Stereotactic Ablative Radiotherapy for Early-Stage Glottic Larynx Carcinoma: Results From the Phase II LT-SABR Study

Abstract

<h3>Purpose/Objective(s)</h3> Traditional radiotherapy for early-stage larynx cancer irradiates the whole larynx over 5.5-6 weeks. Phase I data suggest that stereotactic ablative radiotherapy (SAbR) is a viable strategy in this population to reduce the irradiated volume and compress the treatment time. This phase II study evaluated the efficacy of gLoTtic larynx SAbR (LT-SABR), utilizing a 5 or 16 fraction regimen depending on treatment volume and smoking status. <h3>Materials/Methods</h3> Eligibility required stage 0-II biopsy-proven carcinoma of the true glottic larynx, including squamous cell variants. The arytenoid cartilage could not be involved beyond the vocal process, and patients smoking more than one pack-per-day were excluded. The planning target volume (PTV) consisted of the gross tumor volume, including respiratory motion assessed on a 4D-CT, with a 3 mm AP/LR margin and 5 mm SI margin. Patients without active smoking and PTV volume < 10 cc receive 42.5 Gy in 5 fractions, two fractions per week; all other patients received 58.08 Gy in 16 daily fractions. The routine beam arrangement included 2 coplanar VMAT arcs and 2 non-coplanar arcs. Patients were treated with swallow-gating using surface imaging. The study required 25 patients to show that the local control probability is non-inferior to 75% at 2 years. <h3>Results</h3> A total of 25 patients were accrued to this study, with 21 and 4 treated with 5 and 16 factions, respectively. The stage distribution was CIS (n=1), T1a (n=16), T1b (n=5), and T2 (n=3). The median age was 72 years, with a prior smoking history in 16 and active smoking in one. Dosimetry metrics (mean values) are summarized in the Table. At a median follow-up of 21.1 months (IQR 14-31.8) in surviving patients, there have been two in-field recurrences (one in each dose cohort). One was salvaged with partial laryngectomy and the other died from local and regional disease. The cumulative risks of local failure were 4.2% and 9.3% at 1 and 2 years, respectively. There have been no acute or late grade 3+ toxicities. The baseline, 6 and 12 month total Voice Handicap Index (VHI) scores were: 53.0 (n=25), 9.8 (n=18), and 18.4 (n=15). The improvements in VHI between 6/12 months and baseline were both statistically significant (p<0.001). <h3>Conclusion</h3> Highly conformal stereotactic radiotherapy is safe and efficacious for early-stage glottic larynx cancer, with encouraging patient-reported outcomes. Additional follow-up and ultimately comparative studies are necessary to validate this paradigm.