Complete regression of a choroidal metastasis secondary to breast cancer with stereotactic radiation: case report and review of literature

Abstract

Metastatic choroidal tumors from breast carcinoma are an uncommon entity but the signs must be recognized immediately in order to avoid delays in treatment and irreversible blindness. We present the case of a 49-year-old woman who presented with vision loss and redness of her right eye two years after being treated for a stage I infiltrating ductal carcinoma status-post lumpectomy, chemotherapy, and radiation treatment to the left breast. Computed tomographic (CT) scans and magnetic resonance imaging (MRI) of the head demonstrated an intraocular metastasis to the right eye with development of a serous retinal detachmentcausing vision loss. The posterior pole and peripheral retina of the right globe were treated for the ocular metastasis and received a total dose of 25 Gy in 5 Gy fractions given every other day. MRI obtained one month after completion of radiation therapy demonstrated complete resolution of the right posterior chamber lesion with reduction in retinal thickening and resolution of subretinal fluid. The patient had moderate improvement of her vision and a more comfortable sensation in her eye after treatment. Subsequent PET, CT, and MRI demonstrated progression of pulmonary, abdominal, and CNS metastatic disease, which were unsuccessfully attempted to control with multiple chemotherapeutic and radiotherapy attempts. Despite the continued metastatic progression of her disease 5 years after diagnosis, the patient’s vision remained stable and there was no evidence of recurrence of the choroidal metastasis 3 years after treatment with stereotactic radiation. An overview of the diagnosis and management of metastatic choroidal tumors is presented here.

1. CASE REPORT

In August 2006, a 47-year-old female presented with an abnormal mammogram of the left breast with a mass located superomedially. The patient underwent aggressive treatment with breast preservation surgery. Lumpectomy on November 2006 removed a 2.0 cm grade 3 infiltrating ductal carcinoma with positive margins. Five out of five left axillary sentinel lymph nodes were negative with H&E and cytokeratin stains. In February 2007, repeat excision of the lumpectomy site showed no evidence of residual tumor. Post lumpectomy, the patient received 6 cycles of adjuvant chemotherapy followed by radiation to the entire left breast.

The patient did well over the first two years after diagnosis and had no evidence of recurrence on routine mammograms or any signs/symptoms suspicious of metastasis. However, approximately three years after diagnosis in September 2009, the patient complained of right eye redness over the past 6 weeks that was initially misdiagnosed as conjunctivitis. The redness persisted and was accompanied with a loss of vision. Dilated fundoscopic examination showed an inferior serous retinal detachment associated with multiple cream colored lesions suggestive of choroidal metastases. On CT and MRI, the patient was confirmed to have right eye choroidal metastasis leading to the retinal detachment and a large 2.6 x 2 x 2.2 cm mass in the left parietal lobe with surrounding vasogenic edema (Figure 1).

Figure 1.

Head CT scans with 3 views (A. Horizontal, B. Saggittal, C. Coronal) showing right choroidal metastasis in the posterior globe associated with retinal detachment and hemorrhage.

Restaging work-up revealed simultaneous metastatic disease in the lungs, mediastinum, left breast, and bone. The patient was re-started on chemotherapy for the systemic metastases. Given her age and minimal CNS disease, the patient was treated with stereotactic radiation to the right eye and left parietal area rather than whole brain radiation. The treatment was hypofractionated due to sensitivity of the retina and the size of the parietal metastasis.

Tumor localization was accomplished using 1.25 mm contrast enhanced CT slices with the Varian/ Z-Med stereotactic mask, custom headrest, and custom biteblock with fiducials. The patient was instructed to look straight ahead during the CT and during the treatments, which was adequate for immobilization of the eye itself since the entire posterior surface of the globe was treated. Other possibilities to limit eye motion would include placing colored tape in a cross hair pattern, or a penlight on the ceiling. CT and MR images were transferred to the treatment planning computer and fused. Tumor and critical structure volumes were then determined by the physician. The choroidal lesion was easily visible and outlined with a 2 mm Planning Treatment Volume margin.

The treatment was delivered using a Varian Trilogy linear accelerator with 120 leaf Multileaf collimator and IMRT capability. The patient was positioned for treatment and the target was accurately placed at the isocenter of the treatment machine using the biteblock with fiducials and the optical localizer system. The treatment position was verified with orthogonal kV images compared to planning digitally reconstructed radiographs prior to each treatment.

The entire right retina received a total dose of 25 Gy in 5 Gy fractions given every other day (Figure 2A). The left parietal metastases and adjacent satellite lesion were treated to a total dose of 30 Gy in 6 Gy fractions given every other day (Figure 2B). 6 MV photons were used to treat both sites. No other lesions were visualized on treatment planning CT with contrast.

Figure 2.

Stereotactic radiotherapy treatment plan of the right retina(A) and parietal metastasis (B). The right choroidal metastasis received a total dose of 25 Gy in 5 Gy fractions given every other day. The left parietal metastases were treated to a total dose of 30 Gy in 6 Gy fractions given every other day. 6 MV photons were used to treat both sites.

Six weeks after completing stereotactic radiosurgery to the right posterior globe and left parietal lobe, the patient’s vision improved with partial resolution of the subretinal fluid. Repeat imaging showed improvement in the size of the metastases, con sistent with the patient’s symptomatic improvement. MRI demonstrated a slight decrease in the size of cystic mass of the left parietal region which measured 2.3 x 2.0 x 1.8 cm (from 2.6 x 2 x 2.2 cm) with decreasing surrounding edema. Four months post-treatment, in January 2010, MRI and CT head also showed a complete regression of right eye meta stasis but suggested residual subretinal fluid, which was contributing to her impaired visual field despite treatment of the lesion (Figure 3). The left parietal lesion had also decreased in size to 1.3 cm. The patient’s systemic disease continued to wax and wane as she responded to subsequent treatment.

Figure 3.

MRI of the head (horizontal view) demonstrating a complete regression of right eye metastasis but some posterior globe residual hemorrhage and retinal detachment.

By May 2010, MRI demonstrated interval development of multiple bilateral cerebral enhancing foci (7 in the left cerebral hemisphere and 4 in the right) in the gray-white junction and an enhancing focus in the right cerebral vermis, consistent with multiple brain metastases. The patient was treated with whole brain radiation therapy through right and left parallel opposed fields using 6 MV photons at 2 Gy per fraction for 15 fractions totaling 30 Gy, in June 2010 (Figure 4). The reduced daily dose was chosen in light of her previous stereotactic radiosurgery to the right retina and left parietal masses.

Figure 4.

Single fraction stereotactic radiosurgery treatment plan with 3 views (A. Horizontal, B. Sagittal, C. Coronal) in March 2011 giving a total dose of 18 Gy in one fraction to each lesion using 6 MV photons.

Follow up MRI in January 2011 showed decreased size of the parietal lesion (1.2 cm from 1.4 cm), stable punctate small lesions of the brain, and 3 tiny new lesions (a 8 x 5 mm in the right temporooccipital region, a 3 mm lesion adjacent to the posterior left lateral ventricle, and a 6 x 4 mm lesion in the right parietal occipital region). She was treated for the second time using stereotactic radiosurgery to the brain. She underwent single fraction stereotactic radiosurgery in March 2011 giving a total dose of 18 Gy in one fraction to each lesion using 6 MV photons. Despite the con tinued metastatic progression of her disease 5 years after diagnosis, the patient’s vision remained stable and there was no evidence of recurrence of the choroidal metastasis 3 years after treatment with stereotactic radiation.

2. DISCUSSION

2.1 Background

The first report of carcinoma metastatic to the eye was by Perls in 1872 [1]. In 1971, Bloch and Gartner suggested that metastatic tumors were the most common malignant neoplasms of the eye and in their postmortem examination of breast carcinoma patients, one-third were found to have ocular metastasis [2]. Although they were historically considered a rare finding, intraocular metastases are now known to occur in approximately 2–7% of patients with cancer [3]. The identification of intraocular metastases appears to be increasing, likely due to improvements in diagnostic imaging such as optical coherence tomography and systemic therapies leading to survival prolongation, altering the natural course of metastatic disease [4]. Intraocular metastases are thought to be due to hematogenous spread. The metastatic emboli are carried by the internal carotid artery into the ophthalmic artery, after which they pass into the ciliary vessels and then into the uveal tract [5, 6]. Metastatic carcinoma to the uveal structures is recognized as the most common intraocular neoplasm, followed by the optic nerve and orbit [7, 8]. Among the uveal structures, the choroid is involved in 88% of uveal metastases, the iris in 9%, and the ciliary body in 2% [9]. This high incidence of uveal metastasis is likely due to the fact that the choroid has the high blood flow rate of all tissues [10].

The most common primary source of uveal metastases is breast cancer in females and lung cancer in males [11]. Breast cancer accounts for 39% to 49% of all uveal metastases [12]. Other primary neoplasms which can uncommonly metastasize to the eye are testis, gastrointestinal tract, kidney, thyroid, pancreas, skin, and prostate [9, 13]. Choroidal metastases have been found in approximately 8% of patients with advanced breast cancer. In one-third of these patients, choroidal metastasis is the first symptomatic site of recurrence, as was the case with the patient presented above [9]. The median survival after choroidal metastasis in patients with stage I/II breast cancer was 28.7 months while the median survival of patients with stage III/IV disease was 4.6 months [9, 13-15].

2.2 Clinical Presentation

Patients with choroidal metastasis secondary to breast cancer present with visual symptoms in approximately 93% of cases [12]. The most common symptom in these patients is reduced visual acuity but other symptoms include diplopia, photophobia, photopsia, floaters, ptosis, exophthalmos, pain, secondary glaucoma, and retinal detachment [16]. The pathophysiology of the retinal detachment may be due to the high metabolic needs of a rapidly growing choroidal tumor resulting in localized ischemia and damage of adjacent structures [17]. Since approximately 10% of patients with choroidal metastases are asymptomatic, some authors have suggested ophthalmological screening for high risk patients [3, 18]. Diagnosis is based on a thorough medical history and clinical evaluation including dilated fundoscopic examination, fluorescein angiography and optical coherence tomography [4, 16]. Choroidal metastasis often appear as diffuse, cream colored lesion deep to the retinal vasculature.

2.3 Management/Treatment

The treatment options for intraocular metastases include observation, chemotherapy, endocrine therapy, radiation, resection (only possible with anterior uveal lesions), or enucleation[5]. These treatments often have no effect on survival rates [19], thus therapy is palliative [20]. A clinical accomplishment in the treatment of intraocular metastasis is arresting further deterioration in vision and stabilizing visual acuity [21].

Radiation therapy is the well-known effective and safe treatment of choice for choroidal metastases, with about an 80% response rate [22]. However, chemotherapy has been anecdotally reported by some authors to be as effective as radiotherapy for choroidal metastases, albeit with greater systemic side effects [9, 23]. Different modalities of radiotherapy include external beam radiation therapy (EBRT), plaque brachytherapy, stereotactic radiotherapy, cyber knife gamma surgery, and proton beam radiotherapy (PBT). With regression of the choroidal metastic lesions, resolution of the subretinal fluid is typically seen. As radiation treatment to the retina induces delayed tissue ischemia, careful ophthalmic followup is necessary to monitor for signs of neovascularization of the retina and anterior segment of the eye as well as cataract formation.

2.3.1 External-Beam Radiotherapy (EBRT)

EBRT is a well-established treatment for uveal metastases that was first applied in 1979 [24]. Numerous publications support the use of EBRT in effectively treating ocular metastases. Treatment response rates, measured by lesion regression and improvement or stabilization of vision, is approximately 80% [25-26]. Total dose of radiotherapy recommended is 26–46 Gy, with a median of 39.4 Gy[3, 27-28]. Significant complications of palliative EBRT are infrequent but include cataracts, exposure keratopathy, iris neovascularization, radiation retinopathy, and radiation papillopathy. These complications are seen in about 12% of patients over a median of 5.8 months of follow-up [26]. However, the complications are dose-dependent with incidence of 0% for doses ≤ 30 Gy and 100% at doses ≥ 57 Gy[28, 29]. The main disadvantage of EBRT is the need for repeated daily treatments, of at least 10 fractions [26].

2.3.2 Plaque brachytherapy

Plaque brachytherapy has been used successfully for choroidal melanomas and has more recently been used for choroidal metastasis. In one retrospective study conducted by Shields et al, lesion regression was noted in 94% of the 36 patients studied at a mean follow-up of 11 months [30]. Short term complications were seen in 8% of patients and included radiation retinopathy, papillopathy, and cataract in anteriorly placed plaques [30]. Visual prognosis seems worse than EBRT, with only 19% showing improvement, 39% showing no change, and 42% showing decreased visual acuity [30].

2.3.3 Stereotactic Radiosurgery (SRT)

SRT has been used in the treatment of multiple ophthalmologic disorders including uveal melanomas, advanced glaucoma, age-related macular degeneration, hemangioblastoma, angioreticuloma, pseudotumors, and vegetative pain [31]. This therapy has been used cautiously because single large doses of radiation therapy can damage the several potential structures that are at risk within the eye [32]. In the anterior segment, significant irradiation of the iris can lead to neovascularization and neovascular glaucoma. Radiation of the lens can lead to cataract, with the probability of this side effect 5 years after radiation therapy being 5% when 2 Gy is delivered in a single fraction or 50% when 10 Gy is delivered. In the posterior segment, the fovea is particularly sensitive to radiation toxicity. The optic nerve is generally safe with a single fraction dose of 10 Gy[33]. The patient’s right choroidal metastasis discussed in the case above was treated to a total of 25 Gy, and the dose to the optic nerve was 2.15 Gy per fraction over 5 fractions, well below the safe limit.

SRT has not been used to a great extent to treat choroidal metastases [34, 35]. Marchini et al reported the first case to discuss the use of SRT in treating a cho roidal metastasis secondary to lung cancer. They reported a reduction in size of the lesion with the use of SRT [34]. Bellmann et al invsstigatged the use of SRT with choroidal metastases. This study looked at ten patients with unifocalchoroidal metastasis (three lung carcinomas, three breast carcinomas, three colon carcinomas, one cutaneous melanoma). A dedicated stereotactic linear accelerator (6 MV) was used to administer 12 to 20 Gy in a single dose or 30 Gy over 10 days (3 Gy each session). Within the observation period of 34 months, local tumor control was achieved in all patients. A decrease in tumor size on ultrasonography or MRI was noted in 8 out of 10 patients and no persistent side effects were observed during a median follow-up period of 6.5 months. This study established that SRT is effective in controlling tumor growth and demonstrated the precise administration of focused irradiation to an intraocular tumor [35]. Based on the published studies and the case presented here from our institution, SRT seems like a promising way to deliver a single dose of ionizing radiation to a small target, with steep dose fall-off at the margins, thereby minimizing the adverse effects of radiation.

2.3.4 Proton Beam Radiotherapy (PBT)

PBT was traditionally used for the treatment of uveal melanomas but has recently been applied to choroidal metastases as well. In a retrospective study of 76 eyes treated with PBT, complete regression of the lesion was observed in 84% of patients within 5 months with no recurrence after a mean follow-up of 10 months. Associated serous retinal detachments resolved in 82% of patients within 3.8 months. The possible complications from PBT include lid burn, madarosis, iris neovascularization, neovascular glaucoma, cataract, radiation retinopathy, and radiation papillopathy[36].

2.4 Cost Analysis

Using the 2010 Medicare allowable rates for radiation therapy, we found that the total cost for one fraction of stereotactic radiation therapy was $6,769.05. In comparison, the total cost for external beam radiotherapy was $5627.13 (Table 1). Thus, the difference in cost between SRT and EBRT is only $1141.92. As EBRT needs to be administered over at least 10 fractions while SRT can be accomplished in one visit, the difference in cost is non-substantial.

Table 1.

Cost comparison of stereotactic radiation therapy and external beam radiation therapy using 2010 Medicare rates.

SBRT Fraction 2011 Medicare Rates
Procedure Codes	Description Activity	Quantity	2010 MCR Allowable	MCR Subtotal
99205	Consult	1	200.82	200.82
77290	Simulation	1	566.62	566.62
77263	MD Treatment Plan	1	162.97	162.97
77333	Intermediate Treatment Device	0	61.78	0
77334	Complex Treatment Device (Quantity Varies)	9	161.83	1456.47
77014-TC	CT Place for Radiation Treatment	1	160.98	160.98
77470	Special Treatment Procedure	1	211.5	211.5
77295	3D Plan	1	593.99	593.99
77370	Physics Consult	1	124.91	124.91
77300	Dosimetry Calculation (Quantity Varies)	9	73.41	660.69
77373	Stereo 1 fraction	1	1713.22	1713.22
77336	Continuing Physics	1	56.22	56.22
77435	MD-SRS Weekly Mgmt	1	682.84	682.84
77331	Special Radiation Dosimetry	1	65.37	65.37
77321	Special Teletherapy	1	112.45	112.45
				6769.05

External Beam 3D/4D 2011 Medicare Rates
Procedure Code	Description Activity	Quantity	2010 MCR Allowables	MCR Subtotal
99205	Consult	1	200.82	200.82
77290	Simulation	1	566.62	566.62
77263	MD Treatment Plan	1	162.97	162.97
77334	Treatment Device Complex (Quantity Varies)	3	161.83	485.49
77014-TC	CT Place for Rad Treatment	1	160.98	160.98
77470	Special Treatment Procedure	0	211.5	0
77295	3D Simulation Plan	1	593.99	593.99
77300	Dosimetry Calculation (Quantity varies)	3	73.41	220.23
77370	Physics Consult	0	124.91	0
77331	Special Dosimetry	0	65.37	0
77280	Simple, Verification Sim	1	201.43	201.43
77413	6-10 MeV Complex Treatment	10	252.54	2525.40
77417	Port Films	2	15.93	31.86
77315	Tele Plan, Complex	0	149.07	0
77321	Special Tele Plan	0	112.45	0
77336	Continuing Physics	2	56.22	112.44
77427	MD Weekly Treatment Mgmt	2	182.45	364.9
				5627.13

3. CONCLUSION

With cancer rates rising and cancer survival improving, choroidal metastases may become an increasingly important cause of visual impairment. For patients with acutely symptomatic choroidal metastases in the setting of widespread metastatic disease, stereotactic radiosurgery can be instrumental in providing rapid relief of symptoms while allowing timely initiation of systemic therapy. While comparative data is lacking to prove which radiotherapy modality is superior for treating choroidal metastases, we present here a case demonstrating the successful use of stereotactic radiation in the treatment of a choroidal metastasis secondary to breast cancer resulting in complete lesion regression and improved visual acuity. Since stereotactic radiation allows focused irradiation of choroidal metastases with less damage to surrounding ocular tissues, we believe that stereotactic radiation will become integral in the treatment of this entity.