The UPGRADE-RT trial will investigate whether de-escalation of the 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…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Morbidity: dysphagia measured as the *normalcy of diet* score of the
Performance Status Scale for Head & Neck Cancer Patients (PSS-HN) at 1 year
after treatment.
Secondary outcome
Secundary endpoint: Safety: actuarial rate of recurrence in electively
irradiated lymph nodes at 2 years after treatment.
Other endpoints: Acute toxicity, late toxicity with focus on swallowing
function, thyroid gland and salivary glands function, quality of life after
treatment with focus on xerostomia and dysphagia, loco-regional control and
survival.
Background summary
In definitive radiotherapy for head and neck cancer, generally two dose-levels
are delivered. A high dose, the so called *boost dose* to eradicate macroscopic
tumour and a lower dose, the so called *elective dose* to achieve control of
clinically occult metastasis in cervical lymph nodes.
The current elective dose prescription originates from the 1950s, a time at
which assessment of the neck only consisted of physical examination due to the
lack of sufficiently sensitive imaging. Nowadays, smaller metastasis in
cervical lymph nodes can be detected due to modern high resolution diagnostic.
As a result, occult tumour-load in radiologically uninvolved lymph nodes is
much smaller than in the era before these imaging techniques were available.
Since the dose required to control occult disease is dependent on occult tumour
load, current elective dose prescription is most likely higher than necessary.
For this same reason, it would make sense to refine the traditional binary dose
prescription to a more gradual one that is proportional to tumour-load. For
this purpose, molecular imaging using FDG-PET can guide such gradient dose
prescription as FDG-uptake can be considered as a surrogate parameter for
tumour cell density. The value of FDG-PET in this context is in the risk
assessment of cervical lymph nodes. It is conceivable that borderline-sized
cervical lymph nodes having mild FDG-uptake may not require the boost dose
since they are likely to contain only a small-tumour-load. An intermediate dose
level may be sufficient in such nodes.
Bilateral (elective) irradiation of cervical lymph node regions contribute to
dysphagia, xerostomia and hypothyroidism in a dose dependent way. These often
irreversible radiation sequelae are known for their deteriorating effects on
quality of life after treatment.
Study objective
The UPGRADE-RT trial will investigate whether de-escalation of the 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 (morbidity) whilst the recurrence rate in
electively treated neck should not be compromised (safety).
Study design
UPGRADE-RT is a multicenter, phase III, single blinded, randomized controlled
trial.
A total of 300 patients with head and neck cancer will be randomized ratio 2:1
to the following treatment arms:
- FDG*PET guided gradient dose prescription (intervention arm) (n=200)
- Standard dose prescription (control arm) (n=100)
Intervention
All patients will be treated with accelerated radiotherapy (34 fraction in 5.5
weeks) using an IMRT/VMAT with SIB technique, independent of randomization.
If randomized to the intervention arm, FDG*PET guided gradient dose
prescription will be used. Dose to elective lymph node regions will be
de-escalated. An intermediate dose-level will be introduced to treat borderline
sized lymph nodes identified by FDG-PET-scan. FDG-PET-scan will be evaluated
using standardized methods.
If randomized to the control arm, standard dose prescription will be used with
standard dose to elective lymph node regions and without intermediate
dose-level. FDG-PET-scan will be evaluated by means of visual interpretation.
Study burden and risks
A possible risk of concern is an increased risk of recurrence in electively
irradiated lymph nodes due to a reduction of dose in electively irradiated
lymph node regions. With the current standard treatment, this risk is
approximately 5% at 2 years after treatment.
Dose-response calculations show a comparable control rate with an elective
treatment of 34Gy (in 2Gy fractions) when assuming a detection threshold of 5mm
in diameter for cervical lymph node metastasis. For this reason, an increased
risk of recurrence in electively irradiated lymph nodes is assumed to be
unlikely, despite of dose reduction. However, even in case of regional
recurrence, a salvage neck dissection is still available for treatment with
curative intent.
At the same time, dose reduction to elective lymph node regions has many
advantages.
Permanent radiation sequelae such as xerostomia, dysphagia and hypothyroidism
can be less severe or may be actually prevented. Since these types of radiation
sequelae are known to heavily compromise quality of life after treatment, dose
reduction to elective lymph node regions is expected to improve quality of life
in comparison to treatment with standard elective dose.
In the course of this trial, quantitative and qualitative evaluation of
toxicity will be monitored. Therefore, patients will be asked to fill out
quality of life questionnaires and to undergo non-invasive quantitative
evaluation of swallowing and salivary gland function.
Geert Grooteplein-Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein-Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
1) Newly diagnosed tumours classified as stage T2-4 N0-2 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)
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) 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.
3) Current participation in any other interventional clinical study.
4) Uncontrolled diabetes mellitus.
5) Known or suspected HIV infection.
6) 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, and basal/squamous cell carcinoma of the skin.
7) Any condition (somatic, psychological, familial, sociological or geographical) rendering the patient unable to understand or complete questionnaires.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02442375 |
| CCMO | NL46354.091.15 |