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 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

doi:10.1016/j.ejca.2021.05.021

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 language	English
Pages (from-to)	242-256
Journal	European Journal of Cancer
Volume	153
Early online date	10 Jul 2021
DOIs	https://doi.org/10.1016/j.ejca.2021.05.021
Publication status	Published - Aug 2021

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ART DECO Trial Management Group, Nutting, C. M., Griffin, C. L., Sanghera, P., Foran, B., Beasley, M., Bernstein, D., Cosgrove, V., Fisher, S., West, C. M., Sibtain, A., Palaniappan, N., Urbano, T. G., Sen, M., Soe, W., Rizwanullah, M., Wood, K., Ramkumar, S., Junor, E., ... Hall, E. (2021). Dose-escalated intensity-modulated radiotherapy in patients with locally advanced laryngeal and hypopharyngeal cancers: ART DECO, a phase III randomised controlled trial. European Journal of Cancer, 153, 242-256. https://doi.org/10.1016/j.ejca.2021.05.021

@article{e744025a08e246b99aebedffed937456,

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

abstract = "BackgroundRadical (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.MethodsWe 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.FindingsBetween 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.ConclusionDE-IMRT did not improve locoregional control in patients with laryngeal or hypopharyngeal cancer.The trial is registered: ISRCTN01483375.",

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

year = "2021",

month = aug,

doi = "10.1016/j.ejca.2021.05.021",

language = "English",

volume = "153",

pages = "242--256",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier",

}

ART DECO Trial Management Group, 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 2021, 'Dose-escalated intensity-modulated radiotherapy in patients with locally advanced laryngeal and hypopharyngeal cancers: ART DECO, a phase III randomised controlled trial', European Journal of Cancer, vol. 153, pp. 242-256. https://doi.org/10.1016/j.ejca.2021.05.021

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; Nutting, Christopher M.; Griffin, Clare L. et al.
In: European Journal of Cancer, Vol. 153, 08.2021, p. 242-256.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Dose-escalated intensity-modulated radiotherapy in patients with locally advanced laryngeal and hypopharyngeal cancers

T2 - ART DECO, a phase III randomised controlled trial

AU - ART DECO Trial Management Group

AU - Nutting, Christopher M.

AU - Griffin, Clare L.

AU - Sanghera, Paul

AU - Foran, Bernadette

AU - Beasley, Matthew

AU - Bernstein, David

AU - Cosgrove, Vivian

AU - Fisher, Shelia

AU - West, Catherine M.

AU - Sibtain, Amen

AU - Palaniappan, Nachi

AU - Urbano, Teresa Guerrero

AU - Sen, Mehmet

AU - Soe, Win

AU - Rizwanullah, Mohammed

AU - Wood, Katie

AU - Ramkumar, Shanmugasundaram

AU - Junor, Elizabeth

AU - Cook, Audrey

AU - Roques, Tom

AU - Scrase, Christopher

AU - Bhide, Shreerang A.

AU - Gujral, Dorothy

AU - Harrington, Kevin J.

AU - Mehanna, Hisham

AU - Miah, Aisha

AU - Emson, Marie

AU - Gardiner, Deborah

AU - Morden, James P.

AU - Hall, Emma

PY - 2021/8

Y1 - 2021/8

N2 - BackgroundRadical (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.MethodsWe 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.FindingsBetween 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.ConclusionDE-IMRT did not improve locoregional control in patients with laryngeal or hypopharyngeal cancer.The trial is registered: ISRCTN01483375.

AB - BackgroundRadical (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.MethodsWe 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.FindingsBetween 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.ConclusionDE-IMRT did not improve locoregional control in patients with laryngeal or hypopharyngeal cancer.The trial is registered: ISRCTN01483375.

UR - http://www.scopus.com/inward/record.url?scp=85109587990&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2021.05.021

DO - 10.1016/j.ejca.2021.05.021

M3 - Article

SN - 0959-8049

VL - 153

SP - 242

EP - 256

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

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

Abstract

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