Hyperbaric Oxygen Therapy and Cancer – Further Information
Is Cancer a Contraindication for Hyperbaric Oxygen Therapy?
Introduction
Under the European Code of Good Practice for Hyperbaric therapy, HBOT is consists of breathing oxygen at a pressure higher than local atmospheric pressure for multiple sessions for the treatment or prevention of specific diseases. The code states there is a general consensus that the term HBOT can only be applied when the partial pressure of oxygen in breathing mixture exceeds 1.5 absolute atmosphere (ATA) for a minimum period of 60 minutes (excluding compression and decompression). The FDA definition is slightly different, it defines Hyperbaric oxygen therapy (HBOT) as the administration of ~100% oxygen at pressures greater than atmospheric pressure, typically 2 to 2.5 ATA, in a pressurised chamber.
HBOT is approved by the FDA for the treatment of conditions relevant to oncological treatments, such as non-healing wounds, radiation injuries, and at-risk skin graft flaps (FDA, 2025). The European Committee on Hyperbaric Medicine (ECHM)’s list of accepted indications includes osteoradionecrosis and soft tissue radionecrosis (Mathieu et al., 2017). However, neither the FDA nor ECHM offers explicit guidance regarding HBOT for patients with cancer.
HBOT has been proposed as a supportive therapy to mitigate the side effects of cancer therapy, such as radiation injury, dermatitis, and proctitis (Canarslan Demir et al., 2025). Historically, however, the use of HBOT for patients with malignancy has been approached with caution because, in several systems, HBOT induces angiogenesis, activates growth signalling pathways, modulates the immune system, and increases oxidative stress (Cannellotto et al., 2024), which could – theoretically – influence tumour progression (Feldmeier et al., 2003).
However, these theoretical concerns have not been substantiated by preclinical or clinical data (Canarslan Demir et al., 2025). In fact, HBOT appears to exert neutral or beneficial effects in various cancer models and does not increase recurrence in patients treated for malignancies. However, it is important to note that certain chemotherapy drugs are a contraindication for HBOT. Please refer to the contraindication literature for further information.
Theoretical Concerns Regarding HBOT for Cancer Patients
2.1 Angiogenesis: Angiogenesis stimulated by hypoxia via VEGF is a hallmark of cancer progression. Despite HBOT relieving hypoxia, HBOT may induce VEGF and other growth pathways, leading to increased angiogenesis (De Wolde et al., 2021), and a significant concern is that HBOT could increase tumour vascularisation. In some preclinical models of cancer, HBOT induced markers of angiogenesis (Alagoz et al., 1995; Chen et al., 2021), but this was not associated with increased tumour growth. In contrast, in breast cancer and glioma models, the diameter and density of blood vessels decreased after HBOT (Raa et al., 2007; Stuhr et al., 2007).
2.2 Redox balance: HBOT may increase the generation of reactive oxygen species (ROS) (Cannellotto et al., 2024), which might accelerate mutagenesis or oncogenesis. There are few studies that address this concern, but Wang et al. (2023) suggested that ROS generation may be a ‘double-edged sword’ with potentially both beneficial and detrimental effects on tumour treatment and progression. Several in vitro and preclinical studies have shown a pro-apoptotic effect on cancer cells (Kawasoe et al., 2009; Raa et al., 2007; Stuhr et al., 2007), suggesting that the effect of HBOT-induced ROS generation is primarily beneficial.
2.3 Cell growth and survival: Cancer cells exhibit dysregulated growth signalling and cell death (Glaviano et al., 2025) and in several systems, such as wound healing, HBOT may promote cell growth and survival (Cannellotto et al., 2024). However, several studies have shown no growth-promoting effects of HBOT on tumour cells in vitro (Granowitz et al., 2005) or in vivo (Tang et al., 2008; Chen et al., 2021).
2.4 Immune modulation: The tumour microenvironment is immunosuppressive (Wu et al., 2024) and HBOT may alter this landscape (Wang et al., 2023). However, there are few studies that directly address the effect of HBOT on the immune system of cancer patients and more research is required.
Evidence from Pre-Clinical Studies
Preclinical studies vary widely in terms of cancer models, HBOT regimens, and endpoints, but several studies indicate that HBOT does not promote tumour growth. For example, Tang et al. (2009) showed that HBOT (2 ATA, 100% O2, 90 mins, 20 sessions) did not stimulate tumour growth in a mouse model of prostate cancer and could be used safely with other therapeutic modalities. In mouse models of non-small cell lung cancer (Chen et al., 2021) and breast cancer (Yttersian Sletta et al., 2017), HBOT suppressed tumour growth and metastasis and had no effect on angiogenesis. The lack of a pro-metastatic effect in a mouse model of colorectal cancer led Daruwalla and Christophi (2006) to conclude that HBOT ‘may potentially be used safely in conjunction with other therapeutic treatment modalities’.
However, some studies in animal models suggest that HBOT may have deleterious effects on cancer treatment or may promote tumour progression. For example, although Stuhr et al. (2007) reported that HBOT led to significant inhibition of rat glioma xenograft growth and decreased vascular density, other studies showed an increase in cell and microvessel growth and decreased apoptosis in murine glioma models following HBOT (Wang et al., 2015; Ding et al., 2015). Another study suggested that HBOT had a promoting effect in a model of skin carcinogenesis in mice (Doguchi et al., 2014). Although HBOT accelerated the growth of non-irradiated tumours in a mouse model of head and neck squamous cell carcinoma, survival improved and metastasis was unchanged (Braks et al., 2015).
Several studies have combined HBOT with chemotherapy or radiotherapy and overall, as noted in a review of the anti-cancer effects of HBOT in mice (Klement et al., 2024), there is weak evidence that HBOT prolongs survival times in cancer-bearing mice and strong evidence for synergistic effects with other therapies.
Evidence from Clinical Studies
Clinical data on HBOT in oncology primarily arise from its use in managing radiation-induced injuries, such as osteoradionecrosis, proctitis, and cystitis (Canarslan Demir et al., 2025), in patients undergoing treatment for head and neck, pelvic, or breast cancers.
4.1 HBOT and Solid Tumours
Solid tumours often develop poorly perfused, hypoxic cores that reduce radiosensitivity and contribute to treatment resistance. HBOT can improve tumour oxygenation, potentially enhancing the effectiveness of radiotherapy and chemotherapy (Canarslan Demir et al., 2025). Thus, despite the theoretical concerns about using HBOT to treat cancer patients, HBOT is generally considered safe in patients for the treatment of therapy-induced side effects and comorbidities.
For example, a phase 2–3 trial of HBOT for chronic radiation-induced cystitis in patients with pelvic cancers concluded HBOT is safe and relieves cystitis symptoms (Oscarsson et al., 2019). The improvements in patient-reported symptoms after 30–40 HBOT sessions persisted during the 5-year follow-up (Oscarsson et al., 2025). In one study with 11.6 ± 3.7 years of follow-up, HBOT (2 ATA, 100% O2, 90 mins, 50–74 sessions) was safe for the treatment of radiation cystitis in patients with prostate cancer and led to significant improvements in morbidity scores (Nakada et al., 2012).
As well as individual studies on HBOT in cancer treatment, there have been several reviews that concluded HBOT is safe as an adjunctive oncological therapy with few side effects.
A Cochrane review of HBOT (typically 2–2.5 ATA, 100% O2, 60–120 mins, 30–60 sessions) for late radiation tissue injury affecting tissues of the head, neck, bladder and rectum (Lin et al., 2023) concluded that HBOT improved outcomes for late radiation tissue injury and did not affect the risk of dying over the follow-up period (up to 18 months).
A systematic review of HBOT (~2.5 ATA, 100 O2, 80–90 mins, 20–47 sessions) for late radiation toxicity in breast cancer patients indicated that pain, fibrosis, and lymphoedema, as well as necrosis and skin problems, were reduced in HBOT-treated patients (Meier et al., 2023). Similar results were found in a Dutch cohort study of breast cancer patients receiving HBOT for late radiation toxicity (Batenburg et al., 2021).
A retrospective safety analysis concluded that HBOT (median: 27 sessions, range: 5–81) is a safe and effective adjunctive therapy for managing complications in patients with solid tumours (Canarslan Demir et al., 2025). No evidence was found to suggest HBOT contributes to tumour progression, recurrence, or metastasis over a median follow-up of over 2 years.
Most clinical evidence supports the conclusion that HBOT does not increase the risk of cancer recurrence and may improve patients’ quality of life in selected populations. Reported adverse events associated with HBOT in cancer patients are few (Canarslan Demir et al., 2025) and are mostly associated with the HBOT procedure, such as reversible changes in visual acuity and barotrauma (Camporesi, 2014; Zhang et al., 2023), rather than any effect on the tumour.
4.2 HBOT and haematological malignancies
In haematological malignancies, such as leukaemia, lymphoma, and multiple myeloma, malignant cells reside in the circulation or well-perfused tissues, which may alter the effects of hyperbaric oxygen. There is less evidence for the safety and efficacy of HBOT in patients with haematological cancers, and HBOT is not currently used routinely in such patients.
However, some small studies suggest HBOT may be beneficial and is not associated with disease progression in childhood lymphoma or leukaemia (Bernbeck et al., 2004). In one case study, HBOT was reported to be beneficial for radiation-induced brain necrosis in a patient with primary central nervous system lymphoma (Cihan et al., 2009). HBOT has also been used as a second-line treatment for refractory infection in haematologic malignancies and was beneficial in a subset of patients, particularly those in remission (Kim et al., 2021; Kim et al., 2022).
The absence of large-scale clinical trials in haematological malignancies means that caution is warranted. Nonetheless, there is no definitive evidence that HBOT worsens prognosis or induces relapse in these patients.
Conclusion
Whether cancer is a contraindication for HBOT hinges on theoretical concerns regarding angiogenesis, redox modulation, and tumour proliferation; however, these concerns have not been substantiated by preclinical or clinical data. On the contrary, HBOT appears to exert neutral or beneficial effects in various cancer models and does not increase recurrence in patients treated for malignancies. Thus, HBOT may be a valuable adjunctive treatment in the comprehensive care of oncology patients with solid tumours, particularly for managing complications of cancer therapy. Nevertheless, there are limited data regarding HBOT and different tumour types and robust, controlled clinical trials are needed to define its role in cancer treatment and to optimise therapeutic protocols.
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