Effects of radiation therapy on oral mucosa microcirculation in patients with malignant disease in the head and neck region.

When radiotherapy (RT) is applied as a treatment in head and neck cancer
patients, it is inevitable that damage ensues in the tissues surrounding the
tumor, which results in oral complications that include among others oral
mucositis (OM), xerostomia, mucosal and bone necrosis. These pathological
conditions are classified as acute, consequential and/or late side effects. The
acute injury, which consists of mucositis, arises in 80% of the patients during
the course of curative radiation. Mucositis is mainly caused by the effect of
radiotherapy on the rapidly proliferating cells of the mucosa, shown as atrophy
of the squamous epithelial cells and inflammatory infiltration. Hence no
vascular damage is present at this time except for an increase in permeability
due to the inflammation.

As a late adverse effect, RT injures the microvasculature in the
vasculoconnective tissue (slow turnover of cells). Early damage of the
vasculature by the inflammatory response with the release of vasoactive
cytokines (acute fase) causes fibrin to leak into the tissues, which promotes
collagen deposition. Vascular lumen can get blocked which may lead to reduced
tissue vascularity and regional hypoxia as a late effect of radiotherapy.
Hypocellularity and decreased metabolism may eventually induce ulceration,
and/or atrophy of the epithelium. However, late effects and ulceration usually
does not occur until doses respectively of 50.0 and 65.0 Gy (conventional
fractionation) are used.
Late effects can also arise several years after RT. Tissue invasion, by for
example trauma or surgery, can drive the propensity for wounds to follow a
course of tissue breakdown by impaired healing, wound dehiscence, infection,
and altered repair and regeneration.

Although the effects of RT on the microcirculation have been investigated
previously in other tissues using invasive techniques based on histological
methods and intravital capillaryscopy, it has never before been evaluated using
SDF imaging. SDF technology is built into a practical handheld instrument
providing great ease in mobility with noninvasive data acquisition of images
with high resolution and contrast between microvessels and the surrounding
parenchyma. The compact and noninvasive nature of the technique enables the
investigator to easily apply the instrument to mucosal tissue surfaces, such as
in the oral cavity, and navigate to areas that would otherwise be too
challenging for other imaging techniques to reach.

The aim of this study is to elucidate the effects of RT on the oral
microcirculation in patients with malignant disease in the head and neck
region. We want to test the hypothesis that radiation therapy triggers
microcirculatory derangements which ultimately lead to late effects as
ulceration and osteoradionecrosis (ORN) in cancer patients. The question we aim
to address is the following: what are the effects of radiation therapy on the
microvasculature of the oral mucosa in the acute and late phase regarding
capillary density and morphology of the microcirculation.

This is a single center prospective, longitudinal, observational clinical
investigation on the effects of radiation therapy on the oral mucosal
microcirculation in patients with oropharyngeal malignancies.

Burden: Besides the treatment the patient wil undergo for his malignancy, our
study will only add up the SDF imaging technique to the patients burden. As
mentioned earlier SDF is a non-invasive technique which only requires contact
with the tissue. This might give the patient a unpleasant feeling. This action
will aproximately take 10 min of extra time. This measurement will be repeated
9 times during the study.

Risks: There will be no additional risks for the patient as SDF is an
non-invasive technique.