Hyperbaric Oxygen Therapy

Does It Fit Into the Cancer Care Toolbox?

In hyperbaric oxygen therapy (HBOT), patients inspire pure oxygen inside of a vessel pressurized between 1 and 3 atm. Under these conditions, the concentration of dissolved oxygen in plasma rises because of the increased partial pressure of oxygen. By improving oxygen delivery to tissues, HBOT can reverse cellular hypoxia, promote antimicrobial activity, and subdue inflammation (1). These beneficial effects have led to HBOT gaining several indications beyond the treatment of diving-related decompression illness, for which it is most commonly used (2). To date, HBOT has FDA approval to treat 14 conditions, which are listed below in Table 1:

Table 1: FDA Approved Indications for HBOT

Hyperbaric chambers vary substantially in their capacity, composition, and pressure rating. Multiplace chambers constructed from metal can accommodate multiple patients during a treatment session, whereas monoplace chambers can hold a single user at a time. Over time, advances in material sciences have led to the latter design becoming more common in medical centers. These smaller, lighter, acrylic tubes are generally less expensive to install and retrofit into existing spaces; they can additionally allow for physiologic monitoring (3). Despite their relative affordability, monoplace chambers are expensive (4). The median cost of a hyperbaric monospace stiff chamber is around $151,000, and the cost per session ranges from $250 to $450 at independent HBOT clinics (5)(6). At hospitals, the price of treatment is higher, with the upper range of treatment topping out around $1,000 per session (7). Because HBOT regimens can require upwards of 40 sessions, the total price of treatment can easily reach and eclipse $40,000 (8). Although insurers can defray the cost of treatment in patients with conditions listed in Table 1, those electing for HBOT with other conditions may have to pay out of pocket (6).

Significant controversy surrounds the off-label use of HBOT, where scientific evidence supporting its application is weaker. In particular, the clinical utility of HBOT is unclear in oncology. Authors of an older meta-analysis of existing HBOT trials dating to 2012 conclude that HBOT neither promotes nor inhibits cancer growth and metastasis (9). Evidence from other trials contradict this conclusion and suggest HBOT has considerable medical merit, at least when paired with radiotherapy (RT). With RT, water molecules are exposed to ionizing radiation and decompose into unstable hydroxyl radicals, which form perhydroxyl radicals and hydrogen peroxide in the presence of molecular oxygen.

These species can cause DNA damage and subsequent cell death. Because HBOT increases oxygen availability, it may act as a radiosensitizer that enhances RT and chemotherapies by abolishing hypoxic conditions found inside tumors (10). In oxygen poor environments, tumor cells adapt and survive by activating HIF-1: a transcription factor that regulates the expression of genes involved in angiogenesis, cell proliferation, migration, and glucose metabolism (11). When oxygen concentrations rise, proteins like prolyl hydroxylase domain (PHD) become active and abolish HIF-1 activity by marking the transcription factor for degradation in the proteasome (12).

Because HBOT can abolish hypoxic conditions, it may prove particularly valuable in combatting aggressive cancers resistant to current therapeutic strategies like glioblastoma. In one investigation, researchers applying HBOT to glioblastoma cells observed that the procedure promotes cell cycle progression into the G2/M phase. Although this particular shift actually led to substantial tumor growth, HBOT simultaneously reduced stemness – the ability of cells to perpetuate their lineage and differentiate into other cell types. In addition to downregulating the HIF-1a and HIF-2a transcription factors, HBOT decreased oncogenic Sox2 expression and facilitated chemosensitization(13). This therapeutic synergy with existing chemotherapy drugs is a welcome observation, as these agents alone can only extend survival time by approximately 2 months (14).

Encouragingly, HBOT also has few side effects and a favorable tolerability profile when compared with existing chemotherapy drugs. Most complications stemming from HBOT are attributable to issues related to balancing pressure in the ears and sinuses. More rarely, patients have a slight risk (1:10,000) of experiencing a hyperoxic crisis and tonic-clonic seizure that seldom results in sequelae (15). To manage mild claustrophobia, clinicians can offer patients receiving daily HBOT sedatives, whereas more severe cases may require management through a combination of cognitive-behavioral therapy or long-term drug therapy (16). Untreated pneumothorax and heart failure with an ejection fraction of <30 to 35% are absolute contraindications to HBOT (15). To avoid adverse events, clinicians and patients should work closely together to identify other possible factors that could trigger complications. Overall, HBOT is considered very safe, which makes it an attractive choice as an additional therapy (17).

Soft HBOT chambers, which generally achieve less than 1.5 ATM pressure, are an additional option. These chambers have a lower acquisition cost, generally in the $15,000 to $40,000 range, and providers charge more affordable fees ($50 to $150) for 60-to-90-minute sessions. There is spirited debate on the threshold needed or dose; measured time under treatment at certain ATM pressure to treat various disease conditions.

That said, some elite athletes and performers use these systems at home to optimize recovery from injuries, to treat aging tissue, or to stay healthy longer. Medical grade oxygen condensers are necessary, and medical supervision is suggested but yet not mandated by law. Because these lower pressure devices result in lower oxygen delivery levels, their therapeutic role for treating cancer is considerably more obscure. Most trials require ATM pressures greater than 1.5 thus eliminating many soft chamber systems from participation. Many practitioners believe that the soft chambers can still enhance recovery from side effects of the common treatments, such as surgery, radiation, and chemotherapy.

Going forward, there is a strong need for further, well-designed clinical trials to assess the efficacy of HBOT alone and as an adjunctive therapy. Currently, there are seven trials listed on Clinicaltrials.gov underway that are recruiting participants, which are summarized below (Table 2). Findings from these trials may provide key evidence needed to justify adoption of HBOT in specific oncology settings.

Table 2: HBOT Clinical Trials Recruiting Participants

Stay strong, keep smiling and be your own best doctor,

- Chuck

Charles J. Meakin MD, MHA, MS

Disclaimer: This information is not meant as direct medical advice. Readers should always review options with their local medical team. This is the sole opinion of Dr. Meakin based on a literature review at the time of the blog and may change as new evidence evolves.

---

1 Choudhury R. Hypoxia and hyperbaric oxygen therapy: a review. Int J Gen Med. 2018;11:431-442.

2 Brazier Y. What is hyperbaric oxygen therapy good for? Medical News Today. https://www.medicalnewstoday.com/articles/313155. Published August 20, 2019. Accessed July 21, 2021.

3 Kirby JP, Snyder J, Schuerer DJE, et al. Essentials of hyperbaric oxygen therapy: 2019 review. Mo Med. 2019;116(3):176-179.

4 Villeirs L, Tailly T, Ost P, et al. Hyperbaric oxygen therapy for radiation cystitis after pelvic radiotherapy: systematic review of the recent literature. Int J Urol. 2021;27(2):98-107.

5 Comer M. Hyperbaric chambers, should you buy your own? Wound Care Advantage. https://thewca.com/2011/06/20/blog-201106-hyperbaric-chambers-should-you-buy-your-own/. Published June 20, 2011. Accessed July 21, 2021.

6 Katz A. How much does hyperbaric oxygen therapy cost? Hyperbaric Medical Solutions. https://www.hyperbaricmedicalsolutions.com/blog/how-much-does-hyperbaric-oxygen-therapy-cost. Published August 21, 2017. Accessed July 21, 2021.

7 Banks PG, Ho CH. A novel topical oxygen treatment for chronic and difficult-to-heal wounds: case studies. J Spinal Cord Med. 2008;31(3):297-301.

8 Mayo Clinic Staff. Hyperbaric oxygen therapy. Mayo Clinic. https://www.mayoclinic.org/tests-procedures/hyperbaric-oxygen-therapy/about/pac-20394380. Updated October 28, 2020. Accessed July 21, 2021.

9 Moen I, Stuhr LEB. Hyperbaric oxygen therapy and cancer – a review. Target Oncol. 2012;7(4):233-242.

10 Stepien K, Ostrowski RP, Matyja E. Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies, including brain tumors. Med Oncol. 2016;33(9):101.

11 Masoud GN, Li W. HIF-1a pathway: role, regulation, and intervention for cancer therapy. Acta Pharm Sin B. 2015;5(5):378-389.

12 Fong G-H, Takeda K. Role and regulation of prolyl hydroxylase domain proteins. Cell Death Differ. 2008;15(4):635-641.

13 Wang P, Gong S, Pan J, et al. Hyperbaric oxygen promotes not only glioblastoma proliferation but also chemosensitization by inhibiting HIF1α/HIF2α-Sox2. Cell Death Discov. 2021;7(1):103.

14 Davis ME. Glioblastoma: overview of disease and treatment. Clin J Oncol Nurs. 2016;20(5 Suppl):S2-S8.

15 Fernandez E, Morillo V, Salvador M, et al. Hyperbaric oxygen and radiation therapy: a review. Clin Trans Oncol. 2021;23(6):1047-1053.

16 Heyboer M, Sharma D, Santiago W, et al. Hyperbaric oxygen therapy: side effects defined and quantified. Adv Wound Care (New Rochelle). 2017;6(6):210-224.

17 Bennett MH, Feldmeier J, Hampson NB, et al. Hyperbaric oxygen therapy for late radiation tissue injury (Review). Cochrane Database Syst Rev. 2016;4(4):CD005005.