Dose-escalated intensity-modulated radiotherapy in patients with locally advanced laryngeal and hypopharyngeal cancers: ART DECO, a phase III randomised controlled trial.
Date
2021-08-01Author
Nutting, CM
Griffin, CL
Sanghera, P
Foran, B
Beasley, M
Bernstein, D
Cosgrove, V
Fisher, S
West, CM
Sibtain, A
Palaniappan, N
Urbano, TG
Sen, M
Soe, W
Rizwanullah, M
Wood, K
Ramkumar, S
Junor, E
Cook, A
Roques, T
Scrase, C
Bhide, SA
Gujral, D
Harrington, KJ
Mehanna, H
Miah, A
Emson, M
Gardiner, D
Morden, JP
Hall, E
ART DECO Trial Management Group,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Research team
Clinical Trials & Statistics Unit
Language
eng
Date accepted
2021-05-09
Citation
European Journal of Cancer, 2021, 153 pp. 242 - 256
Publisher
ELSEVIER SCI LTD