Clinical Manifestations and Treatment Results in Accordance with Frontline Treatment Modalities for Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma (OAML)
Authors: Jeon Young-Woo , Yoon Jae-Ho , Lee Sung-Eun , Eom Ki-Seong , Kim Yoo-Jin , Kim Hee-Je , Lee Seok , Min Chang-Ki , Lee Jong Wook , Min Woo-Sung , Cho Seok-Goo 
Published: October 2019

Abstract
Background: localized ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) was effectively treated with frontline radiotherapy. however it is sometimes associated with radiation-related complications of ocular structures, as well as distant relapse or delayed relapse. Although there are no definitive optimal treatment approaches for these patients, we investigated the results in accordance with frontline treatment modalities for OAML.
Patients and methods: 159 patients with biopsy-confirmed primary OAML between 2007 and 2015 were analyzed retrospectively. All the patients were sorted by risk-stratification with Ann-Arbor staging and the tumor, node, metastasis (TNM) staging system, and treatment modalities according to anatomic location, prognosis factors, which were supported by ophthalmologist.
Results: first-line radiotherapy had overall survival(OS) of 100%, event-free survival(EFS) of 90%. However frontline-radiotherapy group has 100% of survival with 55% of moderate to severe dry eye syndrome, 37.4% of cataract incidence, 11% of cataract-related operations, and 1% (n=1) of radiation-related blindness. Although 5-year EFS is good in radiotherapy group (90% vs 64% in radiotherapy group vs chemotherapy, p<0.001), most of aggressive factors (young age at diagnosis, conjunctival lesions, Ann Arbor stage I, early T1N0M0 stage, and no distant extranodal metastasis including of bone marrow involvement) showed in radiotherapy group in comparison with chemotherapy group. In subgroup analysis of first-line chemotherapy, rituximab-containing group has more good response of event-free survival (p= 0.041) with tolerable hematologic toxicities compared to frontline radiotherapy group.
Conclusion: OAML with localized to conjunctiva alone was treated with frontline-radiotherapy and non-conjuctival lesions treated with chemotherapy. Radiotherapy as first-line is good local control-therapeutic option in patients with localized to conjunctiva alone, but management of radiation-associated complication is concerned troubles. In advanced OAML including of extra-conjunctival lesions, systemic chemotherapy is best options. rituximab-based regimen could be feasible to obtain good disease-free survival and response rate.
Table 1. Patient's characteristics between frontline-chemotherapy and radiation group (n= 159) Factors Primary Chemotherapy group(n = 68) Primary Radiation group(n = 91) P-value Gender (male) 37 (54%) 28 (30.8%) 0.003 Age at diagnosis (median, year) 50 43 0.003 involvement of both eyes at diagnosis 22 (32.4%) 23 (25.3%) 0.75 Conjuctival lesion at diagnosis 22 (32.4%) 76 (83.5%) <0.001 Ki-67 on pathologic stain (median, %) 5 4 0.545 Ann-Arbor stage I 23 (66.2%) 3 (96.7%) <0.001 LDH at diagnosis (mg/L) 355 344 0.216 Patients no. with T1N0M0 21 (30.9%) 78 (85.7%) <0.001 Bone marrow involvement 7 (10.3%) 0 (0%) <0.001 Patients no. with N1~N3 staging 10 (14.7%) 0 (0%) <0.001 Patients no. with T0N0M1~2 7 (10.3%) 0 (0%) <0.001
Patients treated with frontline chemotherapy were classified in more aggressive or advanced stage which compare to patients treated with primary radiotherapy statistically.
Table 2. Patient's characteristics between Rituximab containing group and non-rituximab in frontline chemotherapy subgroup (n=68) Factors Ritixumab-containing(n = 26) No Rituximab(n = 42) P-value Gender (male) 0.942 Age at diagnosis (median, year) 52 49 0.411 involvement of both eyes at diagnosis 0.057 Conjuctival lesion at diagnosis 0.087 Ki-67 on pathologic stain (median, %) 4 3 0.540 Ann-Arbor stage I 0.532 LDH at diagnosis (mg/L) 353 356 0.782 Patients no. with T1N0M0 0.585 Patients no. with N1~N3 staging 0.659 Patients no. with T0N0M1~2 0.695
There are statistically no differences between patients treated with Rituximab-containing regimen and non-rixuximab in frontline chemotherapy subgroup.
Figure 1. *event-free survival / overall survival between primary chemotherapy group and patients with radiotherapy * event: from partial response to progressive disease after completion of primary treatments, or death. Figure 1. *event-free survival / overall survival between primary chemotherapy group and patients with radiotherapy * event: from partial response to progressive disease after completion of primary treatments, or death. Figure 2. *event-free survival between patients with rituximab-containing regimen and without rituximab in subgroup analysis of frontline-chemotherapy group * event: from partial response to progressive disease after completion of primary treatments, or death Figure 2. *event-free survival between patients with rituximab-containing regimen and without rituximab in subgroup analysis of frontline-chemotherapy group * event: from partial response to progressive disease after completion of primary treatments, or death Figure 3. Figure 3.

Disclosures
No relevant conflicts of interest to declare.