Management of choroidal metastases

Highlights

• Choroidal metastases are the most frequent malignant tumors of the eye.

• They can lead to severe complications (such as blindness) and significant deterioration of the quality of life.

• Radiation therapy is the treatment of reference: it yields high local control rates and improvement of visual function.

• Palliative fractionation is often recommended but more focused techniques may be discussed.

• Systemic treatments provide promising outcomes in selected cases, thus requiring further assessment.

Abstract

Background

Choroidal metastases (CM) are the most common malignant intraocular lesion observed in up to 4–12% of necropsy series of patients with solid cancer. The spectrum of presentations varies from prevalent CM in disseminated cancer to isolated CM. CM are responsible for visual deterioration. Depending on the primary cancer, estimated life expectancy, overall cancer presentation and ocular symptoms, the management of CM varies widely. We address the multidisciplinary management of CM and technical aspects of radiotherapy.

Material and methods

A systematic review of literature was performed from 1974 to 2014.

Results

Choroidal metastases occur preferentially in breast and lung carcinomas but are reported in all cancer types. The standard treatment remains external beam radiotherapy, applying 30 Gy in 10 fractions or 40 Gy in 20 fractions. The reported complete response and improved visual acuity rates are 80% and 57% to 89%, respectively. Some chemotherapy or new targeted therapy regimens yield promising CM response rates.

Discussion

Radiation therapy consistently shows rapid symptom alleviation, yield excellent local control and functional outcomes. However, there are only few reports on late toxicities after 6 months given the unfavorable prognostic of CM patients. Selected patients may live more than two years, underlying the need to better assess mean and long term outcomes. Some authors have favored exclusive systemic strategies with omission of irradiation. The current literature suffers from the scarcity of prospective trials. Duration of tumor response following systemic therapy is rarely reported but appears less favorable as compared to radiotherapy. Systemic treatments may be proposed for pauci-symptomatic CM in a polymetastatic context while radiation therapy remains necessary in symptomatic CM either upfront or as an alternating treatment. Focalized radiation like brachytherapy and proton therapy may be proposed for isolated CM with long disease-free interval between primary and CM, as these techniques have the potential to yield better tumor and functional outcomes in patients with long life expectancy.

Introduction

Metastatic carcinoma is the most common malignant lesion in the eye and metastasis at the choroid the most frequent localization. The prognostic is usually considered very poor. CM occur in 4–12% of patients with solid tumors (mainly breast and lung cancers but also any other tumor type) in autopsy series and 0–11% in screening programs for patients with disseminated breast or lung cancers [1], [2], [3], [4].

The choroid is a 0.1–0.2 mm thick vascular coat of the eye, lying between the retina and the sclera. Its role is to provide oxygen and nutrients to the outer layers of the retina and its photoreceptor cells. Choroid, ciliary body and iris form the uveal tract. The blood supply of the uvea, the macula and the anterior part of the optic nerve, comes from the posterior ciliary arteries, collateral branches of the ophthalmic artery that are piercing the sclera with no anastomoses between them. That rich terminal vascularization may explain the metastatic predilection for the uveal tract. The blood-ocular barriers are formed by the blood-aqueous and the blood-retina barriers [5], [6]. Intercellular tight junctions (zonula occludens) are major components of these barriers and, as their brain counterpart, prevent many drugs to diffuse into ocular components. The VEGF-TRAP (R1R2) tight junction regulator can suppress choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier [7], [8]. So do TNF alpha and other molecules [9], [10]. Molecular yet unraveled interactions might explain preferential metastatic routes to the choroid, consistent with the visionary “seed and soil” hypothesis coined by Stéphane Paget in 1889 (where the non-random pattern of metastasis is explained by the interactions between the cancer cells-“seed” and the specific microenvironment of the tissue-“soil”) [11].

Radiotherapy is the most common treatment applied and thus, the better studied. Although, the management of CM is not standardized and varies between centers and physician’s local habits and medical resources. Quick alleviation or prevention of symptoms would preserve the quality of life, especially concerning the risk of blindness. In a context where patients have limited life expectancy, sophisticated treatments (more complex technically or stronger, with higher doses of radiation or by combination of chemo- and radiotherapy for instance) are controversial. But the question still remains open if this approach can lead to better complete response rates and/or yields better functional results. Identifying patients that could benefit from it becomes one of the decisional values.

This review addresses the current controversy with respect to multidisciplinary management and focus on radiation therapy. The goal is to help physicians to make therapeutic choices by having a bright view on the former studies. They are indeed highly susceptible to be confronted at least once to this disease in oncologic centers during their all careers.