Background
Phase III, prospective randomized trial (Osaka Medical Center for Cancer and Cardiovascular Disease, Japan). 180 patients with early glottic carcinoma (T1N0M0) randomized to conventional 2 Gy vs slightly hypofractionated 2.25 Gy fractions. Assessed the effect of fraction size and overall treatment time on local control, without increasing acute or late toxicity.
Interventions and follow up
Arm A: 2.0 Gy per fraction; minimal tumors: 60 Gy / 30 fractions / 6 weeks; larger tumors: 66 Gy / 33 fractions / 6.6 weeks (N=89)
Arm B: 2.25 Gy per fraction; minimal tumors: 56.25 Gy / 25 fractions / 5 weeks; larger tumors: 63 Gy / 28 fractions / 5.6 weeks (N=91)
Primary endpoint: 5-year local control rate
mFollow up: Not specified; trial enrolled December 1993–December 2001
Arm B: 2.25 Gy per fraction; minimal tumors: 56.25 Gy / 25 fractions / 5 weeks; larger tumors: 63 Gy / 28 fractions / 5.6 weeks (N=91)
Primary endpoint: 5-year local control rate
mFollow up: Not specified; trial enrolled December 1993–December 2001
Results
5-year local control: 77% (2.0 Gy/fraction) vs 92% (2.25 Gy/fraction), P=.004
5-year cause-specific survival: 97% vs 100% — no significant difference
Acute mucosal reactions: No significant difference between arms
Chronic adverse reactions: No significant difference
5-year cause-specific survival: 97% vs 100% — no significant difference
Acute mucosal reactions: No significant difference between arms
Chronic adverse reactions: No significant difference
Adverse events
Main adverse events: No significant differences in acute mucosal reactions, skin reactions, or chronic adverse effects between the two fractionation schedules. Voice quality outcomes not formally reported.
Conclusions
Slightly hypofractionated RT (2.25 Gy/fraction over a shorter overall treatment time) significantly improved 5-year local control for T1N0M0 glottic carcinoma (92% vs 77%) without increasing toxicity. This supports slightly hypofractionated schedules as preferred for early glottic cancer.
Key Limitations
Key Limitations: Single-institution Japanese trial — patient population and tumor characteristics may differ from Western series. Small sample size (N=180). Cause-specific survival was not significantly different, raising questions about the clinical significance of local control differences. Voice quality outcomes (critical for T1 glottic cancer management) were not assessed. Arms differ in both fraction size AND overall treatment time, making it impossible to isolate which parameter drives the benefit. Long-term voice analysis not performed.
Clinical Context
Early (T1–T2) glottic carcinoma is highly curable with radiotherapy alone (local control ~85–95% for T1). RT is generally preferred over transoral laser microsurgery (TLM) for T1 disease due to superior voice outcomes, though both are acceptable. This trial supports mildly hypofractionated regimens (e.g., 2.25 Gy × 25–28 fractions) over conventional fractionation for T1 glottic cancer. MDACC and other institutions use 63 Gy / 28 fractions or 65.25 Gy / 29 fractions as standard for T1 glottic. Many centers now use IMRT for sparing arytenoid and contralateral structures to preserve voice quality.
References