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
Session type: Oral
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.
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.
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).
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.