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

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 CookTom Roques, Christopher Scrase, Shreerang A. Bhide, Dorothy Gujral, Kevin J. Harrington, Hisham Mehanna, Aisha Miah, Marie Emson, Deborah Gardiner, James P. Morden, Emma Hall

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

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