Primary radiation therapy in stage I/II indolent orbital lymphoma - a comprehensive retrospective recurrence and toxicity analysis

Abstract

Purpose or objective: To provide a comprehensive recurrence and toxicity analysis of patients treated with radiotherapy alone for stage I/II (Ann-Arbor classification) indolent orbital lymphoma.

Material and methods: We retrospectively reviewed the medical charts of 46 patients (and 51 orbits) treated at our centre with radiotherapy between 1995 and 2012 for biopsy-proven stage I/IIE primary orbital lymphomas. We evaluated treatment response and performed a comprehensive toxicity analysis with correlation to delivered radiation dose.

Results: At diagnosis, the median age was 63.5 years (range: 20-92). At initial diagnosis 43 and 3 patients had unilateral, synchronous bilateral involvement while there were 2 cases of contralateral metachronous failure. The predominant histological subtype was extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in 42 (91.3%), follicular in 1 (2.2%), lymphoplasmacytic lymphoma in 1 (2.2%) and other indolent histology in 2 (4.3%) patients. Most lymphomas were located in the conjunctiva (18/35.3%) or eyelids (18/35.3%). Thirty-eight (82.6%) patients presented with stage I while 8/46 (17.4%) with stage II disease. The median radiation dose was 39.6 Gy (range: 21.6-48.6 Gy) delivered in 1.8-2 Gy single fractions. At a median follow-up of 83 months (range: 7-258 months), the complete remission rate was 98%. A local relapse was observed in 2/51 (3.9%) orbits and 4/46 (8.7%) patients had systemic relapse. The 5- and 10-year PFS rates were 79.2% (95% CI: 73.0%-85.4%) and 67.6% (95% CI: 59.4%-75.8%); 5- and 10-year OS was 83.6% (95% CI: 77.9%-89.3%) and 76.5% (95% CI: 69.4%-83.6%), respectively. In total, 66 acute toxicity events (all-grade) were observed: 5/51 (9.8%) ≥G2 acute conjunctivitis, 2/51 (3.9%) cases of G2 acute keratitis, 1/51 (2%) cases of ≥G2 ophthalmagia and 12/51 (23.5%) cases of ≥G2 xerophthalmia. Furthermore, 45 chronic adverse events were observed in 34/51 (66.7%) irradiated orbits with 30 late adverse events attributed to cataract.

Conclusion: Our analysis confirms the role of radiotherapy alone at lower doses in the treatment of indolent orbital lymphomas. Further research is required to assess the efficacy of ultra-low-dose radiotherapy and anti-CD20 monoclonal antibodies to further mitigate long-term sequelae.

Keywords: indolent non-hodgkin lymphoma; orbital lymphoma; radiotherapy; recurrence analysis; toxicity.