Disease Outcomes Following Low-Dose Radiotherapy vs. Moderate-Dose Radiotherapy for Orbital Low Grade Non-Hodgkin Lymphoma

Abstract

Orbital low grade non-Hodgkin Lymphomas (LGNHLs) are a common tumor of the ocular adnexa. Courses of low-dose radiotherapy (LDRT), previously defined as 2 Gray (Gy) x 2 fractions, have resulted in excellent short-term outcomes for orbital LGNHLs. Recent data, however, suggests that higher doses are associated with improvements in response rates and progression free survival. RT is a proven treatment modality for this entity, but no prior data exists comparing outcomes following LDRT to moderate-dose RT (MDRT, RT dose > 4 Gy). Herein, we compare outcomes including overall response rates (ORR), local control (LC) and overall survival (OS) for patients treated with LDRT vs MDRT.We reviewed 38 consecutive courses of RT for 36 patients treated for orbital LGNHL at a single institution. Bilateral disease was present in 15 patients. Nine patients had advanced stage disease or secondary orbital lymphoma following systemic dissemination. Indolent histologies included marginal zone lymphoma (20 patients), follicular lymphoma (11 patients), and mantle cell lymphoma (MCL, 5 patients). ORR were recorded according to Deauville or RECIST criteria with a response characterized as a complete response (CR) or partial response. Time to orbital recurrence (TTOR) and OS were estimated with the Kaplan-Meier (KM) method from start of RT to event or last follow-up. Univariate and multivariate Cox regression analysis was performed for characteristics associated with the studied outcomes. RT toxicity was graded per CTCAEv5.Median follow-up time for all patients was 29 months (m) (range, 4-129m) and median MDRT dose used was 24 Gy (range 21-36 Gy) in 1.5-2 Gy fractions. LDRT was delivered for 14 courses and MDRT for 24 courses. Advanced stage (odds ratio (OR) 7, P = 0.021) and year of RT ≥2016 (OR 24, P = 0.008) were associated with increased use of LDRT as compared to MDRT. Acute grade 1 (G1) and G2 RT toxicities occurred following 22 (58%) and 5 (13%) courses, respectively. No ≥G3 acute toxicities occurred. Late toxicities included 6 patients with G1 dry eye (4 MDRT, 2 LDRT), 3 patients with G2 dry eye (3 MDRT) and one patient with a G1 cataract (1 MDRT). ORR were 100% (CR 50%) and 87.5% (CR 58.3%) following LDRT and MDRT, respectively. No evaluated characteristics, including the use of LDRT, were significantly associated with inferior ORR, TTOR or OS. LC at 2 years was 100% and 95% for the LDRT and MDRT groups, respectively.RT for orbital LGNHL is associated with excellent outcomes in terms of response rates and local control. Due to the exquisite radiosensitivity of orbital LGNHL, LDRT produces similar response rates and TTOR as compared to more protracted RT courses. Present data suggests that LDRT should be considered for patients with orbital LGNHL; however, further multi-center studies with larger patient numbers are warranted to show significant associations.