Adaptive Dose-Escalated Multi-modality Image-guided RadiothErapy (ADMIRE) for head and neck cancer by twice re-imaging, re-delineation and re-planning during the course of radiotherapy

Although tremendous gains have been achieved over the last few decades in
patients with head and neck cancer (HNC) treated by means of (chemo)radiation
with regard to loco-regional control (LRC) and overall survival (OS), the
balance between tumor control and toxicity is still very delicate. The cure
rates remain inadequate in certain subgroups of patients, while treatment
toxicities and deterioration of quality of life (QoL) are considerable.
Most recurrences appear within the FDG-avid area and radioresistance is
heterogeneous within the tumor. A biologically adaptive radiotherapy approach,
where the treatment plan is re-optimized during treatment based on repeat
functional imaging, can increase the dose to the less responding
(radioresistant) parts of the tumor while decreasing the dose to the good
responding parts of the tumor. Thereby improving the therapeutic ratio
(increasing cure rates while maintaining or decreasing treatment-related side
effects).
This trial aims to investigate the feasibility of an adaptive radiation
approach using multi-modality imaging and a PET-guided mild dose escalation to
improve oncologic outcomes.

Primary objective:
To investigate the feasibility of the adaptive radiotherapy scheme.

Secundary objectives:
To examine the toxicity of the adaptive RT scheme
To investigate the locoregional tumor control
To examine the prognostic value of the different imaging modalities

Feasability study of the adaptive radiotherapy scheme.

Patients with primary head and neck squamous cell carcinoma (HNSCC) planned for
treatment with radiotherapy with or without chemotherapy in curative setting
will be treated with an adaptive radiotherapy scheme. An FDG-PET/CT scan for
re-delineation and re-planning will be made at the end of the second and fourth
of week of radiotherapy. The non-responding part of the tumor on FDG-PET will
receive a mild dose-escalation. Depending on the metabolic response, the entire
tumor will receive 70 Gy or the residual FDG-avid area will receive 74 or 78
Gy. If there is a complete metabolic response on the FDG-PET after 2 weeks, the
entire tumor will receive 70 Gy. If there is a complete metabolic response
after 4 weeks of treatment, the residual FDG-avid area will receive 74 Gy. If
there also is no complete metabolic response after 4 weeks of treatment, the
residual FDG-avid area will receive 78 Gy.

Patients included in the study will receive additional imaging with FDG-PET/CT
and MRI as listed in the schedules below. These imaging procedures will be
combined with treatment visits in week 2 and 4. FDG-PET/CT requires 6 hours
fasting. The FDG-PET/CT scans come with an additional radiation burden: 2 x low
dose FDG-PET (2 mSv) + low dose CT (2.5 mSv), for a total of 9 mSv. This is
within the range of normal diagnostic procedures, and is not considered a
significant risk in the selected population with cancer and an indication for
external beam radiotherapy. The increased radiation dose is mild and directed
only to the non-responding part of the gross tumor volume at FDG-PET. Therefore
it is not expected to increase side-effects.