The Effect of Hyperbaric OxygeN Therapy on brEast Cancer Patients With Late Radiation toxicitY - UMBRELLA HONEY Trial

The Effect of Hyperbaric Oxygen Therapy on Breast Cancer Patients With Late Radiation Toxicity

The "Hyperbaric OxygeN therapy on brEast cancer patients with late radiation toxicity" (HONEY) trial aims to evaluate the effectiveness of HBOT on late radiation toxicity in breast cancer patients using the trial within cohorts (TwiCs) design.

Objective: The aim of this study is to assess whether HBOT reduces pain, and improves physical functioning and QoL in breast cancer patients with late radiation toxicity.

Study design: Randomized controlled trial, nested within the prospective UMBRELLA breast cancer cohort according to the TWiC's design. UMBRELLA is a prospective cohort study including all breast cancer patients visiting the University Medical Center (UMC) Utrecht department of Radiotherapy. In total 120 patients will be randomized in a ratio of 2:1.

Study population: Breast cancer patients participating in the UMBRELLA cohort who have given informed consent to be invited for future research (e.g. cmRCT's), and who have reported symptoms of late radiation toxicity.

Intervention: 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.

Main study parameters/endpoints: The primary endpoint of this study is patient reported breast/chest wall pain. Secondary endpoints are: physical functioning, QoL cosmetic outcome, physician reported pain and radiation toxicity (according to CTCAE criteria version 4.03, tissue oxygenation previous to HBOT and after HBOT and side-effects of HBOT.

Inclusion Criteria:

• Self reported pain grade 3-4 (on a scale of 1-4) as assessed by the late radiation toxicity questionnaire;
• Participation >12 months in the UMBRELLA cohort;
• Previous treatment with radiotherapy for breast cancer;
• Completed surgery and (neo)adjuvant systemic therapy except adjuvant endocrine therapy, for breast cancer.

Exclusion Criteria:

• Poor responder to questionnaires (i.e. return of ≤ 2 UMBRELLA questionnaires);
• Previous HBOT;
• Contra-indications for HBOT (e.g. (severe) chronic obstructive pulmonary disease (COPD) or asthma, pacemaker, morbid obesity, epilepsy in medical history, severe heart failure);
• Current metastatic disease or recurrent breast cancer.

Additional exclusions criteria based on screening visit:

• Inability to follow schedule of all consecutive HBO treatments (e.g. due to scheduled holidays > 2 days);
• Not meeting criteria for HBOT (e.g. due to complaints similar to late radiation toxicity, not caused by radiotherapy).