Highlights
- •This phase III RCT does not support dose escalation using accelerated hypofractionation.
- •No benefit in local tumour control or survival was seen.
- •Two-year local tumour failure rate was approximately 30% in both treatment groups.
- •The larynx was preserved in about 90% patients in both treatment groups.
Abstract
Background
Radical (chemo)radiotherapy offers potentially curative treatment for patients with
locally advanced laryngeal or hypopharyngeal cancer. We aimed to show that dose-escalated
intensity-modulated radiotherapy (DE-IMRT) improved locoregional control.
Methods
We performed a phase III open-label randomised controlled trial in patients with laryngeal
or hypopharyngeal cancer (AJCC III-IVa/b, TNM 7). Patients were randomised (1:1) to
DE-IMRT or standard dose IMRT (ST-IMRT) using a minimisation algorithm, balancing
for centre, tumour site, nodal status and chemotherapy use. DE-IMRT was 67.2 gray (Gy)
in 28 fractions (f) to the primary tumour and 56Gy/28f to at-risk nodes; ST-IMRT was
65Gy/30f to primary tumour and 54Gy/30f to at-risk nodes. Suitable patients received
2 cycles of concomitant cisplatin and up to 3 cycles of platinum-based induction chemotherapy.
The primary end-point was time to locoregional failure analysed by intention-to-treat
analysis using competing risk methodology.
Findings
Between February 2011 and October 2015, 276 patients (138 ST-IMRT; 138 DE-IMRT) were
randomised. A preplanned interim futility analysis met the criterion for early closure.
After a median follow-up of 47.9 months (interquartile range 37.5–60.5), there were
locoregional failures in 38 of 138 (27.5%) ST-IMRT patients and 42 of 138 (30.4%)
DE-IMRT patients; an adjusted subhazard ratio of 1.16 (95% confidence interval: 0.74–1.83,
p = 0.519) indicated no evidence of benefit with DE-IMRT. Acute grade 2 pharyngeal
mucositis was reported more frequently with DE-IMRT than with ST-IMRT (42% vs. 32%).
No differences in grade ≥3 acute or late toxicity rates were seen.
Conclusion
DE-IMRT did not improve locoregional control in patients with laryngeal or hypopharyngeal
cancer.
The trial is registered: ISRCTN01483375.
Keywords
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Article info
Publication history
Published online: July 11, 2021
Accepted:
May 9,
2021
Received in revised form:
March 30,
2021
Received:
December 17,
2020
Identification
Copyright
© 2021 Published by Elsevier Ltd.
