Hypofractionated stereotactic photon radiotherapy of choroidal melanoma: 20-year experience.

BACKGROUND: To evaluate the long-term results after hypofractionated stereotactic photon radiotherapy (SRT) in patients with choroidal melanoma treated between 1997 and 2016. MATERIAL AND METHODS: A total of 335 patients (183 male and 152 female) with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated with linear accelerator-based SRT at the Medical University of Vienna. All patients received five fractions with either 10, 12 or 14 Gy per fraction. A complete ophthalmic examination including visual acuity and measurement of the tumor base and height using standardized A- and B-scan ultrasonography was performed every 3 months in the first 2 years, every 6 months until 5 years and yearly thereafter. Early and late adverse side effects were assessed at every follow-up visit. RESULTS: The median overall follow-up was 78.6 months (39.1 to 113.7 months). Local tumor control was 95.4% after 10 and 12 years, respectively. Fifty-four patients developed metastatic disease, and 31 died during the follow-up. Mean visual acuity decreased from 0.55 Snellen at baseline to 0.05 Snellen at the last individual follow-up. Ischemic retinopathy (192/335cases) and optic neuropathy (174/335cases) were the most common radiogenic side effects, followed by radiogenic cataract (n = 127), neovascular glaucoma (n = 71) and corneal epithelium defects (n = 49). Enucleation was performed in 54 patients mostly due to neovascular glaucoma (n = 41) or tumor recurrence (n = 10) during the study period. The eye retention rate was 79.7% after 10 and 12 years. CONCLUSION: Hypofractionated stereotactic photon radiotherapy showed a high rate of local tumor control for choroidal melanoma and an acceptable rate of radiogenic side effects.

Early ultrasonographic tumor regression after linear accelerator stereotactic fractionated photon radiotherapy of choroidal melanoma as a predictor for metastatic spread.

BACKGROUND AND PURPOSE: During extended follow-up (of up to 15 years), approximately fifty percent of patients with choroidal melanoma will develop metastatic disease and eventually die. Thus, continuing research on prognostic factors, early detection and treatment is necessary. Height regression rates both after plaque brachytherapy and proton beam irradiation have been shown to have prognostic value. The purpose of this study was to analyze the influence of early tumor regression rate after treatment of choroidal melanoma with LINAC stereotactic fractionated radiotherapy (SFRT) as an independent risk factor for metastasis. MATERIAL AND METHODS: 256 patients with choroidal melanoma treated with LINAC SFRT were included. Follow-up included standardized echography yielding apical height, smallest and largest basal linear diameter, tumor volume and mean reflectivity. The influence of baseline measurements and of a longitudinal, normalized area under the curve coefficient (NAC) of the latter marker on metastasis risk was assessed. RESULTS: NAC for tumor thickness at months 3, 6, and 12 had a statistically significant (p < 0.001) non-linear effect on risk of metastasis. Additionally, ultrasonographic baseline tumor dimensions, but not internal reflectivity were found to be statistically significant risk factors for metastasis. CONCLUSIONS: Our results demonstrate a non-linear influence of regression rate of choroidal melanoma as independent risk factor of metastatic disease after LINAC SFRT. These prove the clinical experience that, in comparison to rather slow regressions, very quick and very slow early tumor responses to LINAC SFRT are associated with a significantly higher metastasis risk.

Retina dose as a predictor for visual acuity loss in 106Ru eye plaque brachytherapy of uveal melanomas.

BACKGROUND AND PURPOSE: To evaluate the retina dose as a risk factor associated with loss of visual acuity (VA) in 106Ru plaque brachytherapy. MATERIAL/METHODS: 45 patients receiving 106Ru plaques brachytherapy (median follow-up 29.5 months) were included in this study. An in-house developed treatment planning system with Monte Carlo based dose calculation was used to perform treatment planning and dose calculation. Risk factors associated with loss of VA were evaluated using the Cox proportional hazards models, Kaplan-Meier estimates and Pearson correlation coefficients. RESULTS: A significant correlation was found between VA loss and mean (r = 0.49, p = 0.001) and near maximum (r = 0.47, p = 0.001) retina dose D2% and tumor basal diameter (r = 0.50, p < 0.001). The Kaplan-Meier and Cox proportional hazards model yielded a significantly higher risk for VA loss (>0.3Snellen) for patients receiving a maximum dose of >500 Gy (p = 0.002). A Cox multivariate analysis including the macula dose (p = 0.237) and basal diameter (p = 0.791) showed that a high maximum retinal dose is the best risk factor (p = 0.013) for VA loss. CONCLUSION: The study showed that retina dose (D2% and Dmean) is a suitable predictor for VA loss.

Dose-response of critical structures in the posterior eye segment to hypofractioned stereotactic photon radiotherapy of choroidal melanoma.

PURPOSE: To identify modifying factors and dose-/volume-response relationships for the retina and optic nerve related to highly conformal hypofractionated radiotherapy. PATIENTS AND METHODS: Seventy-three patients undergoing hypofractionated stereotactic photon radiotherapy of choroidal melanoma were included in this retrospective study. The volumes of the optic nerve receiving doses of more than 7.5 or 12 Gy, respectively, were defined. Optic nerve circumference included in the 30%, 40%, 50%, or 80% isodose (ON%) and retina included in 30% or 40% were determined as quantal effects. Univariate and multivariate analyses were performed for clinical variables as well as probit analysis to define EDx (doses where a positive response is expected in x% of the cases). RESULTS: Median follow-up was 90.0 (interquartile range 69.0-98.0) months. Fifty-two (71%) and 49 (67%) patients developed radiation retinopathy and optic neuropathy (any grade). Age, length of follow-up and diabetes were significant parameters regarding retinopathy. Optic neuropathy was significantly influenced by age, length of follow-up, and ON30. The probability of optic neuropathy (any grade and grade ≥ 2) significantly increases with the dose (p ranges from 0.0126 to 0.0211). CONCLUSION: Treatment planning should aim at minimizing encompassing isodoses particularly in the low dose region, without compromising PTV coverage.

Hypofractionated stereotactic photon radiotherapy of posteriorly located choroidal melanoma with five fractions at ten Gy--clinical results after six years of experience.

PURPOSE: To evaluate long-term safety and efficacy of hypofractionated stereotactic photon radiotherapy with 5 five fractions at 10 Gy each in patients with centrally located choroidal melanoma. MATERIALS AND METHODS: Ninety-one patients with centrally located choroidal melanoma were treated stereotactically at a linear accelerator with 6 MV photon beams with 5 fractions at 10 Gy each. Examinations were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and yearly thereafter. Median follow-up was 37.8 months (IQR 19.2-49.9). They included visual acuity assessment, routine ophthalmological examinations with fundoscopy, echography for measurement of tumor dimensions, medical examinations and, if necessary, fluorescein angiography. RESULTS: Initial tumor base diameters, height and volume were 11.20mm (IQR 9.10-13.70), 9.80 mm (IQR 7.80-11.70), 4.53 mm (IQR 3.33-6.43) and 253.8mm(3) (IQR 127.5-477.0). Local tumor control and eye retention rates were 97.7% and 86.4% after 5 years, respectively. Eight patients developed metastatic disease and 3 of them died due to metastatic disease during the follow-up period. Median visual acuity decreased from 0.67 initially to 0.05 at the last individual follow-up (p<0.001). The most common toxicities (any grade) were radiation retinopathy (n=39), optic neuropathy (n=32), radiogenic cataract (n=21), neovascular glaucoma (n=15) and dry eye syndrome (n=10). The 5 year probabilities to remain free of these side effects (any grade) were 26.0%, 45.4%, 55.4%, 72.6% and 80.5%, respectively. The most important prognostic factors for toxicities were the largest tumor base diameter, tumor height and tumor distance to the optic disk. CONCLUSION: Hypofractionated stereotactic photon radiotherapy with a total dose of 50 Gy delivered in 5 fractions is a highly effective treatment option in patients with centrally located choroidal melanoma and has a moderate toxicity profile.

Intraocular activation of angiogenic and inflammatory pathways in uveal melanoma.

PURPOSE: To identify and quantify angiogenic and inflammatory cytokines in aqueous and vitreous humor in eyes with untreated uveal melanoma and to analyze clinicopathologic correlations. METHODS: Intraocular fluid samples of patients (uveal melanoma aqueous n = 21, vitreous n = 34) and controls (cataract aqueous n = 41, vitreomacular traction aqueous n = 35, vitreous n = 36) were taken intraoperatively and analyzed using Luminex xMAP suspension array technology. Beadlyte kits were used for detection of 28 different cytokines. RESULTS: Flt-3 ligand, interleukin (IL) 1α, IL-6, IL-8, interferon-γ inducible protein (IP)-10, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α, platelet-derived growth factor AA, and vascular endothelial growth factor were significantly elevated in aqueous and vitreous of melanoma eyes when compared with controls. Eotaxin was significantly elevated in aqueous, and IL-7 and RANTES were significantly elevated in vitreous samples of melanoma eyes. Interferon-γ inducible protein 10, macrophage inflammatory protein 1α (aqueous and vitreous), Flt-3 ligand, IL-6, IL-8, and MCP-1 (vitreous) correlated with tumor dimensions. Further correlations were found between infiltration of Bruch membrane and Flt-3 ligand, MCP-1 (aqueous and vitreous), IL-8, interferon-γ inducible protein 10, macrophage inflammatory protein 1α, and platelet-derived growth factor AA (vitreous). Analyzing 16 paired aqueous and vitreous melanoma samples, Flt-3 ligand, IL-7, interferon-γ inducible protein 10, MCP-1, and platelet-derived growth factor AA were significantly elevated in vitreous, and IL-1α and vascular endothelial growth factor in aqueous samples. CONCLUSION: A range of significantly elevated angiogenic, inflammatory, and chemotactic cytokines in eyes with uveal melanoma supports the link between inflammation and tumorigenesis.

Radiogenic side effects after hypofractionated stereotactic photon radiotherapy of choroidal melanoma in 212 patients treated between 1997 and 2007.

PURPOSE: To evaluate side effects of hypofractionated stereotactic photon radiotherapy for patients with choroidal melanoma. PATIENTS AND METHODS: Two hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at the Medical University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic side effects were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and then once a year thereafter until 10 years after radiotherapy. Adverse side effects were assessed using slit-lamp examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus photography and fluorescein angiography. Evaluations of incidence of side effects are based on an actuarial analysis. RESULTS: One hundred and eighty-nine (89.2%) and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc, respectively. The five most common radiotherapy side effects were retinopathy and optic neuropathy (114 cases and 107 cases, respectively), cataract development (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41 cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma, or corneal epithelium defects 5 years after radiotherapy, respectively. CONCLUSION: In centrally located choroidal melanoma hypofractionated stereotactic photon radiotherapy shows a low to moderate rate of adverse long-term side effects comparable with those after proton beam radiotherapy. Future fractionation schemes should seek to further reduce adverse side effects rate while maintaining excellent local tumor control.

Stereotactic photon beam irradiation of uveal melanoma.

Stereotactic photon beam irradiation has been under clinical investigation for the treatment of uveal melanoma for over 15 years. Single-fraction stereotactic radiosurgery (SRS) is usually done with a gamma knife as well as more recently with a cyberknife. The therapeutic single dose has been reduced to as low as 35 Gy over the past few years without reduction in tumor control. Doses of 40 Gy delivered at the 50% isodose result in good local tumor control and acceptable toxicity. Since radiobiological studies indicate a possible advantage of hypofractionated treatment over a single very large fraction to sterilize uveal melanoma cell lines, fractionated stereotactic radiotherapy (SRT)has gained additional interest. Besides increased tumor control, toxicity should theoretically be reduced by fractionation. Linear accelerators (LINAC) have the advantage of a feasible fractionation. Most LINAC studies employ a hypofractionated scheme of 4-5 fractions and total doses between 50 and 70 Gy. The efficacy of SRT for uveal melanoma has been proven in different studies with local tumor control rates reported over 90%, 5 and 10 years after treatment. Radiogenic side effects after SRT are reported similarly to other forms of radiotherapy, with cataract development, radiation retinopathy, opticopathy and neovascular glaucoma being responsible for the majority of secondary vision losses and secondary enucleations. Overall, stereotactic photon beam radiotherapies (SRS and SRT) are considered effective treatment modalities for uveal melanoma, with promising late tumor control and toxicity rates. Additional studies and longer follow-up are indicated to finally confirm optimal treatment modalities.

Local tumor control, visual acuity, and survival after hypofractionated stereotactic photon radiotherapy of choroidal melanoma in 212 patients treated between 1997 and 2007.

PURPOSE: To evaluate long-term local tumor control, visual acuity, and survival after hypofractionated linear accelerator-based stereotactic photon radiotherapy in patients with choroidal melanoma. METHODS AND MATERIALS: Between 1997 and 2007, 212 patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at a linear accelerator with 6-MV photon beams at the Medical University of Vienna in five fractions over 7 days. Twenty-four patients received a total dose of 70 Gy (five fractions of 14 Gy), 158 a total dose of 60 Gy (five fractions of 12 Gy) and 30 patients a total dose of 50 Gy (five fractions of 10 Gy) applied on the 80% isodose. Ophthalmologic examinations were performed at baseline and every 3 months in the first 2 years, every 6 months until 5 years, and once a year thereafter until 10 years after radiotherapy. Assessment of visual acuity, routine ophthalmologic examinations, and measurement of tumor base dimension and height using standardized A-scan and B-scan echography were done at each visit. Funduscopy and fluorescein angiography were done when necessary to document tumor response. RESULTS: Median tumor height and volume decreased from 4.8 mm and 270.7 mm3 at baseline to 2.6 mm and 86.6 mm3 at the last individual follow-up, respectively (p<0.001, p<0.001). Median visual acuity decreased from 0.55 at baseline to hand motion at the last individual follow-up (p<0.001). Local tumor control was 95.9% after 5 years and 92.6% after 10 years. Thirty-two patients developed metastatic disease, and 22 of these patients died during the follow-up period. CONCLUSION: Hypofractionated stereotactic photon radiotherapy with 70 to 50 Gy delivered in five fractions in 7 days is sufficient to achieve excellent local tumor control in patients with malignant melanoma of the choroid. Disease outcome and vision are comparable to those achieved with proton beam radiotherapy. Decreasing the total dose below 60 Gy seems to be possible.

Choroidal perfusion in eyes with untreated choroidal melanoma.

PURPOSE: Previous studies indicate that ocular blood flow is altered in eyes with choroidal melanoma. In the present study pulsatile ocular blood flow (POBF) was assessed to investigate whether there exists a correlation between tumour size and ocular blood flow parameters. METHODS: Twenty-two patients with unilateral untreated choroidal melanoma were studied using two measurement techniques: POBF was measured with a pneumotonometer and local foveal fundus pulsation amplitude (FPA) by laser interferometry, and results were correlated. Tumour volume was calculated using the ellipsoidal solid model and was correlated to POBF and FPA. RESULTS: Levels of POBF and FPAs tended to be higher in tumour eyes compared with unaffected eyes, but the differences did not reach the level of significance. Both methods showed a high degree of correlation in unaffected eyes. In tumour eyes the correlation was slightly less pronounced. There was no correlation between tumour and POBF or FPA. CONCLUSIONS: Our results do not indicate choroidal hyperperfusion in patients with choroidal melanoma. The clinical usefulness of measuring POBF in tumour patients may be limited.

Rapid improvement of radiation-induced neovascular glaucoma and exudative retinal detachment after a single intravitreal ranibizumab injection.

Neovascular glaucoma is a serious complication arising from irradiation of uveal melanoma. Treatment options include panretinal photocoagulation, peripheral retina cryotherapy, photodynamic therapy with verteporfin, triamcinolone injections and surgical removal of the dying tumour mass. Nevertheless, enucleation of the affected eye often is inevitable. The authors describe a case report of a radiation-induced neovascular glaucoma and exudative retinal detachment caused by malignant melanoma of the uvea that was treated with intravitreal ranibizumab.

Influence of uveal melanoma therapy on patients' quality of life: a psychological study.

PURPOSE: The objective of this study ws to describe the quality of life of 98 patients treated with brachytherapy or stereotactic external beam irradiation, either with the Leksell Gamma Knife or a 6-MV LINAC. METHODS: The EORTC QLQ-C30 and the EORTC QLQ-OPT37 psychological questionnaires and the HADS-D scale were used. Two visual analogue scales (VASs) were applied to compare overall quality of life before and after treatment. RESULTS: The results revealed no significant differences in quality of life (p=0.215) among treatments with different methods of radiotherapy. Comparison of quality of life before and after therapy did, however, indicate a decrease in quality of following radiotherapy. The average binocular visual acuity (VA) was 0.8 (range 0.3-1). Complication arising from the treatment included a reduction in VA in the affected eye, keratitis, cataract, scleral and corneal necrosis, radiation retinopathy, radiation optic neuropathy, retinal detachment and glaucoma. CONCLUSIONS: Due to the diagnosis revealed and the subsequent radiotherapy, patients with uveal melanoma experienced a reduced quality of life. However, compared to patients with other types of cancer, they seemed to feel relatively well and showed fewer signs of deterioration.

Tumour regression of uveal melanoma after ruthenium-106 brachytherapy or stereotactic radiotherapy with gamma knife or linear accelerator.

PURPOSE: This study assesses differences in relative tumour regression and internal acoustic reflectivity after 3 methods of radiotherapy for uveal melanoma: (1) brachytherapy with ruthenium-106 radioactive plaques (RU), (2) fractionated high-dose gamma knife stereotactic irradiation in 2-3 fractions (GK) or (3) fractionated linear-accelerator-based stereotactic teletherapy in 5 fractions (Linac). METHODS: Ultrasound measurements of tumour thickness and internal reflectivity were performed with standardised A scan pre-operatively and 3, 6, 9, 12, 18, 24 and 36 months postoperatively. Of 211 patients included in the study, 111 had a complete 3-year follow-up (RU: 41, GK: 37, Linac: 33). Differences in tumour thickness and internal reflectivity were assessed with analysis of variance, and post hoc multiple comparisons were calculated with Tukey's honestly significant difference test. RESULTS: Local tumour control was excellent with all 3 methods (>93%). At 36 months, relative tumour height reduction was 69, 50 and 30% after RU, GK and Linac, respectively. In all 3 treatment groups, internal reflectivity increased from about 30% initially to 60-70% 3 years after treatment. CONCLUSION: Brachytherapy with ruthenium-106 plaques results in a faster tumour regression as compared to teletherapy with gamma knife or Linac. Internal reflectivity increases comparably in all 3 groups. Besides tumour growth arrest, increasing internal reflectivity is considered as an important factor indicating successful treatment.

Intumescent cataract after topical mitomycin-C for conjunctival malignant melanoma.

PURPOSE: To present the clinical and histologic findings of a patient in whom intumescent cataract developed after successful topical mitomycin-C (MMC) chemotherapy for conjunctival melanoma originating from primary acquired conjunctival melanosis (PAM) with atypia. DESIGN: Observational case report; follow-up at 30 months. METHODS: In a patient with PAM and subsequent conjunctival melanoma that was successfully treated with topical MMC chemotherapy an intumescent cataract developed after two cycles of 0.04% MMC, each for 1 month. RESULTS: After MMC chemotherapy pigmentation of the acquired melanosis vanished almost completely. Histopathology of the check-up specimen revealed local tumor control. Six weeks after the completion of the second cycle, an intumescent cataract developed. Cataract surgery was performed uneventfully. The patient was followed up for 30 months. CONCLUSIONS: In selected cases, topical MMC chemotherapy is effective for treating conjunctival melanoma. Although severe complications are rare and usually transient, development of cataract may be observed. A prospective study should be initiated.

LINAC based stereotactic radiotherapy of uveal melanoma: 4 years clinical experience.

PURPOSE: To study local tumor control and radiogenic side effects after fractionated LINAC based stereotactic radiotherapy for selected uveal melanoma. PATIENTS AND METHODS: Between June 1997 and March 2001, 90 patients suffering from uveal melanoma were treated at a LINAC with 6 MV. The head was immobilized with a modified stereotactic frame system (BrainLAB). For stabilization of the eye position a light source was integrated into the mask system in front of the healthy or the diseased eye. A mini-video camera was used for on-line eye movement control. Tumors included in the study were either located unfavorably with respect to macula and optical disc (<3 mm distance) or presented with a thickness >7 mm. Median tumor volume was 305+/-234 mm3 (range 70-1430 mm3), and mean tumor height was 5.4+/-2.3 mm (range 2.7-15.9 mm). Total doses of 70 (single dose 14 Gy @ 80% isodose) or 60 Gy (single dose 12 Gy @ 80% isodose) were applied in five fractions within 10 days. The first fractionation results in total dose (TD) (2 Gy) of 175 Gy for tumor and 238 Gy for normal tissue, corresponding values for the second fractionation schedule are 135 and 180 Gy, respectively. RESULTS: After a median follow-up of 20 months (range 1-48 months) local control was achieved in 98% (n=88). The mean relative tumor reductions were 24, 27, and 37% after 12, 24 and 36 months. Three patients (3.3%) developed metastases. Secondary enucleation was performed in seven patients (7.7%). Long term side effects were retinopathy (25.5%), cataract (18.9%), optic neuropathy (20%), and secondary neovascular glaucoma (8.8%). CONCLUSION: Fractionated LINAC based stereotactic photon beam therapy in conjunction with a dedicated eye movement control system is a highly effective method to treat unfavorably located uveal melanoma. Total doses of 60 Gy (single dose 12 Gy) are considered to be sufficient to achieve good local tumor control.

A noninvasive eye fixation and computer-aided eye monitoring system for linear accelerator-based stereotactic radiotherapy of uveal melanoma.

PURPOSE: To introduce a noninvasive eye fixation and computer-aided eye monitoring system for linear accelerator-based stereotactic radiotherapy for uveal melanoma. METHODS AND MATERIALS: At the Department of Radiotherapy and Radiobiology, University of Vienna, stereotactic radiotherapy is offered to patients with uveal melanoma considered unsuitable for (106)Ru brachytherapy or local resection. For the present feasibility study, 8 patients were carefully selected according to their ability to fixate a small light source with the diseased eye and whether they had a rather small head to meet the limited geometric space available. A polymethyl methacrylate tube was attached to a stereotactic mask system in craniocaudal orientation supporting a 45 degrees mirror, which was placed in front of the diseased eye. At the other end of the tube, the patient was given a small fixation light, and a small camera was positioned beneath, which was shielded for use during MRI. A computer interface calculated and visualized the spatial difference of the actual and a given reference pupil position, which was defined before CT scanning, during the MRI sequences, and during treatment delivery at the linear accelerator. RESULTS: The described system can be attached to a conventional stereotactic mask system with minor modifications. Because of the large distance between the eye and the fixation light, the optical fixation system was well tolerated by all patients, and a stable position of the eye was obtained. The camera system can be used during CT and MRI without interference. Absorption of the 6-MV photon beam by the mirror and the polymethyl methacrylate tube was negligible. The computer interface designed to determine the pupil position uses an image-processing algorithm that correlates a template of the reference image with the actual image of the eye. Provided sufficient illumination of the pupil, the correlation function showed a pronounced minimum at the reference position. The precision of the algorithm was tested by phantom measurements. For a given 1 mm or 2 mm displacement, the interface reported a mean shift of 0.96 +/- 0.18 mm or 2.07 +/- 0.11 mm, respectively. CONCLUSION: The results of this study demonstrated the feasibility of a new optical fixation system for linear accelerator-based stereotaxis. The artifact-free application of the camera system during image acquisition and irradiation and the use of the computer interface, which automatically monitored eye movements with submillimeter precision, provided large improvements compared with existing techniques. Given well-defined interruption criteria and accelerated image processing, the described system has a high potential to perform automatically gated treatment beam delivery in the near future.

Impact of a micromultileaf collimator on stereotactic radiotherapy of uveal melanoma.

PURPOSE: To evaluate the impact of a micro multileaf collimator (mMLC) on Linac-based stereotactic radiotherapy (SRT) of uveal melanoma by comparing circular arc with static conformal, dynamic arc, and intensity-modulated SRT. MATERIALS AND METHODS: Forty uveal melanoma patients were selected from approximately 100 patients treated with SRT since 1996. For each patient, four treatment plans (BrainSCAN XL, V5.0) were made: conventional arc, static conformal, dynamic arc plan, and intensity-modulated radiotherapy (IMRT). The goal of treatment planning was to fully encompass the planning target volume (PTV) by the 80% isodose while minimizing doses to the optic nerve and lens. The following parameters were evaluated: target conformity; target homogeneity; ratio of the target volume and 50% isodose volume; normal tissue receiving doses >/=80%, >/=50%, and >/=20%; central nervous system volume irradiated to >/=20%; optical nerve volume irradiated >/=50%, D(max) of the lens; lens volume receiving >/=20%; and monitor units. RESULTS: PTVs ranged from 0.68 to 4.90 cm(3) (mean 1.97 +/- 0.97 cm(3)). The average reduction of the prescription isodose volume was 1-1.5 cm(3) for conformal (range 2.6-0.3 cm(3)), dynamic arc (range 2.5-0.3 cm(3)), and IMRT plans (range 3.9-0.1 cm(3)), compared with conventional arc therapy. Central nervous system volumes irradiated to doses >/=20% were smallest for conventional or dynamic arc treatments. Average target dose homogeneity values were 1.74 +/- 0.50 for arc, 1.27 +/- 0.02 for static mMLC, 1.26 +/- 0.01 for dynamic arc, and 1.15 +/- 0.03 for IMRT plans. IMRT helped to reduce doses to the lens but did not provide an advantage for optical nerve sparing. When applying IMRT, the monitor units increased by approximately one-third compared with static mMLC-based SRT. CONCLUSIONS: Conformal mMLC and dynamic arc SRT are the treatment options of choice for Linac-based SRT of uveal melanoma. They present dosimetric advantages, while being highly efficient in treatment planning and delivery.