KEY POINTS
- ARIA is a prospective single-centre phase I feasibility study planning to enroll 20 patients with cT1–2N0M0 glottic squamous cell carcinoma receiving definitive RT at UMC Utrecht. This publication is a study protocol, not a results report.
- Patients will receive 42.5 Gy in 5 fractions of 8.5 Gy, delivered twice weekly over three weeks on a 1.5-T Elekta Unity MR-Linac. No CTV margin is used; the GTV-to-PTV margin is 2 mm anterior–posterior, 2 mm left–right and 4 mm cranio-caudal.
- Active smokers are excluded unless they stop at least two weeks before treatment, reflecting earlier ultra-hypofractionation experience in which severe toxicity occurred preferentially in active smokers. Patients receiving elective nodal irradiation, concurrent chemotherapy or cetuximab are also excluded.
- Each fraction uses an adapt-to-shape workflow with daily contour review and plan reoptimization. If the cricoid cartilage is displaced by >2 mm before irradiation, an adapt-to-position correction is performed.
- Cine MRI provides intrafraction motion monitoring. The beam is automatically interrupted whenever <95% of the GTV remains inside the gating envelope, which extends 2–4 mm around the target depending on direction.
- Feasibility requires at least 16/20 patients to successfully complete all five fractions, with each fraction lasting <1 hour and meeting predefined target and cartilage-dose criteria. Safety is defined as no more than 2/20 patients developing grade ≥3 treatment-related late toxicity at two years.
- Secondary endpoints include two-year local recurrence, voice quality, patient treatment experience and quality of life. Accrual began in November 2025, with recruitment projected through May 2028 and complete two-year follow-up expected in 2030.
CLINICAL TAKEAWAY
ARIA tests whether the precision of daily MR adaptation and real-time laryngeal gating can make an already aggressive five-fraction glottic RT schedule reproducibly deliverable. There are no efficacy or safety outcomes yet, so the paper should be read as a technical phase I roadmap rather than evidence supporting routine MR-guided ultra-hypofractionation.