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Ocular Adnexal Maltomas: Case Series of Patients Treated with Primary Radiation Wesley Russell, MD, Arnold Herskovic, MD, David Gessert, Jack A

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Ocular Adnexal Maltomas: Case Series of Patients Treated with Primary Radiation Wesley Russell, MD, Arnold Herskovic, MD, David Gessert, Jack A Ocular Adnexal MALTomas: Case Series of Patients Treated With Primary Radiation Wesley Russell, MD, Arnold Herskovic, MD, David Gessert, Jack A. Cohen, MD, Jonathan B. Rubenstein, MD, and Stephanie A. Gregory, MD Dr. Russell is a Resident Physician in the Abstract: Background: Ocular adnexal mucosal-associated lymphoid Department of Radiation Oncology, tissue lymphomas (MALTomas) are rare, and there are no phase III Dr. Cohen is Associate Professor of trials to guide treatment. Primary radiation therapy has been the typi- Ophthalmology and Assistant Professor of cal management. This retrospective series reports the experience of Radiation Oncology in the Department of Radiation Oncology, Dr. Rubenstein is a single institution and adds to the current literature. Methods: Our Deutsch Family Professor and Vice-Chair- electronic medical record system and available paper charts were man of Ophthalmology in the Department used to identify patients with MALTomas of the lacrimal gland or sac, of Ophthalmology, and Dr. Gregory is the conjunctiva, and orbital structures, including extraocular muscles. In Elodia Kehm Chair of Hematology and order to determine pathology, staging, treatment information, local Professor of Medicine in the Section of and distant control, salvage treatments, and late toxicity, records were Hematology at Rush University Medical Center in Chicago, Illinois. Dr. Herskovic is reviewed. Results: Sixteen patients with ocular adnexal MALTomas Professor Emeritus at the Cancer Treatment had local radiation between 1992 and 2011 for primary or recurrent Group in Chicago, Illinois. Mr. Gessert is a disease. Fifty percent of patients had lymphoma in the conjunctiva, medical student at Rush Medical College in 25% had lymphoma in the lacrimal sac/gland, and 25% of patients Chicago, Illinois. had lymphoma in the posterior orbit. Stage IAE disease occurred in 75% of patients, 6% had stage IIAE disease, and 19% of patients had a Address correspondence to: Wesley Russell, MD positive bone marrow biopsy. One patient received chemotherapy as Resident Physician part of initial therapy. The median radiation dose was 30 Gy (25.5–36 Rush University Medical Center Gy) delivered with electrons (31%) or photons (69%). After a mean Department of Radiation Oncology follow-up of 62.8 months, 2 patients had residual/progressive disease, 500 S Paulina 2 had contralateral recurrence, and 1 patient had a distant failure, Atrium Building, Ground Floor for local control of 87.5% and overall disease control of 68.75%. Chicago, IL 60612 Phone: 312-942-5751 Recurrence/progression occurred at a median of 35.45 months. Two Fax: 312-942-2339 patients with residual/progressive disease and 1 patient with a contra- E-mail: [email protected] lateral recurrence were followed, successfully salvaged, and have no evidence of disease. Fourteen patients are still alive, and there were no disease-related/toxicity deaths. Seven patients developed cata- racts in the treated eye, 2 patients had radiation retinopathy, 2 had permanent dry eye syndrome, and 1 patient had severe keratopathy requiring enucleation. Six patients (3.75%) had worsening visual acuity of unclear etiology. Conclusions: Primary radiation therapy for ocular adnexal MALTomas with a median dose of 30 Gy led to excel- Keywords MALToma, ocular adnexa, lymphoma, radiation, lent local control. Patients who did recur were successfully salvaged. conjunctiva, lacrimal gland Clinical Advances in Hematology & Oncology Volume 11, Issue 4 April 2013 209 RUSSELL ET AL Radiation was generally well tolerated, with expected Table 1. Patient Characteristics cataractogenesis, given the dose required to achieve local Age at Diagnosis (Years) control (with only 1 patient developing severe keratopathy Median 56.9 after receiving the highest dose in this series). Range 35.25–77.68 Sex Background Male 8 Ocular adnexal mucosal-associated lymphoid tissue lym- Female 8 phomas (MALTomas) are rare entities that comprise a small Stage proportion of both orbital neoplasms and non-Hodgkin IAE 13 lymphomas (NHL). Unlike other NHL types, ocular IV 3 adnexal lymphomas show little difference by sex. Incidence rates tend to be highest among Asians/Pacific Islanders, Location lower in whites, and lower still in blacks.1 Additionally, Conjunctiva 7 the frequency of ocular adnexal lymphomas appears to be Lacrimal apparatus 3 increasing, with annual increases of 6.2% for white males and 6.5% for white females with no evidence of peaking. Orbital 4 By contrast, the rates for other extranodal NHLs increased Multiple subsites 2 at 4.3% and 4.0% per year among males and females, Staging respectively, while the rates for nodal NHL rose less rapidly, at 1.8% and 1.3%, an increase that may partially be sec- Computed tomography (chest, 15 abdomen, and pelvis) ondary to changes in pathologic classification.1 MALTomas represent the most common subtype of ocular adnexal lym- Bone marrow 13 phomas.2 The primary management of these tumors has generally consisted of radiation therapy with the addition of chemotherapy as indicated depending on stage. Because a hematopathologist. Although staging was not standard- of the rarity of this tumor, there are no randomized phase ized, the majority of patients were staged with computed III trials evaluating therapy and outcomes. The aim of this tomography (CT) of the chest, abdomen, and pelvis and retrospective series is to add to the current literature regard- bone marrow biopsy. No patients were staged with posi- ing the management of MALTomas of the ocular adnexa. tron emission tomography (PET)/CT. Overall survival was calculated from the date of diagno- Methods sis. Freedom from progression was measured from the start of treatment until progression or relapse. Patients who died We used our electronic medical record system to iden- from other causes and were otherwise disease-free were cen- tify patients seen in the radiation oncology department sored at the time of death. Survival was verified using elec- between January 1992 and June 2011 with diagnoses tronic medical records and the Social Security Death Index. involving the eye or other ocular structures, as well as those For 15 patients, dates of diagnosis were identified with lymphoma. These results were then reviewed to iden- based on the date of biopsy. For 1 patient who was seen tify patients with MALTomas involving the conjunctiva, for recurrent disease and whose exact date of diagnosis lacrimal sac or gland, extraocular muscles, or other orbital was unavailable, the date of diagnosis was listed as July structures, excluding patients presenting with intraocular 1 of the year in which he was diagnosed. The patient did lymphoma or primary central nervous system (CNS) not receive any definitive treatment until 3 years after his lymphoma. Once these patients were identified in the biopsy, and so this would affect only his age at diagnosis, electronic medical record system, electronic records were as follow-up and overall survival were calculated from the reviewed for the radiation oncology and medical oncol- date of radiation completion. ogy departments. In addition, paper charts were reviewed from the radiation oncology, medical oncology, and oph- Results thalmology departments. Data regarding pathology, dates of diagnoses and treatment completion, treatment details, Among patients who were treated from December 1992 follow-up, recurrence, salvage treatment, and survival to July 2011, 16 patients were identified with MALTomas were analyzed. All pathology specimens were reviewed by of the orbit, conjunctiva, or lacrimal gland/sac (Table 210 Clinical Advances in Hematology & Oncology Volume 11, Issue 4 April 2013 O cular A d n E x al M A LT omas : C ase S eries O f Patie n ts T reate d W ith P rimar y R A d iatio n Table 2. Treatment Characteristics rimal gland/sac disease; both orbits in 1 patient; and an Radiation Dose unspecified “eye” volume in 1 patient with a conjunctival primary. One of the 8 patients treated to the orbit was Median 30 Gy also treated to the involved ipsilateral parotid and another Range 25.2–36.0 Gy to uninvolved preauricular lymph nodes. Fraction Size Complete response was observed in 14 of 16 patients (87.5%). After a mean follow-up of 62.8 months, local Median 1.8 Gy control was achieved in 12 patients (75%), with 2 Range 1.7–2.0 Gy patients having residual disease requiring further treat- Radiation Technique ment that was effectively salvaged. One patient failed in En face electrons 5 the ipsilateral orbit, and 1 patient failed in the contra- lateral orbit (after having been treated to both orbits). Photons 11 Only 1 patient failed distantly. Of those who failed Treatment Volume locally (with either residual disease or recurrence), 1 Conjunctiva 6 patient was controlled after resection followed by further radiation, another patient was controlled after repeat Orbit 9 irradiation followed by chemotherapy, and 1 patient was Both orbits 1 controlled with rituximab (Rituxan, Genentech/Biogen Initial Chemotherapy Idec) alone. The fourth patient had to discontinue care at our institution due to a change in insurance. The 1 Yes 2 patient with a distant failure was treated at an institution No 14 closer to home. Of the 16 patients, there were 2 deaths (1 due to metastatic colon cancer and the other due to 1). The median age at diagnosis was 56.9 years (range, an unclear cause), but both patients had control of their 35–79 years). Half of the patients were male. Sites of disease as of 8 months prior to death at last follow-up. involvement included the conjunctiva in 8 patients, the Three of the patients who underwent local salvage are posterior orbit in 6 patients, and the lacrimal sac/gland currently disease-free, and the other 2 patients with fail- in 4 patients. One patient had involvement of both ure are alive, although their disease status is not known the orbit and lacrimal gland, and another patient had as they were followed at other institutions.
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