Uniform FDG-PET Guided Gradient Dose Prescription to Reduce Late Radiation Toxicity (UPGRADE-RT)

Uniform FDG-PET Guided GRAdient Dose prEscription to Reduce Late Radiation Toxicity (UPGRADE-RT): a Randomised Controlled Trial With Dose Reduction to the Elective Neck in Head and Neck Squamous Cell Carcinoma

The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and introduction of an intermediate dose-level in the treatment of head and neck cancer will results in less radiation sequelae and improved quality of life after treatment whilst the recurrence rate in electively irradiated lymph nodes should not be compromised.

A summary of the study protocol can be found here: http://rdcu.be/qgMv

Study Overview

• Status: Completed
• Conditions: Head and Neck Neoplasms; Carcinoma, Squamous Cell
• Intervention / Treatment: Radiation: standard dose prescription; Radiation: FDG-PET guided gradient dose prescription

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • VU University Medical Center Amsterdam
  • Arnhem, Netherlands
    • Radiotherapiegroep, Arnhem
  • Maastricht, Netherlands
    • MAASTRO clinic, Maastricht
  • Nijmegen, Netherlands
    • Radboud University Nijmegen Medical Center
  • Utrecht, Netherlands
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Newly diagnosed tumours classified as stage T2-4 N0-2 (TNM 7th edition 2009) located in the larynx, oropharynx or hypopharynx (unknown primary and oral cavity are not eligible)
2. Histopathological diagnosis of invasive squamous cell carcinoma in the primary tumour
3. Decision for curative intent external beam radiotherapy with elective treatment of the neck made by a multidisciplinary head-and-neck oncology team. The patient must be expected to complete the treatment.
4. Radiotherapy planned to start within 6 weeks from baseline imaging of tumour assessment
5. No distant metastasis (M0) (TNM 7th edition 2009)
6. WHO performance status 0-2
7. ≥ 18 years of age
8. Written informed consent

Exclusion Criteria:

1. Concomitant chemotherapy or EGFR inhibitors for this tumour.
2. Primary tumour of the oral cavity or unknown primary tumour
3. Prior or current anticancer treatment to the head and neck area (e.g. radical attempted or tumour reductive surgery, neo-adjuvant or concomitant chemotherapy, EGFR inhibitors or radiotherapy), except for endoscopic glottic laser micro surgery.
4. Current participation in any other oncologic interventional clinical study for this tumor.
5. Uncontrolled diabetes mellitus.
6. Known or suspected HIV infection.
7. History of previous malignancy within the last 3 years, with the exception of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, basal/squamous cell carcinoma of the skin, and other non-invasive malignancies (e.g. in situ carcinomas)..
8. Any condition (somatic, psychological, familial, sociological or geographical) rendering the patient unable to understand or complete questionnaires.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: standard dose prescription; FDG-PET-scan in treatment mask for radiotherapy planning; Accelerated radiotherapy IMRT/VMAT with SIB (34 fraction in 5.5 weeks)	Radiation: standard dose prescription; standard elective dose; no intermediate dose-level; visual interpretation of FDG-PET-scan
Experimental: FDG-PET guided gradient dose prescription; FDG-PET-scan in treatment mask for radiotherapy planning; Accelerated radiotherapy IMRT/VMAT with SIB (34 fraction in 5.5 weeks)	Radiation: FDG-PET guided gradient dose prescription; de-escalation of elective dose; intermediate dose-level; standardized methods to evaluate FDG-PET-scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Toxicity: normalcy of diet (score of the performance status scale for head and neck cancer patients)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: recurrence in electively irradiated lymph nodes	A Kaplan-Meier estimate will be calculated	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute toxicity (common toxicity criteria v2.0)		up to 3 months
Late toxicity: swallowing function (water swallowing test)		3, 12 and 24 months
Late toxicity: salivary gland function (stimulated flow rates)		3, 12 and 24 months
Late toxicity: thyroid gland function (thyroid stimulating hormone blood test)		3, 12 and 24 months
Quality of life (EORTC QLQ-C30 and QLQ-H&N35 questionnaires)		3, 6, 12 and 24 months
Xerostomia related quality of life (GRIX questionnaire)		3, 6, 12 and 24 months
Dysphagia related quality of life (SWAL-QOL questionnaire)		3, 6, 12 and 24 months
Loco-regional control	A Kaplan-Meier estimate will be calculated	24 months
Overall survival	A Kaplan-Meier estimate will be calculated	24 months
Disease specific survival	A Kaplan-Meier estimate will be calculated	24 months

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: UMC Utrecht; Amsterdam UMC, location VUmc; Maastro Clinic, The Netherlands; Radiotherapiegroep
• Investigators: Study Chair: Prof. Dr. J.H.A.M. Kaanders, Radboud University Nijmegen Medical Center

Publications and helpful links

General Publications

• van den Bosch S, Dijkema T, Kunze-Busch MC, Terhaard CH, Raaijmakers CP, Doornaert PA, Hoebers FJ, Vergeer MR, Kreike B, Wijers OB, Oyen WJ, Kaanders JH. Uniform FDG-PET guided GRAdient Dose prEscription to reduce late Radiation Toxicity (UPGRADE-RT): study protocol for a randomized clinical trial with dose reduction to the elective neck in head and neck squamous cell carcinoma. BMC Cancer. 2017 Mar 21;17(1):208. doi: 10.1186/s12885-017-3195-7.

Helpful Links

• Study protocol

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): March 8, 2024
• Study Completion (Actual): March 8, 2024

Study Registration Dates

• First Submitted: April 21, 2015
• First Submitted That Met QC Criteria: May 8, 2015
• First Posted (Estimated): May 13, 2015

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: head and neck cancer; dose reduction; FDG-PET; accelerated radiotherapy; dose de-escalation; elective lymph nodes
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Carcinoma; Carcinoma, Squamous Cell
• Other Study ID Numbers: UPGRADE-RT v3.5 dd20201201