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 after proton-beam irradiation of uveal melanomas.

PURPOSE: To evaluate the independent prognostic factors for survival, metastasis, local recurrence, and enucleation in patients who had undergone proton-beam therapy for posterior uveal melanomas. DESIGN: Interventional case series. METHODS: In this retrospective study, 224 consecutive incident cases were treated at the Biomedical Cyclotron Centre (Nice, France) from June 1991 to December 1997. Overall, metastasis-free, local recurrence-free, and enucleation-free survival rates were calculated according to the Kaplan-Meier method using the log-rank test. The multivariate prognostic analysis was performed using the Cox proportional hazards model. RESULTS: The 5-year overall survival rate was 78.1% (SE: 3.7%). A largest basal tumor diameter (LTD) below 10 mm and female sex were independently associated with a better prognosis. The 5-year metastasis-free survival rate was 75.6% (SE: 3.6%). Only an LTD above 10 mm and ciliary body involvement were independently associated with metastasis. Ten patients (4.5%) had a local recurrence, which was correlated with the risk of metastasis (P =.045). The 5-year enucleation-free survival rate was 69.6% (SE: 4.0%). Once again, an LTD below 10 mm and female sex were predictive of a better prognosis. CONCLUSION: Our results with proton-beam therapy correspond to those reported in the literature. This treatment strategy is safe and yields predictably good results. In addition to the two independent prognostic factors for survival and metastasis, namely LTD and ciliary body involvement, sex also had a significant impact in our case series, but the clinical relevance of this finding is unknown.

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.

[Ciliary body melanomas. Survival and prognostic aspects after brachytherapy or proton therapy]. / Mélanomes uvéaux impliquant le corps ciliaire. Analyse de la survie après protonthérapie ou bêta-curiethérapie par ruthénium-106. A propos de 106 cas.

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.

[Choroidal nevi associated with serous macular detachment]. / Décompensation exsudative anatomique et fonctionnelle de 12 naevi choroïdiens.

PURPOSE: To describe the aspect and progression of choroidal nevi associated with macular serous detachment and to analyze different treatments. MATERIAL: and methods: Twelve posterior choroidal nevi were associated with subretinal fluid. The fovea was detached in 11 cases. Tumor thickness was 2 mm or less. RESULTS: No treatment was given in 6 cases and spontaneous subretinal fluid regression was observed in 3 of these 6 cases. Success was also observed in 2 of 3 cases treated with corticotherapy, but subretinal fluid recurred. Gas injection was performed in 1 case and transpupillary thermotherapy in 2 others, all 3 with successful definitive drying of the nevus. Visual acuity decreased in 6 cases (in 3 untreated cases and in 3 cases treated with corticotherapy), remained stable in 3 cases, and increased in 3 cases (in 1 untreated case, in 1 gas injection case, and in 1 case after thermotherapy). Tumor growth was observed in 3 cases, on the average 2 years after diagnosis (25%). CONCLUSION: Subretinal fluid is rarely observed with choroidal nevi and its progression is variable. Various treatments in addition to observation such as corticotherapy, gas injection, transpupillary thermotherapy seem effective in stabilizing or improving visual function. Supervision is nevertheless needed to detect tumor growth that can be frequent in these nevi associated with subretinal fluid.

[Argon laser photocoagulation of circumscribed choroidal hemangiomas]. / Hémangiomes choroïdiens circonscrits traités par photocoagulation au laser Argon.

PURPOSE: Therapeutic retrospective results obtained after Argon laser photocoagulation of 17 circumscribed choroidal hemangiomas were analyzed. MATERIAL AND METHODS: Seventeen circumscribed choroidal hemangiomas associated with serous retinal detachment were analyzed. All patients were symptomatic but one. Duration of visual symptoms varied from 2 weeks to 3 years. Mean tumor thickness was 3,3mm (1 to 6,5mm). Mean tumor diameter was 6,5mm (2.5 to 15mm). Tumors were juxtapapillary in 9 cases (57%). The mean distance from the fovea was 1,5mm (0 to 3mm), and the fovea was pathological in all cases but two. The tumoral surface was covered by Argon laser spots with the central avascular area spared in the case of subfoveal hemangioma. In the case of subretinal fluid persistence 3 months later, 1 or more photocoagulation sessions were carried out. Follow-up was 27 months (6 to 156 months). RESULTS: Success (complete subretinal fluid resolution) was obtained in 82.4% with 1 or 2 laser photocoagulation sessions. Recurrence was observed in 4 cases (23.5%) but treated with success. Final visual acuity, related to the initial foveal condition, was >=0.5 in 23.5% of cases, and >=0.1 in 70.6% of cases. DISCUSSION: Anatomical and functional results were satisfactory considering initial foveal conditions. Irradiation (external beam irradiation, proton beam therapy, brachytherapy) has been used with success for several years. However, radiation-induced damage was described in addition to a few practical disadvantages. CONCLUSION: Argon laser photocoagulation was an effective noninvasive therapy for circumscribed choroidal hemangioma. It remains for us the reference method for treating this tumor.

[Double irradiation for macroscopic radioresistance or recurrence of melanomas of the posterior uvea: clinical, ballistic, therapeutic and prognostic aspects. Series of 19 cases among 462 patients]. / Double irradiation pour radiorésistance macroscopique ou récidive dans les mélanomes de l'uvée postérieure: aspects cliniques, ballistiques, thérapeutiques et pronostiques: A propos de 19 cas sur 462 patients.

We describe two comparative series of patients treated with double-dose betaraysbrachytherapy (106 Ruthenium) between 1983 and 1994, and double-dose proton beam therapy between 1991 and 1996. The indications for double-dose irradiation with the same radio-element corresponded to "macroscopically abnormal" situations: immediate and prolonged radioresistance, recurrence or secondary radioresistance. Thirteen cases are called series 1 (Ruthenium) and 6 cases are called series 2 (protons). The series 1 allows a more reliable study as far as follow-up is higher (5.8 to 7.5 years) than in series 2 where the follow-up is shorter (13.6 to 29 months). Although double-dose irradiation was macroscopically efficient in 11 out of 13 cases in series 1, and in 3 out of 6 cases in series 2 (stabilization or decrease of tumour height measured before the second therapeutic session), 2 patients are deceased and 1 has a metastatic disease in the group "recurrence" of Ruthenium serie. Another one has also a metastatic disease in the group "recurrence" of protons series. Nevertheless double-dose radiotherapy allows a complementary decrease or stabilization of tumour height after a first session. It also decreases the indications for enucleation if there is no severe anatomic complications, when a tumour does not regress or recurs after a first session of radiations.

[Comparative study of the tumor regression rate of 127 uveal melanomas irradiated with 106 Ru/106 Rh. Attempted analysis of the correlations between per-operative cytology and histopathology of the enucleated eye and the tumoral regression on the one hand, and general prognosis on the other hand]. / Etude comparative de la vitesse de régression tumorale de 127 mélanomes uvéaux irradiés par 106 RU/106 RH. Essai d'analyse des corrélations entre la cytologie per-opératoire, l'histophathologie des globes énucléés et la régression tumorale d'une part, le pronostic général d'autre part.

A study of the speed of tumor regression in 127 uveal melanomas treated with beta-rays brachyterapy, since June 1983, allows a division into 2 groups: radiosensitive forms with a volume less than 50% in the following year, and radioresistant forms. Correlation between radio sensitivity and tumor cell type were obtained with intraoperative cytopunction, and showed the prevalence of epithelioid type. The results of enucleation indicate the prevalence of fusiform type inside the radioresistant tumor group. No precise correlation could be brought between death and the previous data, the most important negative criteria being the level of initial tumor height equal or superior to 7 mm.

[The role of beta-ray therapy in the treatment of choroidal and ciliary body melanomas]. / Place de la bêtacuriethérapie de contact dans le traitement des mélanomes de la choroïde et du corps ciliaire.

100 cases of uveal melanomas, were treated with 106RU 106RH beta-brachytherapy, between June 1983 and September 1987. 82 eyes having a follow-up superior or equal to 12 months, were analysed. 13 of these 82 eyes have been enucleated. 4 patients have died. 3 have at this time, hepatic dissemination. The first 43 patients were analysed at the 18th month after irradiation. The majority of tumors with initial thickness inferior to 5 mm had a regression superior to 50%, at the 18th month. The majority of tumors with initial thickness superior to 5 mm, had a regression inferior to 50%, at the same time. Functional results have also been noticed in this series of 43 eyes, and were satisfactory.

[Evaluation of 100 melanomas of the choroid and ciliary body treated by application of ruthenium (RU 106 Rh 106)]. / Bilan de 100 mélanomes de la choroïde et du corps ciliaire traités par applicateur de ruthénium (RU 106 Rh 106).

100 cases of uveal melanomas, were treated with 106 RU 106 RH beta-brachytherapy, between June 1983 and September 1987. 82 eyes having a follow-up superior or equal to 6 months, were analysed. 13 of these 82 eyes have been enucleated. 2 patients, have died, 2 have at this time, hepatic dissemination. The first 43 patients were analysed at the 18th month after irradiation. The majority of tumors with initial thickness inferior to 5 mm had a regression superior to 50%, at the 18th month. The majority of tumors with initial thickness superior to 5 mm, had a regression inferior to 50%, at the same time. Functional results have also been noticed in this series of 43 eyes, and were satisfactory.