Long-Term Follow-up of a Randomized Controlled Trial on Accelerated Radiation Therapy Versus Standard Fractionated Radiation Therapy for Early Glottic Cancer (JCOG0701A3)

Abstract

We previously reported the primary results of JCOG0701, a randomized, multicenter, phase III, non-inferiority trial comparing accelerated fractionation (Ax) to standard fractionation (SF) for early glottic cancer (GC). In the primary results, although the similar efficacy of 3-year PFS and toxicity of Ax compared with SF was observed, the non-inferiority of Ax was not confirmed statistically. To evaluate the long-term follow-up results of JCOG0701, we conducted JCOG0701A3 as an ancillary study of JCOG0701. In JCOG0701, 370 patients were randomly assigned to receive SF of 66-70 Gy (33-35 fractions) (n=184) or Ax of 60-64.8 Gy (25-27 fractions) (n=186). The data cutoff date for this analysis was in June 2020. Overall survival, progression-free survival, and late adverse events including central nervous system ischemia (CNSI) were analyzed. With median follow-up period of 7.1 years (range: 0.1-12.4), PFS of the SF and Ax arms were 76.2% and 78.2% at 5 years and 72.7% and 74.8% at 7 years (p=0.44). OS of SF and Ax arms were 92.7% and 89.6% at 5 years and 90.8% and 86.5% at 7 years (p=0.92). Among 366 patients with a protocol treatment, the cumulative incidence of late adverse events of SF and Ax arms were 11.9% and 7.4% at 8 years (HR: 0.53, 95% CI: 0.28-1.01, p=0.06). CNSI of Grade 2 or higher was observed in 4.1% for SF arms and 1.1% for Ax arm (p=0.098). After a long-term follow-up Ax showed comparable efficacy to SF and a tendency for better safety. Ax may be suitable for early GC because of its convenience in minimizing treatment time, cost, and labor.