Open Access

Gamma knife radiosurgery for the treatment of uveal melanoma and uveal metastases

  • Margaret M. Reynolds1,
  • Andrea L. Arnett2,
  • Ian F. Parney3,
  • Ravi Kumar3,
  • Nadia N. Laack2,
  • Patrick R. Maloney3,
  • Timothy F. Kozelsky2,
  • Yolanda I. Garces2,
  • Robert L. Foote2 and
  • Jose S. Pulido1, 4Email author
International Journal of Retina and Vitreous20173:17

https://doi.org/10.1186/s40942-017-0070-2

Received: 18 January 2017

Accepted: 2 March 2017

Published: 29 May 2017

Abstract

Background

This study retrospectively analyzed outcomes for patients undergoing gamma knife radiosurgery (GKR) for uveal melanoma (UM) and intraocular metastases.

Methods

Patients who underwent GKR for UM or intraocular metastases between 1/1/1990 and 6/1/2015 at Mayo Clinic, Rochester, MN, USA, were retrospectively analyzed.

Results

Eleven patients (11 eyes) had UM while seven patients (7 eyes) had intraocular metastases. Patients with UM were followed for a median of 19.74 ± 10.4 months. Visual acuity (VA) logMAR 0.30 ± 0.53 (Snellen 20/40) versus 0.40 ± 0.97 (Snellen 20/50), tumor thickness (5.30 ± 2.17 vs. 3.60 ± 2.32 mm), were not significantly different between preoperative and postoperative measurements, respectively. Nine percent (1/11) patients required enucleation. Subsequently, no patients experienced metastases. Patients with intraocular metastases were followed for a median of 6.03 ± 6.32 months. They did not have significant changes in VA (logMAR 0.30 ± 0.59 vs. 0.30 ± 1.57; Snellen 20/40 vs. 20/40) or tumor thickness (3.50 ± 1.36 vs. 1.30 ± 0.76 mm) postoperatively. Fourteen percent (1/7 patients) required enucleation. Complications experienced by patients with UM include radiation retinopathy (2/11), papillopathy (1/11), cystoid macular edema (1/11), vitreomacular traction (1/11), exudative retinal detachment (1/11). Patients with metastases had treatment complicated by recurrence (2/7). Dose to the margin, maximum dose of radiation, and clinical target volume did not correlate with post-procedural VA, risk of enucleation, or death in patients with either UM or patients with intraocular metastases.

Conclusions

Visual outcomes were satisfactory for patients undergoing GKR without significant morbidity and without significant risk of enucleation or metastases.

Keywords

Gamma knifeIntraocular metastasisStereotactic radiosurgeryUveal melanomaUveal metastases

Background

Ocular metastases are the most common intraocular malignancy, while uveal melanoma (UM) is the most common primary intraocular malignancy. Cancer treatments have evolved to prioritize the most effective minimally invasive treatments with the fewest side effects. For these reasons, proton beam therapy, plaque brachytherapy, and gamma knife radiosurgery (GKR) have become more common. Recent studies have demonstrated that GKR has a similar efficacy to proton beam therapy and plaque brachytherapy [119].

Patients with cancer are living longer, resulting in higher rates of ocular metastases [20]. Patients with known malignancy have an estimated incidence of ocular involvement at 4–12% in post-mortem studies [18, 2123] and clinical apparent malignancies in 2.3–5% of patients [18, 21, 24]. The most prevalent metastases have been reported to be breast carcinoma and lung carcinoma, which make up 80% of cases [25, 26]. Patients with uveal metastases have a relatively short life expectancy, with a mean survival of 7 months [18]. Still, without treatment, the metastatic disease is typically progressive with a poor visual prognosis and high ocular morbidity [18]. The goal of treatment for patients with ocular metastases is to decrease the tumor burden and ocular morbidity. Therefore, ocular treatments with the most efficacy, shortest duration of treatment, and fewest side effects are prioritized. For these reasons, proton beam therapy, plaque brachytherapy, and GKR have replaced external beam radiation, which requires weeks of treatment with more side effects.

Uveal melanoma is the most common primary intraocular malignancy in adults with an incidence of 5.1 per million people [27]. Since the Collaborative Ocular Melanoma Treatment Study (COMS) revealed that conservative treatments, such as brachytherapy, had the same survival outcome as surgical treatment, i.e. enucleation, physicians have prioritized more conservative treatment with the goal of preserving vision and eyes in patients with UM [28]. Both GKR and proton beam therapy have similar outcomes as enucleation and are, therefore, both utilized for treatment of large UMs [28, 29]. The goal of radiotherapy is to conserve the eye, destroy the tumor, and prevent local recurrence.

With similar efficacy to proton beam therapy and plaque brachytherapy, GKR also has some advantages. Unlike plaque brachytherapy, which requires two procedures on separate dates—placing and removing a plaque, GKR is a same-day procedure. Proton beam therapy facilities are resource intensive and not universally available.

Few reports have been published describing the use of GKR in eyes with UM and uveal metastases. We wish to report our results of patients that underwent GKR for UM and uveal metastases.

Methods

This study retrospectively analyzed patients with primary UM and uveal metastases who were treated with GKR at Mayo Clinic Rochester between 1/1/1990 and 6/1/2015. Approval was obtained from the Mayo Clinic Institutional Review Board.

Individuals considered for this study underwent GKR for choroidal metastases or primary UM. Patients were required to have at least one follow-up appointment. Data obtained from patient records included: date of birth, sex, oncologic diagnosis, preoperative and postoperative visual acuity (VA), tumor thickness, largest-base dimension (LBD), intraocular pressure (IOP), additional ophthalmic procedures such as enucleation, and post-procedural complications such as radiation retinopathy. Patients without follow-up and patients who underwent GKR for orbital rather than intraocular tumors were excluded. Patients were selected for GKR who were not candidates for plaque brachytherapy as they had melanomas, which were larger than the size of the largest plaque used for plaque brachytherapy (24 mm). GKR was chosen over enucleation after discussion with patients. During the period of this study, proton beam therapy was not yet available at Mayo Clinic, Rochester.

All included patients underwent GKR according to the following technique: retrobulbar block was performed. The Leksell stereotactic head frame was applied using local anesthetic and superficial fixation to the outer plate of the skull as described by Safaee et al. [30]. Patients underwent magnetic resonance imaging (MRI) with gadolinium contrast of the orbits and returned to the gamma knife center. Images were imported into the treatment planning system, Leksell GammaPlan, Elekta AB, Stockholm, Sweden. MRI and three-dimensional modeling was utilized to determine the tumor margins. A treatment plan was then developed in conjunction with a radiation oncologist, neurosurgeon, and ocular oncologist (Fig. 1). The clinical target volume (CTV) was determined to be the gross tumor volume (GTV) plus 2 mm on each side. The patient was transferred to the treatment unit, where the stereotactic GKR was performed. All patients were discharged the same day.
Fig. 1

a Representative gamma knife planning MRI of a patient with choroidal melanoma treated with 18 Gy at the 50% isodose line. b gadolinium-enhanced T2 MRI of the orbit of the same patient depicted in tile a, after 7 months, shows interval decrease in size of choroidal mass. c Representative gamma knife planning MRI of a patient with choroidal melanoma treated with 27 Gy at the 50% isodose line. d Gadolinium-enhanced T2 fat saturation MRI of the orbit of the same patient depicted in tile c, after 48 months, shows interval decrease in size of choroidal mass

Categorical variables were compared between patients with uveal metastases and melanoma using the χ2 test, and two-sample t tests were used to analyze continuous patient characteristics. Correlation tests were used to compare radiation doses and visual outcomes. Simple logistic models were constructed to determine variables associated with increased odds of enucleation and death. Statistical analyses were conducted using commercial software JMP (SAS Institute, Cary, NC, USA). All statistical tests were two-sided with a 0.05 level of significance.

Results

Eighteen patients met inclusion criteria; seven patients with uveal metastasis [lung adenocarcinoma (n = 2), breast adenocarcinoma (n = 1), renal cell carcinoma (n = 1), cystic carcinoma (n = 1), metastatic melanoma (n = 1), esophageal carcinoma (n = 1)] and 11 patients with primary UM.

Demographic characteristics are demonstrated in Table 1. Patients with UM were a median of 76.9 ± 10.0 years old. Patients had a median follow-up of 19.74 ± 10.4 (range 3.40–26.7) months. Of note, the three patients who succumbed to UM did so <6 months postoperatively. Patients who did not succumb to the illness were followed between 11.6 and 26.66 months (median: 22.1 ± 7.47 months). Patients with UM had tumors, which were a median of 5.30 ± 2.17 mm thick by ultrasound with a preoperative LBD of 19.9 ± 4.55 mm. Patients with UM were treated with a marginal dose of 25.0 ± 3.36 Gy at the 50% isodose line with a maximum median dose of 50.0 ± 8.61 Gy. The median CTV was 2250 ± 747 mm3 (Table 2). Eight of eleven patients (72.7%) were surviving at completion of the study. The final tumor thickness was 3.60 ± 2.32 mm, and postoperative LBD was 17.6 ± 1.90 mm (Table 1).
Table 1

Demographic characteristics of patients undergoing gamma knife radiosurgery

 

Melanoma

Metastases

Age at gamma knife (years)

76.9 ± 10.0

59.0 ± 12.8

Female (%)

63.6

28.5

Length of follow-up (months)

19.74 ± 10.4

6.03 ± 6.32

Survival (%)

72.7

14.3

Tumor recurrence (% recurrence)

0

28.6

Pre-op tumor thickness by ultrasound (mm)

5.30 ± 2.17

3.50 ± 1.36

Post-op tumor thickness by ultrasound (mm)

3.60 ± 2.32

1.30 ± 0.76

Pre-op VA (logMAR/Snellen)

0.30 ± 0.53/20/40

0.30 ± 0.59/20/40

Pre-op IOP (mmHg)

14.0 ± 2.40

14.0 ± 7.31

VA at last follow-up (logMAR/Snellen)

0.40 ± 0.97/20/50

0.30 ± 1.57/20/40

IOP at last follow-up (mmHg)

15.0 ± 3.49

17.0 ± 3.39

Enucleation (%)

9.09

14.3

Largest base dimension pre-op (mm)

19.9 ± 4.55

14.0 ± 5.55

Largest base dimension post-op

17.6 ± 1.90

13.50 ± 9.62

Table 2

Gamma knife treatment parameters

 

Melanoma

Metastases

Maximum dose of radiation (Gy)

50.0 ± 8.61

44.0 ± 5.52

50% isodose (Gy)

25.0 ± 3.36

20.0 ± 2.34

Clinical target volume (mm3)

2250 ± 747

1770 ± 2791

Of the 10 patients with UM who did not undergo enucleation, VA increased by two or more lines in 0% (0/10), was stabilized in 70% (7/10 eyes), and decreased in 30% (3/10) due cystoid macular edema, radiation retinopathy, and exudative retinal detachment. In patients with UMs, VA, IOP, LBD, and tumor thickness were not significantly different postoperatively (Table 3). Notably, the tumor thickness was less postoperatively 5.30 ± 2.17 versus 3.60 ± 2.32 mm, but this was not statistically significant (p = 0.07), perhaps due to small study size. Dose to the margin, maximum dose of radiation, and CTV did not correlate with post-procedural VA, IOP, risk of enucleation, or death in patients with UM.
Table 3

Preoperative versus postoperative demographic characteristics for patients with uveal melanoma and metastases

 

Pre-op

Post-op

p value

Melanoma

 Visual acuity logMAR/Snellen

0.30 ± 0.53/20/40

0.40 ± 0.97/20/40

0.27

 IOP

14.0 ± 2.40

15.0 ± 3.49

0.62

 Tumor thickness (mm)

5.30 ± 2.17

3.60 ± 2.32

0.07

 Largest base dimension (mm)

19.9 ± 4.55

17.6 ± 1.90

0.43

Uveal metastases

 Visual acuity logMAR/Snellen

0.30 ± 0.59/20/40

0.30 ± 1.57/20/40

0.76

 IOP

14.0 ± 7.31

17.0 ± 3.39

0.92

 Tumor thickness (mm)

3.50 ± 1.36

1.30 ± 0.76

0.01

 Largest base dimension (mm)

14.0 ± 5.55

11.3 ± 9.62

0.58

Of the included patients with UM, 18% (2/11) experienced radiation retinopathy, 9% (1/11) underwent enucleation, 27% (3/11) had papillopathy, 9% (1/11) had cystoid macular edema, 9% (1/11) had vitreomacular traction, and 9% (1/11) had exudative retinal detachment (Table 4). Finally, one patient with UM underwent enucleation after the tumor did not respond and demonstrated growth post-procedurally.
Table 4

Complications experienced by patients undergoing gamma knife radiosurgery

 

Melanoma

Metastases

Length of follow-up (months)

19.74 ± 10.4

6.03 ± 6.32

Radiation retinopathy

2/11

0/7

Vitreous hemorrhage

0/11

0/7

Neovascular glaucoma

0/11

0/7

Recurrence

0/11

2/7

Enucleation

1/11

1/7

Papillopathy

1/11

0/7

Cystoid macular edema

1/11

0/7

Vitreomacular traction

1/11

0/7

Exudative retinal detachment

1/11

0/7

Patients with metastases were a median of 59.0 ± 12.8 years. Patients had a median follow-up of 6.03 ± 6.32 (range 3.28–22.07) months. Tumor thickness was a median of 3.50 ± 1.36 mm with LBD of 14.0 ± 5.55 mm, preoperatively. Patients with metastasis were treated with a marginal dose of 20.0 ± 2.34 Gy at the 50% isodose line with a median maximum dose of 44.0 ± 5.52 Gy. The median CTV was 1770 ± 2791 mm3 (Table 2). Patients with uveal metastases had significantly decreased tumor thickness postoperatively (p = 0.01). They did not have significant changes in VA, IOP, or LBD postoperatively (Table 3).

One out of seven patients (14.3%) with uveal metastases was surviving at completion of the study. The final tumor thickness was 1.30 ± 0.76 mm with an LBD of 13.50 ± 9.62 mm (Table 1). One patient underwent enucleation for pain control. This patient presented with 10 out of 10 pain, presumed to be neuropathic in origin due to metastatic disease. The patient had macular degeneration in the eye not affected by metastasis with a VA of 20/50, so GKR was attempted to spare the eye. Due to persistence of pain, the patient elected for enucleation. Of the six patients with uveal metastases who did not undergo enucleation, visual acuity increased by two or more lines in 14.3% (1/7), was stabilized in 28.6% (2/7), and decreased in 57.1% (4/7). Two of seven patients with choroidal metastases had recurrence at the same location as the previously treated lesions in the eye, but no extraocular progression was attributable to the eye. Of the two patients with recurrence, one had adenoid cystic carcinoma. The other had esophageal adenocarcinoma. It is possible that these tumors were less responsive to radiotherapy, required a higher dose, or were more malignant.

Dose to the margin, maximum dose of radiation, and CTV did not correlate with post-procedural VA, IOP, risk of enucleation, or death in patients with uveal metastases.

Of the patients with metastatic disease, 28.6% (2/7) experienced local recurrence as defined by new choroidal lesions, and 14.3% (1/7) underwent enucleation for post-procedural neuropathic pain. Of note, this pain was present prior to GKR, but GKR was pursued instead of primary enucleation as the patient had macular degeneration and poor vision in the eye unaffected by the metastasis (Table 4).

Discussion

This clinical investigation of GKR for patients with choroidal metastasis and UM found a positive correlation existed for patients with uveal metastases between marginal dose and post-procedural intraocular pressure. Marginal dose, maximal dose, and CTV did not correlate with post-procedural VA, risk of enucleation, or death in patients with either UM or patients with uveal metastases. Though the marginal dose and the 50% isodose were determined and recorded, we did not have the dose to the lens or retina on these cases. This study provides new insights into outcomes of patients with UM and uveal metastases treated with GKR.

For treatment of UM, both GKR and proton beam radiotherapy have been shown to have similar outcomes as enucleation [28, 29]. The COMS trial, which included more than 650 patients treated with plaque brachytherapy, found 88.7% of patients achieved local control with a recurrence rate of 10.3% and a survival rate of more than 80% at 5 years [31, 32].

Other studies on proton beam radiotherapy have demonstrated satisfactory outcomes. A prospective study by Gragoudas et al. reviewed 1922 consecutive patients treated with proton beam radiotherapy over 20+ years with an average follow-up for patients was 5.2 years. Ninety-seven percent of patients achieved local tumor control with a recurrence rate of 4.9% (45 patients). Seventeen patients required enucleation due to suspected tumor progression [33, 34].

A study by Modorati et al. [1] of 78 patients with tumor thickness, ranging from 3.1 to >10 mm over 12 years, treated with between 30 and 50 Gy (50% isodose) with GKR, found a survival rate of 88.8% at 3 years and 81.9% at 5 years, which was independent of dose. After treatment, 91% of patients had local tumor control with median tumor thickness reduced by 1.9 mm from a median baseline of 6.1 mm; 89.7% of patients avoided enucleation, although patients had significantly decreased vision after treatment (from 0.3 before treatment to an average VA of 0). Vision-compromising complications occurred such as exudative retinopathy (33.3%), neovascular glaucoma (18.7%), radiogenic retinopathy (13.5%), and vitreous hemorrhages (10.4%). Another study of single-fraction stereotactic radiosurgery of 23 patients applied 20–25 Gy (mean 21.7 Gy) and found 91% had local control. Three patients developed metastases in 121 months of follow-up, 61% of patients lost vision, 35% of patients maintained vision >20/200 [2]. The outcomes of our study are similar to these. Notably, our percent survival (63.6%) is greater likely attributable to the shorter length of follow-up. Table 5 contains a review of other published studies on GKR for UM.
Table 5

A review of previous studies using gamma knife radiosurgery for uveal melanoma

Study

Eyes

Radiation dose (Gy)

Follow-up (months)

Visual acuity

Complications

Survival (%)

Before

After

Radiation retinopathy (%)

Radiation neuropathy (%)

Neovascular glaucoma (%)

Neovascularization

Radiation maculopathy (%)

Vitreous hemorhage

Enucleation (%)

Modorati et al. [1]

GKR

78

50 (n = 7)

40 (n = 21)

35 (n = 47)

at 50% isodose

31.3 (median)

0.3 (0.05–0.8)

0 (0–0.05)

13.5

15.5

18.7

    

88.8% at 3 years and 81.9% at 5 years

Joye et al. [2] GKR

23

21.7 at 50% isodose

41.5 (median)

20/20-CF

20/20-NLP

8.7

13.0

17.4

8.7

 

8.7

 

91.3%

Marchini et al. [3]

GKR

12

55 ± 10 Gy to 60–90% isodose

6 (median)

Not reported

Not reported

8.33

8.33

8.33

 

8.33

  

Not reported

Chan et al. [4]

GKR

6

25 at 50% isodose

24 (median)

20/40–20/80

20/50-LP

16.7

16.7

16.7

    

100%

Dinca et al. [5]

GKR

170

50–70 (n = 24)

45 (n = 71)

35 (n = 62)

at 50% isodose

63.5 (median)

Patients with more than three lines decrease in VA at 5 years 45% (35 Gy), 89% (45 Gy), 93% (50–70 Gy)

 

25.81–41.67

12.68–20.83

8.06–20.82

    

5-year survival rates: 64% for 35 Gy, 62.71% for 45 Gy, 63.6% for 50–70 Gy

Sarici et al. [6]

GKR

50

30 at 50% isodose

40 (median)

NR visual acuity decreased significantly after treatment (p < 0.0001)

 

24

14

14

    

87%

Sikuade et al. [7]

GKR

85

35 at 50% isodose

39 (mean)

Not recorded

33% better than 6/60. 65% loss of ≥3 Snellen lines

NR

      

84%

Bellman et al. [8]

GKR

5

50 maximum average dose

7.3 (median)

20/20–20/320

20/20-CF

NR

      

No deaths

Furdova et al. [9]

GKR

96

49.0 maximum average dose

24 (mean)

16% ≥ 20/40, 58% < 20/40 ≥ 20/200, 26% < 20/200

11% ≥ 20/40, 47% < 20/40 ≥ 20/200, 42% < 20/200

      

11.5

Tumor local control was successful in 80% of patients in 5 years interval after stereotactic radiosurgery

Suesskind et al. [10]

SDRT

60

25 at 50% isodose

33.7 (median)

20/20-LP

Median loss of −18 Snellen lines

42

24

15

    

83%

Kang et al. [11]

GKR

22

45.6 at 50% isodose

67 (median)

LP to 1.2

NLP to 0.9

22.7

 

9.1

    

90.9%

Eibl-Lindner [12] frameless, single-session, image-guided robotic radiosurgery

217

20.3 at the 69% isodose

29.6 (mean)

A total of 104 patients presented with functional vision (defined as visual acuity ≥0.3) before treatment

Functional vision maintained in 30.9% of patients

13.4

 

15.2

    

Actuarial disease-specific survival was 84.8% (95% CI 77.0–90.1%) at 3 years and 78.4% (95% CI 67.1–86.2%) at 5 years

Haas et al. [13]

GKR

32

50 at 50% isodose

38 (mean)

20% ≤ 20/400

78% ≤ 20/400

84

 

47

    

Metastasis free 94%, overall NR

Langmann et al. [14]

GKR

60

50–70 isodose 50–80%

16–94 (range)

Not recorded

Not recorded

 

20

35

    

Metastasis free 85%, overall NR

Simonova et al. [15]

GKR

81

31.4 minimum dose

32 (median)

Not recorded

Not recorded

 

12.3

25

    

70.4%

Fakiris et al. [16]

GKR

19

40 isodose 50%

40 (median)

Not recorded

Not recorded

 

11

0

    

86% at 5 years

Zehetmayer et al. [17]

GKR

62

45–70 isodose 50%

23.8 (median)

56.8% ≥ 20/200

21% ≥ 20/200

17.3

19.8

12.3

    

84% at 3 years

Current study

GKR

11

25.0 ± 3.36 at 50% isodose

19.74 ± 10.4 (median)

20/30-CF

20/30-LP

18.2

9

0

    

72.7%

NR not recorded

Evaluating outcomes of different treatment methods for ocular malignancies is key in determining the most efficacious treatments with the least amount of morbidity. Table 6 lists a summary of previous studies. In a study which included 36 patients with uveal metastases who underwent plaque treatment, 27 (75%) received plaque brachytherapy as first-line treatment; 9 (25%) patients received plaque treatment as secondary therapy after the tumor failed to respond to external beam radiotherapy, chemotherapy, or hormone treatment [35]. Patients were treated for an average time of 86 h with a mean dose of 68.80 Gy to the apex and 235.64 Gy to the base. Over 11 months, 34 patients (94%) demonstrated regression. Five of six eyes receiving plaque brachytherapy as a second-line treatment were successfully salvaged. Three patients experienced radiation retinopathy, radiation papillopathy, or both (8%) at a mean of 8 months after treatment. Fifty percent of patients survived to completion of the study [35]. Other studies have demonstrated acceptable results [36]. While these results are satisfactory, plaque radiotherapy was not an option for the patients in this study, given the size of patients’ lesions. It is also true that GKR spared patients an additional procedure—plaque placement, required for plaque radiosurgery.
Table 6

A review of previous studies using radiotherapy (SRT, EBRT, GKR) for uveal metastases

Study

Eyes

Radiation dose (Gy)

Follow-up (months)

Visual acuity

Complications

Survival (%)

Before

After

Radiation retinopathy (%)

Radiation neuropathy (%)

Neovascular glaucoma (%)

Bellman et al. [8]

Single-dose or fractionated SRT

10

12–20 Gy in a single dose or 30 Gy over 10 days to 50% isodose

6.5 (median)

20/26–20/320

20/26-LP

NR

  

NR

Bajcsay et al. [19]

EBRT

24

46 Gy (maximum average dose)

24 (mean)

0.1–0.7

Improvement of two lines

3.5

0

0

4.2

Wiegel et al. [18]

Radiotherapy

65

40 Gy in 20 fractions (50% isodose)

5.8 (median)

20/32

Visual acuity increased for two or more lines in 36%, stabilized in 50%, and decreased in 14%

1.5

1.5

 

18

Current study

GKR

7

20.0 ± 2.34 (50% isodose)

6.03 ± 6.32 (median)

20/25–20/600

20/25-HM

0

0

14.3

14.3

Proton beam therapy has also been demonstrated to have satisfactory results [37, 38]. A retrospective study, which included 55 eyes of 49 patients who underwent two fractions of 14 cobalt gray equivalents, found that tumor regression occurred in 84% of patients and stability occurred in 14% of patients. Forty-seven percent of patients had vision that remained stable or improved. Post-proton therapy complications occurred in 29% of patients, including madarosis (28%), lid burns (17%), iris neovascularization and neovascular glaucoma (8%), cataract (11%), radiation maculopathy (19%), and radiation papillopathy (22%) [38]. During the dates of this study, proton therapy was not yet available at Mayo Clinic Rochester; therefore, patients ineligible for plaque therapy were treated with stereotactic radiosurgery.

A stereotactic radiosurgery study, which included ten patients with choroidal metastases, found that local tumor control was achieved in all eyes. Eight of ten patients had decreased tumor size. No significant side effects were noted in follow-up of 1–34 months [8]. While this study only included ten patients, it is notable that they did not experience significant side effects. A review of other studies which looked at radiation and uveal metastases is reviewed in Table 5.

Comparing the study published in this paper to those discussed, it had a higher rate of recurrence (28.6%). Notably, patients included in this study had more rare metastatic cancers (as opposed to breast or lung cancer) and a lower survival rate (28.6%). Weaknesses of this study included retrospective design, a small patient size, limited follow-up, and limited information regarding dose to the macula and optic nerve.

Conclusions

In summary, GKR is a useful alternative to plaque brachytherapy and proton beam therapy. It is particularly useful for patients who cannot or prefer not to undergo the procedures required for plaque brachytherapy or for whose tumor sizes disqualify them. It is also useful for patients who do not have access to proton beam therapy, which is geographically limited.

Abbreviations

COMS: 

Collaborative Ocular Melanoma Treatment Study

CTV: 

clinical target volume

GKR: 

gamma knife radiosurgery

GTV: 

gross tumor volume

IOP: 

intraocular pressure

LBD: 

largest-base dimension

MRI: 

magnetic resonance imaging

UM: 

uveal melanoma

VA: 

visual acuity

Declarations

Authors’ contributions

MMR: Made substantial contributions to conception, design, acquisition of data, as well as analysis and interpretation of data; involved in drafting the manuscript and revising it critically for important intellectual content. ALA: Made substantial contributions to conception, design, acquisition of data, as well as analysis and interpretation of data; involved in drafting the manuscript and revising it critically for important intellectual content. IFP: Made substantial contributions to conception, design, acquisition of data, as well as analysis and interpretation of data; involved in drafting the manuscript and revising it critically for important intellectual content. RK: Made substantial contributions to conception, design, acquisition of data, as well as analysis and interpretation of data; involved in drafting the manuscript and revising it critically for important intellectual content. NNL: Made substantial contributions to conception, design, acquisition of data; involved in drafting the manuscript and revising it critically for important intellectual content. PRM: Made substantial contributions to conception, design, acquisition of data, as well as analysis and interpretation of data; involved in drafting the manuscript and revising it critically for important intellectual content. TFK: Made substantial contributions to conception, design, acquisition of data, as well as analysis and interpretation of data; involved in drafting the manuscript and revising it critically for important intellectual content. YIG: Made substantial contributions to conception, design, acquisition of data; involved in drafting the manuscript and revising it critically for important intellectual content. RLF: Made substantial contributions to conception, design, acquisition of data; involved in drafting the manuscript and revising it critically for important intellectual content. JSP: Made substantial contributions to conception, design, acquisition of data, as well as analysis and interpretation of data; involved in drafting the manuscript and revising it critically for important intellectual content. All authors read and approved the final manuscript.

Acknowledgements

The authors Mrs. Denise Chase for her formatting help.

Competing interests

The authors declare that they have no competing interests.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

This study was approved by the IRB Committee of the Mayo Clinic following review of the Protocol 13-000260 institutional review of all radiosurgery cases for ocular lesions.

Funding

Supported, in part, by an unrestricted grant from Research to Prevent Blindness Inc., NY; VRS Foundation, Minneapolis, MN; the Paul Family; and the Deshong Fund.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Department of Ophthalmology, Mayo Clinic
(2)
Department of Radiation Oncology, Mayo Clinic
(3)
Department of Neurosurgery, Mayo Clinic
(4)
Department of Molecular Medicine, Mayo Clinic

References

  1. Modorati G, Miserocchi E, Galli L, Picozzi P, Rama P. Gamma knife radiosurgery for uveal melanoma: 12 years of experience. Br J Ophthalmol. 2009;93:40–4. doi:10.1136/bjo.2008.142208.View ArticlePubMedGoogle Scholar
  2. Joye RP, Williams LB, Chan MD, Witkin AJ, Schirmer CM, Mignano JE, et al. Local control and results of Leksell gamma knife therapy for the treatment of uveal melanoma. Ophthalmic Surg Lasers Imaging Retina. 2014;45:125–31. doi:10.3928/23258160-20140306-05.View ArticlePubMedGoogle Scholar
  3. Marchini G, Babighian S, Tomazzoli L, Gerosa MA, Nicolato A, Bricolo A, et al. Stereotactic radiosurgery of uveal melanomas: preliminary results with gamma knife treatment. Stereotact Funct Neurosurg. 1995;64(Suppl. 1):72–9.PubMedGoogle Scholar
  4. Chan MD, Melhus CS, Mignano JE, Do-Dai D, Duker JS, Yao KC. Analysis of visual toxicity after gamma knife radiosurgery for treatment of choroidal melanoma: identification of multiple targets and mechanisms of toxicity. Am J Clin Oncol. 2011;34:517–23.View ArticlePubMedGoogle Scholar
  5. Dinca EB, Yianni J, Rowe J, Radatz MW, Preotiuc-Pietro D, Rundle P, et al. Survival and complications following gamma knife radiosurgery or enucleation for ocular melanoma: a 20-year experience. Acta Neurochir. 2012;154:605–10. doi:10.1007/s00701-011-1252-6.View ArticlePubMedGoogle Scholar
  6. Sarici AM, Pazarli H. Gamma-knife-based stereotactic radiosurgery for medium- and large-sized posterior uveal melanoma. Graefes Arch Clin Exp Ophthalmol. 2013;251:285–94. doi:10.1007/s00417-012-2144-z.View ArticlePubMedGoogle Scholar
  7. Sikuade MJ, Salvi S, Rundle PA, Errington DG, Kacperek A, Rennie IG. Outcomes of treatment with stereotactic radiosurgery or proton beam therapy for choroidal melanoma. Eye. 2015;29:1194–8. doi:10.1038/eye.2015.109.View ArticlePubMedPubMed CentralGoogle Scholar
  8. Bellmann C, Fuss M, Holz FG, Debus J, Rohrschneider K, Volcker HE, et al. Stereotactic radiation therapy for malignant choroidal tumors: preliminary, short-term results. Ophthalmology. 2000;107:358–65.View ArticlePubMedGoogle Scholar
  9. Furdova A, Sramka M, Chorvath M, Kralik G, Krasnik V, Krcova I, et al. Stereotactic radiosurgery in intraocular malignant melanoma—retrospective study. Neuro Endocrinol Lett. 2014;35:28–36.PubMedGoogle Scholar
  10. Suesskind D, Scheiderbauer J, Buchgeister M, Partsch M, Budach W, Bartz-Schmidt KU, et al. Retrospective evaluation of patients with uveal melanoma treated by stereotactic radiosurgery with and without tumor resection. JAMA Ophthalmol. 2013;131:630–7. doi:10.1001/jamaophthalmol.2013.697.View ArticlePubMedGoogle Scholar
  11. Kang DW, Lee SC, Park YG, Chang JH. Long-term results of gamma knife surgery for uveal melanomas. J Neurosurg. 2012;117(Suppl):108–14. doi:10.3171/2012.8.GKS121002.PubMedGoogle Scholar
  12. Eibl-Lindner K, Furweger C, Nentwich M, Foerster P, Wowra B, Schaller U, et al. Robotic radiosurgery for the treatment of medium and large uveal melanoma. Melanoma Res. 2016;26:51–7. doi:10.1097/CMR.0000000000000199.View ArticlePubMedGoogle Scholar
  13. Haas A, Pinter O, Papaefthymiou G, Weger M, Berghold A, Schrottner O, et al. Incidence of radiation retinopathy after high-dosage single-fraction gamma knife radiosurgery for choroidal melanoma. Ophthalmology. 2002;109:909–13.View ArticlePubMedGoogle Scholar
  14. Langmann G, Pendl G, Klaus M, Papaefthymiou G, Guss H. Gamma knife radiosurgery for uveal melanomas: an 8-year experience. J Neurosurg. 2000;93(Suppl. 3):184–8. doi:10.3171/jns.2000.93.supplement.PubMedGoogle Scholar
  15. Simonova G, Novotny J Jr, Liscak R, Pilbauer J. Leksell gamma knife treatment of uveal melanoma. J Neurosurg. 2002;97:635–9. doi:10.3171/jns.2002.97.supplement.PubMedGoogle Scholar
  16. Fakiris AJ, Lo SS, Henderson MA, Witt TC, Worth RM, Danis RP, et al. Gamma-knife-based stereotactic radiosurgery for uveal melanoma. Stereotact Funct Neurosurg. 2007;85:106–12. doi:10.1159/000098525.View ArticlePubMedGoogle Scholar
  17. Zehetmayer M. Stereotactic photon beam irradiation of uveal melanoma. Dev Ophthalmol. 2012;49:58–65. doi:10.1159/000328259.View ArticlePubMedGoogle Scholar
  18. Wiegel T, Bottke D, Kreusel KM, Schmidt S, Bornfeld N, Foerster MH, et al. External beam radiotherapy of choroidal metastases—final results of a prospective study of the German Cancer Society (ARO 95-08). Radiother Oncol. 2002;64:13–8.View ArticlePubMedGoogle Scholar
  19. Bajcsay A, Kontra G, Recsan Z, Toth J, Fodor J. Lens-sparing external beam radiotherapy of intraocular metastases: our experiences with twenty four eyes. Neoplasma. 2003;50:459–64.PubMedGoogle Scholar
  20. Chen CJ, McCoy AN, Brahmer J, Handa JT. Emerging treatments for choroidal metastases. Surv Ophthalmol. 2011;56:511–21. doi:10.1016/j.survophthal.2011.05.001.View ArticlePubMedPubMed CentralGoogle Scholar
  21. Albert DM, Rubenstein RA, Scheie HG. Tumor metastasis to the eye. I. Incidence in 213 adult patients with generalized malignancy. Am J Ophthalmol. 1967;63:723–6.View ArticlePubMedGoogle Scholar
  22. Bloch RS, Gartner S. The incidence of ocular metastatic carcinoma. Arch Ophthalmol. 1971;85:673–5.View ArticlePubMedGoogle Scholar
  23. Nelson CC, Hertzberg BS, Klintworth GK. A histopathologic study of 716 unselected eyes in patients with cancer at the time of death. Am J Ophthalmol. 1983;95:788–93.View ArticlePubMedGoogle Scholar
  24. Wiegel T, Kreusel KM, Bornfeld N, Bottke D, Stange M, Foerster MH, et al. Frequency of asymptomatic choroidal metastasis in patients with disseminated breast cancer: results of a prospective screening programme. Br J Ophthalmol. 1998;82:1159–61.View ArticlePubMedPubMed CentralGoogle Scholar
  25. Shields CL, Shields JA, Gross NE, Schwartz GP, Lally SE. Survey of 520 eyes with uveal metastases. Ophthalmology. 1997;104:1265–76.View ArticlePubMedGoogle Scholar
  26. Weiss L. Analysis of the incidence of intraocular metastasis. Br J Ophthalmol. 1993;77:149–51.View ArticlePubMedPubMed CentralGoogle Scholar
  27. Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118:1881–5. doi:10.1016/j.ophtha.2011.01.040.View ArticlePubMedGoogle Scholar
  28. Lund RW. The Collaborative Ocular Melanoma Study, mortality by therapeutic approach, age and tumor size. J Insur Med. 2013;43:221–6.PubMedGoogle Scholar
  29. Koutsandrea C, Moschos MM, Dimissianos M, Georgopoulos G, Ladas I, Apostolopoulos M. Metastasis rates and sites after treatment for choroidal melanoma by proton beam irradiation or by enucleation. Clin Ophthalmol. 2008;2:989–95.PubMedPubMed CentralGoogle Scholar
  30. Safaee M, Burke J, McDermott MW. Techniques for the application of stereotactic head frames based on a 25-year experience. Cureus. 2016;8:e543. doi:10.7759/cureus.543.PubMedPubMed CentralGoogle Scholar
  31. Diener-West M, Earle JD, Fine SL, Hawkins BS, Moy CS, Reynolds SM, et al. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18. Arch Ophthalmol. 2001;119:969–82.View ArticlePubMedGoogle Scholar
  32. Jampol LM, Moy CS, Murray TG, Reynolds SM, Albert DM, Schachat AP, et al. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: IV. Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS Report No. 19. Ophthalmology. 2002;109:2197–206.View ArticlePubMedGoogle Scholar
  33. Gragoudas ES, Lane AM, Munzenrider J, Egan KM, Li W. Long-term risk of local failure after proton therapy for choroidal/ciliary body melanoma. Trans Am Ophthalmol Soc. 2002;100:43–8 (Discussion 8–9).PubMedPubMed CentralGoogle Scholar
  34. Li W, Gragoudas ES, Egan KM. Metastatic melanoma death rates by anatomic site after proton beam irradiation for uveal melanoma. Arch Ophthalmol. 2000;118:1066–70.View ArticlePubMedGoogle Scholar
  35. Shields CL, Shields JA, De Potter P, Quaranta M, Freire J, Brady LW, et al. Plaque radiotherapy for the management of uveal metastasis. Arch Ophthalmol. 1997;115:203–9.View ArticlePubMedGoogle Scholar
  36. Demirci H, Shields CL, Chao AN, Shields JA. Uveal metastasis from breast cancer in 264 patients. Am J Ophthalmol. 2003;136:264–71.View ArticlePubMedGoogle Scholar
  37. Kamran SC, Collier JM, Lane AM, Kim I, Niemierko A, Chen YL, et al. Outcomes of proton therapy for the treatment of uveal metastases. Int J Radiat Oncol Biol Phys. 2014;90:1044–50. doi:10.1016/j.ijrobp.2014.08.003.View ArticlePubMedGoogle Scholar
  38. Tsina EK, Lane AM, Zacks DN, Munzenrider JE, Collier JM, Gragoudas ES. Treatment of metastatic tumors of the choroid with proton beam irradiation. Ophthalmology. 2005;112:337–43. doi:10.1016/j.ophtha.2004.09.013.View ArticlePubMedGoogle Scholar

Copyright

© The Author(s) 2017

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