Low-Dose Radiotherapy Versus Moderate-Dose Radiotherapy for the Treatment of Indolent Orbital Adnexal Lymphomas

Abstract

PurposeRadiation therapy (RT) with doses ranging from 24 Gray (Gy) to 40 Gy is a proven treatment modality for indolent orbital adnexal lymphoma (IOAL), but recently the use of low dose RT (LDRT, defined as 2 Gy x 2 fractions) has become a notable alternative. However, limited data exists comparing outcomes following LDRT to moderate-dose RT (MDRT, RT dose 4 – 36 Gy). We present a single institution retrospective analysis comparing outcomes of patients with IOALs following LDRT or MDRT.MethodsA total of 36 patients treated with 38 consecutive courses of RT were identified; LDRT was delivered for 14 courses and MDRT for 24 courses. Overall response rates (ORR) were recorded according to Deauville or RECIST criteria with a response characterized as a complete response (CR) or partial response. Local control (LC), orbital control (OC), and overall survival (OS) rates were estimated with the Kaplan-Meier method. RT toxicity was graded per CTCAEv5 and compared with the Fisher’s exact test.ResultsMedian follow-up time was 29 months (m) (range, 4-129m), and median MDRT dose used was 24 Gy (range 21-36 Gy). Overall response rates (ORR) were 100% (CR 50%) and 87.5% (CR 58.3%) following LDRT and MDRT, respectively. OS at 2 years was 100% and 95% for the LDRT and MDRT groups, respectively (p=0.36). LC rates at 2 years was 100% for both LDRT and MDRT groups and at 4 years was 100% and 89% for the LDRT and MDRT groups, respectively (p=0.56). The 4-year OC rate (including both ipsilateral and contralateral relapses) was 80% and 85% for the LDRT and MDRT groups, respectively (p=0.79). No patient required treatment with RT to a previously irradiated orbit. Acute toxicities were reported following 6 LDRT courses compared to 20 MDRT courses (p=.014). No Grade 3 or higher acute toxicities occurred in either group. Late toxicities were reported following 2 LDRT courses compared to 10 MDRT courses (p=0.147).ConclusionsLDRT produced similar ORR, LC, OC, and OS rates compared to MDRT with fewer acute and minimal late toxicities reported. Future multi-center studies with larger patient numbers are warranted to show significant associations.

Ultra-low dose radiotherapy in the management of low-grade orbital lymphomas

“…In a recent study, ultra-low versus low dose courses for indolent orbital lymphomas were compared for 36 patients. Although similar oncological outcomes were reported between groups, with a local control of 100% and a CR and 50% in the ultra-low dose group [18], acute and late toxicities were more frequent in the 24 Gy group. Moreover, some of the referred studies [14,18] included mantle cell lymphomas in addition to follicular and marginal zone subtypes.…”

“…Although similar oncological outcomes were reported between groups, with a local control of 100% and a CR and 50% in the ultra-low dose group [18], acute and late toxicities were more frequent in the 24 Gy group. Moreover, some of the referred studies [14,18] included mantle cell lymphomas in addition to follicular and marginal zone subtypes. Although not typically referred as an indolent lymphoma, there are reports that mantle cell could also be successfully managed with ultra-low dose radiotherapy due to its radiosensitivity; trials addressing the outcomes of this scheme in this particular histology are needed.…”

“…Moreover, some of the referred studies [ 14 , 18 ] included mantle cell lymphomas in addition to follicular and marginal zone subtypes. Although not typically referred as an indolent lymphoma, there are reports that mantle cell could also be successfully managed with ultra-low dose radiotherapy due to its radiosensitivity; trials addressing the outcomes of this scheme in this particular histology are needed.…”

Current Status of the Spectrum and Therapeutics of Helicobacter pylori-Negative Mucosa-Associated Lymphoid Tissue Lymphoma

“…Cerrato et al retrospectively analyzed 45 patients with MALT or MZL who were treated with 4 Gy in two 2-Gy fractions as curative or palliative intent, and revealed that low-dose RT (4 Gy) resulted in an ORR of 93% (CR: 51%, PR: 42%) and a 2-year PFS and OS of 76% and 91%, respectively, without causing significant acute and late adverse effects [ 103 ]. Baron et al also showed that among 36 patients with indolent OAL (20 patients with MALT lymphoma), low-dose RT (4 Gy) resulted in a similar ORR rate (100% [CR: 50%] vs. 87.5% [CR 58.3%]) but fewer acute toxicities (6/14 [42.9%] courses vs. 20/24 courses [83.3%], p = 0.014) when compared with moderate-dose RT (21–36 Gy) [ 104 ]. Prospective studies to validate the local control rate and adverse effects of low-dose RT (4 Gy) in larger patients with MALT lymphoma are warranted.…”

High local control and low ocular toxicity using ultra-low-dose “boom-boom” radiotherapy for indolent orbital lymphoma

“…However, the orbital structures are uniquely sensitive to radiation and may develop toxicities including dry eye, conjunctivitis, cataracts, keratoconjunctivitis sicca, and radiation retinopathy (6). Given the competing goals of local control and minimizing ocular toxicities, the ultra-low-dose (4 Gy in 2 fractions) treatment regimen, colloquially termed "boom-boom," has been investigated (7)(8)(9)(10)(11)(12)(13). However, the efficacy of "boom-boom" regimen is still controversial, and not adopted widely.…”