**5. 3D printed models of the intraocular melanoma for planning of stereotactic radiosurgery treatment**

Stereotactic radiosurgery (SRS) is a technically challenging therapeutic irradiating method. It complements or supplies (replaces) classic surgical intervention. It is used for single hightherapeutic irradiation dosage to an exact specified volume, while risk organs and structures are contemporary protected. A prerequisite for this method is a special software and hardware equipment of workstation and professional experiences of specialists of different fields (neurosurgeon trained in stereotactic radiosurgery, radiation oncologist, ophthalmologist, radiologist, clinical physicist and registered nurse trained for radiosurgery).

The surgical operation involves the selection and preparation of the patient prior to surgery intervention, which consists from processing of health and imaging documentation of the patient. It is necessary to analyze the patient's disease and the patient's indication by the Indicating Commission (BTB). The Commission decides about the indication in which the members are neurosurgeons trained in radiosurgery, radiation oncologists, ophthalmologists, radiologists and clinical physicists. The progress committee decides on the basis of a recommendation on the appropriateness of an eye globe oncological surgery, the listed group of experts will evaluate the suitability of classical surgery, stereotactic radiosurgery operations, fractionated stereotactic radiosurgery, intensity modulated radiotherapy (IMRT) or three-dimensional comfort radiotherapy (3D-CRT).

Patients indicated for stereotactic radiosurgical intervention are hospitalized for inpatient care. This is a short-term hospitalization, most often lasts 3 days. The patient admission involves interview with the patient with detailed information about the course of operation, performance benefits as well as acquaintance with potential acute and late postoperative complications (adverse effects). The patient subscribes the informed consent.

Patient's admission in hospital bed department (clinical care) is carried out 2 days before the surgery. A detailed clinical examination will be done, brought documentation is studied, the missing examinations are completed and a preoperative pharmacotherapy treatment in hospital bed department is placed on. Findings, surgery and documentation will be inserted into the hospital information system. The day before the stereotactic radiosurgery (SRS) will be initiated the patient's pharmacotherapy—premedication. Within the preoperative premedication, the patient is receiving the antiedematotic therapy, which intensity depends on the size, location of the lesion and the presence of edema. The presented therapy is continued in the day of surgery and the following day.

Each patient's record includes the tumor size, tumor volume, the maximum height of the tumor, age and gender, the presence and the extent of secondary retinal detachment, and the possible signs of extrascleral extension. The very important step of SRS is tumor volume calculation in each patient directly by results of CT and MRI examination. It is the basic step involved to the stereotactic planning scheme.

Software for target verification, which is used in conjunction with stereotactic frame system and imaging (CT, MRI) modalities, is used to determine the coordinates of the lesion (tumor)

The radiosurgical treatment is calculated by physicist by planning system for treatment (TPS) with the 3-D dose distribution. The result is superimposed onto the certain patient's anatomical status to get an appropriate radiation dose for tumor and also for risk structures (optic

Stereotactic radiosurgery (SRS) is a technically challenging therapeutic irradiating method. It complements or supplies (replaces) classic surgical intervention. It is used for single hightherapeutic irradiation dosage to an exact specified volume, while risk organs and structures are contemporary protected. A prerequisite for this method is a special software and hardware equipment of workstation and professional experiences of specialists of different fields (neurosurgeon trained in stereotactic radiosurgery, radiation oncologist, ophthalmologist,

The surgical operation involves the selection and preparation of the patient prior to surgery intervention, which consists from processing of health and imaging documentation of the patient. It is necessary to analyze the patient's disease and the patient's indication by the Indicating Commission (BTB). The Commission decides about the indication in which the members are neurosurgeons trained in radiosurgery, radiation oncologists, ophthalmologists, radiologists and clinical physicists. The progress committee decides on the basis of a recommendation on the appropriateness of an eye globe oncological surgery, the listed group of experts will evaluate the suitability of classical surgery, stereotactic radiosurgery operations, fractionated stereotactic radiosurgery, intensity modulated radiotherapy (IMRT) or three-dimensional comfort

Patients indicated for stereotactic radiosurgical intervention are hospitalized for inpatient care. This is a short-term hospitalization, most often lasts 3 days. The patient admission involves interview with the patient with detailed information about the course of operation, performance benefits as well as acquaintance with potential acute and late postoperative com-

Patient's admission in hospital bed department (clinical care) is carried out 2 days before the surgery. A detailed clinical examination will be done, brought documentation is studied, the missing examinations are completed and a preoperative pharmacotherapy treatment in hospital bed department is placed on. Findings, surgery and documentation will be inserted into the hospital information system. The day before the stereotactic radiosurgery (SRS) will be initiated the patient's pharmacotherapy—premedication. Within the preoperative premedication, the patient is receiving the antiedematotic therapy, which intensity depends on the size, location of the lesion and the presence of edema. The presented therapy is continued in

**5. 3D printed models of the intraocular melanoma for planning of** 

radiologist, clinical physicist and registered nurse trained for radiosurgery).

plications (adverse effects). The patient subscribes the informed consent.

target into the stereotactic frame reference system.

164 3D Printing

**stereotactic radiosurgery treatment**

radiotherapy (3D-CRT).

the day of surgery and the following day.

nerve, lens, chism, etc.) and radiosurgical procedure [12–14].

Immobilization of the affected eye globe for stereotactic irradiation is achieved by mechanical fixation of the sutures to the Leibinger stereotactic frame. Vicryl sutures from four extraocular muscles (m. rect. sup., m. rect. inf, m. medialis and m. temp.) are placed through the conjunctiva and the lids. The stereotactic frame is fixed to the head, and the sutures are tied to the stereotactic frame. The day after stereotactic irradiation is the patient examined by an ophthalmologist (the slit lamp examination, ophthalmoscopy, and intraocular pressure measuring) and is released for home treatment, he gets antibiotic and corticosteroid eye drops.

In software for data segmentation (3D Slicer, freeware version 4.5.0+), virtual 3D models of the eye globe were created. Imported data set came from CT (computer tomography) with accuracy 1 mm scan thickness. Visualized and created model has basic anatomical structures like globe, corneal segment, lens, optic nerve and tumor mass inside the created 3D model of eye globe. Extraocular muscles and vitreous body are not included in the model. Eye globe anatomical structures—lens and optic nerve—are very important for orientation. They are necessary visible points at the small printed 3D model because the model itself has the same size as the normal human eye globe—from anterior to posterior part is 24 mm. Virtual 3D model of the eye globe is then sliced. Additional support is calculated. The next step can be model preparing for printing in 3D printing slicing software Simplify3D. After creating and refining our models, for process of 3D printing, we used fused deposition modeling (FDM) technology. The 3D models in our study are printed on ZYYX 3D Printer by Magicfirm LLC using one extruder heated to 215–230°C. Chosen material is polylactic acid (PLA) with low deformability during rapid temperature changes and contributing high accuracy of the model. One layer of the model thickness of in vertical line is 100 μm. This provided an ideal proportion of a ratio between accuracy and velocity of a printing process. Estimated time of printing process in 3D printer is usually from 15 to 30 min per one model (**Figures 2** and **3**).

**Figure 2.** 3D printed model of the eye globe with intraocular tumor—arrow shows the tumor mass (melanoma).

of melanoma close to the optic disc, juxtapapillary choroidal melanoma, this stereotactic radiotherapy offers another non-invasive alternative to radical surgery—enucleation—or to

3D Printing Planning Stereotactic Radiosurgery in Uveal Melanoma Patients

http://dx.doi.org/10.5772/intechopen.79032

167

The gamma knife radiosurgery and SRS are evaluated as the alternative in patients with large tumors (stage T3) which are too large for conventional brachytherapy. Studies confirm with their results that treatment with SRS may also be recommended in specific cases of uveal melanoma

Interesting is the comparison with other forms of radiotherapy. Typical side effects of radiation from SRT include: radiation retinopathy, cataract development, secondary neovascular glaucoma, and opticopathy. The result may be loss of visual acuity. In the worst cases, secondary enucleation is necessary. However, even with these risks, SRS and SRT are among the most effective treatments for uveal melanoma. The SRS method belongs to one of the new methods; therefore, it is needed to record and compare results with other methods by a multicenter studies. Treatment of uveal melanoma using a combination of stereotactic photon therapy and CT and MRI scans is considered very safe and accurate and guarantees excellent local control. A reduction in visual acuity was observed in a large number of patients. This condition was a result of the unfavorable size and position of the tumor near critical structures, such as the optic nerve and the macula. Obtained patient observations confirmed that stereotactic irradiation for uveal melanoma using LINAC is feasible and well tolerated. This treatment preserves the patient's eye globe and is offered in the case of moderate or unfavorably localized uveal

Optical neuropathy may rarely occur after radiosurgical treatment of lesions that are located near visual pathways. A highly effective method in these cases for the treatment of small and moderate uveal melanomas is a one-step LINAC-based SRS with a single dose of 35.0 Gy. This treatment involves the use of a mechanical immobilization system with four

3D printing has gained its new role in ophthalmology by confirming and demonstrating the real shape and size of tumors by creation of accurate 3D models. With current advances of precise modeling process, material to build the 3D models can be printed at 600 μm resolution. This approach is already in use within the other fields of ophthalmological surgery. An example is the use in cataract surgery—development of Cana's Ring (CR) and a special expansion

Another example of the practical use of 3D printing in ophthalmology is the eye fundus examination. The correct collocation of the patient, the smartphone and the Volk spherical lens is extremely important. To secure the correct position, a 3D printed adapter from plastic

Different studies evaluated the efficacy of stereotactic radiosurgery as a treatment modality for uveal melanoma. Tumor control rates 5 and 10 years after therapy were over 90% in several studies. Results of these studies did not show a significant difference between radiogenic side

was created to connect the lens with the smartphone together [20].

brachytherapy treatment with high tumor control rate [9, 15].

[16, 17].

melanomas [5].

stitches [18].

device for 3D pupils [19].

**Figure 3.** MRI scan of eye globe with uveal melanoma (choroidal melanoma stage T1b)—red color, lens—green color, optic nerve—yellow color.

Stereotactic one-day session therapy of intraocular uveal melanoma, based on CT and MRI images, is a precise treatment option and safe. The results of the treatment were summarized in the study and demonstrated that the local control was excellent. Among other results, they have further shown that in patients with an unfavorable tumor size and localization near critical structures such as the optic nerve, lens and macula, visual acuity has been reduced. In the patient's follow-up after 6 months, visual acuity was evaluated. The study included a group of 77 patients in whom 85.5% of patients had a visual acuity of 0.1 or higher before radiotherapy. In the cases with intraocular uveal melanoma, these patients may be recommended to undergo LINAC-based one-day session stereotactic irradiation, especially in the cases of medium-sized uveal melanomas. Important advantage of this treatment method is preserving of the eye globe [5, 6].

### **6. Discussion**

In the treatment of the uveal melanoma patients, stereotactic irradiation has been used over 20 years. Over time, the therapeutic single dose decreased and stabilized at 35.0 Gy. In the studies, this reduction did not lead to tumor control reduction. The studies also documented that hypofractionated treatment is beneficial. This treatment uses a very large fraction to stabilize the intraocular uveal melanoma cell lines.

In the last years, additional interest in fractionated stereotactic radiotherapy (SRT) was obtained. Feasible fractionation advantage is used by Linear accelerators (LINAC). Nowadays, therapeutic schemes for hypofractionated therapy for five fractions with total doses from 50.0 to 70.0 Gy are employed by most LINAC studies. Different studies report local tumor with control rates more than 90% by the efficacy of SRT in uveal melanoma treatment. In treatment of melanoma close to the optic disc, juxtapapillary choroidal melanoma, this stereotactic radiotherapy offers another non-invasive alternative to radical surgery—enucleation—or to brachytherapy treatment with high tumor control rate [9, 15].

The gamma knife radiosurgery and SRS are evaluated as the alternative in patients with large tumors (stage T3) which are too large for conventional brachytherapy. Studies confirm with their results that treatment with SRS may also be recommended in specific cases of uveal melanoma [16, 17].

Interesting is the comparison with other forms of radiotherapy. Typical side effects of radiation from SRT include: radiation retinopathy, cataract development, secondary neovascular glaucoma, and opticopathy. The result may be loss of visual acuity. In the worst cases, secondary enucleation is necessary. However, even with these risks, SRS and SRT are among the most effective treatments for uveal melanoma. The SRS method belongs to one of the new methods; therefore, it is needed to record and compare results with other methods by a multicenter studies. Treatment of uveal melanoma using a combination of stereotactic photon therapy and CT and MRI scans is considered very safe and accurate and guarantees excellent local control. A reduction in visual acuity was observed in a large number of patients. This condition was a result of the unfavorable size and position of the tumor near critical structures, such as the optic nerve and the macula. Obtained patient observations confirmed that stereotactic irradiation for uveal melanoma using LINAC is feasible and well tolerated. This treatment preserves the patient's eye globe and is offered in the case of moderate or unfavorably localized uveal melanomas [5].

**Figure 3.** MRI scan of eye globe with uveal melanoma (choroidal melanoma stage T1b)—red color, lens—green color,

Stereotactic one-day session therapy of intraocular uveal melanoma, based on CT and MRI images, is a precise treatment option and safe. The results of the treatment were summarized in the study and demonstrated that the local control was excellent. Among other results, they have further shown that in patients with an unfavorable tumor size and localization near critical structures such as the optic nerve, lens and macula, visual acuity has been reduced. In the patient's follow-up after 6 months, visual acuity was evaluated. The study included a group of 77 patients in whom 85.5% of patients had a visual acuity of 0.1 or higher before radiotherapy. In the cases with intraocular uveal melanoma, these patients may be recommended to undergo LINAC-based one-day session stereotactic irradiation, especially in the cases of medium-sized uveal melanomas. Important advantage of this treatment method is

In the treatment of the uveal melanoma patients, stereotactic irradiation has been used over 20 years. Over time, the therapeutic single dose decreased and stabilized at 35.0 Gy. In the studies, this reduction did not lead to tumor control reduction. The studies also documented that hypofractionated treatment is beneficial. This treatment uses a very large fraction to sta-

In the last years, additional interest in fractionated stereotactic radiotherapy (SRT) was obtained. Feasible fractionation advantage is used by Linear accelerators (LINAC). Nowadays, therapeutic schemes for hypofractionated therapy for five fractions with total doses from 50.0 to 70.0 Gy are employed by most LINAC studies. Different studies report local tumor with control rates more than 90% by the efficacy of SRT in uveal melanoma treatment. In treatment

optic nerve—yellow color.

166 3D Printing

preserving of the eye globe [5, 6].

bilize the intraocular uveal melanoma cell lines.

**6. Discussion**

Optical neuropathy may rarely occur after radiosurgical treatment of lesions that are located near visual pathways. A highly effective method in these cases for the treatment of small and moderate uveal melanomas is a one-step LINAC-based SRS with a single dose of 35.0 Gy. This treatment involves the use of a mechanical immobilization system with four stitches [18].

3D printing has gained its new role in ophthalmology by confirming and demonstrating the real shape and size of tumors by creation of accurate 3D models. With current advances of precise modeling process, material to build the 3D models can be printed at 600 μm resolution.

This approach is already in use within the other fields of ophthalmological surgery. An example is the use in cataract surgery—development of Cana's Ring (CR) and a special expansion device for 3D pupils [19].

Another example of the practical use of 3D printing in ophthalmology is the eye fundus examination. The correct collocation of the patient, the smartphone and the Volk spherical lens is extremely important. To secure the correct position, a 3D printed adapter from plastic was created to connect the lens with the smartphone together [20].

Different studies evaluated the efficacy of stereotactic radiosurgery as a treatment modality for uveal melanoma. Tumor control rates 5 and 10 years after therapy were over 90% in several studies. Results of these studies did not show a significant difference between radiogenic side effects of SRS and other forms of radiotherapy. Majority of visual acuity decline and necessity of secondary enucleation are neovascular glaucoma. Radiation therapy of stereotactic photon beams for the treatment of intraocular melanoma is considered effective nowadays. However, it is still recommended for future studies and follow-up actions to focus on finding optimal treatment modalities [21].

**Author details**

Alena Furdova1

Bratislava, Slovakia

Bratislava, Slovakia

14, 2018]

**References**

Slovakia

\*, Adriana Furdova1

\*Address all correspondence to: alikafurdova@gmail.com

University College of Health and Social Work, Bratislava, Slovakia

macology *&* Therapeutics. Oct 2014;**39**(10):704-711

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Practice. Jan 1, 2018;**19**(1):1-2

, Miron Sramka2

1 Department of Ophthalmology, Faculty of Medicine, Comenius University, Bratislava,

2 Department of Stereotactic Radiosurgery, St. Elisabeth Cancer Institute, St. Elisabeth

3 Department of Information Systems, Faculty of Management, Comenius University,

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[4] Huang W, Zhang X. 3D printing: Print the future of ophthalmology. Investigative Ophthal-

[5] Furdová A, Sramka M, Thurzo A, Furdová A. Early experiences of planning stereotactic radiosurgery using 3D printed models of eyes with uveal melanomas. Clinical

[6] Furdová A, Furdová A, Thurzo A, Šramka M, Chorvát M, Králik G. Possibility of 3D printing in ophthalmology—first experiences by stereotactic radiosurgery planning scheme of intraocular tumor. Ceská a Slovenská Oftalmologie. Fall 2016;**72**(3):80-84 [7] Shields JA, Shields CL. Intraocular Tumors: An Atlas and Textbook. Philadelphia, Pa.:

4 Department of Medical Physics, Faculty of Medicine, Slovak Medical University,

, Robert Furda<sup>3</sup>

3D Printing Planning Stereotactic Radiosurgery in Uveal Melanoma Patients

and Gabriel Kralik<sup>4</sup>

http://dx.doi.org/10.5772/intechopen.79032

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3D printed model of eye globe with tumorous mass is due to our experience helpful during the stereotactic planning process. Planning of stereotactic radiosurgery is based on fusion of CT and MRI data. Understanding of the collocation of all the structures of the eye globe with critical structures inside, such as lens, optic disc and the tumor size and its location, is a basic condition for the planning software.

By introducing a new 3D modality for visualization of the eye globe with the tumor, we provided real model of the eye globe for the specialists, which enabled them increase effectiveness of the planning process during the stereotactic radiosurgery. Virtual 3D model can be seen on computer only, but real printed 3D model of the eye globe held by the physician and physicist in their hands gives them a better perspective of the real situation inside the eye globe, like the size, the distance of the tumor to critical structures, the lens, optic disc and optic nerve [5].
