*3.1.2 Stereotactic radiosurgery for uveal melanoma: Our results*

Treatment of uveal melanoma in Slovakia is performed on direct quickening agent LINAC. One-fraction LINAC radiotherapy/radiosurgery is an unusual approach to treatment of choroidal melanoma. Hypofractionation with a broad shoulder in linear-quadratic model for radioresistant tumors like choroidal melanoma is still in discussion.

We evaluated in our study local failure which leads into enucleation as an end point in patients treated by SRS with long-term follow-up having accrued at the time of analysis. We evaluate in our study the treatment of posterior uveal melanoma by one-day session of LINAC stereotactic radiosurgery.

The first goal of our study was to evaluate treatment BCVA decline in patients who has posterior uveal melanoma treated with SRS in 6 months interval 24 months after SRS.

The second goal was to find out whether the group of patients with better initial visual acuity on the beginning of treatment would have also a better chance to preserve vision. The observed after-treatment decline in BCVA was 24 months interval after the treatment.

The third goal was observation of the tumor regression by the maximum elevation measurement using B-scan ultrasound in the group of patients with single irradiation (SRS) in interval 1 and 2 years after the treatment.

For patients treated by SRS in the period 2001–2008 was a retrospective analysis was undertaken. At the Department of Ophthalmology, Comenius University in Bratislava we reviewed 84 patients records with choroidal melanoma or with ciliary body melanoma treated in this period. 44 patients underwent primary enucleation (52.4%) out of 84 patients and 40 patients underwent SRS as an initial treatment (47.6%). The diagnosis was established on the basic of ophthalmological examination, ultrasound, CT or MRI examination. Excluded from analyzed cohort were metastatic intraocular tumors, juxtapapillary localized tumors and melanocytomas.

Each patient record must have details such as the age at treatment, tumor size, tumor volume, the maximum height of the tumor by A, B scan ultrasound, the presence and the extent of secondary retinal detachment, and if there are signs of extrascleral spread.

The tumors were divided into 3 groups as follows: small up to 4 or 5 mm of maximal elevation, middle 4–8 mm, and large over 8 mm.

In the group of one stereotactic irradiation, an increase in the tumor was observed in a 6-month interval by ultrasound with a B-scan ophthalmologist. We compared tumor regression by measuring maximal elevation using B-scan ultrasound in a group of 25 patients with single irradiation (SRS) at 12 and 24 months post-treatment.

## *3.1.3 Enucleation versus stereotactic radiosurgery: Our results*

We analyzed the treatment outcome and possible survival difference between radical surgical treatment (primary enucleation) and stereotactic radiosurgery (SRS) at the Department of Ophthalmology, Comenius University in Bratislava, in patients with posterior uveal melanoma.

Patients treated for uveal melanoma in posterior during the period 2001–2008 are analyzed in the study. The goal of the study was to compare the relapse-free survival in the cohort of patients initially treated by SRS or they primary underwent enucleation. Together we included 84 patients. Treatment was determined on a case-by-case basis.

We analyzed each patient's record with ciliary body or choroidal melanoma treated by enucleation. We divided them into two groups: first group had 44 patients (52%) using surgical treatment and the second group had 40 patients (48%) using SRS treatment. The therapeutic attitude was set up based on ophthalmoscopy, ultrasound (A, B mode), other ophthalmological findings, visual acuity, and general status of each patient and MRI examination. Volume of the tumor was determined by using the formula:

$$\text{Tumor volume} = \frac{\pi}{6} \ast \text{length} \ast \text{width} \ast \text{height} \tag{1}$$

$$\text{Td} = \frac{0,30103 \text{\textdegree of months}}{\log\_{10}(\text{final volume}) - \log\_{10}(\text{starting volume})} \tag{2}$$

The disease-free interval was defined as the period from treatment (either enucleation or SRS) until the development of metastasis, or the death of the patient. The patients after enucleation were examined by ophthalmologist every six months, with a monthly interval in the first six months, dependent on problems with using individual prosthesis. The patients after stereotactic radiosurgery were examined by an ophthalmologist every three months: visual acuity, biomicroscopy (slit lamp), intraocular pressure, ultrasound in A and B mode, fundus photography and since the year 2007 also OCT (optical coherence tomography) was routinely done. Post radiation complications and tumor dimension and extent of secondary retinal detachment were observed. The patients were observed in the period from 2001 (01/01) to 2008 (31/12) and the data were analyzed.

The disease-free interval was defined as the time from treatment until the development of metastases. Patients were seen in three months interval in the first year after the SRS, later in six months interval following SRS. Patients in both groups were regularly in six months interval recommended to their oncologist to a liver ultrasound, abdominal ultrasound, liver function test, brain CT, chest X-ray to confirm or exclude the presence of metastases. In individual cases they were recommended to brain CT or PET/CT.

In the period 2001–2008 a total number of 84 patients with intermediate or large uveal melanoma were treated with either radical surgical removal of the whole eyeball (enucleation), or SRS. In a group of 40 patients who underwent SRS there were 22 male and 18 female - the total median age was 55 years; the median age of female was 54 years and 58 years of male. In a group of 44 patients with enucleated eyes the median age was 68.5 year. In the group there were 21 males (median age 64), and 23 females (median age 73). The median tumor volume in group of stereotactic patients was 0,65 cm3 (0,4 - 0,8), in group of enucleated patients 1,1 cm3 (0,8 - 1,25).

Five patients treated in the first step with SRS required subsequent enucleation due to the complications - secondary neovascular glaucoma. Three patients of this subgroup underwent pars plana vitrectomy with endoresection of the tumors plus silicon oil, but the enucleation was necessary due to the complication - relapse of the tumor.

Histopathologically in the group of enucleated eyes after SRS due to complications in four patients with malignant melanoma of the mixed cell type, in two cases an epithelioid type, and in one case a spindle-cell type A was confirmed.

In the group of primary enucleated eyes, there were four findings of an epithelioid-cell type, one case of a nodular type, as well as 10 cases of both, a mixed-cell type and 29 cases of a spindle-cell type (A or B) melanoma.

**23**

performed.

vein.

subsequent assessment:

than 30% of its periphery is irradiated.

*Uveal Melanoma*

both predictors.

*DOI: http://dx.doi.org/10.5772/intechopen.95321*

*3.1.4 Complications after stereotactic radiosurgery: Our results*

The age and tumor volume are important explanatory variables (termed covariates) that are assumed to be associated with survival and need to be incorporated in the model. Results on logistic regression confirmed significance of the model with the predictors age and tumor volume (P = 0.01). The tumor volume was a significant unique predictor (P = 0.035); age with its borderline probability value of 0.1 could be assumed as possibly associated with the outcome. The estimator of survival rates adjusted for these predictors was constructed based on Cox's regression model which examines the relationship between survival and

The fundamental objective of radioactive therapy is to control malignancy while maintaining useful vision. Present techniques result in a high incidence of tumor control for intermediate and small lesions (< 8 mm in height). Tumor control for enormous sores is not ideal, also, here is a higher frequency of late complexities bringing about hindered vision in huge sores. All things considered, radiation portion decrease to the uninvolved piece of the eye will lessen the rate of late difficulties while keeping up a high occurrence of tumor control for more modest tumors. Utilizing of 3-D radiation dosimetry is accepted that will have significant advantage as far as therapy enhancement and lower frequency of late inconveniences. Such a 3-D framework grants exact pre-treatment arranging and adjustments of the arrangement at short notification, for example, on account of new intraoperative discoveries. There is overpowering proof that threatening melanoma of the uveal plot can be dealt with securely with radioactive plaques with long haul endurance rates equivalent to those of enucleation. We think, that the vessels around the optic plate are harmed by full portion light, prompting retinal ischemia, and this courtesies the presence of neovascular glaucoma. Safeguarding of the eye work is normal in most of radioactive-plaque treatment treated patients. Utilization of low energy isotopes, collimation of individual seeds, and routine utilization of 3-D imaging and 3-D dosimetry should assist with promoting improve episcleral plaque treatment. In writing the rate of post-radiotherapy enucleation from all causes is about 20%. The diminishing of the occurrence of intricacies as waterfall, radiation papillitis, radiation maculopathy, optional glaucoma is because of extremely exacting signs of back uveal melanoma. Today, no randomized planned investigation of the impact of the elective moderate medicines for choroidal melanoma on visual result have been

In our group of patients after Ru106/Rh106 plaque treatment the accompanying late intricacies prompted crumbling of visual keenness and were seen at the last

• macular pulverization due to scarring around the tumor, optic nerve decay,

• macular degeneration, retinopathy, fractional focal point haziness, complete waterfall, glassy discharge, optional glaucoma, apoplexy of the focal retinal

The patient will develop radiation cataract if more than 30% of the periphery of the lens is irradiated. If the diameter of the tumor is large, invasion of the iris may occur, or if the anterior margin of the tumor is well in front of the equator, the lens may be more sensitive to irradiation. Post-radiation cataracts can occur even if less

#### *Uveal Melanoma DOI: http://dx.doi.org/10.5772/intechopen.95321*

*Melanoma*

determined by using the formula:

(01/01) to 2008 (31/12) and the data were analyzed.

mended to brain CT or PET/CT.

reotactic patients was 0,65 cm3

(0,8 - 1,25).

the tumor.

We analyzed each patient's record with ciliary body or choroidal melanoma treated by enucleation. We divided them into two groups: first group had 44 patients (52%) using surgical treatment and the second group had 40 patients (48%) using SRS treatment. The therapeutic attitude was set up based on ophthalmoscopy, ultrasound (A, B mode), other ophthalmological findings, visual acuity, and general status of each patient and MRI examination. Volume of the tumor was

Tumor volume length width height <sup>6</sup>

The disease-free interval was defined as the period from treatment (either enucleation or SRS) until the development of metastasis, or the death of the patient. The patients after enucleation were examined by ophthalmologist every six months, with a monthly interval in the first six months, dependent on problems with using individual prosthesis. The patients after stereotactic radiosurgery were examined by an ophthalmologist every three months: visual acuity, biomicroscopy (slit lamp), intraocular pressure, ultrasound in A and B mode, fundus photography and since the year 2007 also OCT (optical coherence tomography) was routinely done. Post radiation complications and tumor dimension and extent of secondary retinal detachment were observed. The patients were observed in the period from 2001

The disease-free interval was defined as the time from treatment until the development of metastases. Patients were seen in three months interval in the first year after the SRS, later in six months interval following SRS. Patients in both groups were regularly in six months interval recommended to their oncologist to a liver ultrasound, abdominal ultrasound, liver function test, brain CT, chest X-ray to confirm or exclude the presence of metastases. In individual cases they were recom-

In the period 2001–2008 a total number of 84 patients with intermediate or large

Five patients treated in the first step with SRS required subsequent enucleation due to the complications - secondary neovascular glaucoma. Three patients of this subgroup underwent pars plana vitrectomy with endoresection of the tumors plus silicon oil, but the enucleation was necessary due to the complication - relapse of

Histopathologically in the group of enucleated eyes after SRS due to complications in four patients with malignant melanoma of the mixed cell type, in two cases

In the group of primary enucleated eyes, there were four findings of an epithelioid-cell type, one case of a nodular type, as well as 10 cases of both, a mixed-cell

an epithelioid type, and in one case a spindle-cell type A was confirmed.

type and 29 cases of a spindle-cell type (A or B) melanoma.

(0,4 - 0,8), in group of enucleated patients 1,1 cm3

uveal melanoma were treated with either radical surgical removal of the whole eyeball (enucleation), or SRS. In a group of 40 patients who underwent SRS there were 22 male and 18 female - the total median age was 55 years; the median age of female was 54 years and 58 years of male. In a group of 44 patients with enucleated eyes the median age was 68.5 year. In the group there were 21 males (median age 64), and 23 females (median age 73). The median tumor volume in group of ste-

0,30103\* number of months Td =

<sup>10</sup> ( ) <sup>10</sup> ( )

log final volume – log starting volume (2)

<sup>π</sup> =∗ ∗ ∗ (1)

**22**

The age and tumor volume are important explanatory variables (termed covariates) that are assumed to be associated with survival and need to be incorporated in the model. Results on logistic regression confirmed significance of the model with the predictors age and tumor volume (P = 0.01). The tumor volume was a significant unique predictor (P = 0.035); age with its borderline probability value of 0.1 could be assumed as possibly associated with the outcome. The estimator of survival rates adjusted for these predictors was constructed based on Cox's regression model which examines the relationship between survival and both predictors.
