Clinical outcomes of hypofractionated radiation therapy for choroidal metastases: Symptom palliation, tumor control, and survival.

PURPOSE: External beam radiation therapy (RT) is an effective palliative treatment for patients with choroidal metastases and is aimed at preserving vision and obtaining local tumor control. Delivery of 30 to 40 Gy in 2-Gy daily fractions is a standard approach at many centers. This study reports the outcomes of a hypofractionated schedule of 20 Gy in 5 fractions in this palliative setting. METHODS AND MATERIALS: We conducted a retrospective review of patients who were treated with RT (20 Gy in 5 fractions) for choroidal metastases between January 1999 and November 2012. The primary outcome measures were change in visual acuity and tumor response. Secondary outcomes included toxicities of RT, tumor control, and overall survival (OS) from diagnosis of choroidal metastases. Univariate and multivariable Cox regression modeling was used to investigate the predictors for OS. RESULTS: Fifty-five patients with 71 affected eyes were included. Decreased vision was the presenting symptom in 43 eyes (61%). Visual acuity improved from a median of 20/70 at baseline to 20/40 at last follow-up and remained stable or improved in 56 eyes (80%). Tumor regression was observed in 64 eyes (91%) with complete response in 47 eyes (67%). Local progression occurred in 4 eyes (6%). The median survival after diagnosis of choroidal metastases was 13 months. No acute complications were observed in 49 patients (89%). Mild acute toxicities included transitory dryness in 5 patients and episcleritis in 1 patient. Cataracts, retinopathy, optic neuropathy, pigmentary maculopathy, and neovascular glaucoma developed in 4 eyes (6%), 1 eye, 7 eyes (10%), 5 eyes (7%), and 1 eye, respectively. No variables were statistically significantly associated with OS. CONCLUSIONS: A short fractionation schedule of 20 Gy in 5 fractions is a well-tolerated treatment that effectively preserves vision and gains local tumor control for many patients with choroidal metastases. This hypofractionated approach would help reduce the burden of a longer treatment course in this palliative patient population.

Orbital radiation therapy for Graves' ophthalmopathy: measuring clinical efficacy and impact.

PURPOSE: Graves' ophthalmopathy (GO) is an autoimmune condition primarily managed with prolonged courses of glucocorticoids, which can be associated with significant side effects. Orbital radiation therapy (RT) is an alternative treatment that has shown variable efficacy in improving orbital and visual symptoms. In this study, the therapeutic benefit of RT was evaluated in terms of patient's ability to taper their corticosteroid requirements, which may better reflect the proposed mechanism of RT and provide a clinically relevant response endpoint. METHODS AND MATERIALS: This is a retrospective review of consecutive patients treated with orbital RT for GO between 2000 and 2010 at a single tertiary hospital with a dedicated ocular radiation therapy clinic. The primary measure of treatment response was defined as the ability to taper glucocorticoids following RT without any further exacerbation of orbitopathy symptoms. Additional endpoints including ocular symptoms (diplopia, proptosis, visual acuity, extraocular movement) and need for surgical intervention were reported. RESULTS: Of 86 eligible patients, with a mean follow-up of 9.3 months, 81 (94%) patients responded to RT. Of patients taking corticosteroids at baseline, 91% were able to taper off corticosteroids completely and the remaining patients had decreased their doses by 83%. Diplopia, visual acuity, and extraocular movements improved in 29%, 81%, and 58% of patients, respectively. The median reduction in proptosis was 2.5 mm and 2 mm in the left and right eyes, respectively (range, -18 mm to 23 mm). CONCLUSIONS: Orbital RT is a generally well-tolerated treatment that helps minimize the dose and duration of corticosteroid therapy for patients with GO while improving ocular symptoms, including proptosis and diplopia. Prospective research should consider using corticosteroid requirement as a measure of response to orbital RT for GO.

Unusual orange-colored choroidal metastases.

PURPOSE: To report the clinical and paraclinical features of two patients with orange- colored choroidal metastases in whom the primary cancers have not previously been associated with such lesions. CASE REPORT: Orange-colored choroidal lesions were detected on the fundus examination of one patient with metastatic small cell neuroendocrine tumor of the larynx and oropharynx, and in another subject with metastatic alveolar soft part sarcoma of the leg. Although ultrasonographic characteristics of the choroidal masses were comparable to those of choroidal hemangiomas, fluorescein angiography revealed delayed initial fluorescence along with minimal fluorescence in subsequent phases of the angiogram which were in clear distinction from the earlier appearing and progressively intense fluorescence observed with circumscribed choroidal hemangiomas. CONCLUSION: Small cell neuroendocrine tumors and alveolar soft part sarcomas should be considered among the differential diagnoses for orange-colored choroidal metastases. Identifying these choroidal lesions could facilitate localizing the occult primary tumor. Fluorescein angiography may differentiate a unifocal orange choroidal metastasis from a circumscribed choroidal hemangioma.

Ocular toxicity of targeted therapies.

Molecularly targeted agents are commonly used in oncology practice, and many new targeted agents are currently being tested in clinical trials. Although these agents are thought to be more specific and less toxic then traditional cytotoxic chemotherapy, they are associated with a variety of toxicities, including ocular toxicity. Many of the molecules targeted by anticancer agents are also expressed in ocular tissues. We reviewed the literature for described ocular toxicities associated with both approved and investigational molecularly targeted agents. Ocular toxicity has been described with numerous approved targeted agents and also seems to be associated with several classes of agents currently being tested in early-phase clinical trials. We discuss the proposed pathogenesis, monitoring guidelines, and management recommendations. It is important for oncologists to be aware of the potential for ocular toxicity, with prompt recognition of symptoms that require referral to an ophthalmologist. Ongoing collaboration between oncologists and ocular disease specialists is critical as the use of molecularly targeted agents continues to expand and novel targeted drug combinations are developed.

Progressive tumefactive fibroinflammatory lesion of the infratemporal fossa treated by radiation therapy.

Tumefactive fibroinflammatory lesion (TFIL) is a rare benign tumor in the head and neck region. We present a case of a 40-year-old female with a benign but progressive lesion of the infratemporal fossa, which was diagnosed as TFIL. Patient responded briefly to a course of steroid treatment but eventually showed progression and was unresponsive to further steroids. She was then treated with external beam radiation to a dose of 60 Gy in 30 fractions. After radiation a slow, gradual decrease in tumor size was noted over the course of years and she is free of disease after more than 11 years of follow-up. The major long-term side effect this patient developed was an expected unilateral radiation-induced retinopathy, due to the close proximity of the lesion to the orbit. The dilemma of treatment of benign disease with radiation with potential long-term complications is discussed and a review of the literature on TFIL is presented.

Factors predictive of radiation retinopathy post (125)Iodine brachytherapy for uveal melanoma.

OBJECTIVE: To report the host, tumour, and radiation-related predictive factors for developing radiation retinopathy post (125)Iodine brachytherapy for uveal melanoma. DESIGN: A retrospective clinical case series. PARTICIPANTS: Three hundred consecutive patients with uveal melanoma treated with (125)Iodine brachytherapy. METHODS: Electronic chart review of demographic, clinical, treatment, and follow-up data. Proliferative and (or) nonproliferative radiation retinopathy patients were included. Cumulative incidence rates were calculated using Kaplan-Meier estimates. Univariate and multivariate statistical regression analyses were performed to identify factors predictive of radiation retinopathy. RESULTS: The mean follow-up period was 48 months. Radiation retinopathy occurred in 107 patients (36%). Actuarial incidence of radiation retinopathy was 30% (CI 24%-36%) at 24 months post-treatment. In the multivariate model, the predictive factors were a younger age (hazard ratio [HR] 0.98, p < 0.03), diabetes (HR 2.17, p < 0.007), and hypertension (HR 2.17, p < 0.004). Tumour-related factors were proximity to optic disc (HR 0.95, p < 0.02) and proximity to foveola (HR 0.96, p < 0.02). Pretreatment tumour dimensions, other tumour characteristics, and total radiation dose did not demonstrate statistically significant risks for developing radiation retinopathy. CONCLUSIONS: Radiation retinopathy affects 30% of patients 2 years following (125)Iodine brachytherapy for uveal melanoma. The predictive factors for radiation retinopathy are a younger age, comorbidity with diabetes or hypertension, and proximity of the tumour margin to the optic disc or foveola. Identifying the predictive factors for developing radiation retinopathy can modify follow-up for patients at risk, which may permit earlier management of the developing radiation-induced ischemic retinal changes.

Localized orbital mucosa-associated lymphoma tissue lymphoma managed with primary radiation therapy: efficacy and toxicity.

PURPOSE: To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). METHODS AND MATERIALS: From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. RESULTS: The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade ≥2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). CONCLUSIONS: POML responds favorably to moderate doses of RT but results in significant late morbidity. The majority of late effects were successfully managed. Lens shielding reduced the risk of cataracts and other late sequelae.

Paraneoplastic vitelliform retinopathy in metastatic cutaneous melanoma.

PURPOSE: To report the clinical picture and investigative findings of unusual paraneoplastic retinopathy lesions in a patient with metastatic skin melanoma. METHODS: A middle-aged man presented with mild blurring of vision in one eye. He had metastatic skin melanoma to the axillary lymph nodes, which was treated by interferon. Fundus photographs showed bilateral unusual multiple vitelliform lesions. Retinal and serologic investigations were performed. RESULTS: These vitelliform lesions involved the outer retinal layers and retinal pigment epithelium (RPE) as demonstrated by optical coherence tomography and have completely blocked choroidal fluorescence without late staining in angiography. There was only minimal reduction of Arden ratio in electro-oculography, although electroretinography was essentially normal. Antibipolar cells autoantibodies were not detected in this case. CONCLUSION: This melanoma-related paraneoplastic retinopathy may represent a separate entity from the classic findings in melanoma-associated retinopathy (MAR) syndrome. Optical coherence tomography is helpful to differentiate it from simulating lesions. Recognition of this presentation can help to diagnose the presence of an occult metastaticmelanoma in some cases.

Transpupillary thermotherapy in the management of juxtapapillary and parafoveal circumscribed choroidal hemangioma.

BACKGROUND: Circumscribed choroidal hemangioma (CCH) is a rare, vascular tumor that may be associated with formation of subretinal fluid, cystic retinal de-generation, and serous retinal detachment. Studies have suggested that proximity of this tumor to the fovea or optic nerve precludes the use of trans-pupillary thermotherapy (TTT) for treatment. We report our experience using TTT in managing patients with juxtapapillary and parafoveal CCH. METHODS: We reviewed the records of consecutive patients with CCH treated by TTT at Princess Margaret Hospital, Toronto, between November 1999 and March 2003. This resulted in 11 eyes of 11 patients with juxtapapillary or parafoveal tumors. Treatment was delivered via slit lamp using an 810 nm diode laser with 350 to 800 mW, a 3.0 mm spot, and duration range from 5 s to 90 s. Outcome measures were reduction in tumor thickness, resolution of serous fluid, tumor control, visual acuity, and complications of treatment. RESULTS: Mean age of patients was 47.6 years. Symptoms included blurred vision, metamorphopsia, light flashes, and floaters. Macular and optic disk edema, field defect, presence of subretinal fluid, and retinal detachment were noted. At presentation, Snellen visual acuity ranged from 20/70 to hand motions. Mean tumor base diameter was 6.0 mm and tumor thickness at baseline was 3.0 mm. Mean follow-up was 18.0 months. Post-TTT, mean tumor thickness was 2.8 mm. Macular and optic disk edema resolved in the majority of patients. Partial regression of the tumor was noted in 4 cases (36%) and good tumor control in 9 cases (82%). Visual acuity improved in 6 patients (55%). INTERPRETATION: TTT can be effective for treating juxtapapillary and para-foveal CCH. Proximity to the fovea and optic nerve may not be predictive of poor post-treatment visual acuity, although statistical analysis with a larger sample size would more clearly demonstrate a clear advantage.