Anatomical stability during proton beam therapy of uveal melanoma

Uveal melanoma (UM) is the most common malignant primary tumour of the eye in
Caucasian adults, where it represents 79-88% of primary intraocular cancers.
About 90% of uveal melanomas arise from the choroid, 5-10% from the ciliary
body and 2-3% from the iris.

The objectives of treatment are primarily to prevent metastasis and secondary
to conserve the eye and vision. The treatment modalities for managing UM
include, on one hand eye preserving therapies such as plaque brachytherapy,
proton beam radiotherapy, stereotactic radiotherapy and local tumour resection,
and on the other hand enucleation.

The optimal therapy is primarily determined on the size and location of the
tumour and secondarily on the presence of extrascleral extension of the tumour.
Proton beam therapy, an external radiation therapy with protons, is the optimal
treatment to spare the eye for larger tumours (thickness > 7 mm or basal
diameter > 16) or smaller tumours located in close proximity of the optic
nerve3.

After the diagnostic work-up, the patient will undergo surgical placement of
tantalum markers. These are placed at the tumour border on the sclera and serve
as radiographic markers of the tumour edge for treatment planning and daily
image guidance. Two weeks after surgery, the patient undergoes a radiation
simulation in which an immobilization device is prepared and the markers are
imaged on X-ray for confirmation of the 3D-clipposition in the eye. Finally,
the treatment plan can be completed and treatment can be performed.

In the planning of PBT for other tumours more advanced image based planning is
performed sometimes even with adaptive planning. Where the treatment plan is
adjusted daily based imaging. PBT planning for UM is based on 2D imaging and
manual measurements. These measurements are translated into a 3D model. In the
treatment only a 0.8 mm margin is included for the measurements errors. Slight
cumulative errors can lead to underdosage of the tumour increasing risk of
reoccurrence and metastasis.

As the tumour localization is currently exclusively based on the marker
position it is imperative to obtain insight into the stability of the clip
position and surrounding structures over time.

It is assumed that the tumour, clips and the surrounding tissue remains stable
during treatment however, it has been shown that the tumour enlarges (due to
welling) in the first month after treatment. Changes in tumour size might lead
to underdosage of the tumour. This research aims to evaluate the accuracy of
the current treatment (planning) method and find opportunities to improve
treatment and move to MRI-based treatment planning.

We aim to assess the stability of the ocular structures and tantalum clips
during the complete PBT treatment, so no part of the tumour is missed during
radiotherapy, to reduce the total burden for the patient.

The study is a multi center longitudinal study: the patients will be included
at the LUMC, after which the MRI-scans for the study will take place in
HollandPTC. The study will include fifteen patients undergoing proton beam
therapy for uveal melanoma. On average one patient per 2-3 weeks will be
included. The additional MRIs will take approximately thirty minutes and will
be scanned with. The duration of the study will be approximately one year.

The risks of this study are the standard risks related to MRI. These risks will
be minimized by screening the subjects through a questionnaire for MRI safety
prior to the examination. The questionnaire will cover the risk factors
associated with MRI. Based on the answers the subject will be allowed or not
allowed to go into the scanner. Certified researchers/technicians will assist
to maintain overall safety of the subject.