Salvage Irradiation for Ocular Adnexal Mucosa Associated Lymphoid Tissue Lymphoma Refractory to Chlamydia psittaci Eradication

Purpose: Prospective trials show that Chlamydia psittaci (Cp) eradication with doxycycline is followed by lymphoma regression in 2-thirds of patients with ocular adnexal marginal zone lymphoma (OAMZL). Postponing orbit irradiation, a standard treatment for OAMZL, while waiting for the tumor response to antibiotic, could raise concern. Herein, we report the safety and efficacy of salvage radiation therapy in patients with OAMZL relapsed after or refractory to Cp eradication. Methods and Materials: Patients with stage IEA OAMZL diagnosed at our institution between 2005 and 2023 were evaluated for the safety and efficacy of radiation therapy as salvage treatment after doxycycline. Inclusion criteria were as follows: (1) first-line Cp-eradicating therapy with doxycycline; (2) lymphoma relapsed or progressed locally; and (3) orbital irradiation as salvage treatment. Results: A total of 28 patients (median age 66 years; range, 37-92; 16 males) were assessable; all patients but 2 (relapsing after partial response) experienced progressive disease during or after doxycycline (median 9 months; IQR, 4-40). Radiation therapy (30-36 Gy in 15-18 fractions) was well tolerated, with only 3 cases of grade-2 cataract and 3 cases of grade-1 blepharitis; all irradiated patients achieved a lymphoma regression (overall response rate = 100%), with a complete response rate of 89% (95% CI, 80%-97%). At a median follow-up of 60 months (range, 12-166) from radiation therapy, 8 patients experienced relapse, within the irradiated volume only in 2 (7%), with a 4-year progression-free survival of 74% (95% CI, 72%-75%). All patients but one are alive at a median follow-up from initial lymphoma diagnosis of 96 (IQR, 47-128) months; 22 (79%) patients are disease free. Conclusions: The postponing of orbit irradiation until relapse/progression after Cp-eradicating antibiotic therapy is a safe and effective strategy in patients with limited-stage OAMZL. The vast majority of patients with OAMZL can be safely managed without chemotherapeutic agents, and radiation therapy can be delayed until relapse without affecting patients’ survival.