眶腺样囊性癌的治疗与预后分析

目的 分析总结眼眶腺样囊性癌的治疗方法及影响预后的因素,为改善预后提供帮助.方法 采用回顾性系列病例研究,分析1991年1月至2006年7月就诊的75例眼眶腺样囊性癌患者的手术记录、病理分型及随访记录.相关数据采用χ2检验和Fisher精确检验进行统计分析.结果 眼眶实体型腺样囊性癌的2年复发率为85%(17/20)、5年复发率为100%(19/19),而腺样.管状型则分别为23.53%(8/34)和64.52%(20/31),差异有统计学意义(2年,χ2=19.14,P=0.000;5年,Fisher精确检验,P=0.003).前者发生局部蔓延和远处转移例数亦多于后者.肿瘤切除术后放射治疗的5年复发率为70%(14/20),低于单纯手术切除的复发率92.86%(13/14)(Fisher精确检验,P=0.198).首次手术行眶内容物剜除术的5年复发率为25%(1/4),低于复发后再行眶内容物剜除术的病例为75%(6/8)(Fisher精确检验,P=0.222),γ刀、粒子刀、化疗及生物治疗的效果不能确定.局部蔓延主要是至颅内、副鼻窦和颞窝,远处转移可到达肺、骨、肝、耳前淋巴结.5年远处转移率为25.71%(9/35),肺转移和骨转移各占33.33%(3/9).5年生存率74.29%(26/35),死亡率25.71%(9/35),无瘤生存率37.14%(13/35),10年无瘤生存率17.14%(6/35).最常见的死亡原因是颅内蔓延.肿瘤切除联合放射治疗可以使5年生存率提高到80%(16/20).结论 腺样囊性癌是高度恶性的眼眶肿瘤,复发率和死亡率均较高,病理分型、治疗方法均影响预后.采取综合治疗方法,可以减少复发,提高生存率.     

Survival after malignant tumors of the orbit and periorbit treated by exenteration.

PURPOSE: In order to further assess the survival value of orbital exenteration in malignant orbital and periorbital tumors. METHODS: The charts of 44 patients exenterated for a neoplasm of the orbit or periorbit were reviewed in a retrospective study. RESULTS: The overall 4-year survival was 45%. 26 patients had free margins on histological examination and 24 patients had developed local recurrence or metastasis. Local recurrence or metastasis were significantly more common in the group with transected margins than in the group with free-margins (p= 0.01). Survival between the group of patients with local recurrence or metastasis and the group without local recurrence or metastasis showed statistically significant difference (p=0.0025). In contrast, survival between the group of patients with free margins and the group with transected margins did not show statistically significant difference (p=0.13). CONCLUSION: Surgical free margins section is a key element in successful cancer surgery but seems not the only prognosis variable.     

125I plaque brachytherapy for anterior uveal melanomas

PURPOSE: To describe the results of 125I plaque brachytherapy of uveal melanomas anterior to the equator in terms of local control and the associated complications while trying to identify their risk factors (patients' demographic data, ocular, and tumour characteristics). METHODS: Retrospective analysis of a series of patients treated by 125I between 1990 and 2000 in a single institution. The main outcome measures are evaluation of local tumour control and complications associated with 125I plaque brachytherapy of these melanomas. RESULTS: During the study period, 136 patients were treated for an anterior tumour. The median follow-up was 62 months. The overall 5-year survival rate was 88.3%, the 5-year metastasis rate was 4% and the local recurrence rate was 1.5%. The mean final visual acuity was 20/40. The ocular complications most frequently observed at 5 years were cataract (50.3%), maculopathy (18.3%), intraocular inflammation (19.3%), and glaucoma (10.6%). Optic neuropathy, retinal detachment, keratitis, and intravitreous haemorrhage were also described. Risk factors for worse survival were age greater than 65 years and initial tumour thickness greater than 4 mm. Risk factors for the development of cataract were age more than 65 years old, male gender, and tumour diameter of more than 10 mm. Risk factors for intraocular inflammation were tumour thickness of more than 4 mm and invasion of the ciliary body. CONCLUSIONS: The use of 125I plaque brachytherapy to treat melanomas situated anterior to the equator allows good local and systemic control with a low rate of macular and optic disc complications. The most frequent complication was cataract formation.     

Ciliary body melanomas. Survival and prognostic aspects after brachytherapy or proton therapy

INTRODUCTION: Our main goals were to study the survival of patients with uveal melanomas involving the ciliary body 5 and 10 years after treatment and to review prognosis. MATERIAL AND METHODS: This study investigated 106 tumors (27 ciliary body melanomas and 79 choroidal-ciliary melanomas) of patients treated between June 1983 and April 1998. Seventy-two patients were treated with 106-ruthenium applicators and 34 were treated with proton therapy. Some large tumors or recurrences required a second treatment. The mean follow-up period was 91 months. RESULTS: The mean tumor sizes before treatment were 6,6mm for melanoma thickness and 10.3mm for mean largest basal melanoma diameters (LTD). Of the patients studied, 71% were still alive at 5 years, 35% had metastasis and 27.7% developed recurrences. Multivariate analysis showed that the risk factors for melanoma-related death were LTD greater than 13mm, presence of exudative retinal detachment, macroscopic iris root involvement at the time of diagnosis, and choroidal-ciliary location. DISCUSSION AND CONCLUSION: With 71% of patients still alive at 5 years, this review shows that melanomas involving the ciliary body do not seem less severe than more posterior uveal tumors. Because of size differences between ciliary body melanomas and choroidal-ciliary melanomas, we cannot come to the conclusion that choroidal-ciliary melanomas have a poorer prognosis than ciliary body melanomas. Largest tumor diameter over 13mm, presence of exudative retinal detachment, and macroscopic iris root involvement at the time of diagnosis are important risk factors for melanoma-related death, as shown by the multivariate analysis.     

Margins of excision for cutaneous melanoma of the eyelid skin: the Collaborative Eyelid Skin Melanoma Group Report

PURPOSE: To evaluate the practice patterns among surgeons who treat melanomas of the eyelid skin with respect to margins of excision and to look for possible correlation between margins of excision and the incidence of local and regional recurrence and distant metastasis. METHODS: A retrospective survey of the members of the American Society of Ophthalmic Plastic and Reconstructive Surgery and the European Society of Ophthalmic Plastic and Reconstructive Surgery yielded 44 cases. The patients' age, sex, date of diagnosis, histologic classification of melanoma, Breslow thickness, Clark level, location of melanoma, size of margins of excision, and findings of local or regional recurrence or distant metastasis were recorded in each case. Patients were stratified on the basis of margins of excision: 5 mm but <10 mm; and >/=10 mm. Patients were also stratified by Breslow thickness. A Cox regression model was used to evaluate the predictive value of each factor for recurrence. Main outcome measures were the incidences of local and regional recurrence and distant metastasis as a function of margins of excision and Breslow thickness. RESULTS: The majority of patients for whom reliable information was available had excision margins of /=10 mm, but this difference was not statistically significant because very few patients had melanomas at least 2 mm thick. Breslow thickness was the only statistically significant predictor of local, regional, and distant metastasis. Margins of excision did not have a statistically significant effect on local, regional, or distant recurrence. CONCLUSIONS: Breslow thickness is an important prognostic indicator for eyelid skin melanomas. A 5-mm margin of excision may be adequate for thin melanomas of the periocular skin, but because of the small number of patients in this series who had >5-mm margins, a definitive comparison of outcome with larger margins of excision cannot be made. For melanomas >/=2 mm, wider margins of excision may be prudent, and careful surveillance for local and regional recurrence is indicated.     

Iris melanoma: Prognostication for metastasis

Uveal melanoma prognostication studies have mainly included posterior uveal melanomas located in the ciliary body and choroid, often excluding iris melanoma. In this study, we report prognostic status and survival outcomes in a series of 35 patients with biopsy-proven iris melanoma. Fluorescence in situ hybridization was performed in 10 (29%) cases and 2 (5%) underwent multiplex ligation-dependent probe amplification. In total, 9 cases demonstrated disomy 3, 2 cases with monosomy 3 (fluorescence in situ hybridization), and 1 had a technical failure. On gene expression profile testing, 20 of the 23 cases (90%) were gene expression profile class 1A, and the remaining 3 (10%) were class 1B. No patient had a Class 2 status. The median follow-up period was 49 months (mean 59, range 2–156 months). No metastasis was reported during follow-up, and metastasis-free survival was 100%. A review of the published literature revealed 47 cases with high-risk status on molecular prediction, of which only 6 (13%) developed metastasis. Ciliary body involvement was reported in 5 cases and was unknown in 2 cases. We conclude that molecular prognostication of iris melanoma demonstrates low-risk prognostic status in the majority of cases irrespective of the technique used. Even those with high-risk status do not develop metastasis unless the tumor involves the ciliary body.     

Radiation complications and tumor control after plaque radiotherapy of choroidal melanoma with macular involvement.

PURPOSE: To determine the outcome of plaque radiotherapy in the treatment of macular choroidal melanoma and to identify the risk factors associated with the development of radiation complications, tumor recurrence, and metastasis. METHODS: Chart analysis of 630 consecutive patients (630 eyes) with macular choroidal melanoma managed by plaque radiotherapy between July 1976 and June 1992. RESULTS: The median largest basal tumor diameter was 10 mm, and the median tumor thickness was 4 mm. By means of Kaplan-Meier estimates, visually significant maculopathy developed at 5 years in 40% of the patients, cataract in 32%, papillopathy in 13%, and tumor recurrence in 9%. Vision decrease by 3 or more Snellen lines was found in 40% of the patients at 5 years. Sixty-nine eyes (11%) were enucleated because of radiation complications and recurrence. Twelve percent of the patients developed metastasis by 5 years and 22% by 10 years. Results of multivariate Cox proportional hazards analyses showed that the significant predictors for tumor recurrence were a distance of tumor margin from the optic disk of less than 2 mm (P = .003) and retinal invasion (P = .009). The significant variables that were predictive of metastasis included tumor thickness greater than 4 mm (P = .02) and largest basal tumor diameter greater than 10 mm (P = .03). CONCLUSIONS: Plaque radiotherapy offers a 91% 5-year local tumor control rate for macular choroidal melanoma. Despite good local tumor control, the risk for metastasis is 12% at 5 years and 22% at 10 years. In 11% of the patients, enucleation eventually became necessary because of radiation complications and tumor recurrence.     

Prognostic factors for survival after enucleation for choroidal and ciliary body melanomas

PURPOSE: To evaluate prognostic factors for the survival of patients treated by enucleation for choroidal and ciliary body melanomas. METHODS: The study included 293 consecutive patients (147 men and 146 women) treated by enucleation for a choroidal or ciliary body melanoma during the period 1955-2000. The median age at treatment was 61 years (range 26-88 years). Clinical and histopathological findings, vital status at October 1st, 2002, and cause of death were registered. Prognostic factors for survival were evaluated by univariate and multivariate Cox proportional hazards analysis and by Kaplan-Meier survival analysis. RESULTS: Follow-up was complete. The median follow-up time was 6.2 years (range 21 days to 43.4 years) and the median potential follow-up time was 25.7 years (range 1.9-47.7 years). In multivariate Cox proportional hazards analysis an increased risk of melanoma-related death was found for largest basal diameter (n = 264, p < 0.001, mortality rate ratio (RR) = 1.09 for continuous parameter in mm), anterior tumour margin at the iris/ciliary body versus choroid (p < 0.001, RR = 2.22), and non-spindle cell type versus spindle cell (p = 0.047, RR = 1.45). An increased risk of death from all causes was found for men versus women (n = 266, p = 0.02, RR = 1.41), high age (p < 0.001, RR = 1.41 for continuous parameter in 10-year age groups), largest basal diameter (p < 0.001, RR = 1.07), anterior tumour margin at the iris/ciliary body (p = 0.02, RR = 1.52), and non-spindle cell type (p = 0.04, RR = 1.34). CONCLUSION: The risk of melanoma-related death after enucleation for a choroidal or ciliary body melanoma was high for tumours with large basal diameter, of non-spindle cell type and anterior location. Additional risk factors for death from all causes were male sex and high age.     

Metastatic pattern and survival in disseminated conjunctival melanoma: implications for sentinel lymph node biopsy

PURPOSE: To study the pattern of metastasis and overall survival in patients with disseminated conjunctival melanoma. DESIGN: Population-based, retrospective cross-sectional study. PARTICIPANTS: Eighty-five Caucasian patients with primary malignant conjunctival melanoma diagnosed between 1967 and 2000. METHODS: Data were collected from the Finnish Cancer and Population Registries and all involved hospitals. The pattern (regional or systemic) and site of first metastasis were recorded. The time to first metastasis and survival by pattern were estimated by cumulative incidence analysis, which takes competing risks into account, and by Kaplan-Meier analysis, respectively. MAIN OUTCOME MEASURES: Metastatic pattern, time to metastasis by pattern, overall survival. RESULTS: In 45% (95% confidence interval, 23%-68%) of 20 patients with metastasis, regional lymph node metastases were detected before systemic ones. Median times to initial regional and systemic metastasis were 2.3 and 3.4 years, respectively, and the median time from regional to systemic metastasis, 1.0 year. The 10-year cumulative incidence of initial regional metastasis was 0.11, and it tended to be higher for tumors more than 2 mm thick (0.18 vs. 0.05, P = 0.062). The corresponding incidence of initial systemic metastasis was 0.18, and it was higher for nonlimbal tumors (0.38 vs. 0.07, P = 0.00023) and for tumors more than 2 mm thick (0.28 vs. 0.06, P = 0.026). Overall survival was longer after initial regional metastasis than after systemic metastasis (30 vs. 8 months, P = 0.012). CONCLUSION: Initial regional lymph node metastasis was as common as systemic metastasis, but initial lymph node metastasis was associated with better prognosis. Metastasis, especially initial regional lymph node metastasis, from limbal tumors and tumors less than 2 mm thick was rare. These patients may have less benefit from sentinel lymph node biopsy, a method that is currently under evaluation regarding its potential to improve survival.     

Adjuvant therapy for orbital non-rhabdomyosarcoma soft tissue sarcoma: comparison of long-term outcome between radiotherapy and chemotherapy

AIM: To illustrate clinicopathological features of orbital non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), and to compare the treatment outcome between postoperative radiotherapy (RT) and chemotherapy in a retrospective analysis nearly 20y. METHODS: A retrospective cohort study of 56 patients with orbital NRSTS were reviewed, 34 of whom received postoperative RT, and 22 received postoperative chemotherapy. The clinicopathological features, local recurrence, metastases, and survival data were recorded. Survival analysis was performed using the Kaplan-Meier method. RESULTS: During follow-up (111.8mo, ranged 8-233mo) for 56 patients, 19 patients of them developed local recurrence, and 7 patients developed distant metastases. Fifteen patients died during follow-up period. Overall survival rates considering the whole study group was 78.57% at 5y, and 72.16% at 10y after the initial diagnosis. Compared with chemotherapy, RT was associated with lower risk of local recurrence [hazard ratio for RT vs chemotherapy, 0.263, 95% confidence interval (CI), 0.095-0.728, P=0.0015]; with lower risk of distant metastasis (hazard ratio for RT vs chemotherapy, 0.073, 95%CI, 0.015-0.364, P=0.0014); and with lower risk of death from disease (hazard ratio for RT vs chemotherapy, 0.066, 95%CI, 0.022-0.200, P<0.0001). The 5-year survival rate in RT group was 97.06% compared to 50% in chemotherapy group. CONCLUSION: In patients with orbital NRSTS, postoperative RT provides better control of local recurrence, distant metastasis, and death from disease than chemotherapy. RT is the more preferrable adjuvant therapy compared to chemotherapy possibly.     

Stereotactic radiosurgery using the Gamma Knife for large uveal melanomas

BACKGROUND: We report the results over 3 years with stereotactic radiosurgery using the Gamma Knife for large and unsuitably located uveal melanomas. PATIENTS AND METHODS: A total of 100 patients (51 male, 49 female) have been treated since 1997 following a standardised treatment protocol (outpatient single-shot treatment, maximum dose 50 Gy, tumour margin dose min.25 Gy, retrobulbar anaesthesia alone for globe fixation). The localisation and/or dimension of the tumours did not allow radiation brachytherapy with Ru106 plaques. Of the tumours 18 were located in the ciliary body, 61 were located at the posterior pole, and 21 were located in the mid-periphery. All patients were followed and tested ophthalmologically and neuroradiologically at regular intervals. The 1-year follow-up data were available for 73 patients, 2-year follow-up data for 33 patients and 3-year follow-up-data for 17 patients. RESULTS: Before therapy the maximum apical tumour height (MAH) was median 7.8 mm (95% CI 2.9-12.5 mm): 1 year after treatment (73 patients) the MAH was median 5.7 mm (95% KI 2.4-10.2 mm),2 years after treatment (33 patients) the MAH was median 4.3 mm (95% KI 2.2-8.8 mm),and 3 years after treatment (17 patients) the MAH was median 4.6 mm (95% KI 2.4-8.5 mm). All differences to the MAH of the corresponding patients before treatment were statistically significant (paired t-test). Within the first year after treatment seven patients were enucleated due to a painful secondary glaucoma,within the second year after radiation two patients (one tumour recurrence, and one secondary glaucoma) and within the third year one more patient (tumour recurrence) was enucleated. CONCLUSIONS: Our 3-year results demonstrate that radiosurgery using the Gamma Knife is beneficial in achieving a local tumour control in 98% of eyes with large and unsuitably located uveal melanomas. The risk for a secondary enucleation is highest in the first year after treatment with a favourable overall rate of 10%. Due to the excellent local tumour control rate we decreased the maximum dose to 40 Gy (min.tumour margin dose 20 Gy) in the subsequently treated patients.     

Patterns of regional and distant metastasis in patients with conjunctival melanoma: experience at a cancer center over four decades.

OBJECTIVE: The regional lymph nodes generally are believed to be the most common first site of metastasis for conjunctival malignant melanoma, but the pattern of nodal metastasis in this disease has not been well established. The goal of this study was to determine the frequency, location, and timing of regional lymph node metastasis in patients with conjunctival melanoma treated at one cancer center over four decades. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-seven patients. METHODS: The clinical records of 27 patients with conjunctival malignant melanoma were reviewed retrospectively. MAIN OUTCOME MEASURES: The rates of local conjunctival recurrence, regional nodal metastasis, and distant metastasis were analyzed along with overall survival. The follow-up time ranged from 2.5 to 17 years (median, 6 years). RESULTS: Eleven patients (41%) experienced clinical regional lymph node metastasis 1.5 to 6.0 years (mean, 3.2 years) after the initial diagnosis. The involved lymphatics were the preauricular (parotid) nodes in 8 patients (73%), the submandibular nodes in 1 patient (9%), and the deeper cervical nodes in 2 patients (18%). In seven patients (26%), distant metastasis developed without evidence of prior or concurrent regional nodal disease. Patients in whom distant metastasis developed without clinical evidence of regional nodal involvement were more likely to have had local conjunctival recurrence (P = 0.03) and a higher number of local recurrences (P = 0.05) compared with patients with regional lymph nodes as the site of first metastasis. The 5- and 10-year overall survival rates were 74% and 41%, respectively. CONCLUSIONS: Regional lymph node metastasis occurred in a higher percentage of patients with conjunctival malignant melanoma than has been reported previously. Preauricular lymph nodes were most commonly involved. Distant metastasis without prior or concurrent lymph node involvement was not a rare event.     

Metastasis from uveal melanoma after proton beam irradiation

The incidence of metastasis and prognostic factors for metastasis in 780 consecutive patients with uveal melanomas treated with proton beam irradiation were evaluated. Metastasis developed in 64 patients (8%). The median time from treatment to the diagnosis of metastasis was 2.1 years (range, 3 months to 7.3 years). The liver was primarily involved in 58 (90%) patients. The 5-year cumulative probability of metastasis developing was 20%. Prognostic factors for metastasis developing were quite comparable to those found for patients treated by enucleation and included largest tumor diameter, involvement of the ciliary body, older age, and extrascleral extension. Surgical localization, tumor height, and elevated liver enzymes before treatment were not important factors in the development of metastasis.     

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.     

Uveal metastasis from breast cancer in 264 patients

PURPOSE: Breast cancer is an increasingly important health problem in women and is the most common tumor to metastasize to the uvea. This study was designed to evaluate the clinical features, management, and prognosis of patients with uveal metastasis from breast cancer. DESIGN: Retrospective interventional case series. METHODS: We retrospectively reviewed 264 consecutive patients with uveal metastasis from breast cancer. We assessed the clinical features of the patient and tumor at the time of presentation, management, and prognosis. Kaplan-Meier survival estimates were used to analyze the probability of death as a function of time. RESULTS: Uveal metastasis was the initial manifestation of breast cancer in seven patients (3%) and the first systemic metastatic site of previously diagnosed breast cancer in 43 (16%). Associated with uveal metastasis, optic disk metastasis was found in 13 patients (5%), eyelid metastasis in one patient (1%), and conjunctival and orbital in one patient (<1%). Of 264 patients with uveal metastasis, 225 (85%) had choroidal metastasis, eight (3%) iris metastasis, two (<1%) ciliary body metastasis, and 29 (11%) had metastasis in multiple uveal sites. In the 264 patients with uveal metastasis, the most common symptom was blurred vision in 197 patients (88%), floaters in 15 (5%), photopsia in 12 (5%), and 19 (7%) were asymptomatic. The uveal metastases were bilateral in 99 patients (38%) and unilateral in 165 (62%). In 55 (56%) of the 99 bilateral cases, a uveal metastasis was found in the asymptomatic fellow eye during follow-up examination. External beam radiotherapy was used in 137 patients with uveal metastasis (52%), providing tumor control in 116 patients (85%) at a mean follow-up of 21 months. Using Kaplan-Meier estimates, survival rates of all patients with uveal metastasis from breast cancer was 65% at 1-year, 34% at 3-year, and 24% at 5-year follow-up. CONCLUSIONS: Patients with uveal metastasis from breast cancer presented to ophthalmologists with visual symptoms in 93% of cases. However, asymptomatic metastases were commonly detected in the fellow eye. Local ocular tumor control was excellent with current therapies. However, systemic prognosis for all patients, including those who had been treated with different management options, was poor with survival rates of 65% at 1-year and 24% at 5-year follow-up.     

Impact of local tumor relapse on patient survival after cobalt 60 plaque radiotherapy

The authors investigated the impact of local intraocular tumor relapse on survival in a matched-group comparison study of patients with primary choroidal or ciliary body melanoma managed with cobalt 60 plaque radiotherapy. Sixty-two patients with local relapse were matched with an equal number of relapse-free patients in terms of known clinical prognostic factors for both melanoma-specific mortality (largest linear tumor dimension, location of anterior tumor margin, age) and local tumor relapse (location of posterior tumor margin). The follow-up of every relapse-free patient equaled or exceeded the interval to relapse for each matched patient with local relapse. The estimated 5-year survival (Kaplan-Meier) in the relapse-free patients was 87% (standard error = 4%), while that in the local relapse group was 58% (standard error = 6%). This difference is statistically significant (P less than 0.0001, log rank test). These results support the hypothesis that local tumor relapse after cobalt 60 plaque radiotherapy is an important post-treatment clinical indicator of the tumor's greater malignant potential and the patient's increased risk of melanoma-specific mortality.