First Results of ART DECO (CRUK/10/018): a randomised trial of dose escalated intensity modulated radiotherapy (DE-IMRT) versus standard dose IMRT (ST-IMRT) in locally advanced head and neck cancer


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Christopher Nutting1,James Morden2,Matthew Beasley3,David Bernstein4,Vivian Cosgrove5,Sheila Fisher6,Bernadette Foran7,Teresa Guerro-Urbano8,Dorothy Gujral4,Elizabeth Junor9,Hisham Mehenna10,Nachi Palaniappan11,Shanmugasundaram Ramkumar12,Paul Sanghera13,Mehmet Sen5,Amen Sibtain14,Win Soe15,Catharine West16,Deborah Piercy2,Stephanie Witts2,Marie Emson2,Emma Hall2
1Royal Marsden Hospital,2The Institute of Cancer Research,3University Hospitals Bristol NHS Foundation Trust,4The Royal Marsden NHS Foundation Trust,5The Leeds Teaching Hospitals NHS Trust,6University of Leeds,7Sheffield Teaching Hospitals NHS Foundation Trust,8Guy's and St Thomas' NHS Foundation Trust,9NHS Lothian,10University of Birmingham,11Velindre NHS Trust,12University Hospital Southampton NHS Foundation Trust,13University Hospitals Birmingham NHS Foundation Trust,14Barts Health NHS Trust,15Betsi Cadwaladr University Health Board,16The University of Manchester

Abstract

Background

Radical (chemo)radiotherapy offers curative treatment for patients with locally advanced laryngeal or hypopharyngeal cancer. IMRT permits safe dose-escalation and hence potential improved locoregional control given reduction in volume of normal tissue receiving high dose radiation.

Method

Patients with histologically squamous cell laryngeal or hypopharyngeal cancer (AJCC III-IVa/b) were randomised to DE-IMRT (primary tumour: 67.2Gray(Gy)/28 fractions(f), at risk nodes: 56Gy/28f) or ST-IMRT (primary tumour: 65Gy/30f, at risk nodes: 54Gy/30f). Patients received 2 cycles concomitant cisplatin, and up to 3 cycles platinum-based induction chemotherapy. Treatment allocation (1:1) used minimisation, balancing for centre, tumour site, nodal status and planned chemotherapy. Primary endpoint was locoregional failure- free rate (LRFFR) i.e. time to locoregional relapse or completion of radiotherapy in patients with persistent disease 3 months after treatment (clinical assessment). Target recruitment was 354 patients; 100 events required to detect improvement in 2-year LRFFR from 60% to 77.5% (two-sided α=0.05, 90% power). LRFFR was analysed using competing risks methodology (with death as competing event), compared between groups by Gray’s test. Secondary endpoints (α=0.01) included toxicity (CTCAEv4.0, LENT SOMA), patient-reported quality of life and overall survival.

Results

276 patients (138 ST-IMRT; 138 DE-IMRT) were randomised (2011-2015) from 32 UK centres. 84% were male, 66% had laryngeal tumours, 98% were N0-2, mean age was 62 years. Planned chemotherapy was 40% induction and concomitant, 48% concomitant only, 13% none. Recruitment stopped early due to planned interim futility analysis (subhazard ratio (SHR)>1 after 50% required events). 32/138 (23%) ST-IMRT and 37/138 (27%) DE-IMRT patients reported LRFFR events, SHR for DE-IMRT 1.22 (95%CI 0.76–1.94), p=0.42. Grade≥2 acute pharyngeal mucositis and 3 month post-RT pharyngeal dysphagia was higher with DE-IMRT (p=0.008, p=0.01 respectively).

Conclusion

There was no evidence for a statistically significant improvement in locoregional control with DE-IMRT compared with ST-IMRT. DE-IMRT was associated with worse toxicity profile.