Anti-cancer effects of hyperbaric oxygen therapy in mice: a meta-analysis

Abstract

Objectives Hypoxia is a ubiquitous condition in solid tumors and is associated with increased glycolysis, therapy resistance and disease progression. Hyperbaric oxygen therapy (HBOT) systemically elevates O2 tension in tissues and thus counteracts hypoxia. Here, we conducted a meta-analysis to quantify the effects of HBOT on survival in mice with cancer. Methods Studies retrieved from PubMed and Google Scholar were included if they allowed extracting restricted mean survival times in an HBOT-treated and control group. Meta-analyses were conducted using standardized mean differences (SMDs) and the log-transformed response ratio (lnRR) between the RMST of the treatment and control group with multilevel random effects models in order to account for non-independence of effect sizes. Publication bias was tested using a multilevel version of Egger’s regression. Results All studies applied HBOT with pressures between 2 and 3 atmospheres absolute (ATA). When administered without additional treatments, HBOT was associated with longer mouse survival times (pooled SMD=1.359 ± 0.624, p=0.0446; lnRR=0.065 ± 0.029, p=0.0399). Higher pressure was significantly associated with higher efficacy of hyperbaric oxygen monotherapy. When combined with chemotherapy, radiotherapy, targeted therapy or a ketogenic diet, HBOT was associated with significantly prolonged survival times compared to mice receiving these treatments without HBOT (SMD=2.696 ± 0.545, p<0.0001; lnRR=0.228 ± 0.042, p<0.0001). The combination of HBOT with chemotherapy was associated with lower efficacy than the combination with other treatment modalities. Conclusions We found weak evidence that HBOT prolongs survival times in cancer-bearing mice and strong evidence for synergistic effects with other therapies. The translational potential of these findings and extrapolation to lower-pressure HBOT remain to be determined.