ÌÇÐÄvlog

QuestionÌý Will response-adapted ultralow-dose radiation therapy for indolent orbital B-cell lymphoma result in excellent disease outcomes with minimal toxic effects?

FindingsÌý Among 50 prospective patients in this phase 2 nonrandomized controlled trial of response-adapted ultralow-dose radiation therapy with an initial dose of 4 Gy, followed by 20 Gy for disease that responds incompletely, the 2-year local control rate was 89.4%, and 90.0% of patients had a complete response with no grade 3 or higher toxic effects.

MeaningÌý Response-adapted ultralow-dose radiation therapy is an effective approach for indolent orbital B-cell lymphoma, conferring high rates of local control and sparing most patients from standard radiation doses.

ImportanceÌý Radiation therapy to doses of 24 to 36 Gy is currently used to treat indolent B-cell lymphoma of the ocular adnexa; however, ocular adverse effects are common.

ObjectiveÌý To determine if a response-adapted radiation therapy strategy will result in excellent disease outcomes while reducing orbital morbidity.

Design, Setting, and ParticipantsÌý This single-institution, phase 2 prospective nonrandomized controlled trial of a response-adapted strategy involved 50 evaluable patients with stage I to IV indolent B-cell lymphoma of the ocular adnexa enrolled between July 2015 and January 2021. This treatment approach was also retrospectively evaluated with a separate 55-patient cohort treated between March 2013 and October 2021. All data were analyzed between November 2021 and December 2023.

InterventionsÌý Patients were treated with ultralow-dose radiation therapy to 4 Gy in 2 fractions and assessed for response at 3-month intervals. Patients with persistent orbital lymphoma were offered an additional 20 Gy in 10 fractions to complete the response-adapted treatment.

Main Outcome and MeasuresÌý The primary end point was 2-year local orbital control within the irradiated field after response-adapted therapy. Secondary end points included overall survival and complete response rate.

ResultsÌý The 50 prospective patients were a median (range) of 63 (29-88) years old, and 31 (62%) were female. Among the 50 patients, 32 (64%) had mucosa-associated lymphoid tissue lymphoma, 12 (24%) had follicular lymphoma, and 6 (12%) had unclassifiable low-grade B-cell lymphoma. Thirty-one patients (62%) had stage I disease, and 36 (72%) were newly diagnosed. At a median follow-up of 37.4 (95% CI, 33.7-52.5) months, the 2-year local control rate was 89.4% (95% CI, 81.0%-98.7%), and the 2-year overall survival rate was 98.0% (95% CI, 94.1%-100%); 45 patients (90.0%; 95% CI, 78.2%-96.7%) experienced a complete response to response-adapted radiation, including 44 patients with a complete response to ultralow-dose radiation and 1 patient with a complete response after an additional 20 Gy. No local recurrences were observed among patients with a complete response to response-adapted therapy. No grade 3 or higher toxic effects were observed. In a planned subset analysis of 22 patients with newly diagnosed, untreated stage I mucosa-associated lymphoid tissue lymphoma, the 2-year local control rate was 90.7% (95% CI, 79.2%-100%), and the 2-year freedom from distant relapse rate was 95.2% (95% CI, 86.6%-100%).

Conclusion and RelevanceÌý In this nonrandomized controlled trial, response-adapted ultralow-dose therapy for indolent orbital B-cell lymphoma resulted in reduced radiation exposure, negligible toxic effects, and excellent disease outcomes.

Trial RegistrationÌý ClinicalTrials.gov Identifier: