Rand Simpson

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.

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.

Factors predictive of radiation retinopathy post 125Iodine 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.

Diffuse metastatic melanoma to the retina: a clinicopathologic report

A 54-year-old female was referred to evaluate a peripheral melanotic fundus lesion in the left eye. A month prior, she noticed a temporal field defect in the same eye. Three months before the ocular symptoms, she underwent bowel resection for small intestinal obstruction caused by multiple tumours in the intestinal wall and regional lymph nodes, which are suggestive of hematogenous metastatic disease. Excised masses were pathologically proved to be metastatic melanoma. The patient provided no definite history of a previous primary melanoma; however, she had a curious account of a pigmented lesion appearing in her forearm skin during pregnancy 20 years earlier, for which a biopsy was not performed and that had spontaneously disappeared postpartum. No other relevant ocular or medical history was obtained. On examination, the visual acuity was 20/20 in both eyes. Bilateral anterior segment examination was normal, and intraocular pressure was 16 mm Hg. Funduscopy of the right eye was normal, but the left eye demonstrated a pre-equatorial diffuse pigmented lesion. The lesion extended as a patch between 7and 11-o’clock meridians, accumulating at the fundus periphery, covering the underlying retina, and extending anterior to ora serrata (Fig. 1A). The surface of the lesion had a velvety friable appearance with few pigmented particles dispersed into vitreous adjacent to the main lesion (Fig. 1B). A single, small, pigmented spot was also observed temporal to the macula adjacent to the inferotemporal arcade. However, on magnified fundus imaging, multiple minute pigmented particles could be detected scattered over the retinal surface (Fig. 1C). Ultrasonography demonstrated a diffuse lesion with medium internal reflectivity, 3 mm in thickness (Fig. 1D). Systemic staging with magnetic resonance imaging showed evidence of a few small liver nodules and 5 brain lesions. The largest brain lesion was associated with hemorrhage, which was subsequently excised through craniotomy and was pathologically proved to be a melanoma. This was followed by full-brain irradiation of the smaller brain lesions, with inclusion of the eyes within the radiation field. The patient continued to notice gradual decline in vision and progressive pain in her left eye. Two months after irradiation, the left eye vision deteriorated to light perception, and intraocular pressure became 50 mm Hg. The anterior chamber contained a dark pseudohypopyon of tumour cells, and ultrasonography confirmed full involvement of the vitreous cavity with dispersed cells. The left eye, becoming blind and painful, was subsequently

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.

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.

Choroidal melanoma and rhegmatogenous retinal detachment.

A 74-year-old woman was referred to the Ocular Oncology Service with retinal detachment in association with a choroidal melanoma in her left eye. Six months earlier she had noted photopsia in that eye, followed by progressive deterioration of vision. She reported that the vision in her left eye had been blurry for a long time and the cause was unclear. She had controlled hypertension. Ocular examination showed a visual acuity of 20/50 with +0.25 in the right eye and counting fingers with +0.25 in the left. The intraocular pressure, as measured by applanation tonometry, was 18 mm Hg bilaterally. There was a relative afferent pupillary defect in the left eye. Funduscopy of the left eye with the pupil dilated revealed a pigmented mass at the posterior pole measuring 10.5 mm by 6.5 mm in basal diameters. Lipofuscin pigment was visible on the surface of the lesion. An infe-

Outcomes of hypofractionated palliative radiotherapy for choroidal metastases.

194 Background: External beam radiotherapy (RT) is an effective palliative treatment for choroidal metastases aimed at preserving vision and obtaining local tumor control. Delivery of 30-40 Gy in 2 Gy daily fractions is a standard approach in many centers. At our center, a shorter, more convenient schedule of 20 Gy in 5 fractions has been used in this palliative setting. This study reports the efficacy and toxicity of this hypofractionated RT approach. METHODS We conducted a retrospective review of patients treated in the Ocular Oncology clinic at Princess Margaret Cancer Center who received RT (20 Gy in 5 fractions) for choroidal metastases between January 1, 1999 and November 30, 2012. Primary outcome measures were change in visual acuity and tumor response. Secondary outcomes included toxicities of RT, tumor control, and overall survival from the date of choroidal metastases diagnosis. RESULTS A total of 55 patients with 71 involved eyes were included. Decreased vision was the presenting symptom in 43 eyes (61%). Visual acuity improved from a median of 20/70 to 20/40 between baseline assessment and last follow-up, and remained stable or improved in 56 eyes (80%). On ultrasound, tumor regression was observed in 64 eyes (91%) with complete response in 47 eyes (67%). Metastases progressed in 4 eyes (6%) despite RT with 1 eye requiring enucleation. Median survival after diagnosis of choroidal metastases was 13 months with estimated overall survival at 1, 2, and 3 years to be 50% (36-62), 23% (12-35), and 8% (3-18), respectively. Forty-nine patients (89%) did not experience any acute complications. Mild acute toxicities included transitory dryness in 5 patients and episcleritis in 1 patient. Cataracts developed in 4 eyes (6%), retinopathy in 1 eye, optic neuropathy in 7 eyes (10%), pigmentary maculopathy in 5 eyes (7%), and neovascular glaucoma in 1 eye. 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.