A multicentre randomised phase III trial comparing Positron Emission Tomography - computed tomography guided watch and wait policy versus planned NECK dissection for the management of locally advanced (N2/N3) nodal metastases in patients with head and neck squamous cancer

ISRCTN	ISRCTN13735240
DOI	https://doi.org/10.1186/ISRCTN13735240
ClinicalTrials.gov (NCT)	NCT00720070
Protocol serial number	HTA 06/302/129; PET-NECK V1.0 5Feb07
Sponsor	University Hospitals Coventry and Warwickshire NHS Trust (UK)
Funder	Health Technology Assessment Programme

Submission date: 21/05/2007
Registration date: 12/06/2007
Last edited: 24/03/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerhelp.org.uk/trials/a-trial-looking-at-the-treatment-of-local-cancer-spread-in-head-and-neck-cancers

Contact information

Mr Hisham Mehanna
Scientific

University Hospitals Coventry and Warwickshire NHS Trust
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Phone	+44 (0)2476 965 606
Email	hisham.mehanna@uhcw.nhs.uk

Study information

Primary study design	Interventional
Study design	Two-arm multi-centre randomised trial. Randomisation 1:1 with stratification (centre, chemotherapy schedule, N stage, T stage)
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A multicentre randomised phase III trial comparing Positron Emission Tomography - computed tomography guided watch and wait policy versus planned NECK dissection for the management of locally advanced (N2/N3) nodal metastases in patients with head and neck squamous cancer
Study acronym	PET-CT
Study objectives	Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide with approximately 500,000 new cases/year. It poses a significant therapeutic problem as it has a high mortality and morbidity and survival rates have not considerably improved over the past two decades despite newer aggressive surgical and chemoradiotherapy (CRT) regimens. CRT is the preferred first line of treatment for several types of HNSCC. For patients with large metastasis to the neck nodes, evidence for management is sparse. Current standard care is neck dissection either before/after CRT. There is debate regarding whether a neck dissection is needed or whether CRT alone is sufficient. Controversy continues mainly due to poor quality and contradictory evidence from prospective and retrospective case series for both management strategies. Furthermore the advent of newer, more accurate functional modalities for the detection of persistent disease, e.g., Positron Emission Tomography - Computed Tomography (PET-CT) scanning have further strengthened this debate. Aim: To test the hypotheses that a PET-CT guided watch and wait policy (experimental arm) is non-inferior to the current practice of planned neck dissection (control arm) when comparing overall and disease-specific survival in the management of advanced (N2 or N3) nodal metastasis in patients treated with CRT for their HNSCC primary. Recurrence, quality of life and cost effectiveness will be assessed as secondary outcomes.
Ethics approval(s)	Oxford Research Ethics Committee A, 09/05/2007, ref: 07/Q1604/35
Health condition(s) or problem(s) studied	Head and neck squamous cell carcinoma (HNSCC)
Intervention	CRT regimens: All patients must receive concomitant CRT to be included in the trial. For each patient, the participating centre must specify the schedule that they will use. This regimen must be: 1. A CRT schedule that the centre uses in their normal, peer-reviewed practice AND 2. The CRT schedule selected must be present in the list of approved trial schedules The recommended standard radiotherapy schedule for the trial is radiotherapy doses of 65 to 70 Gy in 30 to 35 daily fractions of 2 Gy or more with at least two doses of concomitant three/four weekly intravenous cisplatin 75 to 100 mg/m^2 or carboplatin (4.5 to 5 AUC). Control arm: planned pre-CRT neck dissections - neck dissections must be performed within two to four weeks of randomisation. The recommended surgical procedure is a modified radical neck dissection This involves removal of lymphatic structures in levels I-V, with preservation of one or more of the following: spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle. Experimental arm: PET-CT scan Both groups will be followed up for two years.
Intervention type	Other
Primary outcome measure(s)	1. Overall survival, measured at at two years 2. Health economics (Quality Adjusted Life Years [QALYs]), measured at at two years
Key secondary outcome measure(s)	1. Disease-specific survival, measured at pre-treatment and 3, 6, 12 and 24 months post randomisation 2. Recurrence in the neck, measured at pre-treatment and 3, 6, 12 and 24 months post randomisation 3. Quality of life, measured at pre-treatment and 3, 6, 12 and 24 months post randomisation 4. Complication rates, measured at pre-treatment and 3, 6, 12 and 24 months post randomisation 5. Accuracy of PET-CT scanning for assessing the primary tumour
Completion date	31/03/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	560
Key inclusion criteria	1. Histological diagnosis of oropharyngeal, laryngeal, oral, hypopharyngeal or occult HNSCC 2. Clinical and CT/Magnetic Resonance Imaging (MRI) evidence of nodal metastases staged N2 (a, b or c) or N3 3. Indication to receive curative radical concurrent CRT for primary 4. Fitness for neck dissection surgery
Key exclusion criteria	Current exclusion criteria as of 28/01/2011: 1. Patients undergoing resection for their primary tumour, e.g., resection of tonsil or base of tongue with flap reconstruction (diagnostic tonsillectomy not considered an exclusion criteria) 2. Patients with N1 nodal metastasis 3. Patients receiving neo-adjuvant chemoradiotherapy with no concomitant chemotherapy 4. Patients receiving adjuvant chemotherapy 5. Patients undergoing chemo +/- radiotherapy for palliative purposes 6. Patient undergoing radiotherapy alone (not optimal treatment for neck node disease) 7. Distant metastases to chest, liver, bones or other sites 8. Unfit for surgery or chemoradiotherapy 9. Previous treatment for head and neck squamous cell carcinoma 10. Patients have had another cancer diagnosis in the last five years (except basal cell carcinoma or carcinoma of the cervix in situ). 11. Pregnant patients 12. Patients under 18 years of age Previous exclusion criteria: 10. Patients with occult nodal metastasis, i.e., large nodal metastasis but no proven primary site on clinical assessment
Date of first enrolment	01/04/2007
Date of final enrolment	20/09/2012

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

University Hospitals Coventry and Warwickshire NHS Trust

Coventry
CV2 2DX
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	14/04/2016		Yes	No
Results article	results	01/04/2017		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results			24/03/2022	No	Yes

Editorial Notes

24/03/2022: Plain English results added.
18/04/2017: Publication reference added.
05/05/2016: Publication reference added.
04/02/2011: The overall trial end date for this trial was changed from 31/03/2013 to 31/03/2015.