Hyperbaric oxygen therapy (HBOT) has emerged as a promising treatment for radiation enteritis (RE), a debilitating complication affecting up to 80% of patients undergoing pelvic radiotherapy, with 5–20% developing chronic severe RE. A systematic review and meta-analysis of 22 clinical studies involving 1,318 patients (8 randomized controlled trials and 14 non-randomized interventional trials) evaluated the efficacy, safety, and mechanisms of HBOT in managing RE.
The findings revealed that HBOT significantly reduced the overall incidence of RE compared to standard treatments (OR = 0.32; P = 0.006) and lowered the occurrence of severe RE (grade 3 or higher) according to RTOG/EORTC criteria (OR = 0.37; P = 0.01). HBOT notably improved intestinal symptoms, as evidenced by reductions in LENT-SOMA scale scores (MD = −1.31; P = 0.03), and alleviated inflammation by reducing levels of pro-inflammatory cytokines such as IL-6, TNF-α, and CRP. It also enhanced immune function by increasing serum IgA, IgG, and IgM levels, supporting mucosal repair.
Mechanistically, HBOT improves tissue oxygenation, activates Nrf2/HO-1 signaling, promotes angiogenesis via VEGF and FGF, and modulates macrophage polarization toward an anti-inflammatory M2 phenotype. The typical treatment protocol involves 2.0–2.5 ATA pressure, 90–120 minutes per session, 5 days a week, over 30–40 sessions. While combination therapies with agents like mesalazine showed synergistic benefits, HBOT alone demonstrated high adherence (>90%) and a favorable safety profile, with only mild side effects such as ear barotrauma and transient myopia. Importantly, no link to cancer recurrence was reported.
Although HBOT shows significant promise in reducing RE severity and improving quality of life, further large-scale, multicenter randomized controlled trials are needed to optimize treatment protocols, evaluate long-term safety, and assess cost-effectiveness for broader clinical adoption.