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A rare presentation of choroidal metastasis from primary esophageal adenocarcinoma successfully treated with intensity-modulated radiation therapy

Purpose In this case report, we present a case of choroidal metastasis from a primary esophageal adenocarcinoma that was treated successfully with intensity-modulated radiation therapy. Observations A 65-year-old male with known stage IV esophageal adenocarcinoma presented with a central scotoma in his left eye and was ultimately found to have a large choroidal metastatic lesion with overlying subretinal fluid. IMRT was administered over the course of four weeks, resulting in restoration of the patient's vision, regression of the metastatic lesion, and resolution of the subretinal fluid. As of 16 months following completion of radiation, there remains no evidence of choroidal recurrence or radiation-associated ocular complications. Conclusions and Importance: To our knowledge, this is the first published case report of a choroidal metastasis from esophageal cancer responding durably to IMRT. IMRT should therefore be considered a viable treatment option for this rare disease.


Introduction
The choroid is an uncommon but well-documented site for metastasis of solid tumors, most commonly breast and lung carcinomas. On autopsy, choroidal metastasis can be found histologically in 0-11% of patients with any known metastatic malignancy and 4-12% of patients with breast and lung cancer. [1][2][3][4] However, choroidal metastases originating from the esophagus are exceedingly rare. In fact, a recent review of multiple case series found that only 8 of 918 cases (0.87%) of choroidal metastases were attributed to an esophageal origin. 5 In this report, we summarize the presentation and management of a patient who developed a choroidal metastasis from primary esophageal adenocarcinoma and then review the limited published literature pertaining to this rare clinical entity.

Case report
A 65-year-old Caucasian male was diagnosed with Her-2 positive, locally advanced adenocarcinoma of the lower esophagus and treated definitively with chemotherapy, radiation, and Ivor-Lewis esophagectomy. Eighteen months later, his cancer recurred in bone, non-regional lymph nodes, and the surgical bed. Palliative radiation to an iliac metastasis and systemic chemoimmunotherapy (capecitabine, oxaliplatin, trastuzumab) were initiated, and subsequent imaging showed response to therapy.
Ten months into treatment, however, the patient noticed a central scotoma in his left eye and was referred to an ophthalmologist who reported visual acuity of 20/20 in the right eye and 20/25 in the left eye without an afferent pupillary defect. Dilated funduscopic examination revealed a large, elevated yellow choroidal lesion in the temporal macula with RPE changes and overlying subretinal fluid (Fig. 1a). Spectral-domain optical coherence tomography (SD-OCT) revealed subretinal fluid overlying the area of choroidal infiltration with shaggy photoreceptors and RPE debris, as well as irregular foveal contour caused by the choroidal mass ( Fig. 1b and c).

Discussion
To our knowledge, this is the first published report of a choroidal metastasis from primary esophageal cancer that responded in a complete and durable manner to radiotherapy. While esophageal cancer metastasizing to the choroid is exceedingly rare, choroidal metastases are the most common intraocular malignancy. 5 A substantial portion of patients with choroidal metastases may be asymptomatic, but common presenting symptoms include blurred vision, metamorphopsia, floaters, and photopsias. Visual acuity at presentation can vary, depending on the extent of the lesions and the presence or absence of subretinal fluid. When Shields et al. 6 examined 520 eyes in 420 patients with metastatic uveal lesions, they localized 88% of metastatic lesions to the choroid, while iris and ciliary body lesions were far less common. 6 The propensity of tumor cells to seed the choroid preferentially likely stems from its rich vascular supply.
Uveal metastases are most commonly attributed to primary tumors of the breast and lung. 2, 7-9 Only 4% of uveal metastases arise from the gastrointestinal tract, and only a small percentage of these originate in the esophagus. 6, 10-19 Furthermore, most reported cases of esophageal cancer metastasizing to the uvea are of squamous histology. Only a few cases of uveal metastases from adenocarcinoma of the esophagus have been reported in the literature. 10,11,[15][16][17][18] Management of choroidal metastases depends on a number of factors, including primary tumor site, tumor histology, extent and burden of extra-uveal disease, the patient's underlying health, overall prognosis, and symptomatology. Once choroidal metastases have arisen, prognosis is generally poor, so the goal of treatment is salvaging vision in a minimally-invasive manner. 5 Whether or not systemic chemotherapy alone can effectively treat choroidal metastases is debatable, but most agree that local therapy is generally warranted. 5,20 Standard fractionated external beam radiotherapy (EBRT) is the modality most commonly used to treat choroidal metastases, yielding tumor regression  in 85-93% of patients. 5,20 Despite its anti-tumor activity, EBRT can cause cataracts, exposure keratopathy, iris neovascularization, and radiation retinopathy. Approximately 12% of EBRT patients will experience one or more of these side effects within six months of treatment. 20 EBRT is also intensive, requiring daily fractions for weeks to months in patients with limited life expectancy. 20 Other types of radiation therapy, including plaque brachytherapy, stereotactic radiosurgery, and proton beam therapy have also been utilized for treating choroidal metastases, but with variable success. 20,21 Non-radiation therapeutic strategies including intravitreal anti-VEGF injections, transpupillary thermotherapy, laser photocoagulation, photodynamic therapy, cryotherapy, and surgical excision have also been attempted, but further evaluation and comparative studies are needed to establish their roles in the management of metastatic disease. 20 Based on limited published data, choroidal metastases from esophageal adenocarcinoma have been treated with systemic chemotherapy, EBRT, and enucleation. However, outcomes have been poor, and no single modality has demonstrated clear benefit. 15,17,18 Samuel et al. describe a patient whose first presentation of esophageal adenocarcinoma was retinal detachment due to a metastasis involving the macula. Systemic chemotherapy (carboplatin and 5-fluorouracil) induced regression of the macular lesion and subretinal fluid, but visual acuity did not improve. Within three months after chemotherapy was discontinued due to intolerance, the uveal metastasis lesion had clearly progressed. 15 The same authors reported a patient with esophageal adenocarcinoma who presented with compromised visual acuity due to a foveal metastasis. He underwent external beam radiotherapy, yielding  However, the patient expired two months later due to progressive systemic disease. 15 Similarly, Buskens, et al. report a choroidal metastasis from primary esophageal adenocarcinoma treated with palliative EBRT, but the patient expired before she could be assessed for any potential benefit of therapy. 18 In contrast to the patients described in these reports, our patient manifested significant symptomatic and anatomic improvement after 40 Gy of IMRT. An advanced subtype of external beam radiation which utilizes 3-D imaging to determine the dose intensity pattern best conforming to the tumor contour, IMRT allows delivery of higher radiation doses to the tumor while minimizing radiation exposure of surrounding tissue (e.g., lens, lacrimal gland, brain). IMRT offers certain benefits over plaque radiotherapy such as the avoidance of an invasive surgical procedure and the associated anesthesia; however, the treatment duration is generally longer. IMRT has been used successfully as a treatment modality for choroidal metastasis from gastric adenocarcinoma 22 and breast cancer. 23 The precision of IMRT over standard EBRT may therefore account for our patient's ongoing tumor response and absence of ocular toxicity 16 months post-radiotherapy. Clearly, tumor relapse and/or delayed radiation toxicity may still arise, so continued observation will be important. Nevertheless, to our knowledge, our patient has experienced the longest post-treatment overall survival and event-free ocular outcome reported in the medical literature. Future studies involving a larger cohort of patients treated for this rare primary malignancy are needed.

Conclusions
Choroidal metastasis from primary esophageal adenocarcinoma is exceedingly rare. IMRT may be an effective and well-tolerated treatment option.

Patient consent
Consent to publish the case report was obtained. This report does not contain any personal information that could lead to the identification of the patient.

Disclosures
No funding or grant support was received. The following authors have no relevant financial disclosures: RCD, MKA, BST, BLM, AMF, ACS, CYW. All authors attest that they meet the current ICMJE criteria for Authorship.