PMID- 34256319
OWN - NLM
STAT- MEDLINE
DCOM- 20211207
LR  - 20240210
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 153
DP  - 2021 Aug
TI  - Dose-escalated intensity-modulated radiotherapy in patients with locally advanced 
      laryngeal and hypopharyngeal cancers: ART DECO, a phase III randomised controlled 
      trial.
PG  - 242-256
LID - S0959-8049(21)00330-0 [pii]
LID - 10.1016/j.ejca.2021.05.021 [doi]
AB  - 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.
CI  - Copyright (c) 2021. Published by Elsevier Ltd.
FAU - Nutting, Christopher M
AU  - Nutting CM
AD  - The Royal Marsden Hospital, London, UK. Electronic address: 
      chris.nutting@rmh.nhs.uk.
FAU - Griffin, Clare L
AU  - Griffin CL
AD  - The Institute of Cancer Research, London, UK.
FAU - Sanghera, Paul
AU  - Sanghera P
AD  - Queen Elizabeth Hospital, Birmingham, UK.
FAU - Foran, Bernadette
AU  - Foran B
AD  - Weston Park Hospital, Sheffield, UK.
FAU - Beasley, Matthew
AU  - Beasley M
AD  - Bristol Haematology & Oncology Centre, Bristol, UK.
FAU - Bernstein, David
AU  - Bernstein D
AD  - Department of Physics, The Royal Marsden Hospital, London, UK.
FAU - Cosgrove, Vivian
AU  - Cosgrove V
AD  - St James' Hospital, Leeds, UK.
FAU - Fisher, Shelia
AU  - Fisher S
AD  - University of Leeds, Leeds, UK.
FAU - West, Catherine M
AU  - West CM
AD  - University of Manchester, Manchester, UK.
FAU - Sibtain, Amen
AU  - Sibtain A
AD  - St Bartholomew's Hospital, London, UK.
FAU - Palaniappan, Nachi
AU  - Palaniappan N
AD  - Velindre Hospital, Cardiff, UK.
FAU - Urbano, Teresa Guerrero
AU  - Urbano TG
AD  - Guy's and St Thomas' Hospitals, London, UK.
FAU - Sen, Mehmet
AU  - Sen M
AD  - St James' Hospital, Leeds, UK.
FAU - Soe, Win
AU  - Soe W
AD  - Glan Clywd, Rhyll, UK.
FAU - Rizwanullah, Mohammed
AU  - Rizwanullah M
AD  - Beatson West of Scotland Cancer Centre, Glasgow, UK.
FAU - Wood, Katie
AU  - Wood K
AD  - Royal Surrey County Hospital, Guildford, UK.
FAU - Ramkumar, Shanmugasundaram
AU  - Ramkumar S
AD  - Southampton General Hospital, Southampton, UK.
FAU - Junor, Elizabeth
AU  - Junor E
AD  - Western General Hospital, Edinburgh, UK.
FAU - Cook, Audrey
AU  - Cook A
AD  - Cheltenham General Hospital, Cheltenham, UK.
FAU - Roques, Tom
AU  - Roques T
AD  - Norfolk and Norwich University Hospital, UK.
FAU - Scrase, Christopher
AU  - Scrase C
AD  - Ipswich Hospital, Ipswich, UK.
FAU - Bhide, Shreerang A
AU  - Bhide SA
AD  - The Royal Marsden Hospital, London, UK.
FAU - Gujral, Dorothy
AU  - Gujral D
AD  - The Royal Marsden Hospital, London, UK.
FAU - Harrington, Kevin J
AU  - Harrington KJ
AD  - The Royal Marsden Hospital, London, UK.
FAU - Mehanna, Hisham
AU  - Mehanna H
AD  - The Institute for Head and Neck Studies and Education, University of Birmingham, 
      Birmingham, UK.
FAU - Miah, Aisha
AU  - Miah A
AD  - The Royal Marsden Hospital, London, UK.
FAU - Emson, Marie
AU  - Emson M
AD  - The Institute of Cancer Research, London, UK.
FAU - Gardiner, Deborah
AU  - Gardiner D
AD  - The Institute of Cancer Research, London, UK.
FAU - Morden, James P
AU  - Morden JP
AD  - The Institute of Cancer Research, London, UK.
FAU - Hall, Emma
AU  - Hall E
AD  - The Institute of Cancer Research, London, UK.
CN  - ART DECO Trial Management Group
LA  - eng
SI  - ISRCTN/ISRCTN01483375
GR  - C1491/A15955/CRUK_/Cancer Research UK/United Kingdom
GR  - 21993/CRUK_/Cancer Research UK/United Kingdom
GR  - 11570/CRUK_/Cancer Research UK/United Kingdom
GR  - DH_/Department of Health/United Kingdom
GR  - 28724/CRUK_/Cancer Research UK/United Kingdom
GR  - C1491/A9895/CRUK_/Cancer Research UK/United Kingdom
GR  - C8262/A11570/CRUK_/Cancer Research UK/United Kingdom
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210710
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
SB  - IM
MH  - Aged
MH  - Female
MH  - Humans
MH  - Hypopharyngeal Neoplasms/*radiotherapy
MH  - Laryngeal Neoplasms/*radiotherapy
MH  - Male
MH  - Middle Aged
OTO - NOTNLM
OT  - Clinical outcomes
OT  - Dose escalation
OT  - Head and neck cancer
OT  - Hypopharynx cancer
OT  - IMRT
OT  - Larynx cancer
OT  - Phase III
OT  - Randomised controlled trial
OT  - Toxicity
COIS- 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.
EDAT- 2021/07/14 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/07/13 20:21
PHST- 2020/12/17 00:00 [received]
PHST- 2021/03/30 00:00 [revised]
PHST- 2021/05/09 00:00 [accepted]
PHST- 2021/07/14 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/07/13 20:21 [entrez]
AID - S0959-8049(21)00330-0 [pii]
AID - 10.1016/j.ejca.2021.05.021 [doi]
PST - ppublish
SO  - Eur J Cancer. 2021 Aug;153:242-256. doi: 10.1016/j.ejca.2021.05.021. Epub 2021 
      Jul 10.