Hyperbaric Oxygen Therapy Shows Some Benefit After Breast Cancer Irradiation

Hyperbaric oxygen therapy (HBOT) was not effective for reducing pain, but was effective for reducing fibrosis, among women with late local toxic effects after irradiation for breast cancer, a Dutch randomized study showed.

In an intention-to-treat analysis, moderate or severe pain at follow-up was reported by 50% of women in the intervention arm and 62% in the control arm (OR 0.63, 95% CI 0.32-1.23), while moderate or severe fibrosis was reported by 33% and 51%, respectively (OR 0.36, 95% CI 0.15-0.81), reported Helena M. Verkooijen, MD, PhD, of the University Medical Centre Utrecht in the Netherlands, and colleagues.

Of note, only 25% of women who were offered HBOT accepted and completed treatment. The most common reason for not accepting HBOT was high treatment intensity, the authors noted in JAMA Oncology.

In an editorial accompanying the study, Benjamin Corn, MD, of Hebrew University in Jerusalem, and colleagues said that the 25% acceptability rate of HBOT “is an instructive finding.”

HBOT involves breathing 100% oxygen at 2.0 to 2.5 atmospheres absolute. The rationale for its use is that the combination of high pressure and inhalation of 100% oxygen leads to elevated partial pressure of oxygen in blood and tissue, which induces angiogenesis and regeneration of the irradiated tissue.

Patients in the intervention group were required to breathe 100% oxygen during four intervals of 20 minutes in a 2-hour session, for 30 to 40 sessions, over the course of 6 to 8 weeks.

This time and treatment burden “reminds us that convenience has become a factor weighted heavily by patients during the process of decision-making,” observed Corn and colleagues. “Despite experiencing relatively severe symptoms, many declined hyperbaric therapy after being counseled by HONEY investigators about the time commitment imposed.”

In the HONEY trial, 125 women (median age 56 years) with late local toxic effects were offered HBOT, while 61 (median age 60 years) received usual follow-up care, from November 2019 to August 2022. Of the women offered HBOT, just 31 accepted and completed treatment.

In an attempt to compensate for the low HBOT acceptance rate and “the resulting dilution of the HBOT effect,” Verkooijen and colleagues performed a complier average causal effect (CACE) analysis comparing outcomes between women who underwent HBOT against an estimated subgroup in the control arm who would have completed HBOT if offered. In CACE, HBOT was associated with decreased pain (32% vs 75%, OR 0.34, 95% CI 0.15-0.80, P =0.01).

Fibrosis was also reported less frequently in the CACE analysis, with 17% of women who completed HBOT reporting moderate or severe fibrosis compared with 86% of women who would have completed HBOT if offered (OR 0.14, 95% CI 0.04-0.48, P=0.001).

There were no significant differences in breast edema, movement restriction, and quality of life between groups in either the intention-to-treat or CACE analyses.

Both the study authors and editorialists noted that a limitation of the study was the possibility of reporting bias, which could be reduced by conducting a sham-controlled randomized trial. However, Verkooijen and colleagues explained it would have unnecessarily exposed participants to a high treatment burden.

The authors also acknowledged that with the smaller-than-anticipated number of patients randomized in the trial and willing to undergo HBOT, HONEY was underpowered.

Yet, ‘”we now have modest evidence to justify the use of HBOT in treating the chronic morbidities associated with breast irradiation,” Corn and colleagues wrote, adding that adequately powered randomized, sham-controlled, double-blind trials are needed to “truly determine the benefit of HBOT.”

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