Precision Medicine: MRI-Guided Stereotactic Ablative Radiotherapy (MRI-SABR) for Early-Stage Glottic Laryngeal Cancer (SMART - 1_1)

A Prospective, Randomized, Three-Arm, Open-Label Clinical Trial Comparing Transoral CO₂ Laser Microsurgery, Volumetric Modulated Arc Therapy (VMAT), and MRI-Guided Stereotactic Ablative Radiotherapy (MRI-SABR) in the Treatment of Early-Stage Glottic Laryngeal Cancer

This randomized phase III trial will compare the outcomes of three treatment modalities for early-stage glottic laryngeal cancer (T1-T2N0): transoral CO₂ laser microsurgery (TLM), volumetric modulated arc therapy (VMAT), and MRI-guided stereotactic ablative radiotherapy (MRI-SABR). The primary endpoint is local control (LC). Secondary endpoints include laryngectomy-free survival (LFS), progression-free survival (PFS). overall survival (OS), functional voice, swallowing and breathing outcomes, treatment-related complications, and the evaluation of radiomic and dosiomic biomarkers. Patients will be randomized in a 1:1:1 ratio. Total planned enrollment is 105.

Study Overview

• Status: Recruiting
• Conditions: Laryngeal Neoplasm; Glottic Carcinoma
• Intervention / Treatment: Procedure: Transoral CO₂ laser cordectomy (Type I-VI depending on tumor localization); Radiation: VMAT radiotherapy; Radiation: MRI-SABR

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Viktoras Rudzianskas; Phone Number: +37068745515; Email: viktoras.rudzianskas@kaunoklinikos.lt

Study Locations

• Lithuania
  • Kaunas, Lithuania
    • Recruiting
    • Lithuanian University of Health Sciences Kaunas Clinics
    • Contact: Vita Simonyte-Verbickiene; Phone Number: +37067140693; Email: vita.simonyte-verbickiene@kaunoklinikos.lt

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years.
• Histologically confirmed squamous cell carcinoma of the glottic larynx, including verrucous carcinoma.
• Stage T1-T2N0 (8th TNM edition).
• ECOG performance status 0-2.
• Able to understand Lithuanian and complete questionnaires.
• Signed informed consent.

Exclusion Criteria:

• AJCC stage III-IV laryngeal cancer.
• Prior radiotherapy for head and neck cancer.
• Pregnancy or breastfeeding.
• Contraindications for radiotherapy or inability to follow-up.
• Presence of another active malignancy.
• Uncontrolled intercurrent illness (e.g., active infection, symptomatic CHF, unstable angina, clinically significant arrhythmia) or any condition that would preclude radiotherapy or adequate follow-up per investigator judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: Transoral CO₂ Laser Microsurgery (TLM); Participants undergo transoral CO₂ laser microsurgery for the treatment of early-stage glottic laryngeal cancer.	Procedure: Transoral CO₂ laser cordectomy (Type I-VI depending on tumor localization); Surgical removal of the tumor with at least 2 mm margins; intraoperative frozen section biopsies; short hospitalization (1-3 days).
Active Comparator: Arm B: Volumetric Modulated Arc Therapy (VMAT); Participants receive definitive external beam radiotherapy using volumetric modulated arc therapy.	Radiation: VMAT radiotherapy; Accelerated fractionation schedule: T1N0 - 63 Gy/28 fractions; T2N0 - 65.25 Gy/29 fractions; delivered using Eclipse planning system.
Active Comparator: Arm C: MRI-Guided Stereotactic Ablative Radiotherapy (MRI-SABR); Participants receive definitive MRI-guided stereotactic ablative radiotherapy.	Radiation: MRI-SABR; 42.5 Gy total dose in 5 fractions, 2 fractions per week, planned with CT and MRI simulation and delivered with MRI-LINAC system.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Tumor Control Rate Assessed by Endoscopy and Imaging	Proportion of participants without local tumor recurrence, assessed by laryngoscopic examination and radiological imaging.	At 2 years after completion of treatment; At 5 years after completion of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Laryngectomy-Free Survival (LFS)	Time from randomization to total laryngectomy or death from any cause, whichever occurs first.	Up to 2 years after randomization; Up to 5 years after randomization
Progression-Free Survival (PFS)	Time from randomization to disease progression (local, regional, or distant) or death from any cause, whichever occurs first.	Up to 2 years after randomization; Up to 5 years after randomization
Overall Survival (OS)	Time from randomization to death from any cause.	Up to 2 years after randomization; Up to 5 years after randomization
Objective Voice Parameters Assessed by Acoustic Analysis (lingWAVES)	Objective voice parameters derived from acoustic signal analysis using the lingWAVES system.	Baseline, and at 1, 3, 6, 12, 18, and 24 months after completion of treatment
Patient-Reported Voice Outcome Assessed by Voice Screen Application	Patient-reported voice outcome assessed using the Voice Screen mobile application.	Baseline, and at 1, 3, 6, 12, 18, and 24 months after completion of treatment
Swallowing Function Score Assessed by Anderson Dysphagia Inventory	Swallowing function assessed using the Anderson Dysphagia Inventory questionnaire (total score).	Baseline, and at 1, 3, 6, 12, 18, and 24 months after completion of treatment
Health-Related Quality of Life Scores Assessed by EORTC QLQ-C30 and QLQ-H&N35	Health-related quality of life assessed using the EORTC QLQ-C30 and QLQ-H&N35 questionnaires (global health status and domain scores).	Baseline, and at 1, 3, 6, 12, 18, and 24 months after completion of treatment
Quantitative Radiomic and Dosiomic Feature Values and Their Statistical Associations With Clinical Outcomes	Quantitative radiomic feature values extracted from baseline and follow-up imaging (CT, MRI, PET/CT) and quantitative dosiomic feature values derived from radiotherapy treatment plans. Associations with clinical outcomes (local tumor control, progression-free survival, overall survival) will be summarized using correlation coefficients and hazard ratios.	From baseline imaging through 5 years after completion of treatment

Collaborators and Investigators

• Sponsor: Viktoras Rudzianskas

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): March 1, 2034

Study Registration Dates

• First Submitted: January 15, 2026
• First Submitted That Met QC Criteria: January 29, 2026
• First Posted (Actual): February 5, 2026

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: VMAT; transoral laser microsurgery; radiomics; stereotactic radiotherapy; Early-stage glottic laryngeal cancer; MRI-SABR; dosiomics
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Head and Neck Neoplasms; Respiratory Tract Neoplasms; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Laryngeal Diseases; Laryngeal Neoplasms
• Other Study ID Numbers: BE-2-45

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No