Pacific Hyperbaric & Regenerative Center
Hyperbaric Oxygen Therapy — Evidence-Based Research & Clinical Reference
This page summarizes recent published research on Hyperbaric Oxygen Therapy (HBOT) across several clinical applications. Each study is presented in two parts — a plain-language summary for patients and families, and a detailed clinical reference for medical practitioners.
Safety question in oncology patients; supportive-care context only.
Many cancer patients ask whether receiving oxygen under pressure could stimulate cancer growth or spread. This concern is understandable particularly for patients with radiation-related tissue injury or delayed wound healing who remain under oncology care.
A 2025 retrospective study in Medicina (Kaunas) reviewed 45 patients with active or previously treated solid tumors who received HBOT for cancer treatment-related complications. The study evaluated recurrence, metastasis, mortality, and HBOT-related adverse events during follow-up.
The study did not find a statistically significant association between HBOT exposure and metastasis or mortality. No HBOT-related complications were reported during treatment in this patient group.
What this means in plain terms
In this study, HBOT used for treatment complications did not appear to worsen cancer-related outcomes. However, HBOT is not a cancer treatment and should not be presented or used as one. Its role in oncology patients is limited to selected complications of cancer therapy, such as delayed radiation injury, impaired wound healing, or post-surgical tissue-healing concerns.
Bottom line: In a small retrospective oncology cohort, HBOT was not associated with increased metastasis or mortality during follow-up. Use should be limited to selected treatment-related complications and coordinated with the patient's oncologist.
Clinical reference
Canarslan Demir K, Avci AU, Ozgok Kangal MK, et al. Hyperbaric Oxygen Therapy for Managing Cancer Treatment Complications: A Safety Evaluation. Medicina (Kaunas). 2025;61(3):385. doi:10.3390/medicina61030385.
Study design / evidence type
Retrospective cohort; 45 oncological patients with solid tumors; single-center experience from Gulhane Research and Training Hospital / University of Health Sciences, Ankara.
Key findings
No statistically significant association was reported between HBOT exposure and tumor recurrence, metastasis, or mortality during follow-up; no HBOT-related adverse events were reported during treatment.
Clinical interpretation
The findings support cautious reassurance that HBOT, when used for indicated treatment-related complications, is not shown in this dataset to promote tumor progression. This is consistent with the clinical use of HBOT for delayed radiation injury, soft tissue radionecrosis, osteoradionecrosis, and selected wound-healing complications.
Limitations
Retrospective design; small sample size; single center; not powered to prove oncologic safety across tumor types; does not establish causality or cancer-treatment efficacy.
Appropriate clinical use / positioning
Adjunctive management of selected cancer treatment-related complications only. Do not present as antineoplastic therapy. Coordinate referrals with the treating oncologist and relevant surgical or radiation oncology team.
Radiation-induced cystitis and delayed radiation tissue injury.
Pelvic radiotherapy for prostate, cervical, bladder, rectal, and other pelvic cancers can sometimes cause chronic bladder injury known as radiation-induced cystitis. Symptoms may include urinary frequency, urgency, visible blood in the urine, pain with urination, and reduced quality of life.
The RICH-ART trial (Radiation-Induced Cystitis treated with Hyperbaric Oxygen therapy — a Randomized Trial) was a Phase 2-3 randomized controlled study conducted across five Nordic university hospitals. The original controlled trial showed greater improvement in urinary symptoms among patients who received HBOT compared with standard care alone.
The 5-year long-term follow-up published in eClinicalMedicine in April 2025 reported that symptom improvements among treated patients were maintained over time. Chronic radiation-induced cystitis affects approximately 5 to 10 percent of patients who undergo pelvic radiotherapy, and symptoms such as blood in the urine, urgency, frequency, and painful urination significantly affect quality of life. The durability of response reported in the RICH-ART follow-up is clinically meaningful given the chronic and progressive nature of radiation-associated tissue damage.
What this means in plain terms
For selected patients with persistent bladder symptoms after pelvic radiation therapy, HBOT may provide significant and sustained symptom improvement. This is one of the more robustly studied HBOT applications in the delayed radiation injury category.
Bottom line: HBOT may be considered for selected patients with chronic radiation-induced cystitis after clinical evaluation, particularly when symptoms persist despite standard management.
Clinical reference
Oscarsson N, Rosen A, Muller B, et al. Radiation-Induced Cystitis Treated with Hyperbaric Oxygen Therapy (RICH-ART): Long-Term Follow-Up of a Randomised Controlled, Phase 2-3 Trial. eClinicalMedicine. 2025;83:103214. doi:10.1016/j.eclinm.2025.103214. Original trial: Oscarsson N, Muller B, Rosen A, et al. Lancet Oncol. 2019;20(11):1602-1614.
Study design / evidence type
Prospective randomized controlled Phase 2-3 trial with long-term follow-up at five Nordic university hospitals. Patient population with chronic radiation-induced cystitis after pelvic radiotherapy.
Key findings
Original controlled phase showed significantly greater improvement in urinary symptom burden with HBOT versus standard care. Long-term follow-up reported sustained symptom improvements over time among treated patients.
Clinical interpretation
HBOT is a recognized and evidence-supported adjunctive treatment option for selected patients with chronic radiation-induced cystitis and delayed radiation tissue injury. The durability of response is clinically relevant in a chronic radiation-injury population.
Limitations
The long-term follow-up did not maintain a separate untreated control group, as a proportion of control patients crossed over to receive HBOT after the original trial phase. Long-term results therefore reflect durability of response among treated patients rather than a continuing direct comparison with untreated patients.
Appropriate clinical use / positioning
Established adjunctive indication category: delayed radiation tissue injury. Referral is appropriate following multidisciplinary evaluation, particularly involving urology, radiation oncology, oncology, and/or wound-healing specialists when applicable.
Adjunctive treatment in advanced non-healing wounds.
hronic wounds, such as venous leg ulcers, arterial ulcers, and pressure injuries, may persist when poor circulation, pressure, inflammation, or tissue oxygen deficiency interferes with healing. HBOT is most relevant for selected advanced, non-healing wounds that have stalled despite appropriate standard clinical treatment.
What the research found
A Cochrane systematic review published in 2015 and updated in 2020 analyzed 12 randomized clinical trials involving 577 participants with chronic wounds. The review found evidence of reduced wound area in venous leg ulcers at 6 weeks when HBOT was added to standard care. For isolated arterial ulcers or pressure ulcers, evidence was insufficient to refute or confirm benefit.
What this means in plain terms
For selected chronic wounds that have not improved with standard care, HBOT may be considered as a supportive option, particularly when tissue oxygen deficiency is part of the problem. It is not a first-line treatment and should not replace standard wound care.
Bottom line:
For selected, non-healing chronic wound that have shown no progress under appropriate standard care, HBOT is a clinically recognized adjunctive treatment option to help reduce wound size.
Clinical reference
Kranke P, Bennett MH, Martyn-St James M, Schnabel A, Debus SE, Weibel S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database of Systematic Reviews. 2015; Issue 6:CD004123. doi:10.1002/14651858.CD004123.pub4.
Study design / evidence type
Systematic review of randomized controlled trials; 12 trials; 577 participants with chronic wounds.
Key findings
For venous leg ulcers, one small trial suggested a statistically significant reduction in ulcer surface area at 6 weeks with adjunctive HBOT. Evidence was insufficient to confirm or refute net benefit for arterial ulcers and pressure injuries.
Clinical interpretation
The clinical rationale is strongest when a wound is hypoxic and has failed to progress despite optimized standard care. HBOT increases plasma-dissolved oxygen, which may support angiogenesis, fibroblast activity, collagen deposition, and modulation of inflammation, but wound etiology remains the primary driver of treatment choice.
Limitations
High heterogeneity across included studies, small sample sizes in non-diabetic wound subgroups, variable follow-up periods, and limited data for arterial and pressure ulcers. Evidence does not support HBOT as primary monotherapy.
Appropriate clinical use / positioning
Adjunctive, second-line consideration for selected chronic non-healing wounds after multidisciplinary evaluation. It should not replace vascular intervention, compression therapy, off-loading, debridement, infection treatment, or surgical wound-bed preparation when indicated.
Concurrent management
Integrate with compression for venous disease, vascular assessment and revascularization when indicated, sharp or surgical debridement, moisture-balanced dressings, off-loading, nutrition optimization, and infection surveillance.
Neurological rehabilitation; investigational application.
Stroke recovery depends on neuroplasticity — the brain's ability to reorganize and form new connections — along with rehabilitation, risk-factor control, and prevention of recurrence. HBOT has been studied as a possible adjunctive approach for selected patients in the chronic phase of stroke, but it is not currently standard stroke care.
A 2013 prospective randomized controlled crossover trial in PLOS ONE enrolled 74 patients, with 59 included in the final analysis. Participants were 6 to 36 months post-stroke and had at least one motor dysfunction. The protocol involved 40 HBOT sessions over two months.
The study reported improvements in neurological function, activities of daily living, and quality-of-life measures after HBOT. SPECT imaging findings were interpreted as consistent with changes in activity in brain regions with potential residual function, which the authors described as consistent with HBOT-mediated neuroplasticity.
What this means in plain terms
This study suggests that HBOT may have a possible role in supporting neurological recovery in selected chronic stroke patients by promoting neuroplasticity in brain tissue that retains residual function. However, the evidence is not yet strong enough to describe HBOT for stroke as standard care. Patients should continue evidence-based stroke rehabilitation and medical management under their treating physicians.
Bottom line: HBOT for stroke remains investigational. It may be discussed only as an adjunctive, non-standard option after physician evaluation and should never replace established stroke rehabilitation, secondary prevention, or neurologist-directed care.
Clinical reference
Efrati S, Fishlev G, Bechor Y, et al. Hyperbaric Oxygen Induces Late Neuroplasticity in Post Stroke Patients: A Randomized, Prospective Trial. PLOS ONE. 2013;8(1):e53716. doi:10.1371/journal.pone.0053716.
Study design / evidence type
Prospective randomized controlled crossover trial; 74 patients enrolled (59 analyzed); patients 6–36 months post-stroke with at least one motor dysfunction; single center (Assaf Harofeh Medical Center, Israel). HBOT protocol: 40 sessions over 2 months, 90 minutes each, 100% oxygen at 2 ATA.
Key findings
Reported improvements in NIHSS, activities of daily living, and quality-of-life measures following HBOT; SPECT findings were interpreted as consistent with increased neuronal activity in regions with brain anatomy-perfusion mismatch.
Clinical interpretation
Findings support biological plausibility of HBOT-mediated neuroplasticity in selected chronic post-stroke patients. The interpretation should remain cautious because this is not a broadly established guideline indication.
Limitations
Modest analyzed sample size; single-center design; crossover methodology; need for larger independent multicenter trials; imaging findings require cautious interpretation.
Appropriate clinical use / positioning
Investigational application. Not a standard UHMS-recognized indication. Patients must continue evidence-based stroke rehabilitation, risk-factor control, and physician-directed medical therapy.
Compromised wound healing, grafts/flaps, and irradiated tissue.
Most uncomplicated surgical wounds heal without HBOT. However, healing can be impaired by poor circulation, diabetes, infection, prior radiation exposure, compromised grafts or flaps, or chronic non-healing wounds.
A 2026 narrative review in Cureus summarized recent literature on HBOT across multiple surgical disciplines. The review described plausible mechanisms for HBOT in supporting surgical wound healing: increased tissue oxygenation, support for new blood vessel formation (angiogenesis), fibroblast activation, collagen synthesis, modulation of inflammation, and antimicrobial defense enhancement.
The authors identified the strongest clinical rationale for HBOT in settings involving compromised tissue perfusion, threatened grafts and flaps, radiation-injured tissue beds, chronic non-healing wounds, diabetic and vascular ulcers, and hypoxic soft tissue infections.
What this means in plain terms
If a patient has undergone surgery and their wound is not healing normally because of poor oxygen delivery, previous radiation, compromised tissue, or a threatened graft or flap, or another factor that reduces oxygen delivery to tissue, HBOT may be considered as an adjunctive treatment to support healing. It is not routinely recommended for uncomplicated surgical recovery or routine aesthetic recovery.
Bottom line: HBOT may be considered in selected post-surgical cases involving compromised grafts or flaps, radiation-injured tissue, chronic non-healing wounds, or impaired tissue oxygenation. It is not indicated for routine uncomplicated surgical recovery.
Clinical reference
Gonzalez Flores JE, Vazquez Hernandez DB, Gonzalez Espinosa A, et al. Hyperbaric Oxygen Therapy in Modern Surgical Practice: Mechanistic Basis and Clinical Applications Across Specialties. Cureus. 2026. doi:10.7759/cureus.102116.
Study design / evidence type
Targeted narrative review of PubMed/MEDLINE literature from January 2020 to November 2025; 89 articles identified and 38 met inclusion criteria.
Key findings
HBOT modulates redox signaling, downregulates pro-inflammatory pathways, optimizes HIF-1α/VEGF dynamics, and balances MMP/TIMP activity, thereby improving matrix quality and microvascular integrity.
Clinical interpretation
The strongest clinical rationale exists where tissue hypoxia or compromised perfusion contributes to healing failure, especially compromised grafts/flaps, radiation-injured tissue, chronic wounds, diabetic/vascular ulcers, and selected soft tissue infections.
Limitations
Narrative review rather than meta-analysis; evidence strength varies by surgical indication. Claims relating to routine cosmetic or aesthetic recovery should be avoided unless the patient has a specific medical indication and physician assessment supports HBOT.
Appropriate clinical use / positioning
Use as an adjunctive option in selected compromised surgical or wound-healing scenarios after physician assessment. Avoid routine post-operative wellness, cosmetic recovery, or guaranteed healing claims.
Adjunctive treatment in advanced non-healing wounds.
Diabetes can affect circulation, nerve function, immune response, and wound healing. Some diabetic foot wounds remain open despite appropriate wound care and are at risk of serious infection or amputation.
A 2025 systematic review published in Cureus assessed six clinical studies involving 391 patients with diabetic foot ulcers. Across several studies, HBOT added to standard wound care was associated with improved wound-healing outcomes. Some studies also reported lower major amputation rates in patients receiving HBOT, although results varied across study designs and patient populations.
This does not mean HBOT is appropriate for every diabetic foot wound. It is most relevant for selected advanced wounds that have not improved after appropriate standard treatment.
What this means in plain terms
For diabetic patients with advanced foot ulcers that have not healed with proper wound care, HBOT may be considered as part of a comprehensive plan. Standard wound care remains essential and includes infection control, debridement, off-loading, vascular assessment, nutrition support, and blood sugar management. It is not a guaranteed limb-saving treatment or a first-line treatment for all diabetic foot wounds.
Bottom line: For selected advanced diabetic foot ulcers that have not improved with appropriate standard wound care, HBOT is a recognized adjunctive option.
Clinical reference
Damineni U, Divity S, Gundapaneni SRC, Burri RG, Vadde T. Clinical Outcomes of Hyperbaric Oxygen Therapy for Diabetic Foot Ulcers: A Systematic Review. Cureus. 2025. doi:10.7759/cureus.77947.
Study design / evidence type
Systematic review of six clinical studies; 391 patients with diabetic foot ulcers.
Key findings
Adjunctive HBOT was associated with improved wound-healing outcomes in several included studies and lower major amputation rates. Results varied across study designs and patient subgroups.
Clinical interpretation
Heterogeneity exists across studies, but aggregate evidence supports consideration of HBOT in chronic diabetic foot ulcers demonstrating inadequate response to conventional therapy. Benefits appear most relevant in advanced wounds characterized by tissue hypoxia and impaired healing.
Limitations
Small evidence base in the reviewed dataset; heterogeneous study designs, ulcer severity, standard-care protocols, and patient selection; not a substitute for vascular, infectious disease, surgical, and endocrine management.
Appropriate clinical use / positioning
HBOT is recognized for selected diabetic lower-extremity wounds, particularly Wagner Grade III or higher lesions that fail to respond adequately to optimal wound care. Patients should be assessed individually by their physicians.
Concurrent management
HBOT should be used alongside comprehensive wound care, vascular assessment, infection control, off-loading, nutritional support, and glycemic optimization.
DISCLAIMER: PHRC services are provided within a clinically supervised framework, with certain therapies physician-guided and others delivered by qualified personnel under supervision. All treatments are supportive in nature and not a substitute for primary medical care. Outcomes vary based on individual condition and adherence to the recommended program. No specific results are guaranteed. Medical-grade Hyperbaric Oxygen Therapy (HBOT) is provided as an adjunctive treatment.