Stereotactic ablative radiotherapy for T1-2 glottic larynx cancer: mature results from the phase II LT-SABR trial

Purpose 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 to reduce the irradiated volume and compress treatment time. This phase II study evaluated the efficacy of gLoTtic larynx SAbR (LT-SABR) in 5 or 16 fractions. Methods Eligibility required stage 0-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 (PTV). Patients without active smoking and PTV volume < 10 cc receive 4250 cGy in 5 fractions, twice per week; other patients received 58.08 Gy in 16 daily fractions. The primary endpoint was 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 one (4%). At a median follow-up for surviving patients of 3.7 years (IQR 3.1-4.4 years), there have been two in-field recurrences (one 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, 6, 12 and 24 month Voice Handicap Index scores were 57 (IQR, 32-69), 28.5 (8-48), 4 (0-12), 7.5 (0-12), and 5 (0-24). Conclusions Highly conformal stereotactic radiotherapy appears safe and efficacious for early-stage glottic larynx cancer, with encouraging patient-reported. These results need to be interpreted with caution given the small sample size and large non-inferiority margin. Additional follow-up and ultimately comparative studies are necessary to validate this paradigm.