Ординатура / Офтальмология / Английские материалы / Ocular Oncology_Albert, Polans_2003

The key to successful treatment of a tumor with an ocular plaque is its accurate placement. Surgically, the technique begins with a peritomy followed by surgical isolation of the extraocular muscles. The tumor is localized using transillumination or scleral indentation and a dummy plaque is sutured to the overlying sclera. Some centers use intraoperative ultrasonography to confirm the position of the plaque in relation to the tumor [75]. Once this has been done, the active plaque is sutured and left in place for a prescribed period of time (often 3–7 days), after which it is surgically removed. At a number of centers, radiotherapists and dosimetrists are present in the operating room to ensure proper orientation and placement of the plaque.

Tumor regression following radiotherapy can be delayed up to a year. Initial response may include resorption of subretinal fluid followed later by pigmentary changes and decreased tumor height (Fig. 6A,B). Over time, vascular changes can be appreciated on fluorescein angiography, and certain tumors demonstrate increased internal reflectivity on echography [90]. Some clinicians consider lack of tumor growth a successful response to radiotherapy. Partly because of the various definitions used by authors to assess tumor regression, studies vary in published response rate. Nonetheless most findings suggest a local control rate of 85–90% following plaque brachytherapy [40,43,63,84,91–94]. The majority of tumors stabilize in height or regress over the first 2–6 years after treatment.

Tumor recurrence has been described years after radiotherapy and thus obligates the ocular oncologist to long-term serial assessment of his or her patient. Generally, recurrence is seen within 3 years of therapy and can be managed with enucleation, additional plaque radiotherapy, or adjuvant laser treatment [95]. Margin failure may be more amenable to the last two approaches. Enucleation following failed plaque radiotherapy is most commonly due to tumor recurrence or neovascular glaucoma [55,89,96,97].

Complications to this technique vary. Initially patients may complain of diplopia or ocular irritation. Uveitis can be observed following radiation of an anterior segment lesion; rarely, there may be scleral melting (Fig. 7). Retinal detachment (exudative and rhegmatogenous), subretinal exudation, and vitreous hemorrhage may occur [76]. Radiation-related toxicities are often delayed for 2–3 years and include cataracts, radiation vasculopathy (Fig. 8A,B), papillopathy (Fig. 9A,B) and neovascular glaucoma [42,43,56,57,60,70,77–84]. Visual loss is more likely to occur when there is increased proximity to the fovea and optic nerve [72,84–88]. Complications tend to occur in those eyes with larger tumors treated at higher dose rates [77,89].

B.Charged-Particle Radiotherapy

The availability of charged particles at a number of research institutions and their use in treating other malignancies led to the development of protons and helium ions for the treatment of uveal melanomas [98]. This modality, in theory, offers advantages over traditional brachytherapy. The Bragg peak effect affords less radiation to adjacent structures and provides a uniform dose to the entire tumor. This differs from brachytherapy, where the tumor base receives a larger dose than the tumor apex. In addition, the use of charged particles avoids radiation exposure to the operative team.

Figure 6 (A) Pretreatment photograph of an inferonasal uveal melanoma 7.4 mm thick.

(B) Two years following 125I brachytherapy treatment, the tumor has shrunk to a height of 2.4 mm and shows pigmentary mottling with secondary fibrotic scarring.

The surgical technique is similar to that used for brachytherapy. After the lesion is localized, a series of tantalum marker clips are sutured to the sclera in a circumferential pattern surrounding the tumor. Unlike plaque radiotherapy, only one surgical procedure is required. Once in place, the clips are used as localizing markers for physicists planning treatment. Patients are immobilized during therapy using a bite block and mask. Treatments are often fractionated over three to five sessions.

Figure 7 Photograph documenting a scleral melt following 125I brachytherapy treatment. A scleral patch graft was required.

Tumor response following charged-particle radiotherapy is similar to that after brachytherapy [99]. Some reports suggest local control rates as high as 98% and an ocular retention rate of 90% [100]. However, charged-particle radiotherapy carries an increased risk of anterior segment complications, including dry eye and lash loss [98,101–104]. Neovascular glaucoma is more likely to develop when a significant portion of the anterior segment is irradiated [105,106]. Some authors advocate a twofield technique to decrease this complication. Poor visual outcomes following charged-particle radiotherapy correlate not only with tumor location (fovea, optic nerve) but also with tumor size greater than 8 mm [103,107–111].

Some centers use this form of radiation exclusively for all choroidal and ciliary body melanomas. Others limit its use to lesions less amenable to plaque radiotherapy, such as juxtaand circumpapillary tumors. A few centers have treated selected iris melanomas with reported success. The greatest limitation of chargedparticle radiotherapy is the associated cost and requirement of a cyclotron. This has limited its use to two or three centers in the United States.

C.Gamma Knife and LINAC Stereotactic Radiotherapy

The increased use of stereotactic and gamma-knife radiotherapy to treat intracranial as well as head and neck lesions of various shapes has made it appealing in the management of intraocular tumors [112]. The Leksell gamma knife is a computercontrolled device that delivers radiotherapy precisely through a series of cobalt ports [113–115]. A similar modality, stereotactic LINAC radiotherapy, offers the advantage of external-beam radiation that can be fractionated and conformed to any tumor size and shape [116,117]. Plans can be constructed that allow radiation to enter the eye in such a fashion as to avoid critical anterior segment structures. Early

Figure 9 (A) Photograph OS taken 1 year following 125I brachytherapy treatment of a uveal melanoma nasal to the optic disc. (B) Fluorescein angiogram documenting development of radiation-induced optic neuopathy with loss of vision to the hand motion level. The vision remained permanently reduced, though the tumor remained stable.

D.External-Beam Radiotherapy

Traditional external-beam radiotherapy is used largely as an adjuvant modality for extraocular melanomas. Indications include gross orbital disease detected on presentation or after enucleation and microscopic extraocular extension appreciated on pathological review. Patients with painful bone and brain metastasis may also benefit from palliative radiation.

Pre-enucleation radiotherapy (PERT) was once administered as a means of decreasing the risk of hematogenous dissemination ascribed to surgical intervention. Numerous studies, including early results from the COMS trial, have failed to demonstrate a benefit from this approach; as a result it has largely been abandoned [124–130] (see discussion of enucleation, Sec. VII).

V.THERMORADIOTHERAPY

The response of uveal melanomas to hyperthermia and radiotherapy has led to techniques that incorporate both modalities. This approach is successful in managing other malignancies and often permits the use of lower doses of radiation.

Methods used to administer thermoradiotherapy include modified iodine plaques that deliver hyperthermia via microwave applicators or ferromagnetic thermoseeds [131–134]. Ultrasound-induced hyperthermia has also been combined with proton-bean radiotherapy [135]. Recent reports describe transpupillary thermotherapy (TTT) used in conjunction with brachytherapy. The ‘‘sandwich’’ technique involves the administration of diode laser hyperthermia in combination with traditional plaque radiation. The timing and frequency of laser treatments vary among different protocols. Some centers administer TTT prior to plaque surgery, while others do so months later. Early results suggest high rates of local tumor control; however, significant visual loss can occur [22,25,26,68,69]. At this time there is limited data to suggest the optimum method of combining these modalities.

VI. LOCAL TUMOR RESECTION

Local tumor excision is an approach used in the management of many other solid tumors, such as breast, lung, and gastrointestinal cancer. Resection of intraocular melanoma was first reported in the early twentieth century, Initially to treat anterior segment tumors. Later, ophthalmologists such as Peyman, Foulds, and Shields advanced methods to resect posterior uveal lesions. While the procedures vary in technique, they all represent means of surgically resecting the tumor while maintaining the structural and physiological integrity of the eye and surrounding structures. Unlike brachytherapy, they provide the patient with pathological confirmation of the diagnosis and avoid potential radiation-induced side effects. Selecting which method to use involves consideration of tumor size, location, and potential complications.

Surgical iridectomy is indicated for the excision of isolated iris tumors not involving the ciliary body or angle. Following a limbal incision, the tumor is resected using scissors. Depending on the size of the tumor, the pupil can be reapproximated with nonabsorbable suture. While this procedure is often successful in resecting the lesion, some patients are left with large iris defects that can cause polyopia and photophobia. Colored contact lenses and iris implants may be helpful in addressing these complaints.

Iridocyclectomy is a procedure used to resect tumors of the ciliary body and adjacent iris (Fig. 10 A,B). The technique begins with construction of a scleral flap hinged at the limbus. After application of diathermy to the scleral bed, the underlying tumor is excised with scissors. The sclera is then closed with interrupted

Figure 10 Photograph showing (A) the anterior extent of an iridociliary body melanoma and (B) postoperative appearance two years following an iridocyclectomy procedure. The patient remains free of tumor.

sutures. The technique works best when less than four clock hours of ciliary body are involved; excision of larger areas is technically feasible but associated with a higher rate of complications, such as hypotony [136].

Posterior lesions can be excised from both the ab interno and ab externo approaches. Eye wall resections involve a full-thickness excision of sclera, choroid, and overlying retina. Some clinicians advocate treating the tumor and its margins with cryotherapy or laser photocoagulation preoperatively to create retinal

adhesions and reduce the risk of detachment. A ring stabilizer or eye-wall basket is used to maintain ocular integrity during the procedure. Following tumor localization, the sclera, choroid, and overlying retina are excised in toto. A vitrectomy is performed and the ocular defect is closed with a patch graft of donor sclera or dacron [137–139].

Modification of this approach includes dissection of a flap prior to the excision of the underlying tumor. Partial lamellar sclerouvectomy maintains the integrity of the outer wall by first dissecting a hinged 90% scleral flap (Fig. 11 A,B). Following diathermy to the scleral bed, the tumor is resected using scissors and is teased away from the retina using a blunt-tipped instrument. The sclera is then closed with interrupted suture. An encircling band is applied by some surgeons [140–142].

Resection of a posterior uveal tumor can be a technically difficult procedure. Some authors recommend that the surgery be performed under hypotensive conditions to minimize complications. For certain patients, this is an absolute contraindication to use of this modality [143]. A number of acute and long-term complications have been described with this technique, including retinal detachment, vitreous hemorrhage, macular edema, and hypotony. Among the more serious complications are expulsive choroidal hemorrhage and orbital seeding. Results suggest that tumors less than 10 mm in diameter located anterior to the equator have the best outcome, although lesions up to 18 mm have been removed successfully [140–142,144–147]. Intraocular and orbital recurrence is possible and has been described following what was felt to be complete surgical excision. Given these complications, some centers advocate adjuvant brachytherapy when proceeding with lamellar sclerouvectomy; following removal of the lesion, the sclera is reapproximated and a plaque is sutured to the overlying the area [148,149].

Tumors not accessible to external excision can be removed using an ab interno approach. Endoresection is best suited to posterior tumors, including those that are peripapillary in location. Lesions nasal to the disc afford the best postoperative visual potential [150,151]. Following pretreatment laser hyperthermia, a three-port vitrectomy is performed. A retinotomy is made and the tumor is removed in piecemeal fashion using the vitrector. Following excision, endodiathermy, gas-fluid exchange, and endolaser are used to prevent rebleeding, create retinal adhesions, and destroy residual tumor cells. Silicone oil is then injected and the sclerotomy ports are treated with cryotherapy [152,153]. The potential risk of incomplete resection, dispersion of tumor cells following a piecemeal excision, and extraocular extension through sclerotomy sites has led to controversy regarding the use of this technique. As a result, some clinicians limit its role to tumors within one disc diameter of the optic nerve and those less than 10 mm in basal diameter [151,154]. Attempts at pretreating larger tumors with gamma-knife radiotherapy have also been described [155].

VII. ENUCLEATION

As the number of therapeutic options available for uveal melanomas continues to expand, there remain fewer indications for primary enucleation. For much of the early twentieth century, most eyes thought to be harboring melanomas were removed. As a result, some patients underwent unnecessary surgery. The poor

Figure 11 Intraoperative photographs of a lamellar sclerouvectomy procedure. (A) A partial thickness scleral flap has been raised over the base of the tumor, which was then followed by placement of diathermy around the base of the tumor. (B) Surgical removal of the tumor, leaving intact the underlying retina. The scleral flap was then closed and a pars plana vitrectomy procedure was performed.

prognosis associated with metastasis of this cancer was considered justification for this aggressive approach.

As plaque radiotherapy grew in acceptance and smaller lesions were observed with greater confidence, an increasing number of eyes that would have been enucleated were spared. Yet there remained concern that these modalities might