Efficacy of Radiation Treatement in Ocular Adnexa Mucosa-Associated Lymphoid Tissue Lymphoma: A Retrospective Evaluation in a Single Center Experience

BACKGROUND: The ocular adnexa mucosa-associated lymphoid tissue lymphoma (OAML or MALT lymphoma) is the most common form of ophthalmic Non-Hodgkin's Lymphoma (NHL) and accounts for approximately 1-2% of all lymphomas. The great majority of ophthalmic NHL is of B-cell origin and involves ocular adnexal regions, which include orbit, conjunctiva, lacrimal gland or eyelid. OAML is a disease of the elderly population (median age 65 years) with greater prevalence among females. Several studies have shown a correlation between autoimmune and inflammatory disorders and ocular adnexa MALT lymphoma. In fact, patients with Sjögren disease or thyrotoxicosis with/without thyroid orbitopathy are at much greater risk for developing OAML. Similarly, inflammatory disorders such as chronic conjunctivitis are significant etiological factors. Recently, Chlamydia psittaci (Cp) infection has been identified as a risk factor of OAML development. Morphologically, adnexa MALT lymphoma is characterized by heterogenous cell population with CD20+, CD10⁻, CD23⁻, BCL6⁻, Cyclin D1⁻. Treatment options include surgery, (immuno)chemotherapy and radiotherapy, but some new approaches have been introduced, such as Cp eradication antibiotic therapy or radioimmunotherapy.

PATIENTS AND METHODS: We performed a retrospective analysis on 82 patients (42 females and 40 males, mean age 62.96 ± 15,03) with OAML treated with radiotherapy from January 1986 to December 2017 at Veneto Institute of Oncology-IRCCS. All patients had stage IE at the diagnosis and didn't present systemic symptoms, while the most common local symptoms were eye swelling (45 pts, 55%), conjunctivitis (14 pts, 17%) and exophthalmos (12 pts, 14%). The desease was localized in the left eye in 42 patients (51%), in the right eye in 33 (40%) and bilaterally in 7 patients (9%). The diagnosis was obtained by pathological or cytological examination whereas the staging was performed with haematological tests, total body computer tomography (TBCT), magnetic resonance imaging (MRI) and bone marrow biopsy. Since 2008, the staging was obtained also by using positron emission tomography (PET). All patients were treated with 3D-conformal radiotherapy (RT); CO60 ɣ rays were used in 7 patients (8,5%) and 6 MV photons in the rest of the 75 pts (91,5%). The median dose was 30,6 Gy (range 30-40 Gy) with a standard fractioning (1,8 Gy per day).

RESULTS: The median follow up was 8,4 years. Complete response (CR) was obtained in all 82 patients (pts). Local relapse was observed in 2 patients (2,5%), both in contralateral eye, and systemic in 10 (12%). Of these, Rituximab monotherapy was administered in 4 patients, Rituximab and Chlorambucil in 2, R CVP in 1 patients, R CHOP in 2 and the regimen MVP-BV in 1 patient. The cumulative progression free survival (PFS) was 88%. Twenty-two patients (27%) died, all for non-oncological reasons. The radiotherapy was well tolerated with grade toxicity, according RTOG scale, ranging from G1 (36 pts) to G2 (20 pts). Most frequent acute side effects were conjunctivitis (23 pts, 28%), erythema (22 pts, 27%) and edema (11 pts, 13.5%), whereas the most common late toxicities were cataract (33 pts) and xerophthalmia (8 pts). Total dose > 30,6 Gy resulted significantly associated with cataract (p>0,005). Fifty percent of the patients had no late toxicity.

CONCLUSIONS: In patients with ocular adnexa MALT lymphoma, 3D conformal radiotherapy is an effective treatment with PFS of 88%. Such therapy is well-tolerated in terms of acute and late toxicities and with eyesight well preserved. Cataract represents the most common late side effect and it seems to be associated with a total dose > 30,6 Gy.