Dose-escalated intensity-modulated radiotherapy in patients with locally advanced laryngeal and hypopharyngeal cancers: ART DECO, a phase III randomised controlled trial

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Authors

  • ART DECO Trial Management Group
  • Christopher M. Nutting
  • Clare L. Griffin
  • Paul Sanghera
  • Bernadette Foran
  • Matthew Beasley
  • David Bernstein
  • Vivian Cosgrove
  • Shelia Fisher
  • Catherine M. West
  • Amen Sibtain
  • Nachi Palaniappan
  • Teresa Guerrero Urbano
  • Mehmet Sen
  • Win Soe
  • Mohammed Rizwanullah
  • Katie Wood
  • Shanmugasundaram Ramkumar
  • Elizabeth Junor
  • Audrey Cook
  • Tom Roques
  • Christopher Scrase
  • Shreerang A. Bhide
  • Dorothy Gujral
  • Kevin J. Harrington
  • Hisham Mehanna
  • Aisha Miah
  • Marie Emson
  • Deborah Gardiner
  • James P. Morden
  • Emma Hall

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.

Details

Original languageEnglish
Pages (from-to)242-256
JournalEuropean Journal of Cancer
Volume153
Early online date10 Jul 2021
Publication statusPublished - Aug 2021

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