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

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.

Informations de copyright

Copyright © 2021. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: B.F. reports personal fees and other fees from BMS, outside the submitted work. D.B. reports support from National Institute for Health Research during the conduct of the study. E.H. reports grants from Cancer Research UK, during the conduct of the study, grants from Accuray Inc., grants from Varian Medical Systems Inc., grants and non-financial support from Merck Sharp & Dohme, grants and non-financial support from AstraZeneca, grants from Janssen-Cilag, grants and non-financial support from Bayer Healthcare Pharmaceuticals Inc., grants from Kyowa Hakko UK, grants from Alliance Pharma (previously Cambridge Laboratories) and grants from Aventis Pharma Limited (Sanofi), outside the submitted work. H.M. reports personal fees from Warwickshire Head Neck Clinic Ltd, personal fees from AstraZeneca, personal fees from MSD, Sanofi Pasteur and Merck, grants from GSK Biologicals, MSD, Sanofi Pasteur, Silence Therapeutics, GSK PLC and AstraZeneca and other from Sanofi Pasteur, MSD and Merck, outside the submitted work. K.J.H. reports grants and personal fees from AstraZeneca, personal fees from Amgen, personal fees from BMS, grants and personal fees from Boehringer Ingelheim, grants and personal fees from MSD, personal fees from Merck Serono, personal fees from Pfizer and grants and personal fees from Replimune, outside the submitted work. P.S. reports personal fees from advisory board work for AbbVie and non-financial support from Phillips and Accuray, outside the submitted work. The below mentioned authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article: C.M.N., C.L.G., M.B., V.C., S.F., C.M.W., A.S., N.P., T.G.U., M.S., W.S., M.R., K.W., S.R., E.J., A.C., T.R., C.S., S.A.B., Do.G., A.M., M.E., De.G. and J.P.M.