Ординатура / Офтальмология / Английские материалы / Tumors of the Eye and Ocular Adnexa_Char_2001

Figure 8–65. Anterior lateral wedge pair ports used to deliver five 400 cGy fractions to a total dose of 20 Gy of photon irradiation, for poor-risk uveal melanomas.

Follow-up after Enucleation and Exenteration and Treatment of Metastatic Uveal Melanoma

Metastatic evaluations are performed every 6 months after enucleation or exenteration. This includes screening liver function tests, physical examination, and chest radiography. The use of abdominal ultrasonography has been shown in

Figure 8–67. Recurrent orbital melanoma 5 years after enucleation. On metastatic evaluation, widespread tumor was noted.

Figure 8–68. Sagittal schematic for a lid-sparing exenteration.

Figure 8–70. Sagittal schematic of an anterior exenteration that is used for invasive conjunctival carcinoma.

Figure 8–71. Lid approach for a lid-sparing exenteration. An incision is made 2 mm distal to the lash margins. Myocutaneous flaps are mobilized past the bony orbital rim.

some studies to be more sensitive than serum liver function tests, but not in others.260 While initally having some theoretical promise, the use of PCR technology to detect tyrosinase messenger RNA (mRNA) have not been effective to detect early metastases. In our experience, PCR for tyrosinase mRNA has not been effective in detecting early metastases (unpublished data).261,262

Metastases of uveal melanomas are usually first found in the liver. The peak incidence of metastasis is within the first 24 to 36 months after treat- ment.263–265 Unfortunately, uveal melanoma, unlike breast carcinoma, can metastasize as late as 50 years after treatment, and therefore, all patients have to be followed up throughout their lives.266–268 In melanomas from all body sites that metastasized more than 10 years after initial therapy, 12 of 168 were from the eye and the longest intervals (45 and

Figure 8–73. Whether the lids are spared or (as shown) sacrificed, the area of the lashes and lid margins is grasped with a towel clip for traction after an incision is made through the periosteum at the orbital rim to free orbital contents from the orbital bones.

47 years) were from the ocular, compared with the cutaneous, cases.269

The mean survival with live involvement of metastatic melanoma is approximately 7 months.270,271 Single or combined forms of chemotherapy have had rather dismal results in controlling visceral metastatic melanoma. In our experience, both singledrug chemotherapy with DTIC or methyl-CCNU and chemotherapy with as many as five agents pro-

duce only a partial response in up to 20 percent of patients with visceral metastases. The results with current chemotherapy are so poor and have sufficient toxicity that we do not believe it is indicated as adjunctive therapy in patients who do not have symptomatic metastases.279,280 Bedikian and colleagues reported 201 patients with a response rate of < 1 percent. Various other drug regimes have produced incomplete responses in 36 percent of

A

B C

Figure 8–77. A to C, A partial-thickness skin graft is obtained using a Brown dermatome from the buttock or lateral thigh. This is sutured to the cut edge of skin with interrupted and running 6-0 plain gut sutures. It is placed into the orbital apex and pressure-packed with Xeroform gauze. The pressure-packing is changed weekly.

patients with metastatic melanoma Leyvraz and his colleagues in Switzerland have treated asymptomatic uveal melanoma patients, whose metastases were found on routine ultrasonography, with a third-generation nitrourea, fotemustin, and found that they had objective responses in 12 of 30 patients, with a median duration of 11 months.282 Unfortunately, in that later study, the treatment of asymptomatic patients probably did not obtain an increase in life span above and beyond what one might have noted if they had been treated after they developed symptoms. In some centers, the combination of hepatic resection of metastases with intraarterial chemotherapy appeared to prolong survival; however, most patients could not have the entire tumor removed, and the mean survival was not significantly different from historic controls.

Several patients with solitary metastatic disease to the liver have had resection.289

While there has been some early promise with interferon-alpha (IFN-α ) and interleukin-2 (IL-2) as

adjuvant therapy, it has not shown benefit in metastatic melanoma.290–292 Other groups have been working on either in vitro or in vivo studies with immune modulation and uveal melanoma, but those approaches have similarly been relatively disap- pointing.293–296

Figure 8–78. Appearance of an exenterated socket covered by a split thickness skin graft.

UVEAL MELANOMA MANAGEMENT:

CONCLUSION

Significant progress has been made in uveal melanoma management. Inaccurate diagnoses in ocular oncology units have virtually been eliminated. In our experience, over 80 percent of the melanoma-containing eyes that we examine can be salvaged. The two major goals over the next decade will be to decrease ocular morbidity in eyes that are retained, and to decrease metastases, especially in larger tumors that are not amenable to alternative therapies. Several problems will make the attainment of those goals difficult. (1) While we are able to retain many eyes with current techniques, it is uncertain if funding of research will allow the same degree of advances we have observed until now. (2) Especially for metastatic melanoma, there has been very little advancement in our ability to treat this problem effectively, regardless of the site of the primary tumor. Several groups, including our own, have noted tumor-infiltrating lymphocytes in uveal melanomas, and these may be exploitable for therapy in the future. Further, while most immunomodulatory approaches for primary uveal melanoma have not shown promise, in one case report, a melanoma-derived vaccine appeared to decrease tumor size.300,301

UVEAL METASTASES

The management of choroidal metastases is dependent on the patient’s general health, the presence or absence of CNS spread, and chemotherapy status. Therapeutic decisions must be made in conjunction

with the patient’s medical oncologist, after a complete metastatic evaluation, including brain MRI with contrast performed when ocular metastases are diagnosed. In most cases, the presence of choroidal metastatic disease is a very poor prognostic sign; most patients die within 1 year of diagnosis.302 In a series of 32 ocular metastases, of which 18 involved the choroid, the mean interval between diagnosis and death was 7 months. Patients with choroidal metastases had slightly longer survival than those with orbital disease.303 In that study, 10 of 32 patients developed CNS metastases. Some patients have isolated choroidal metastases and live for a number of years after diagnosis. There are five treatment options for most forms of choroidal metastases: observation, chemotherapy, radiation, laser, and enucleation.302–312 Only when an eye with metastatic disease has intractable pain is enucleation indicated. Choroidal metastatic foci are as responsive as other body sites to systemic chemotherapy. Especially when the primary cancer is a breast carcinoma, chemotherapy is probably the first choice for treatment of choroidal metastases (Figures 8–80A and B). We have seen some metastatic breast tumors respond to just tamoxifen. As has been known for many years, tamoxifen can produce intraretinal crystals, although this side effect usually occurs after long-term administration.313 There is usually some residual tumor after effective treatment, and often there are overlying RPE changes.

When multiple uveal metastases are present and they are not overly amenable to chemotherapy or various drugs have been tried without success, and both the choroidal and systemic tumors are progres-

186 TUMORS OF THE EYE AND OCULAR ADNEXA

Figure 8–82. Lesion shown in Figure 8–81 after 40 Gy of photon irradiation.

A

B

Figure 8–83. A, Solitary metastasis involving only a discrete area of choroid. FNAB was positive for estrogen receptor breast carcinoma. B, Case in Figure 8–83A after 40 Gy of 125I brachytherapy.

therapy was given above 35.5 Gy. Overall, in that study, 62 percent had improved vision.212

CHOROIDAL HEMANGIOMA

Historically, difuse lesions have been difficult to treat, and focal lesions were treated with laser. It often took up to three laser sessions to heavily scar the tumor surface and dry up the subretinal fluid. Usually, a tumor was not destroyed, but the subretinal fluid would be resorbed with this techniuque (Figure 8–85).

Unfortunately, while we could often obliterate the exudative detachment, the long-term visual results were not excellent. In one study, less than one-third of patients had better than 20/200 acuity 10 years later.303 Visual loss can be due to subretinal

A

B

Figure 8–84. A, Breast cancer metastasis lateral to the fovea. B, Lesion shown above was controlled with laser; however, the patient developed widespread metastases and 2 weeks prior to death, activation along the posterior-inferior edge was noted.

Figure 8–85. Successfully treated choroidal hemangioma.

fluid, overlying photoreceptor degeneration, or cystoid retinal change.315

In many centers, including our own, we have altered therapy to use radiation as the first-line approach. The rationale for this is threefold: (1) it appears to flatten the tumor, which, in some cases, will result in better vision; (2) it does not have as high a recurrence rate as with laser, and (3) we believe that the visual results are better, especially if it is a macular tumor.

In patients with a diffuse hemangioma that involves the fovea and produces subretinal fluid (most frequently in Sturge-Weber syndrome), we have successfully dissipated the subretinal fluid with return of vision, using 10 fractions of 200 cGy of photon irradiation.

We have also treated isolated hemangiomas, especially those that have failed with laser, with radiation. The choice of a radiation delivery system and the dose in the latter setting is uncertain. We have preferred to give 20 Gy to the tumor apex, using either protons or brachytherapy, in the belief that we might obtain more vascular closure with this rapid radiation dose delivery. Other workers have used plaques, particles, or photons at doses between

12.5 and 60 Gy.306–309,316–318

In some hemangiomas, the fluid dissipates, but vision does not return. In one study, thicker larger tumors had a worse visual outcome.319 In a study using photon radiation, Schilling noted a lower inci-

dence of fluid resorption than we and others have observed with plaques or protons.315, 319–322 Zografos and colleagues similarly have evaluated both protons and brachytherapy.317,323

In the experience from the group in Switzerland, they have been able to decrease doses to near what we have used; in addition, they have observed that treatment with protons at over 30 Gy may produce visual loss.317

A few authors have used TTT. This appears to be a possible option for tumors that are away from the vital visual structures, although the question of local recurrence still remains unanswered.324 One patient treated with hyperthermia had macular edema 2 years after treatment.309

Figure 8–86 shows an additional isolated hemangioma that responded well to low-dose proton radiation.

A

B

Figure 8–86. Isolated choroidal hemangioma prior to and after

188 TUMORS OF THE EYE AND OCULAR ADNEXA

THERAPY OF INTRAOCULAR

LYMPHOID PROCESSES

Isolated intraocular lymphoid tumors (see Chapter 10) or posterior scleritis can usually be managed with a short-term course of high-dose oral steroids (10 days of 80 mg of daily oral prednisone). Although, rarely, such lesions may not respond to this form of treatment, 20 Gy of photon irradiation can be used to destroy them.

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