Tumors Intraocular Malignant for Chemotherapy• 44 chapter

Figure 44.3  Uveal metastasis before chemotherapy.

Figure 44.4  Uveal metastasis after chemotherapy.

(BCNU) using gelatine sponges for temporary arterial occlusion results in a median survival of only 5.2 months.74 Intra-arterial intrahepatic fotemustin, a third-generation nitrosourea, delivers a 36% response and 15-month median survival for patients with hepatic metastases.75 Including one of 24 patients showing a partial response, 33% of patients exhibited disease stabilization after gemcitabine plus treosulfan.76 The addition of cisplatin to the gemcitabine plus treosulfan regimen does not improve efficacy, with a median survival of 7.7 months at the expense of excessive hematological toxicity.77 A study evaluating the combination of dacarbazine and treosulfan failed to find any objective tumor response.78

INTRAOCULAR LYMPHOMA

GENERAL CONSIDERATIONS

Primary intraocular lymphoma is a rare entity involving the retina, vitreous, subretinal pigment epithelial space, or optic nerve head.79 Almost always, histopathology reveals diffuse large B-cell lymphoma, though occasionally it can be of T-cell origin.80 Many experts consider primary intraocular lymphoma a subset of primary CNS lymphoma. Though primary intraocular lymphoma presents independently of primary CNS lymphoma, 60–85% of patients eventually develop intracranial involvement. Of patients with primary CNS lymphoma, 15–25% will have concomitant ocular involvement.80 Many patients with primary intraocular lymphoma are misdiagnosed with uveitis, resulting in a delay of diagnosis of 6–13 months.81,82 Patients show initial response to corticosteroids and often develop brain involvement at the time of correct diagnosis.81 Diagnosis is usually made by vitreous or direct choroidal/retinal biopsy. In a cohort of 83 variably treated patients without initial brain involvement, median overall survival was 58 months. Fifteen percent of patients had positive cerebrospinal fluid cytology at time of ocular diagnosis, and 56% ultimately progressed to develop brain lymphoma.81 When the brain is involved, prognosis is poorer.

TREATMENT

Given the rarity of primary intraocular lymphoma, optimal treatment standards have not been established. Current options include ocular radiotherapy, intravitreal methotrexate, whole-brain radiotherapy, and intravenous or intrathecal chemotherapy. The largest study of primary intraocular lymphoma in the literature (n = 83) retrospectively found no difference in outcome between those treated with ocular radiotherapy and/or intraocular methotrexate versus more extensive treatments, including whole-brain radiotherapy, systemic chemotherapy, and/or intrathecal chemotherapy. Of note, all patients with positive CSF cytology were treated with more extensive measures. For patients with primary intraocular lymphoma, the researchers recommend focused ocular treatment with close follow-up for ocular, CNS, or systemic relapse.81

Intravitreal methotrexate has shown encouraging response rates, with almost 100% tumor eradication.83 Adverse effects include conjunctival irriation, corneal epitheliopathy, cataract, vitreous hemorrhage, maculopathy, optic atrophy, sterile endophthalmitis,83 and neovascular glaucoma.84

Case reports of patients undergoing intrathecal methotrexate and cytarabine for intraocular and CNS lymphoma are encouraging, reporting tumor regression and suggesting improved survival.85

Systemic chemotherapy for primary intraocular lymphoma is often methotrexate-based.81 For primary cerebral lymphoma, regimens including high-dose methotrexate confer a better survival than radiation alone or other chemotherapy regimens (cytarabine or nitrosurea).86 Primary intraocular lymphoma has been treated with high-dose methotrexate, high-dose cytarabine, trofosfamide, and ifosfamide.87,88 Experts recommend high-dose methotrexate alone or in combination with other active chemotherapy agents for primary CNS lymphoma, followed by whole-brain radiotherapy unless contraindicated.89

Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD 20 antigen on the surface of normal and malignant B lymphocytes.90 Animal and case reports of intravitreal rituximab fail to reveal toxicity; this may hold promise as a future treatment option for primary intraocular lymphoma.91 Intrathecal rituximab was evaluated in a phase I study of 10 patients with recurrent CNS lymphoma, reporting meningeal responses in six, intraocular responses in two, and resolution of brain parenchymal lymphoma in one. This treatment modality warrants further investigation.92