Gothard, L., Stanton, A., MacLaren, J., Lawrence, D., Hall, E., Mortimer, P., . . . Yarnold, J. (2004). Non-randomized phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphedema and tissue fibrosis after radiotherapy for early breast cancer. Radiotherapy and Oncology, 70(3), 217–224.

To examine hyperbaric oxygen in the treatment of chronic arm lymphedema after radiotherapy

Patients received treatment with hyperbaric oxygen, compressed to 2.4 atmospheres absolute (ATA) in a multiplace category 1 hyperbaric chamber at Royal Hospital. Patients received 100% oxygen at pressure via a transparent hood. Total time at 2.4 ATA was 100 minutes, including two five-minute air breaks. Each participant received a total of 30 pressure exposures, treating five days per week for six weeks. The primary endpoint was an absolute change of greater than 20% in relative volume of the ipsilateral arm versus contralateral arm. The secondary endpoints were lymphoscintigraphy, patient self-assessments, and physician assessments. An unplanned endpoint was patient comments about arm softening and mobility as part of one relative change in arm volume. 

• The study sample was comprised of 20 female patients and 1 male patient.
• Patients were included if they had greater than or equal to 30% increase in arm volume, were free from cancer recurrence, physical and psychologic fitness for hyperbaric oxygen, and availability for follow-up and informed consent.
• All patients had axillary or supraclavicular radiotherapy.

The study took place at Royal Marsden Hospital based on observation from a previous study at the same institution evaluating hyperbaric oxygen in radiation-induced brachial plexopathy. In that study, two of the six patients with chronic lymphedema experienced major and persistent improvement in lymphedema.

• Magnetic resonance imaging of the supraclavicular fossa, axilla, and brachial plexus was done prior to treatment to exclude recurrence.
• Subcutaneous induration within the radiotherapy volume was clinically assessed.
• Arm volume was measured using a Perometer.
• Quantitative lymphoscintigraphy was used.
• Clinical photographs were taken.
• Patient completed self-assessments using EORTC QOL (QLQ-C30 and BR23)
• Clinical assessment and Perometer measurements were taken within one week of completing 6 weeks of treatment and at 6 and 12 months after start of therapy.
• Self-assessments occurred at the same intervals as clinical assessments plus three and nine months after start of treatment.
• Lymphoscintigraphy and clinical photos repeated at 12 months only.

Compliance with treatment was 100%. All questionnaires were returned, and only two patients missed follow-up assessments (one patient was hospitalized and the other moved); as a result, 94% of patients had Perometer measures. Only 71% participated in lymphoscintigraphy because of logistics, 7% missed follow-up scan at 12 months, and one scan was erased accidentally. Three patients responded according to defined 20% or greater reduction in arm volume, 16 were nonresponders. Mean percentage reduction in arm volume was 7.68. Quality-of-life measures were not clinically significant post-treatment. Comments by participants indicated they may not have been appropriate measures. Lymphoscinitgraphy improvement showed statistically significant changes.

Patients had good compliance with the treatment plan despite rigorous treatment. Median time since completion of the treatment is 14 years, which is encouraging given improvement in lymphoscintigraphy measures and limb tissue softening (a subjective measure).

• The sample size was small.
• The study did not have a control group or comparison group.

The study has sufficient data to justify a randomized controlled trial. Careful screening of participants is needed.