Stereotactic radiosurgery of large uveal melanomas with the gamma-knife

doi:10.1016/S0161-6420(00)00150-0

Ophthalmology

Volume 107, Issue 7, July 2000, Pages 1381-1387

Presented in part at the annual meeting of the American Academy of Ophthalmology, Orlando, Florida, October 1999.

https://doi.org/10.1016/S0161-6420(00)00150-0 Get rights and content

Abstract

Objective

To present our experience with the Gamma-knife in treating large uveal melanomas with stereotactic radiosurgery.

Design

Prospective, noncomparative, interventional case series.

Participants

Fifty-eight patients with unilateral uveal melanomas were treated from 1996 through 1999 with stereotactic radiosurgery using the Gamma-knife. From these we report the results of 35 patients who had a follow-up of more than 1 year after irradiation.

Intervention

Stereotactic radiosurgery with the Gamma-knife.

Main outcome measures

Tumor control, maximum apical tumor height, eye retention rate, and visual acuity.

Results

In 34 eyes (97%), local tumor control was achieved. The maximum apical tumor height decreased from a median of 9.1 mm (95% confidence interval [CI], 3.2–13.9 mm) before treatment to 6.2 mm (95% CI, 2.1–11.9 mm) at 1 year after treatment (P < 0.001, paired t test). The tumor volume decreased from a median of 0.8 cm³ before treatment to 0.5 cm³ 1 year after treatment (P < 0.001, paired t test). Two eyes required enucleation (one radiation failure, one secondary glaucoma). The median visual acuity decreased from 20/60 (95% CI, hand movement [HM] to 20/20) before treatment to 20/200 (95% CI, HM to 20/30) at 1 year after treatment (P = 0.001, paired t test).

Conclusions

Stereotactic radiosurgery using the Gamma-knife is an alternative to enucleation in treating large uveal melanomas. The visual function may be preserved in selected cases.

Section snippets

Patients and methods

From 1996 through 1999 we treated 58 consecutive unilateral large uveal melanomas with the Gamma-knife. The treatment protocol was reviewed and approved by the ethics committee of the Ludwigs-Maximilians-University. We now report on 35 of these 58 patients with a follow-up time of more than 1 year. None of these tumors was suitable for radiation brachytherapy with ruthenium 106 (Ru¹⁰⁶) plaques because of the tumor dimensions (maximum apical tumor height >6 mm, largest basal tumor diameter >19

Results

In most patients, the first signs of tumor regression could not be detected before 6 months after treatment. Additionally, nearly all patients showed an initial increase in maximum apical tumor height, tumor volume, or both as soon as 5 to 15 weeks after treatment. This was possibly the result of an edema of the tumor stroma in reaction to the radiation treatment. Thus, for comparison of the tumor parameters before and after treatment, it is reasonable to report only data of patients with a

Discussion

It has been clearly demonstrated that large uveal melanomas that would be refractory to brachytherapy may be treated with charged particles as proton beams or helium ions.2, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 However, both forms of therapy depend on large-scale facilities that are expensive and therefore scarce. Up to the current year, we did not have access to a proton beam facility in Germany. However, alone in our institution we see approximately 25 to 30 patients per year with tumors

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This retrospective study included 594 consecutive patients referred to our clinic for the treatment of choroidal and ciliary body melanomas with robotic radiosurgery (CyberKnife) from 2005 to 2019. Eye retention, local control and disease-specific survival rates were calculated as Kaplan−Meier and actuarial estimates. The impact of prescription dose, tumor size, and ciliary body involvement was assessed by likelihood ratio tests and Cox regression.
Among all patients who were staged according to the TNM classification system (8th edition), 22.7% were I, 57.9% were II, 18.9% were III, and 0.5% were IV. Median apical tumor height and base diameter were 5.8 and 11.4 mm. The mean follow-up was 41.7 months. Local control after 3 and 5 years was 92.0% (95% CI = 88.2%-94.7%) and 84.3% (95% CI = 77.9%-89.0%), respectively, for 21 to 22 Gy and 86.9% (95% CI = 79.7%-91.7%) and 77.7% (95% CI = 68.5%-84.6%), respectively, when treated with 20 Gy or less. Eye retention was achieved in 89.9% and 81.0% after 3 and 5 years with 21 to 22 Gy and 85.9% and 80.0% for 20 Gy or less. Disease-specific survival rates were 93.1% (95% CI = 90.2%-95.2%) after 3 years, 89.8% (95% CI = 86.0%-92.6%) after 5 years, and 87.8% (95% CI = 82.8%-91.4%) after 7 years.
This is the largest series of patients treated for choroidal and ciliary body melanomas with CyberKnife. Our results reflect an improvement in the outcome of CyberKnife therapy for patients with choroidal and ciliary body melanoma treated with single-session radiosurgery in the last decade.
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443 patients with 445 UMs were treated via CyberKnife®. According to the COMS classification, 70% of the tumors were small/medium and 30% were large. Median total RT dose was 54 Gy, median BED10 was 151 Gy. After a median 74-months follow-up, SRS/FSRT yielded an 83% overall LC rate. The 5- and 10-year LRFS rate was 74% and 56%, respectively. Patient age and the COMS size were prognostic for all survival endpoints. An increased SRS/FSRT dose was associated with higher LRFS and EFS rates. SRS/FSRT-related toxicity was observed in 49% of the eyes. Median visual acuity (VA) significantly deteriorated after SRS/FSRT in 76% of the treated eyes. The overall eye preservation rate was 62%, and the 5- and 10-year EFS rate was 64% and 36%, respectively. The delivery of FSRT every other day resulted in a significantly lower rate of toxicity and enucleation compared to FSRT on consecutive days.
A total dose of ≥45 Gy and BED_10Gy ≥ 112.5 SRS/FSRT is associated with a higher LC rate in patients with UM. Despite the favorable outcomes, treatment toxicity is the major limitation of this treatment. Toxicity and enucleation can be minimized by treating the eye every other day.
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Citation Excerpt :
In view of this tumor's tendency to produce late systemic metastases, years after enucleation, therapeutic success is more appropriately recorded in terms of tumor control rather than survival. With one exception, tumor control in different series has varied between 90% and 100% (Fakiris et al., 2007; Kang et al., 2012; Langmann et al., 2000, 2002; Marchini et al., 1995, 1996; Modorati et al., 2009; Mueller et al., 2000; Rennie et al., 1996; Schirmer et al., 2009; Sinyavskiy et al., 2016; Toktas et al., 2010). These figures do not always specify the time at which tumor control was registered.
GKNS for uveal melanoma has become a recognized valued treatment which avoids enucleation of the eye. In the early days, the eccentric location of these tumors made treatment difficult, but Gamma Knife Perfexion has solved that problem. It is known that larger tumors and tumors with an anterior location have a worse prognosis. GKNS has also been of rather unexpected benefit in optic nerve gliomas that require treatment. Choroidal hemangiomas may benefit from treatment as can secondary glaucoma. It has also been found to be beneficial in the treatment of thyrotoxic ophthalmopathy.
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The 20 non-English-language publications included ten studies reporting on overlapping cohorts that were already included in the systematic review, four case reports, one study reporting another form of stereotactic radiosurgery, and five case series13–17 reporting on an additional 109 patients who were not included in our analysis due to unavailability of a full-text translation. The 52 studies in the systematic review9,10,18–61 included 44 studies of gamma knife radiosurgery for uveal melanomas, of which the majority were retrospective case series; four studies describing the treatment of uveal metastases; and four reporting on the treatment of both. The systematic review also included six case reports (appendix p 8).
Gamma knife radiosurgery is regarded as the gold-standard stereotactic radiosurgery modality for the treatment of intracranial tumours, and its use has been expanded for the treatment of intraocular malignancies. The aim of this study was to systematically evaluate the efficacy, outcomes, and complications of gamma knife radiosurgery for uveal melanomas and metastases.
We did a systematic review and meta-analysis to aggregate the clinical outcomes of patients with uveal melanomas or intraocular metastases treated primarily with gamma knife radiosurgery. We searched MEDLINE and Embase for studies published between Sept 1, 1960, and Feb 1, 2020, reporting the use of gamma knife radiosurgery as primary treatment for uveal melanoma or uveal metastases. The search was restricted to clinical studies and relevant grey literature published in English. Studies reporting treatment of benign tumours, extraocular tumours, or other forms of stereotactic radiosurgery were excluded to reduce heterogeneity. No restrictions were placed on participant criteria. Local tumour control and tumour regression were extracted as the primary outcomes and analysed via a random-effects meta-analysis of proportions using the DerSimonian and Laird method with a Freeman-Tukey double arcsine transformation. This study is registered with PROSPERO, CRD42019148165.
Our search returned 454 studies, of which 109 were assessed for full-text eligibility. 52 studies, reporting on 1010 patients with uveal melanoma and 34 intraocular metastases, were eligible for systematic review. 28 studies were included in the meta-analysis. 840 of 898 patients (0·96, 95% CI 0·94–0·97; I²=16%) from 19 studies had local control, and 378 of 478 patients (0·81, 0·70–0·90; I²=83%) from 16 studies experienced tumour regression.
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View full text

Stereotactic radiosurgery of large uveal melanomas with the gamma-knife

Abstract

Objective

Design

Participants

Intervention

Main outcome measures

Results

Conclusions

Section snippets

Patients and methods

Results

Discussion

Surv Ophthalmol

Am J Ophthalmol

Ophthalmology

Int J Radiat Oncol Biol Phys

Am J Ophthalmol

Bull Cancer Radiother

Int J Radiat Oncol Biol Phys

Bull Cancer Radiother

Exp Eye Res

Am J Ophthalmol

Management of small elevated pigmented choroidal lesions

Br J Ophthalmol

The time course of irradiation changes in proton beam-treated uveal melanomas

Ophthalmology

Ein neuer Weg zur konservativen Therapie intraokularer Tumoren mit Betastrahlen (106Ru/106Rh) unter Erhaltung der Sehfähigkeit

Klin Monatsbl Augenheilkd

Transpupillary thermotherapy in choroidal melanomas

Arch Ophthalmol

Diagnosis and treatment of uveal melanoma

Semin Oncol

Diagnose und Therapie maligner Melanome der Uvea (Aderhaut und Ziliarkörper)

Ophthalmologe

An approach to the management of patients with uveal melanoma

Eye

Adjunctive plaque radiotherapy after local resection of uveal melanoma

Front Radiat Ther Oncol

Local resection and other conservative therapies for intraocular melanoma

Curr Opin Ophthalmol