PET-NECK: A multi-centre, randomized, phase III, controlled trial (RCT) comparing PETCT guided active surveillance with planned neck dissection (ND) for locally advanced (N2/N3) nodal metastases (LANM) in patients with head and neck squamous cell cancer (HNSCC) treated with primary radical chemoradiotherapy (CRT)
1InHANSE, University of Birmingham, Birmingham, UK,2Paul Strickland Scanner Centre, Mount Vernon Hospital, Middlesex, UK,3Warwick University Clinical Trials Unit, Coventry, UK,4Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle, UK,5Queen Elizabeth Hospital Birmingham, Birmingham, UK,6Royal Marsden Hospital, London, UK,7HPV Oncology Group, Institute of Cancer Genetics, Cardiff University, Cardiff, UK,8Bristol Haematology and Oncology Centre, Bristol, UK,9Weston Park Hospital, Sheffield, UK,10Edinburgh Cancer Centre, Western General Hospital, Edinburgh, UK,11University of Leeds, Leeds, UK,12St James University Hospital, Leeds, UK
Planned ND after radical CRT for LANM remains controversial. 30% of ND specimens show histological evidence of tumour, albeit tumour viability cannot be confirmed. Consequently, many clinicians still practice planned ND. In mainly retrospective single-institution studies, FDG-PETCT demonstrated high negative predictive values for persistent nodal disease, providing a possible alternative paradigm to ND. This study aimed to determine the efficacy and cost-effectiveness of PETCT guided surveillance, compared to planned ND, in a multicentre randomised setting.
Eligibility: Patients with LANM of oro-, hypo-pharynx, larynx, oral or occult HNSCC receiving CRT and fit for ND. Randomisation (1:1): to planned ND before or after CRT (control), orCRT followed by FDG-PETCT 10-12 weeks post CRT with ND only if PETCT showed incomplete or equivocal response of nodal disease (intervention). Balanced by centre, planned ND timing, CRT schedule, disease site, T / N stage. Primary outcome: Overall Survival (OS), minimum follow-up 2 years. Analysis: 560 patients needed to detect non-inferior OS in the intervention arm with 80% power, Type I error 5%, defining non-inferiority as having a hazard ratio (HR) no higher than 1.50. Intention to treat analysis was performed by Cox proportional hazards model.
564 patients recruited (282 ND arm, 282 surveillance arm; 17% N2a, 61% N2b, 18% N2c, 3% N3). 84% had oropharyngeal cancer. 75% of tested cases were p16+ve. Median follow-up 36 months. The HR for OS was 0.92 (95% CI: 0.65, 1.32) indicating non-inferiority. HR margin of 1.50 lies at the 99.6 percentile of this estimate, p = 0.004. There were no differences by p16 status. There were 54 NDs performed in the surveillance arm with 22 surgical complications; 221 NDs in the ND arm with 85 complications.
PETCT surveillance was cost effective compared to planned neck dissection with a £1, 415 per person saving and an additional gain of 0.07 QALY.
PETNECK is the largest surgical head neck trial to be done in the UK, and one of the largest in the world. PETCT guided active surveillance showed similar survival outcomes to ND arm, but resulted in considerably fewer NDs, and fewer complications, and is more cost-effective, supporting its use in routine practice.
Presented as oral presentation at ASCO June 2015.