Response Adapted Ultra Low Dose Radiation Therapy for the Definitive Management of Orbital Indolent B-Cell Lymphoma

Abstract

<h3>Purpose/Objective(s)</h3> Radiation therapy (RT) to doses of 24-30 Gy is used for the treatment of indolent B-cell lymphoma (BCL); however, significant acute and late ocular effects are common. We aimed to develop a response adapted (RA) strategy that maintains excellent disease outcomes but reduces orbital morbidity. <h3>Materials/Methods</h3> We performed a phase II prospective study of a RA strategy in 50 patients (pts) with stage I-IV orbital indolent BCL. Pts were treated with ultra-low dose (ULD) RT to 4 Gy in 2 fractions and assessed in 3-month intervals for response. Pts with persistent orbital lymphoma were offered an additional 20 Gy in 10 fractions. Pts that had a complete response (CR) to ULD RT were observed. We also evaluated this treatment strategy in a separate 55 pt retrospective cohort. <h3>Results</h3> From July 2015-January 2021 51 pts were enrolled. Fifty evaluable pts had follow-up for study inclusion. The median age was 63 years (29-88); 62% were female (n=31). Pts had MALT lymphoma (n=32, 64%), follicular lymphoma (FL, n=16, 32%) and low grade BCL (n=6, 12%). Most pts (62%, n=31) had stage I disease limited to one (n=28) or both (n=3) orbits. Pts had newly diagnosed (n=36, 72%); relapsed (n=9, 18%) and refractory lymphoma (n=5, 10%). At a median follow up of 35 months [95% CI 22.2 – 37.4], 90% of pts (n=45) experienced a CR to RA RT, including 44 pts that had a CR to ULD RT (median time to CR 3.4 months) and 1 pt that had a CR after an additional 20 Gy. No local recurrences were observed. Treatment was well tolerated with no grade ≥3 toxicity. Five pts did not have a CR to planned RA therapy including 1 pt that refused additional RT, one pt treated with rituximab, one pt that had a PR on initial evaluation but has not returned for subsequent in person evaluations due to COVID, one pt being observed with stable disease and a final pt that received an additional 20 Gy to the orbit that has a persistent stable mass after the 20 Gy. In a planned subset analysis of 26 pts with newly diagnosed stage 1 disease (MALT, n=22; FL, n=3; low grade BCL, n=1); 92.3% (n=24) had a CR to RA RT, with one pt requiring an additional 20 Gy. For all 26 pts with newly diagnosed stage 1 disease, the 3-year freedom from distant relapse rate was 90.4% with 3 distant relapses (contralateral orbit, n=2; paratracheal nodes, n=1). The median follow-up among the 55 pts (MALT, n=38; FL, n=13; low grade B-cell lymphoma, n=4) treated in the retrospective cohort between March 2013 and October 2021 was 28.7 months (95% CI 21.2 - 36.1); 98% (n=54) of pts had a CR with RA RT, including 2 pts with a CR after an additional 20 Gy. The remaining pt went on to receive systemic therapy in lieu of additional RT for persistent disease. Among the 54 pts that had a CR with RA RT there was one local relapse in a pt with conjunctival FL 27.8 months after experiencing a CR to ULD RT. This pt received 20 Gy with resolution of the locally relapsed disease. <h3>Conclusion</h3> We observed excellent disease control with negligible toxicity in the first prospective study assessing this novel approach of RA ULD RT for pts with indolent B-cell lymphoma.