Reduction of complications for head and neck cancer: Individual lymph node irradiation (iNode)

Radiotherapy applied for head and neck cancer causes long-term complications in
many patients. A recent study showed 48% of all patients still have swallowing
complaints 8 years after radiotherapy treatment. A dry mouth was still apparent
in 66% of all patients. 23-53% of all patients had dysfunction of the thyroid.
And, in 29% of all patients carotid stenosis was observed with possible
vascular brain injury. Radiotherapy treatment for these patients consists of a
high dose to the primary tumor and visible regional metastasis, and a lower
dose to the lymph node levels. The lower dose that serves as treatment of
possible non-visible regional lymph node metastases, plays an important role in
the occurrence of long-term complications. With MRI non-suspect lymph nodes
possibly containing metastasis are better visualized. Accordingly, non-suspect
lymph nodes could be irradiated instead of the larger lymph node levels in
which the nodes are located in. A more precise way of applying irradiation to
treat occult metastasis could cause a decrease in long-term complications.

In the iNode project we want to show it is technically possible to irradiate
individual lymph nodes. For this reason, we will treat 20 patients with
laryngeal, hypopharyngeal or oropharyngeal cancer with radiation. The radiation
dose will be applied to the individual lymph nodes instead of the larger lymph
node levels. The treatment will be administered with the MR-linac, a
combination of a MRI-scanner and a radiation device that was developed in the
UMC Utrecht. We consider the study procedures clinical acceptable if on average
16 out of 20 fractions could be performed on the MR-Linac.

This is a monocenter phase I feasibility study, that will be performed in the
UMC-Utrecht.

In this study individual lymph nodes will be irradiated with the full elective
dose, the lymph node levels possibly containing small invisible lymph nodes
will be irradiated with a lower dose. In this way the risk of regional
recurrence will remain low.

Patients in the iNode study will receive a lower dose to the elective neck
volumes compared to conventional treatment. Based on the results of our
planning study, we expect a substantial reduction of dose in the carotid
arteries, thyroid and submandibular glands. These dose reductions could lower
RT related toxicity. The risk of RR might be higher, since the dose applied to
the elective neck volumes is lower. However, based on our dose calculations for
occult metastases we do not expect a higher RR.
The treatment time on the MR-linac will be approximately twice as long compared
to conventional treatment (15 vs 30-60 min). If patients cannot endure
treatment on the MR-linac it is still possible to finish treatment on the
conventional linac. Switching to conventional treatment will not have
consequences for the treatment
outcome.
Hearing protection is provided in compliance with standard procedures, and
hearing loss is therefore not expected to occur as a result of the noise
exposure caused by the MR. However, there is little experience with repetitive
MR noise exposure in a time span of several weeks as is encountered in the RT
schedules of 35 fractions on the MR-linac. There is only one retrospective
cohort study describing similar exposure, in which no clinical relevant hearing
loss was concluded (Bongers et al., 2017). To ascertain that there is no
permanent hearing damage after the repetitive exposure to the MR noise, hearing
loss will be closely monitored by an audiologist.