Stereotactic Ablative Radiotherapy for T1 to T2 Glottic Larynx Cancer: Mature Results From the Phase 2 GLoTtic Larynx-SABR Trial.

ABSTRACT

PURPOSE: Traditional radiation therapy for early-stage larynx cancer irradiates the whole larynx over 5.5 to 6 weeks. Phase 1 data suggest that stereotactic ablative radiotherapy (SABR) is a viable strategy to reduce the irradiated volume and compress treatment time. This phase 2 study evaluated the efficacy of gLoTtic larynx-SABR in 5 or 16 fractions. METHODS AND MATERIALS Eligibility required stage 0 to II squamous cell carcinoma of the glottic larynx. The arytenoid cartilage could not be involved beyond the vocal process, and patients smoking more than one pack per day were excluded. The treatment volume consisted of the gross tumor volume, with a 3 mm margin (5 mm craniocaudal) to create the planning target volume. Patients without active smoking and planning target volume <10 cc received 4250 cGy in 5 fractions, twice per week; other patients received 58.08 Gy in 16 daily fractions. The primary endpoint was the 2-year incidence of local failure. RESULTS: Twenty-five patients were accrued to this study, with 21 and 4 treated with 5 and 16 fractions, respectively. The stage distribution was in situ (n = 1, 4%), T1a/b (n = 16/5, 64%/20%), and T2 (n = 3, 12%). The median age was 72 years, with a prior smoking history in 16 (64%) and active smoking in 1 (4%). At a median follow-up for surviving patients of 3.7 years (IQR, 3.1-4.4 years), there have been 2 in-field recurrences (1 in each dose cohort). The cumulative incidences of local failure were 4% (90% CI, 0.8%-20%) and 8% (90% CI, 3%-24%) at 1 and 2 years, respectively. There have been no acute or late grade 3+ toxicities in disease-free patients. The median baseline, 1, 6, 12, and 24 months Voice Handicap Index scores were 57 (IQR, 32-69), 28.5 (8-48), 4 (0-12), 7.5 (0-12), and 5 (0-24), respectively. CONCLUSIONS: Highly conformal stereotactic radiation therapy appears safe and efficacious for early-stage glottic larynx cancer, with encouraging patient-reported outcomes. These results need to be interpreted with caution given the small sample size and large noninferiority margin. Additional follow-up and ultimately comparative studies are necessary to validate this paradigm.