Hyperbaric Oxygen Therapy for Late Local Toxic Effects in Patients Receiving Adjuvant Radiotherapy for Breast Cancer

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In a Dutch study (HONEY) reported in JAMA Oncology, van der Molen et al found that patients with breast cancer and late local toxic effects after adjuvant radiotherapy who completed hyperbaric oxygen therapy (HBOT) had reductions in pain and fibrosis. However, only a minority of patients offered HBOT received the treatment.

Study Details

A total of 189 women with patient-reported moderate or severe breast, chest wall, and/or shoulder pain in combination with mild, moderate, or severe edema, fibrosis, or movement restriction ≥ 12 months after breast irradiation were enrolled in the open-label multicenter trial between November 2019 and August 2022. Patients were randomly assigned 2:1 to be offered HBOT consisting of 30 to 40 sessions over a period of 6 to 8 consecutive weeks (n = 125) or to a control group (n = 61).

The primary outcome measure was breast, chest wall, and/or shoulder pain 6 months after random assignment as measured by the EORTC QLQ-BR23 questionnaire. Data were analyzed according to intention-to-treat (ITT) and complier average causal effect (CACE) principles, the latter to estimate the effect of undergoing HBOT.

Key Findings

Among the 125 patients offered HBOT, 31 (25%) accepted and completed treatment. The most common reason for not accepting HBOT was high treatment intensity.

In ITT analysis, moderate or severe pain at follow-up was reported by 58 (50%) of 115 evaluable women in the intervention group vs 32 (62%) of 52 in the control group (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.32–1.23, P = .18). In CACE analysis, the proportion of women reporting moderate or severe pain at follow-up was 32% (n = 10/31) among those completing HBOT and 75% (n = 9.7/12.9) among control patients expected to complete HBOT if offered the treatment (adjusted OR = 0.34, 95% CI = 0.15–0.80, P = .01). Of women who completed HBOT, 5 (17%) of 30 evaluable patients reported moderate or severe fibrosis vs 10.6 (86%) of 12.3 control patients who would have completed HBOT if offered the treatment (adjusted HR = 0.14, 95% CI = 0.04–0.48, P = .001).

In ITT analysis, moderate or severe fibrosis was reported by 35 (33%) of 107 evaluable patients in the intervention arm vs 25 (51%) of 49 evaluable patients in the control group (OR = 0.36, 95% CI = 0.15–0.81, P = .02). No significant differences in breast edema, movement restriction, or quality of life were observed between groups on ITT or CACE analyses.

The investigators concluded, “In this randomized clinical trial, offering HBOT to women with late local toxic effects was not effective for reducing pain, but was effective for reducing fibrosis. In the subgroup of women who completed HBOT, a significant reduction in pain and fibrosis was observed. A smaller-than-anticipated proportion of women with late local toxic effects was prepared to undergo HBOT.”

Helena M. Verkooijen, MD, PhD, of the Imaging Division, University Medical Centre (UMC) Utrecht, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was partially funded by The Da Vinci Clinic. For full disclosures of the study authors, visit

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