Clinical Outcomes and Safety of Ultra-Low-Dose Radiotherapy for Ocular Adnexal Lymphoma: A Systematic Review
Grujić M. Volchenkov S. Akhmetali A. Živković Radojević M. Milosavljević N. Janković K. Krasić K. Mihajlović M. Shelan M. Nicosia L. Marinković M.
September 2025Multidisciplinary Digital Publishing Institute (MDPI)
Cancers
2025#17Issue 17
Background/Objectives: Ultra-low-dose radiotherapy (ULD-RT), an ultra-low-dose regimen delivering 4 Gy in two fractions, has emerged as a promising treatment for indolent ocular adnexal lymphoma (OAL), offering disease control with minimal toxicity. However, the clinical outcomes and safety profile of ULD-RT remain inconsistently reported across studies. Methods: We conducted a systematic review of peer-reviewed studies evaluating ULD-RT in patients with OAL, including prospective, retrospective, and comparative cohorts published between 2000 and 2025. A comprehensive search was performed in PubMed, Embase, and Scopus. Eligible studies reported clinical outcomes (e.g., response rates, local control, progression-free survival) and safety data (acute and late toxicities). Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Results: Ten studies comprising 591 patients met the inclusion criteria. The overall response rate to ULD-RT ranged from 88% to 100%, with complete response rates of 50% to 95%. Local control rates ranged from 63% to 100%, and 2-year progression-free survival exceeded 85% in most studies. Importantly, no grade ≥ 3 toxicities were observed following the regimen of 4 Gy in two fractions. Acute toxicities occurred in up to 42% of patients, typically grade 1 dry eye or conjunctivitis. Late toxicities were uncommon (16–33%), with cataracts rarely requiring surgery. All included studies were rated as good quality (NOS score ≥ 7), indicating low risk of bias. Conclusions: ULD-RT is a highly effective and safe treatment modality for OAL, providing excellent local control with a favorable toxicity profile. These findings support the adoption of ULD-RT as a first-line radiotherapy strategy for indolent OAL. Future prospective trials with longer follow-up and standardized toxicity reporting are warranted to confirm and refine its clinical role.
indolent lymphoma , local control , ocular adnexal lymphoma , systematic review , toxicity , ultra-low-dose radiation , ultra-low-dose radiotherapy
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Center for Radiation Oncology, University Clinical Center Kragujevac, Kragujevac, 34000, Serbia
Department of Clinical Oncology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 34000, Serbia
National Medical Research Center of Oncology N.N. Petrov, St. Petersburg, 197758, Russian Federation
Outpatient Care Department, Hematology Center LLP, Karaganda Medical University, Karaganda, 100000, Kazakhstan
Clinic for Oncology, University Clinical Center Nis, Nis, 18000, Serbia
Faculty of Medicine, University of Nis, Nis, 18000, Serbia
Department of Radiation Oncology, Inselspital Bern, University of Bern, Bern, 3010, Switzerland
Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Verona, 37034, Italy
Clinic for Radiation Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, 11000, Serbia
Faculty of Medicine, University of Belgrade, Belgrade, 11000, Serbia
Center for Radiation Oncology
Department of Clinical Oncology
National Medical Research Center of Oncology N.N. Petrov
Outpatient Care Department
Clinic for Oncology
Faculty of Medicine
Department of Radiation Oncology
Advanced Radiation Oncology Department
Clinic for Radiation Oncology
Faculty of Medicine
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