Factors affecting eye conservation and metastasis in posterior uveal melanomas.

PURPOSE: To determine the effect of patient and tumor features and different treatments on eye removal (enucleation or exenteration) and metastasis in posterior uveal melanoma (PUM). METHODS: Retrospective analysis. Patient age (≤60 vs >60 years), sex (female vs male), visual acuity (VA, ≤20/40 vs >20/40), largest tumor basal diameter (LTBD), tumor thickness, tumor stage according to American Joint Committee on Cancer (AJCC) 8th edition, ciliary body involvement, distance to optic disc (OD)/fovea (≤3 mm vs >3 mm), OD involvement, and histopathology were evaluated. Primary treatment options were transpupillary thermotherapy, plaque radiotherapy, Cyberknife radiosurgery, exoresection, and eye removal. Risk factors for primary eye removal were determined using logistic regression test and those for secondary eye removal and metastasis with Cox regression analysis. RESULTS: Of 387 cases, 153 (39.5%) underwent primary eye removal. Multivariable risk factors for primary eye removal included AJCC tumor stage (p = 0.001, OR:4.586; p < 0.001, OR:34.545; p < 0.001, OR:103.468 for stages T2, T3, and T4 vs stage T1, respectively), and VA≤20/40 (p = 0.014, OR:2.597). Multivariable risk factors for secondary eye removal were VA≤20/40 (p = 0.019, RR:2.817) and AJCC stage T3 vs T1 (p = 0.021, RR:2.666). Eye preservation rates in patients undergoing eye-conserving treatments were 80.3%, 69.6%, and 51.5% at 5, 10, and 15 years, respectively. Metastasis-free survival rates were 81.0%, 73.0%, and 56.7% at 5, 10, and 15 years, respectively. Multivariable risk factors for metastasis included eye removal as primary treatment (p = 0.005, RR:2.828) and mixed type histopathology (p < 0.001, RR:4.804). DISCUSSION: Early diagnosis is crucial for both eye preservation and survival in PUM. Increasing AJCC tumor stage and lower VA were risk factors for eye removal in this study. Mixed type histopathology and primary eye removal were risk factors for metastasis.

Surgical Approach in Intraocular Tumors

Surgery in intraocular tumors is done for excision/biopsy and the management of complications secondary to the treatment of these tumors. Excision/biopsy of intraocular tumors can be done via fine-needle aspiration biopsy (FNAB), transretinal biopsy (TRB), partial lamellar sclerouvectomy (PLSU), and endoresection. FNAB, TRB, and PLSU can be used in tumors that cannot be diagnosed by clinical examination and other ancillary testing methods. PLSU is employed in tumors involving the iridociliary region and choroid anterior to the equator. Excisional PLSU is performed for iridociliary and ciliary body tumors with less than 3 clock hours of iris and ciliary body involvement and choroidal tumors with a base diameter less than 15 mm. However, for biopsy, PLSU can be employed with any size tumor. Endoresection is a procedure whereby the intraocular tumor is excised using vitrectomy techniques. The rationale for performing endoresection is based on the fact that irradiated uveal melanomas may cause complications such as exudation, neovascular glaucoma, and intraocular pigment and tumor dissemination (toxic tumor syndrome), and removing the dead tumor tissue may contribute to better visual outcome. Endoresection is recommended 1-2 weeks after external radiotherapy. Pars plana vitrectomy is also used in the management of complications including vitreous hemorrhage, retinal detachment, and epiretinal membrane that can occur after treatment of posterior segment tumors using radiotherapy and transpupillary thermotherapy. It is important to make sure the intraocular tumor has been eradicated before embarking on such treatment.

Comparison between patient-reported outcomes after enucleation and proton beam radiotherapy for uveal melanomas: a 2-year cohort study.

BACKGROUND: Uveal melanomas affect 2-8 per million Europeans each year. Approximately 35%, are treated by enucleation. Proton beam radiotherapy (PBR) can be an eye-conserving alternative to enucleation for patients who wish to retain the eye. Both treatments have adverse effects, and it is difficult for clinicians and patients to make fully informed choices between them because the relative effects of enucleation and PBR on patient-reported outcomes are unknown. METHODS: We compared differential effects of enucleation and PBR on patient-reported outcomes on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Ophthalmological module (EORTC QLQ- OPT30) in a consecutive sample of 115 treated patients ~ 6, 12 and 24 months after diagnosis. Pre-treatment demographic variables, unrelated health problems, vision in the fellow eye, tumour characteristics and prognosis for metastatic disease were statistically controlled. RESULTS: Patients treated by enucleation experienced greater functional problems at 6 months, which abated at 12 and 24 months (P = 0.020). PBR patients reported greater impairments of central and peripheral vision (P = 0.009) and reading difficulties (P = 0.002) over 24 months. Treatment modality did not influence difficulty in driving (P = 0.694), ocular irritation (P = 0.281), headaches (P = 0.640), appearance concerns (P = 0.187) or worry about recurrence (P = 0.899). CONCLUSIONS: When making treatment decisions, it is important that patients and clinicians consider long-standing difficulties of visual impairment associated with PBR and temporary 6-month difficulties in activities related to depth perception associated with enucleation.

Management of uveal tract melanoma: A comprehensive review.

Uveal tract melanoma is the most common primary intraocular malignancy in adults, accounting for about 5-10% of all the melanomas. Since there are no lymphatic vessels in the eye, uveal melanoma can only spread hematogenously leading to liver metastasis. A wide variety of treatment modalities are available for its management, leading to dilemma in selecting the appropriate therapy. This article reviews the diagnostic and therapeutic modalities available and thus, can help to individualize the treatment plan for each patient.

Secondary Enucleations for Uveal Melanoma: A 7-Year Retrospective Analysis.

PURPOSE: To describe the indications for secondary enucleations in uveal melanoma and analyze associations and outcomes. DESIGN: Retrospective interventional case series. METHODS: Data of patients who underwent secondary enucleation for uveal melanoma in the London Ocular Oncology Service, between 2008 and 2014, were retrieved from medical records analyzed. Cox regression model was performed to analyze associations with secondary enucleation and metastases and Kaplan-Meier estimates to assess the probability of metastatic spread and death. RESULTS: During the study period 515 enucleations were performed for uveal melanoma, 99 (19%) of which were secondary enucleations. Tumors were located at the ciliary body in 21 eyes (21%), juxtapapillary in 31 (31%), and choroid elsewhere in 47 (48%). Primary treatment included Ru(106) plaque radiotherapy, proton beam radiotherapy, and transpupillary thermotherapy in 85, 11, and 3 eyes, respectively. Indications for secondary enucleation were tumor recurrence in 60 (61%), neovascular glaucoma in 21 (21%), and tumor nonresponse in 18 eyes (18%). Twenty patients (20%) were diagnosed with metastasis and 12 out of 20 died of metastatic spread. On multivariate analysis, juxtapapillary tumor location was found to associate with tumor nonresponse (P = .004) and nonresponding patients with metastatic spread (P = .04). CONCLUSIONS: Indications for secondary enucleations for uveal melanoma were tumor recurrence, neovascular glaucoma, and tumor nonresponse. This review identified a possible high-risk group (nonresponse), which proved radioresistant to treatment. These tumors were more frequently found in the juxtapapillary location and were associated with metastatic spread.

One-day session LINAC-based stereotactic radiosurgery of posterior uveal melanoma.

PURPOSE: LINAC-based stereotactic radiosurgery (SRS) of posterior uveal melanoma is a conservative method to treat uveal melanoma. METHODS: This was a retrospective clinic-based study of patients with posterior uveal melanoma in stage T2/T3 who underwent 1-day session SRS at LINAC accelerator or SRS plus combined methods from 2001 to 2008. RESULTS: Thirty-nine patients with posterior uveal melanoma were treated with SRS (age 25-80 years, median 54 years). Median tumor volume at baseline was 0.6 cm3 (range 0.2-1.3 cm3). The therapeutic dose (TD) was 35.0 Gy, median of maximal dose applied was 49.0 Gy (range 37.0-60.0 Gy). Patient data were analyzed in groups: group 1, single SRS irradiation; group 2, SRS with subsequent endoresection or cyclectomy or additional transpupillary thermotherapy (TTT) or brachytherapy by Ru106 plaques; group 3a, enucleation after single SRS; group 3b, enucleation after SRS and endoresection/cyclectomy or TTT or brachytherapy Ru106. In patients with visual acuity of 20/40 or better, the median rate of best-corrected visual acuity (BCVA) decline was higher than that of the total and significantly higher than the rate of decline in the complementary group of patients with BCVA less than 20/40 (p=0.0077; Mann-Whitney U test). CONCLUSIONS: One-step LINAC-based SRS with a single dose 35.0 Gy is a method to treat middle-stage posterior uveal melanoma and to preserve the eye globe or as the first step of combined methods: irradiation before endoresection or cyclectomy.

Preliminary experience with transarterial chemoembolization (TACE) in liver metastases of uveal malignant melanoma: local tumor control and survival.

PURPOSE: To evaluate results in the palliative treatment of patients with liver metastases of uveal malignant melanoma using transarterial chemoembolization (TACE). MATERIALS AND METHODS: Superselective TACE was repeatedly performed in 12 patients with liver metastases of uveal malignant melanoma. Six patients presented with solitary liver metastases (6-12 cm in size) and six patients with oligonodular metastases (n < or = 6). The embolization suspension consisted of a maximum of 10 mg/m(2) Mitomycin C, 10 ml Lipiodol, and an injection of 200-450 mg resorbable microspheres for vascular occlusion. In the follow-up, magnetic resonance imaging was performed in 3-month intervals. RESULTS: The TACE procedure was well tolerated in all patients without any relevant side effects. Three patients responded to TACE with a size reduction of more than 50% (partial response), five patients with stable disease, and four patients with progressive disease with an increase in volume of more than 25%. Mean survival following primary tumor treatment was 32.9 months, and after first embolization 19.5 months. Lower survival rates were recorded for the progressive group (16.5 months). CONCLUSION: Repeated TACE offers a palliative treatment option in patients with oligonodular liver metastases of uveal malignant melanoma.

Uveal melanoma and poor treatment compliance: an atypical outcome with literature review.

BACKGROUND: A uveal melanoma is the most common primary intraocular malignancy and is the primary intraocular disease that can be fatal in adults. Until recently, data were limited regarding growth characteristics and at what stage metastases are likely to occur. CASE REPORT: A 49-year-old white male presented on January 19, 1989, for a second opinion regarding a spot that had been discovered in the right eye 13 months prior. Ophthalmologic evaluation and echography were consistent for a uveal melanoma of 5 mm elevation and 13.5 x 6 mm in diameter. The patient refused treatment or enrollment into the Collaborative Ocular Melanoma Study. On December 9, 1991, the eye was enucleated with a modified exenteration due to severe proptosis, tumor thickness of 22 mm, and three areas of extrascleral extension. The patient refused postoperative radiation treatment and refused clinical follow-up. This case was reviewed from the initial evaluation date through the last clinical visit. The patient was recently interviewed with respect to his use of homeopathic medicine, change in lifestyle, and the effect he felt it might have had on his life. DISCUSSION: The literature published by the Collaborative Ocular Melanoma Study regarding the histopathologic characteristics of eyes enucleated and the initial mortality findings of a large choroidal melanoma indicate that this is a most unusual case. The patient has defied the mortality findings of the most recent and largest study to date (mean survival rate, 82 months). The patient is still alive 181 months after the original finding of the lesion and refusal of advised treatment recommendations in favor of homeopathic medicine.

Eyewall resection for a uveal malignant melanoma under local anesthesia.

A 44-year-old man was referred to our hospital for ciliary body tumor management. A uveal melanoma in the left eye without systemic metastasis was our impression after a series of examinations. We treated this patient with eyewall resection under local anesthesia. Eyewall resection was previously regarded as a complicated procedure that should be performed under general anesthesia. Our surgery was successful, and there were no complications related to the local anesthesia. We followed up this patient for 3 years, and no recurrence was found. Eyewall resection is a good alternative to enucleation for treating a ciliary body melanoma. Under a premise of survival, eyewall resection can maintain part of the visual function and cosmetics. General anesthesia is not indispensable when a patient's health does not allow its use.

[Current therapy aspects of intraocular tumors]. / Aktuelle Therapieaspekte intraokularer Tumoren.

The most frequent primary intraocular malignancies are uveal melanoma in adults and retinoblastoma in children. Genetic findings in uveal melanoma now allow a better risk-prediction with regard to metastatic disease. New treatment modalities like endo-resection, trans-scleral resection, proton beam irradiation and trans-pupillary thermotherapy are now being established in clinical routine. Management of retinoblastoma has changed during the last years considerably. In hereditary retinoblastoma external beam radiotherapy (EBR) results in a sixfold increased risk for the development of secondary, non ocular malignant tumors in these patients. New treatment regimens based on systemic chemotherapy were developed to replace EBR. In combination with chemotherapy there has been a continuing trend toward more conservative focal treatment for retinoblastoma. Indications and first results of these new treatment modalities are presented.

Ultrasonically induced hyperthermia for adjunctive treatment of intraocular malignant melanoma.

PURPOSE: This report describes results of a prospective pilot trial to evaluate the safety and efficacy of hyperthermia as an adjunct to enucleation or brachytherapy in the treatment of patients with intraocular malignant melanoma. METHODS: Twenty-five patients with intraocular malignant melanomas were treated with ultrasonically induced hyperthermia. In 14 patients, hyperthermia was administered before enucleation (median follow-up period, 44 months), and in 11 patients, hyperthermia was used as an adjunct to brachytherapy (median follow-up period, 79 months). RESULTS: Patient survival in each group was compared with that of a control group treated with enucleation or brachytherapy alone, using Kaplan-Meier and Cox analysis. Taking into account the simultaneous effects of tumor size and location, the relative risk ratios and 95% confidence bounds associated with adjunctive hyperthermia were 1.68 (range, 0.60-4.72) and 0.68 (range, 0.16-2.89) for the enucleation and brachytherapy groups, respectively. CONCLUSIONS: Patients receiving adjunctive hyperthermia with brachytherapy showed increased survival, whereas those receiving hyperthermia before enucleation showed decreased survival. Neither trend was statistically significant in this small series. The synergism of hyperthermia with radiation may offer the possibility of improved tumor management.

Computer model of ultrasonic hyperthermia and ablation for ocular tumors using B-mode data.

Computer simulations have been conducted to examine hyperthermia and ablation for treating ocular tumors. An interactive software package has been implemented that permits relevant tissue dimensions to be determined from B-mode data. This package also permits interactive beam positioning, and it provides image displays depicting computed absorbed doses and temperature rises. Results are presented showing how hyperthermia temperature patterns are influenced by beam position, beam geometry and frequency. Images showing ablative temperature rises at various time intervals are also presented. For hyperthermia, geometric models of beam profiles showed that a non-uniform beam pattern (with a central low-intensity region) can produce more uniform heating of small ocular tumors than a beam with a uniform intensity profile. For a given tumor, the uniformity of hyperthermia temperatures was found to be a function of frequency, with 4.75 MHz providing reasonably uniform results for typical tumor heights (near 7 mm). For ablation, diffraction computations were employed to calculate beam intensity profiles; results show an initially rapid rise in temperature levels with subsequent, slower heating beyond the -3-dB limits of the focal volume. The model is now being refined, and additional phenomena, including nonlinear propagation, will be incorporated.

Relative survival rates after alternative therapies for uveal melanoma.

Survival in a group of 556 patients with uveal melanoma treated by proton beam irradiation with a median follow-up of 5.3 years was compared with that of 238 patients enucleated during the same 10-year period as irradiated patients (July 1975 to December 1984) with a median follow-up of 8.8 years, and 257 patients enucleated during the preceding 10 years (January 1965 to June 1975) with a median follow-up of 17.0 years. Adjustments were made for known prognostic factors including age, tumor location, tumor height, and clinical estimate of tumor diameter (for enucleated patients this was estimated in a regression equation relating histologic to clinical measurement). The overall rate ratio for all cause mortality was 1.2 (95% confidence interval, 0.9-1.6) for the concurrent enucleation series versus proton beam, and 1.6 (95% confidence interval, 1.2-2.1) for the earlier enucleation series versus proton beam. Relative rates of metastatic death, cancer death, and all cause mortality comparing alternative treatments were found to vary with time after treatment. Interval-specific rate ratios were evaluated using proportional hazards models fitted to separate time intervals after treatment. For all three outcomes, rate ratios were over two and statistically significant for the first 2 years after treatment and closer to one and nonsignificant after year 6 comparing the two enucleation groups with proton beam. Results suggest that treatment choice has little overall influence on survival in patients with uveal melanoma.

A contact Nd:YAG laser to resect large ciliary body and choroidal tumors.

We used a contact Nd:YAG laser fit with a 0.2-mm diameter sapphire tip to excise a large (5 1/2 clock hour) iris ciliary body-choroidal tumor and a large (15 X 8 X 3 mm) choroidal tumor. The cutting and coagulation action of the laser helped to minimize intraoperative and postoperative hemorrhage.