Effects of hyperbaric oxygen therapy on resuscitating mucosal microcirculation and tissue repair in patients who received radiotherapy for malignant disease in the head and neck region

Common complications associated with head and neck irradiation are mucositis
(acute phase), xerostomia, and necrosis of both the mucosa and the underlying
jaw bones. A late side effect of radiotherapy is damage of tissue
microcirculation as a result of obliterative endarteritis, this causes
decreased vascularity and consequently induces regional hypoxia. These late
side effects may occur years after radiation. Tissue invasion, later in life,
by trauma or surgery could result in wound dehiscence, infection, and altered
healing and regeneration.
Patients that received radiation therapy for malignancies in head and neck
often are treated with hyperbaric oxygen therapy (HBOT) before a tooth gets
extracted, implants are placed or any other form of oral surgery is performed.
It is thought that through improving oxygenation of the tissue by HBOT, the
risk of developing osteoradionecrosis (ORN) is reduced and the potential for
healing is sustained. However, until this day clear evidence behind the
efficacy and the exact working mechanism of HBOT is still lacking. Wound
healing responses to HBOT, quantified by parameters such as perfusion and blood
flow, were studied using different techniques and yielded often inconsistent
results. Currently, patients with oral tissue complications are treated with
sessions of HBOT without following a standardized protocol that specifies the
amount of treatment sessions necessary to achieve curative goals of the
pathology in question; improvement of symptoms is used as a guideline for
identifying the required HBOT sessions.
Osteoradionecrosis (ORN) currently appears to emerge less frequently after
tooth extraction in irradiated patients compared to the past. Studies show that
the incidence of ORN is 2% after 1990 compared to 16% prior to the 1990s,
presumably due to improved surgical methods and refined approaches to head and
neck irradiation. Despite these improvements, an important question is raised
as to whether hyperbaric oxygen should be applied as a supportive therapy; it
has so far yielded controversial scientific results, is not easily available,
and remains an expensive service. Furthermore, preparations usually take a
month and are a burden for the patient. We aim to elucidate the efficacy of
HBOT and its clinical applicability in preventing ORN and improving wound
healing in patients with ORN. This is important as not every patient benefits
from hyperbaric oxygen, also it will be possible to estimate the degree of
efficacy per patient in advance.

With the SDFI technique it is possible to visualize the oral microcirculation,
its changes, and red blood cell flow dynamics with high resolution. The SDFI
device is built as a compact practical handheld instrument. This gives
advantages in navigating areas that would otherwise be too challenging for
other imaging techniques to reach. To our knowledge there are no *real time*
clinical studies showing direct effects of HBOT on parameters of tissue
perfusion and microcirculation.

With this study we aim to elucidate the effects of HBOT on the oral
microcirculation in patients with malignant disease in the head and neck region
after receiving radiotherapy (RT). We want to test the hypothesis that HBOT
improves RT-induced microcirculatory derangements, which may ultimately prevent
or improve effects as ulceration and osteoradionecrosis (ORN) in head and neck
cancer patients. The question we aim to address is the following: what are the
effects of HBOT on the microvasculature of the oral mucosa after enduring
irradiation in the past regarding capillary density and morphology of the
microcirculation.

This is a prospective, single center, longitudinal, observational clinical
investigation on the effects of hyperbaric oxygen therapy on the oral mucosal
microcirculation in patients with oropharyngeal malignancies after receiving
radiotherapy in the past.

The burden associated with participation will be minimal given that the SDF
imaging technique is non-invasive and only requires contact with the oral
tissue. This might be an unpleasent feeling in patiënts who have a painful
mucosa. The measurement requires 10 minutes of the patients time and will be
repeated 8 times. There will be no risks associated with participation.