The effect of Hyperbaric OxygeN therapy on brEast cancer patients with late radiation toxicitY

With both an increase in breast cancer incidence and an increase in breast
cancer survival, the number of breast cancer survivors living with
treatment-induced morbidity have increased. Over the past years, there has been
a shift towards less invasive treatment of breast cancer. Radiotherapy plays an
important role in the treatment of most breast cancer patients. Most breast
cancer patients are nowadays treated with breast conserving therapy, a
combination of lumpectomy and radiotherapy. However, radiotherapy on the chest
wall may also be indicated after mastectomy when tumour was irradical resected,
or with a remaining macroscopic tumour on the chest wall after resection. Also,
radiotherapy in the axilla can be used to replace axillary lymph node
dissection. Radiotherapy is crucial in reducing the risk of local recurrence
and improving disease free survival. However, it may also lead to (late)
radiation toxicity. Radiation toxicity is characterized by fibrosis, edema,
pain, impaired mobility of the arm and decreased cosmetic outcome. (Late)
radiation toxicity can decrease the quality of life (QoL) after breast cancer
treatment. Treatment with hyperbaric oxygen therapy (HBOT) is being used to
treat late radiation toxicity after i.e. head- and neck cancer, gynaecologic
malignancies, urologic malignancies and breast cancer. HBOT induces
neovascularisation and stimulation of collagen formation by fibroblasts. Even
though HBOT is currently used in the treatment of late radiation toxicity in
the breast, and reimbursed by insurers, the evidence is scarce. Only a small
number of (mostly single-arm) studies have been performed and shown improvement
of complaints.

To assess whether HBOT reduces pain, and improves physical functioning and QoL
in breast cancer patients with late radiation toxicity.

Randomized controlled trial, nested within a prospective cohort (UMBRELLA, METC
no. 15-165) according to the cmRCT design. UMBRELLA is a prospective cohort
study including all breast cancer patients visiting the University Medical
Center (UMC) Utrecht department of Radiotherapy. In total 240 patients will be
randomized in a ratio of 2:1.

Eligible patients will be referred to the HBO center for a standard HBO
treatment. HBOT consists of 30-40 treatment sessions (1 session per day during
5 days per week). During the hyperbaric oxygen (HBO) sessions patients breath
in 100% oxygen during 4 times 20 minutes in a hyperbaric chamber.

: Eligible patients will be referred to the HBO center as part of standard
care. These patients will be offered to undergo a standard HBO treatment. HBOT
consists of a total of 30-40 2 hours sessions in a hyperbaric chamber. In this
hyperbaric chamber, which allows for a maximum of 12 people, patients wear
oxygen masks for 4 times 20 minutes. During these sessions people may read or
watch a movie. We expect that HBOT is beneficial for patients with late
radiation toxicity. A reduction of pain and fibrosis and improvement of arm
mobility and QoL might be expected. Possible side-effect of HBOT are
(transient) myopia, fatigue, barotrauma (i.e. problems with clearing the ears
due to the high pressure).
To assess the degree of late radiation toxicity (fibrosis, edema, (impaired)
arm mobility and cosmetic outcome) in the HBOT group, an extra physical exam is
performed at baseline and 3 months after HBOT. To evaluate cosmetic outcome, a
medical photograph will be taken at both occasions. Skin oxygenation with
transcutaneous oxygen measurement (TCOM) is measured as well. This is a
non-invasive measurement. However, it might be a burden since patients will be
undressed during this examination. At the end of the study, patients in the HBO
group fill out the late radiation toxicity questionnaire.
Yet, HBOT is approved and reimbursed care, despite long term results are still
unclear.