Hyperbaric Oxygen Therapy to Reduce Lymphedema After Breast Cancer -an Explorative Clinical Trial

Lymphedema (LE) is a potential complication of primary breast cancer treatment and the influence of LE on the quality of life is well-established. To date there is no established treatment that can reverse lymphedema. Patients are dependent on compression garments and manual lymphatic drainage to prevent progression of LE and worsening of discomfort, pain, upper limb dysfunction/sensation, skin problems and infections.

As a development in treatment of tissue damage after radiation treatment HBOT is used in the treatment of radiation induced mandibular necrosis, hemorrhagic cystitis or proctitis following pelvic radiation. The pathology, which correlates to the effect of HBOT include neovascularization, as well as organization and reduction in fibrous tissue, and new evidence also shows an increase in the number of lymphatic vessels in irradiated oral mucosa. Some studies have found that HBOT might also reduce arm edema in breast cancer patients, but evidence is inconsistent and mainly based on chronic and long existing lymphedema in long term BC survivors. The investigators argue that the possibility of remodeling of mature fibrotic tissue is less pronounced when the lymphedema has been present over prolonged periods of years, limiting the possibility of treatment success. Although HBOT is a lengthy and time-consuming treatment, it is documented safe in all aspects with little risk of side effects, and the potential health gains from the treatment are immense.

This explorative HBOT trial was designed to generate hypotheses about the conditions under which HBOT is effective to reduce lymphedema, and to reveal new aspects of the role of tissue composition on the effectiveness of HBOT. The early initiation of HBOT is the key factor in this set up, which is different from the previous studies in the field. To be able to do so, all participants in a randomized controlled exercise trial (LYCA), who develop lymphedema during the first year after surgery will be invited to participate in the HBOT trial.

This trial was accepted with regards to the experimental use of medical oxygen in a pressure chamber for the treatment of lymphedema in the National Health and Medicines Authority in 2015; protocol number R96- A6604-14- S22, EUDRACT no: 2015-000604-25.

Aims and hypothesis The primary aim in this explorative trial is to examine whether HBOT is effective in treating early LE. Secondly, the aim is to examine the importance of the conditions under which HBOT is more effective in treating LE. Effects of HBOT (primary endpoints) will be evaluated as objective measurements of the affected and contralateral arm volume assessed by DXA scan and Light perometry. Changes in lymphatic clearance rate before and after HBOT (secondary endpoint) will be measured by lymphoscintigraphy and biomarkers of inflammation and collagen levels in blood samples. Other secondary endpoints are patient reported outcomes of symptoms of lymphedema, physical and psychological function, fatigue, and quality of life, and will be assessed by questionnaire.