Ординатура / Офтальмология / Английские материалы / Orbital Tumors Diagnosis and Treatment_Karcioglu_2005

The anatomy of the orbit provides unique challenges for radiation therapy. By definition, orbital tumors occur in the space between the

eyeball and bony orbital walls. While the bones, muscle, and fat within the orbit can tolerate a relatively high radiation dose, components of the eye and lacrimal system are more radiation sensitive. Side effects such as dry eye, eyelash loss, cataract, neovascular glaucoma, radiation retinopathy, and optic neuropathy are all potential complications of orbital radiation therapy.1–3, 4–9 Therefore, though tumor control is the primary goal, when possible treatment plans are shaped to avoid the retina, lacrimal system, and natural lens. Radiation therapy continues to play an integral role in the treatment of both malignant and benign orbital tumors.

TECHNIQUES

External beam radiation therapy (EBRT) is currently delivered utilizing photons ( -rays or x-rays), or particles (e.g., protons and neutrons) with linear accelerators doing the bulk of the work.10–21 The linear accelerator creates energetic photons by using highfrequency electromagnetic waves to accelerate electrons through a microwave accelerator structure. The high-energy electron beam can be used either by itself to treat superficial tumors or to strike a high-Z target to produce a bremsstrahlung x-ray beam (for treating deep-seated tumors).21–24

Charged particles (e.g., protons) have also been used in the treatment of orbital tumors.12,25,26 The absorption characteristics of charged particles allow radiation treatment with dose distributions that are highly conformal with target-volume shapes. It is important to note that protons travel relatively straight paths through tissue, slowing as a result of contacts with surrounding electrons and owing to occasional nuclear interactions. There is a fairly constant dose over the entry “plateau” followed by a sharp Bragg peak in dose at the end of the particles’ path. Dose at the peak is typically four times that at the plateau in laboratory situations. In clinical practice, techniques that spread out each Bragg peak to cover a tumor target volume reduce the plateau-to-peak ratio (increase the entry dose).3,22,23

Neutron beam radiation therapy is being investigated in the treatment of orbital tumors refractory to current radiation modalities.13,27 Modern neutron therapy machines produce neutron beams with depth– dose characteristics equivalent to 6 MV x-rays.11 Fission neutrons, although suitable for neutron capture therapy, cannot be used for teletherapy because of their low energy and poor penetration. Therefore, the proton Berylium (pBe) reaction is the most commonly used in modern isocentric neutron therapy machines.22,23

ORBITAL DISEASES

Vascular Tumors

Infantile hemangiomas can occur in the eyelids and orbit (Figure 33.1). When they occur in the eyelids, they can cover the visual axis, deviate the eye, and induce amblyopia. When posterior to the eye, these tumors can also produce proptosis, corneal exposure, and optic nerve compression. Though capillary hemangiomas are radiation sensitive (5–7.5 Gy in two to three fractions), those not causing optic nerve compression, amblyopia, or strabismus can be watched over 3 to 4 years for spontaneous regression or treated with intralesional steroids.28–32 Because of concerns about secondary carcinogenesis and long-term effects of irradiation, we consider radiotherapy for infantile hemangiomas only when other treatments have failed.31,32

In contrast, radiation therapy for Kaposi sarcoma is very effective.33 Here radiation is typically given to older patients for localized disease (vs systemic chemotherapy for systemic manifestations). Typically, electron beam radiation is used to limit penetration.33

Lymphoid Tumors

Lymphoid tumors can present in the orbit, eyelids, and conjunctiva (see Chapter 13). They can be divided into atypical lymphoid hyperplasia (pseudolymphoma), and lymphomas (Figure 33.2). Observation, resection, steroid therapy, antibiotics, and radiation therapy have been employed for local control. Each lesion is treated differently, but all have been noted to be relatively

FIGURE 33.1. Orbital hemangioma of childhood involving the eyelids and orbit. (Courtesy of Dr. Barrett Haik, Memphis, Tennessee.)

radiation sensitive. In general, the more benignappearing tumors tend to respond less dramatically than malignant lesions.10,15,34,35

Radiation therapy has been reported to consist of a single exposure of 8 Gy through an anterior portal, to a more typical 20 to 25 Gy (in 10 to 14 daily fractions) for MALTomas and benign lymphoid hyperplasia. Malignant lymphomas have been treated to as much as 35 to 45 Gy (in 18–24 fractions). Bolek et al. reported a 95% local control rate (at a median 25 Gy external beam radiation therapy).10,36

Thyroid-Related Ophthalmopathy

Thyroid-related “Graves” ophthalmopathy can occur in hyperthyroid, euthyroid, and hypothyroid patients. Indications for radiation include progressive exophthalmos, corneal exposure, and optic nerve compression (typically with vasculopathy). In practice, steroid therapy is typically a first-line treatment followed by radiation or surgery as needed. Radiation is typically applied via a single lateral portal to a dose of 20 Gy in 10 to 12 fractions.16,37 Electrons (12–15 MeV) may be preferred in that they minimize treatment of the fellow eye and orbit, although the dose to the involved orbit is less homogeneous. Sandler and associates reported that 71% of patients receiving doses in this range required no further steroid treatment or surgical decompression.38 The main prognostic factor for failure was radiation at less than 6 months from the time of onset of ophthalmopathy. There is now controversy about the efficacy of radiation for thyroidrelated orbitopathy.39,40

Conjunctival, Eyelid, and Sinus Tumors

Eyelid, adnexal, and sinus tumors can invade the orbit, making local resection difficult or impossible.41–45 In these cases, adjuvant radiation therapy can be used

to treat the nonresectable margins.41,45 Radiation is typically done with photon-based external beam therapy. Adjuvant chemoreduction of orbital tumors prior to radiation has also been tried.41,46 The doses required for treatment of basal cell, squamous cell, and malignant melanoma typically exceeds the tolerance of the eye and lacrimal system (45–60 Gy).47–49 Therefore, techniques utilizing protective eye shields, intensitymodulated radiation therapy, and brachytherapy boosts have been employed.48 External beam radiation is also used for presumed residual microscopic disease (after resection of the primary tumor).

Sebaceous Carcinoma of the Meibomian Gland

Though it occurs in less than 5% of eyelid tumors, sebaceous carcinoma has been reported to carry a significant mortality rate. This is thought to result from its tendency toward pagetoid spread and multifocality. Radiation therapy has been used in treatment of selected cases when surgery has failed or when negative surgical margins are not obtainable.50 Sebaceous carcinoma is a relatively radiation resistant tumor, and doses in excess of 60 to 65 Gy (in 2 Gy daily fractions) are required. Pardo et al. reported a large series of patients treated for nonresectable orbital sebaceous carcinoma or for palliation.51,52

Meningiomas

Orbital meningiomas may arise from the intracranial cavity, optic nerve, paranasal sinuses, or (rarely) the orbital soft tissues.53,54 These slow-growing tumors tend to present by compression or displacement of orbital tissues. Intracranial meningiomas are most likely to cause bilateral vision loss, while optic nerve sheath

FIGURE 33.2. This case of biopsy proven bilateral orbital lymphoma was treated with external beam radiation therapy (40 Gy) to both orbits. Axial CT image demonstrates bilateral soft tissue densities centered posterior to each globe.

meningiomas more typically present early with compressive optic neuropathy. Most intracranial meningiomas that affect the orbit arise from the dura of the sphenoid bone.54

Total surgical excision is recommended after progression has been documented.55 Radiation therapy is typically employed when surgical margins are not possible, when the tumor is recurrent, or when the remaining sighted eye is affected (vision has been lost in the fellow eye).54,56–61 When radiation is used as an adjuvant to resection, postoperative doses of 50 to 54 Gy over 5 to 6 weeks are typical. Conformal fields are used to avoid normal brain tissue. As primary treatment, doses of 60 Gy in 33 fractions can be employed.62 At these levels, the long-term prognosis for vision is poor.

Orbital Metastasis

The incidence of orbital metastasis is difficult to quantify. Typically the goals of treatment for orbital metastasis are palliative (to improve the patient’s quality of life by salvaging vision and the cosmetic use of the globe). We treat to avoid the development of a blind and painful eye that may require enucleation or exenteration. Treatment options include observation, systemic drug therapy, EBRT, brachytherapy, exenteration, and stereotactic radiosurgery.

For decades, EBRT has been employed in the treatment of orbital tumors.63–66 Typically palliative, techniques vary depending on the proximity of radiationsensitive structures to the orbital tumor (Figure 33.3). Normal tissue tolerance and a patient’s long-term prognosis will often guide the selection of technique, dose, and dose rate.

Patients with orbital metastasis may have a slightly prolonged median survival. Therefore, it is reasonable to select from among such lens-sparing techniques as right-angled wedged fields, direct lateral field posterior to the lens (where the anterior margin

FIGURE 33.3. A three-dimensional reconstruction of a computed radiographic tomogram reveals the position of a metastatic adenocarcinoma in the medial portion of the right orbit (arrow).

is positioned at the temporal canthus, posterior to the lens), oblique lateral field with lens shielding, and anterior field with lens block. Rectangular field sizes typically range from 3 to 5 cm. Typical energies range from 4 to 16 MeV for electrons or 4 to 15 MeV for photons. Higher energy photons are used to generate greater depth within the orbit, sinuses, or brain.

Commonly accepted doses range from 30 to 40 Gy (typically delivered in 2–3 Gy daily fractions) over 2 to 4 weeks. There is considerable controversy about the correct dose. A dose escalation study would be invaluable.

Optic Glioma

Optic nerve glioma typically affects children under 15 years of age and occurs as only 1% of all central nervous system tumors. There may be a genetic component with a higher incidence in patients with neurofibromatosis and in females. Optic nerve gliomas grow slowly, are initially asymptomatic, and involve the optic chiasm in 50% of cases.67 When symptoms occur, they include exophthalmos, visual field defects, nystagmus, optic atrophy, and intracranial signs (with hypothalamic involvement).68

Treatment should include complete surgical excision (when possible); positive margins are treated aggressively.26 Radiation is used when intracranial or progressive symptoms are evident. Multiport beam arrangements are typically used to minimize the entry dose and concentrate the radiation within the targeted zone.12,69 Orbital tumors are typically treated with a wedged-pair external (photon beam) technique. Doses of 45 to 50 Gy (in daily fractions of 1.8–2.0 Gy) are typically employed.26,70 To avoid the side effects of radiation in young children, chemotherapy is considered to be an alternative.68

Numerous reports document the value of radiation for patients with optic glioma. Long-term survival rates have been reported to be as high as 80 to 100%. Khafaga et al. reported on 50 children with optic glioma.71 Sixteen were treated with primary radiation therapy to a median dose of 50 Gy. The overall 10year, relapse-free survival was as high as 87.5% at 5 years and 75% at 10 years. Overall, patients with tumors affecting the anterior visual pathway fared better than those with posterior tumors.71

Rhabdomyosarcoma

Rhabdomyosarcoma is the most common primary malignancy of the orbit in children. Parents might first notice ptosis followed by rapid progressive proptosis. Most tumors are located in the superonasal orbit, with imaging showing a tumor adjacent or attached to one of the ocular muscles. When the tumor has metastasized to the brain or lung, prognosis is poor. But for

lesions localized to the orbit, a combination of biopsy, chemotherapy, and irradiation currently offers a 90% survival rate (Figure 33.4).72,73

Sagerman et al. and Schulla et al. have suggested that a minimum tumor dose should be 45 to 50 Gy over 5 to 7 weeks.17,18 Lens blocks are typically placed to protect the anterior segment (when possible). Though survival has been excellent, doses in this range typically develop late radiation side effects.5

Lacrimal Gland Tumors

The high mortality associated with lacrimal gland tumors is associated with the difficulty of obtaining negative surgical margins and the tendency of certain tumors (e.g., adenoid cystic carcinoma of the lacrimal gland) to invade surrounding tissues.74

Adenoid cystic carcinoma is considered to be radiation resistant. Most believe that the orbit should be irradiated only after resection, to reduce the incidence of postoperative recurrences.25,43,75–77 If the tumor is removed within a well-defined capsule, recurrence is uncommon and postoperative radiation may be deferred. Many such tumors have been subjected to biopsy or extend outside the capsule prior to surgery. In these cases, orbital exenteration with secondary EBRT is employed.

Recent investigations of brachytherapy boosts to the tumor bed together with complete irradiation of the orbit has allowed for organ (eye) preservation. Others advocate neutron radiation therapy for adenoid cystic carcinoma of the lacrimal gland (Figure 33.5). Other orbital tumors of the lacrimal fossa include benign mixed tumor, adenocarcinoma, sarcoidosis of the lacrimal gland, and inflammatory diseases.

Orbital Pseudotumor

Inflammatory tumors of the orbit can mimic neoplasia and are termed “orbital pseudotumor.” Typically,

A

45o

45o

L

21Gy

19.95Gy

18.9 Gy

14.7 Gy

10.5 Gy

6.3 Gy

Wedged Pair Isodose Plan for Adenoid

BCystic Carcinoma of the Right Orbit

FIGURE 33.5. (A) A patient with adenoid cystic carcinoma of the lacrimal gland being treated at the University of Washington Fast Neutron Radiotherapy facility. (Courtesy of Dr. George E. Laramore, Seattle.) The isocentric gantry and multileaf collimator make it possible to use angled, shaped fields that spare the optic chiasm and contralateral eye. (B) An isodose curve for a 66 MeV fast neutron beam in treatment of an adenoid cystic carcinoma of the lacrimal gland. (Courtesy of Fermilab Visual Media Services and Dr. Arlene Lennox.)

biopsy samples are removed from these orbits to establish the diagnosis. Blood tests and radiographic images are obtained to rule out known infectious, inflammatory, and neoplastic tumors.78,79

Most patients found to have idiopathic orbital pseudotumor are treated with systemic steroids or immunosuppressive or cytotoxic-immunosuppressive agents.46 Radiation is also employed to suppress the immune reaction and secondary fibrosis.80–85 The author has found the subset of fibrosing pseudotumors to be less radiation sensitive (Figure 33.6). They occasionally require exenteration surgery to prevent extension into the cavernous sinus.

INTRAOCULAR TUMORS

THAT REQUIRE ORBITAL

RADIATION THERAPY

Uveal Metastasis

The most common intraocular cancer, uveal metastasis, can be treated with EBRT.86 Although these metastases are mostly derived from breast cancer in women and from lung cancer in men, other common primary sites include the colon, kidney, prostate, and thyroid.87,88 Most intraocular metastases are asymptomatic, go undiagnosed, and are left untreated.

In clinical practice, most patients are examined when they develop involvement of the macular retina and/or visual symptoms. In these cases, prompt treatment with EBRT (25–40 Gy in 2–3 Gy daily fractions) typically offers the best chance for preservation of vision.89,90

It is important to have the ophthalmic oncologist determine whether both eyes are affected and to ascertain whether tumor is present in the anterior chamber. Then the radiation oncologist will know whether to treat one or both eyes and whether a shield can be

FIGURE 33.6. This patient with fibrosing orbital pseudotumor with secondary proptosis failed to exhibit any response to EBRT (20 Gy) delivered in 11 fractions after a surgical debulking procedure.

placed to spare the lens. Uveal metastases should not be treated until the primary or cell type is known. In some cases, the intraocular tumor may be the only source of tissue to indicate the source of cancer. In practice, most patients with uveal metastasis are found to have multiorgan disease or a history of metastatic cancer.

Since both breast and lung cancer are radiation sensitive, most patients with uveal metastasis can be treated with relatively low-dose external beam radiation therapy.89–92 Ophthalmic plaque irradiation or enucleations are occasionally required for radiation resistant tumors (e.g., renal metastasis) and for uncontrollable glaucoma secondary to anterior segment metastasis.20,87,88,93

The author has noted that current improvements in survival among patients with uveal metastases have been accompanied by an increase in the incidence of secondary radiation retinopathy and local tumor recurrence. Though rare, both are becoming more common, which suggests divergent needs to lower the dose (or dose volume) to protect against radiation retinopathy and to increase the dose to prevent tumor recurrence.

Extrascleral Extension of Choroidal Melanoma

Gross extrascleral extension of uveal melanoma is rare, but microscopic evidence of intrascleral tumor and invasion of emissary veins has been found in as many as 50% of enucleated specimens.94 Studies suggest that when there is “gross” or visible evidence of extraocular tumor extension, patients have a worse prognosis for survival.95 On the other hand, massive extrascleral melanomatous extension with orbital invasion is often treated by exenteration with or without adjuvant radiation therapy.3,20

External beam radiotherapy is an alternative to exenteration for patients with extrascleral (orbital) extension of their uveal melanoma. Hykin studied 17 patients enucleated for choroidal melanoma with localized extrascleral extension whose tumor had not visibly extended into orbital tissues.95 In this study, patients received 50 Gy in 22 fractions within 2 months of enucleation. The actuarial melanomarelated survival rate was 51% at 5 years with one local orbital recurrence.95 Though this survival rate is comparable to that of patients with large melanomas treated by enucleation alone, orbital tumor margins are often difficult or impossible to obtain, and radiotherapy offers a treatment for residual microscopic melanoma cells. Clearly, most patients would prefer to undergo some form of treatment for their residual melanoma.

I typically offer postenucleation 50 Gy (in 1.8–2 Gy daily fractions) adjuvant external beam radiotherapy for patients noted to have encapsulated or well-defined

nodules of extrascleral extension present after enucleation surgery. When there are large areas of extrascleral spread, removal of all pigmented tissue followed by external beam radiotherapy for presumed microscopic orbital melanoma is prescribed (as a reasonable approach to obtaining definable treated-tumor margins). Such an approach offers a method to decrease the rate of recurrence with a result that is more cosmetically acceptable than orbital exenteration.

Retinoblastoma

Despite concerns of secondary carcinogenesis, EBRT continues to play an important role in the treatment of extrascleral and intraneural extension of retinoblastoma (Figure 33.7).46,96 Residual and recurrent orbital retinoblastoma is a significant risk factor for metastasis and typically is treated by a combination of systemic chemotherapy and external beam irradiation.46,97

The most common complication (with the lenssparing technique) of external beam irradiation for retinoblastoma is radiation retinopathy.7,98 First described by Stallard (following radon seed application for treatment of retinoblastoma), radiation retinopathy is characterized by retinal capillary microaneurysms, cotton-wool spots, retinal neovascularization, and vitreous hemorrhage.99 Other radiation complications include ischemic optic neuropathy and neovascular glaucoma.100 Less common complications include dry eye and eyelash loss.2,100,101

In general, with schedules of 2 Gy daily fractions and long-term follow-up, radiation retinopathy has been reported to occur in as many as 10% of eyes dosed to 35 Gy (EBRT), in 66% of eyes treated to 45 Gy, and 100% of eyes given 80 Gy or more.2,7,98,101–103 On a histopathologic basis, the retinal vessels have been

FIGURE 33.7. Extrascleral extension of retinoblastoma (arrow) is a significant risk factor for metastasis and is treated by EBRT to the orbit after enucleation surgery.

shown to develop hyalinized walls, and the lumen may be partially or completely obliterated. Narrowing of the central retinal and ciliary arteries has also been observed.

Radiation optic neuropathy has been reported after high-dose EBRT and ophthalmic plaque radiation therapy. It is believed to be secondary to radiation vasculopathy.7,100,103

Growth retardation of irradiated orbital bones can result in significant facial malformations.100,104 Modern authors believe that the incidence of bony dysgenesis is less with modern megavoltage radiation techniques (in comparison to the older orthovoltage machines).6,7,98,106–108 In addition, doses for treatment of retinoblastoma have been reduced to 35 to 45 Gy.

Postlaminar optic nerve and orbital extension of retinoblastoma are known risk factors for metastasis and are typically treated with radiation therapy.97 In addition, the chemotherapeutic agents cisplatinum, etoposide, vincristine, and cyclophosphamide are often employed.46,96 Some centers add intrathecal methotrexate or craniospinal irradiation.46 Pradhan et al. treated 28 eyes with EBRT to the orbit for retinoblastoma extension. Nineteen patients were also given chemotherapy. Local control was maintained in 71% for a mean follow-up of 22.6 months.103

Sagerman et al. described a dose–response relationship demonstrating an increased risk of second malignant tumors with increasing radiation dose.101,109,110 This was confirmed by Alberti et al., who showed a 47.5% incidence at 16 years for second tumors within the radiation field in patients treated to 55 Gy or more versus a 5% incidence in those treated with smaller doses (p 0.0006).7,101

SIDE EFFECTS OF ORBITAL

RADIATION THERAPY

It was not long after the discovery of the x-ray that Chalupecky published his study on its effect on the eye.111 The eye was noted to be relatively radiation sensitive by Birch-Hirshfeld and Ammon, who reported the first radiation-induced cataract.112,113 Sagerman and Alberti have provided a relatively current review of the management of radiation effects on the eye and orbit.114

Eyelids

Skin changes associated with radiation therapy include acute erythema, depigmentation, atrophy, telangiectasias, hair loss, and ectropion or entropion of the eyelid.33,115,116 Radiation typically travels through the skin of the eyelids on its way to treat orbital tumors. Eyelid skin reacts like skin of other sites, but it is thinner and has less integument. The first reaction

is erythema (typically 2–4 weeks after starting treatment), followed by dry and moist desquamation (and rarely necrosis). Erythema is usually transient and disappears rapidly. Silver sulfadiazine cream can be helpful to treat the acute reaction and to prevent secondary infection.

Moist desquamation is more common after doses of 50 to 60 Gy (in 1.8–2.2 Gy daily fractions) over 5 to 6 weeks and also more common where superficial lesions break the skin. Healing is typically slow and may take up to 4 weeks. There is usually no resultant radiation-related scar unless high dose rates are used or secondary infection occurs.114

Cicatricial scarring can result in entropion or ectropion of the eyelids. Slowly progressive skin changes (which may appear over subsequent years) include thinning of the skin, depigmentation, and telangiectasias.114

Eyelash loss may be incomplete or complete depending on the dose and dose rate. It may occur with as little as 10 Gy but can be permanent with as little as 30 Gy. At more than 50 Gy, radiation has been used to produce permanent epilation in patients with trichiasis and secondary corneal disease. The tarsus and meibomian glands appear to tolerate doses in the range of 40 to 50 Gy.114

Lacrimal Apparatus and Dry Eye

The lacrimal gland, accessory lacrimal glands, punctum, and lacrimal sac make up the lacrimal apparatus. Radiation damage to the lacrimal glands can produce irreversible dry eye. Published studies indicate that doses in the range of 30 to 40 Gy can be delivered to the entire orbit without long-term keratitis sicca. Evidence of histopathologic atrophy of the lacrimal gland has been reported with single doses of 20 Gy and after 50 to 60 Gy given over a 6-week period.15 Parsons has reported symptomatic dry eye in 0% of patients treated with less than 30 Gy and in 100% of patients treated with more than 57 Gy (in standard fractions).114,117

Cornea, Lens, and Conjunctiva

Though direct corneal injury can result from highdose irradiation, most acute corneal toxicity results from loss of the tear film with secondary keratitis sicca. Fairly high doses of brachytherapy have been delivered to the cornea with no long-term se-

quelae.3,93,118,119

Cataracts are common complications of radiation therapy (Figure 33.8).120 Merriam and Focht have shown that as little as 2 Gy in a single fraction or 8 Gy in multiple fractions can induce cataract.9,121–123 Because cataracts are common in the elderly, studies on children with retinoblastoma are particularly

FIGURE 33.8. A posterior subcapsular (PSC) “radiation” cataract. Though PSC cataracts are most commonly associated with radiation, the author has also observed anterior subcapsular and progression of nuclear sclerotic cataracts immediately after irradiation.

telling. Schipper et al. delivered 45 Gy to the retina in 15 fractions in 5 weeks to 73 eyes of 39 children with retinoblastoma.7,19,98 Cataracts developed in 18 eyes (where Schipper noted that more than 1 mm of the posterior lens was included in the field). In this study, 8 Gy in 15 fractions was the minimum cataractogenic dose.

Sclera

The sclera is particularly resistant to radiation (like the cornea).119 No scleral radiation damage has been reported after external beam radiation doses of 60 Gy.114 In contrast, it has been my experience that the relatively high scleral brachytherapy doses (e.g., 600 Gy) can cause melting of the sclera.3 In practice, stron- tium-90 (90Sr) and ruthenium-106 (106Ru) are more likely to deliver much higher scleral doses than io- dine-125 (125I) or palladium-103 (103Pd) during plaque radiation therapy of intraocular tumors.3,124

Iris

Iritis has been reported with a single dose of 10 to 20 Gy, but more severe anterior uveitis has been observed with doses of 30 to 40 Gy (in 10 Gy fractions) and after 70 to 80 Gy (over 6–8 weeks).114,116 Radiation therapy can cause a dry eye–related corneal ulceration that can exacerbate iritis and iris neovascularization. Secondary glaucoma can also be related to iritis or iris neovascularization. Localized iris atrophy has been noted after plaque radiation therapy for iridociliary melanomas but not after external beam radiation therapy for orbital tumors.80,93,119,125

Retina, Choroid, and Optic Nerve

Radiation-related chorioretinal changes have generally been attributed to external beam radiation doses of 45

to 60 Gy. In the author’s experience, doses as low as 18 Gy can induce radiation retinopathy in patients with compromised chorioretinal circulation (e.g., due to diabetes) and those on chemotherapy (Figure 33.9). Patients receiving 35 to 50 Gy carry a moderate risk, and those getting more than 50 Gy will eventually develop some form of the disease.102 Radiation retinopathy is characterized by closure of small retinal capillaries, microinfarctions of the retina (cotton-wool spots), intraretinal hemorrhages, and neovascularization.114,126 Radiation retinopathy in the macula causes vision loss and blindness.

In addition, radiation can cause closure of the blood vessels within the optic nerve (radiation optic neuropathy).49,127 Parsons et al. described radiation optic neuropathy in 12 patients out of 131 whose optic nerves had been irradiated. No optic nerve that received less than 59 Gy developed optic neuropathy. Among optic nerves that received greater than 60 Gy, the 15-year actuarial risk of optic neuropathy was 11% when fraction size was less than 1.9 Gy per day and 47% with larger fractions.102

Hypothalamus and Pituitary Dysfunction

Hypothalamic and pituitary dysfunction is most often seen in children who have been irradiated for optic nerve glioma.26,68,71,128 Brauner et al. described the effect of optic nerve glioma and its radiation therapy in 21 patients treated with intracranial radiation to 55 Gy. Growth hormone deficiency was present in 1 patient before irradiation and in 21 afterward. Height loss was also noted.129 Clearly, patients irradiated for optic nerve gliomas should be monitored for hypothalamic and pituitary dysfunction.

FIGURE 33.9. Fundus photograph of radiation retinopathy. Note the vascular sheathing, ghost vessels, intraretinal exudation, intraretinal microangiopathy, and optic neuropathy.

FIGURE 33.10. For a brachytherapy boost, surgically placed catheters are afterloaded with radiation sources placed in an array within the orbit and tumor bed (after resection of an adenoid cystic carcinoma of the orbit).

NEW FRONTIERS IN ORBITAL

RADIATION THERAPY

Stereotactic Radiosurgery and the

“Gamma Knife”

Stereotactic techniques were developed to deliver relatively high radiation doses to small fixed targets.14,53,69 This is accomplished by creating multiple small entry beams that intersect within a threedimensional target volume. Gamma knife and stereotactic radiosurgery treatments are typically given in a single or a few large fractions using either a linear accelerator or a cobalt source (gamma knife). Using multiple entry beams, the “entry dose” radiation is divided among several locations outside the target zone. This technique was initially used in the treatment of intracranial malignancies, arteriovenous malformations, and acoustic neuromas.69 To date, no evidencebased results suggest that stereotactic radiosurgery is better than standard external beam techniques to prevent local recurrence or side effects related to radiation therapy of orbital tumors.

Brachytherapy Boost Technique

A new multidisciplinary approach to orbital radiation therapy is emerging to spare patients from exenteration surgery. Instead of removing the eyelids and orbital tissue as is done in exenteration, the bulk of the tumor is removed and a pattern of radiation (seeds or afterloaded sources) is placed temporarily (for several days) in the tumor bed (Figure 33.10). The seeds deposit a bolus of radiation where residual microscopic tumor cells are most likely to have escaped resection. Then, an additional (reduced) external beam radiation dose is delivered to the entire orbit including the tumor bed (boost volume). This overlay of radiation is

given to provide an additional margin of safety. The reduced external beam dose is still high, leaving the patient with a high probability of both ocular complications and organ preservation.

Indications for the brachytherapy boost technique are as follows:

1.When the standard EBRT dose would likely result in a blind and painful eye owing to radiation retinopathy, keratopathy, and/or neovascular glaucoma

2.When exenteration of the orbit is the only option but offers historically poor local control rates (e.g., adenoid cystic carcinoma)

3.When a recurrent tumor has already received maximal EBRT

4.When a patient refuses exenteration surgery

Our local control rates have been over 75% using this brachytherapy boost technique for selected cases of adenoid cystic carcinoma, orbital basal cell, and sebaceous carcinoma and hemangiopericytoma of the orbit.

Abramson et al. have used orbital brachytherapy in a case of recurrent orbital rhabdomyosarcoma.130 Tijl et al. used it for a recurrent hemangiopericytoma, and Sealy and Stannard have used it as an alternative to external beam irradiation of the orbit in retinoblas- toma.131–133 Bacskulin and Kim have developed applicators specifically for treating the orbit after enucleation or exenteration.134,135

CONCLUSIONS

Radiation therapy has played an important role in the management of benign and malignant orbital tumors, as well as sinus, intraocular, and adnexal tumors with orbital extension. Research on neutron therapy, stereotactic radiosurgery, and brachytherapy boost techniques appears promising for the goals of increasing local control and decreasing secondary radiation complications.

Acknowledgments This work was supported by The EyeCare Foundation, Inc., New York City.

The author thanks Drs. Anthony Berson and Madhavi Kurli for reviewing this chapter.

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