Clinical Outcomes of Minibeam Radiotherapy for Superficial Skin and Soft Tissue Malignancies.

BACKGROUND: Minibeam radiotherapy (MBRT) is a spatially fractionated technique delivering alternating submillimeter high-dose peak and low-dose valley regions using orthovoltage x-rays. Preclinical studies demonstrate normal tissue sparing and antitumor activity, but clinical data are limited. Following a prior report of commissioning and treatment in two patients, we report the first clinical series evaluating clinical outcomes with MBRT for superficial malignancies. METHODS: Patients with superficial cutaneous and soft tissue malignancies were treated with MBRT at a single institution using a clinical orthovoltage unit and tungsten collimators producing 0.5-mm beams spaced 1.1 mm center-to-center. Cumulative incidence functions were used to estimate local progression. Toxicity was graded by CTCAE v5.0. RESULTS: Thirty-six patients with 46 lesions were treated between December 2023 and August 2025; 85% received MBRT alone. Median follow-up was 15.1 months. Median peak and valley doses per fraction were 25.9 Gy and 3.4 Gy; median number of fractions was 2. Patients were heavily pretreated, with 90% receiving ≥2 prior systemic therapies and 43% prior radiation. Symptomatic improvement occurred in 86%. Among 40 evaluable lesions, complete response occurred in 22.5%, partial response in 25%, and stable disease in 45%. Twelve-month local progression was 11% overall and 8% for MBRT alone. Documented abscopal responses occurred in 11% without systemic therapy changes. Grade 1-2 dermatitis occurred in 61%; two grade 3 adverse events occurred in patients with baseline tissue compromise. No grade 4-5 toxicities were observed. CONCLUSIONS: MBRT is well tolerated and yielded encouraging symptomatic benefits and local control in treatment-refractory superficial malignancies.