Conquering COVID Part 1.8 A & B (HBOT Double Issue!):

“HBOT for some cancer side effects or COVID-19?!”

(aka more medical centers face "pressure” to offer this option)

May 1, 2020

by Mark A. Moyad, MD, MPH

“I am concerned, of course, but I am also incredibly optimistic.”

HBOT-Part A

Hi everyone! Thank you for joining me today and we are going to start with another unique subject that could, not only have an impact on COVID-19 treatment, but separately could benefit some cancer patients around the globe. You may have noticed that throughout this series I use it as a platform to, not only discuss the latest with COVID, but also to quietly and sometimes loudly, mix in the relevance for overall health and cancer. For example, in a past issue I talked about the ADD-ASPIRIN trial, which is one of the largest studies ongoing and ever conducted on the planet to help determine if taking aspirin after being treated for breast, prostate, and several other cancers could reduce the risk of cancer returning/recurrence ( addaspirintrial.org). We hope to see some results soon! Also, when I discussed the side potential benefits of BCG and BCG vaccines in a past issue, it may be easy to forget that some patients with prostate cancer (and other cancers) have also had to deal with bladder cancer and have already received this immunotherapy. So again, the bigger picture is also provided in these COVID updates. Additionally, whether we talk about gout or another condition from a past column, the lifestyle advice for improving heart health is virtually identical in terms of what is known about improving overall health and personally trying to fight prostate cancer. Remember, I think we all share the goal of wanting to live better and longer and this comes from learning what improves prostate health and overall health. Regardless, stop wasting time Moyad (I like to talk to myself) and cut to the column (aka chase)!

Have you heard of H.B.O.T. or HBOT? Sounds like something robotic or futuristic, but in the medical world it is better known as HyberBaric Oxygen Therapy (HBOT). Many medical centers are now utilizing it for a variety of things and many others that do own an HBOT device are feeling the “pressure” (dad joke alert) to offer it. HBOT usually involves getting into a chamber that temporarily houses one person (aka “monoplace chamber”), or alternatively getting in a larger chamber (looks like a miniature submarine to me - also called a “multiplace chamber”) with several or many other people. These chambers can be quite comfortable in some cases, for example, offering larger reclining chairs and big screen TV (no kidding). The goal here is to simply breath pure or 100% oxygen while under increased atmospheric “pressure” from the chamber. The air pressure is generally 1.5 to 3 times higher than normal pressure in an attempt to cause your lungs to receive more oxygen than normal, which then also potentially allows your blood and tissues to ultimately receive the maximum amount of oxygen. There is something called “Henry’s Law” which essentially states the amount of oxygen dissolved in the blood or tissues (aka a “solution”) is directly proportional to its partial pressure (BTW I love physics). Increase the atmospheric pressure in the HBOT chamber, and then you could dramatically increase the amount of oxygen delivery to the body (by many multiples). So, this is not the same as using an oxygen tank or mask, which simply uses normal (ambient) air pressure, which is basically normobaric oxygen therapy (NBOT) and not HBOT.

The excess delivery of oxygen at these higher pressures with HBOT appears to stimulate the production of compounds in the body that could help with healing from a variety of different types of injuries or side effects from treatment. For example, HBOT can cause new blood vessels to be produced in the body around the area of injury (called “angiogenesis”), and other compounds are released that can further increase the blood supply to the injury and may accelerate healing.

HBOT has been a well-known treatment for decompression sickness from scuba diving, some cases of carbon monoxide poisoning, burn recovery, and other wounds that are having a tough time healing.  Today, it has become a generally accepted option or treatment from some specific forms of radiation injury (side effects) from cancer treatment. It has the potential to reduce the inflammation or injury to the bladder and even the rectum (aka proctitis), but more on this later . Wow! So, it really sounds like there are no catches or side effects? Sorry, but everything in life comes with a catch or a potential side effect, my friends. 

Basically, HBOT definitely needs more clinical research (just like everything else) but, in the meantime, you should know the stance the FDA has taken on this treatment option. First, they make it pretty clear HBOT is NOT (that rhymes) been proven to be effective in the treatment of cancer itself (aka eliminating cancer cells). Remember, in cancer it may treat some of the side effects of some treatment, but it does not treat the actual cancer. The FDA lists a series of concerns and medical conditions that do NOT have proof when it comes to HBOT and it was published many years ago, but it is still a good general overview today, so check it out: ( https://www.fda.gov/consumers/consumer-updates/hyperbaric-oxygen-therapy-dont-be-misled). I love the fact that the FDA did this!

The FDA has “cleared” HBOT for multiple indications (Peterson K, et al. VA Evidence Synthesis Program Briefs, Feb. 2018.), which is fascinating and most of them are placed in an abbreviated and alphabetical order below for my/our convenience. I highlighted the one side effect HBOT could improve, in general, that is of interest to some cancer patients: 

One of the most well-known uses of HBOT from the list above, as mentioned earlier, is for decompression sickness, or “the bends”. Scuba divers have to learn all about this stuff before they get certified because surfacing too quickly from deeper water can cause it and, in some cases, it can be life-threatening. Yet, what is the real origin of these words to describe decompression sickness? “The bends” actually describes the pain in the joints or other locations from bubbles coming out of the blood and tissues, and it was an observation documented from watching some divers actually having trouble walking and bending over from discomfort after experiencing the problem. This bending over posture due to pain was also reminiscent to what was known as a “Grecian Bend,” or stooped walking posture from the 1800s - this is believed to be the actual origin of the word “bends” (Kindwall EP. Diving Medicine 1990; WB Saunders, Philadelphia, PA; & Carson WK. et al. Military Medicine 2005;170:57-62). 

Okay, interesting history lesson aside we need to move on. HBOT continues to garner more attention in cancer for a potential treatment for some of the side effects of radiation, including radiation cystitis (RC) or inflammation of the bladder as a side effect of conventional treatment. RC is an uncommon (5-10% of patients) side effect of radiation therapy to the pelvic area, but it still occurs often enough to be a concern. In reality, RC refers to a group of potential symptoms including some or all of the following:

RC may occur early (during or in the first few weeks after radiation treatment) or long after (years, even decades later), but the average time to occurrence is approximately two to three years (of course this varies). The early (acute) symptoms such as urinary frequency, discomfort when urinating or pelvic pain/discomfort usually improve or begin to go away weeks to months after radiation treatment. If you are experiencing any of this during or right after treatment, talk to your doctors about potential simple treatments for this situation. I have noticed that many doctors have numerous tricks up their sleeves and pills that can help with certain types of discomfort. However, similar or other bladder inflammation symptoms (if they occur at all), which can include blood in the urine, can occur many years or even decades after the last radiation treatment. 

There are many options for treating RC, which includes bladder irrigation with a variety of solutions and various other techniques to improve symptoms and stop the bleeding and damage. HBOT is also an option and it should continue to receive more attention, and this is actually beginning to happen as more and more medical centers face “pressure” (okay that was simply a repeat of my previous Dad Joke to annoy my kids) to offer it. HBOT for radiation injury is not just for symptom relief, but slowing or stopping the progression of the problem. It is believed to stimulate numerous body healing processes along with improving nitric oxide delivery, which could accelerate the recovery from this problem. Interestingly, it can also constrict some injured blood vessels and reduce the bleeding that can arise from this area of the body, and HBOT is actually one of the most studied treatment options for potentially reducing this type of bleeding when it occurs . For example, a recent clinical practice report from the Canadian Urological Association (Goucher G, et al. Can Urol Assoc 2019;13:15-23) concluded that several studies have found HBOT “safe and effective and should be considered an early treatment option” for bladder inflammation that includes bleeding, especially in those patients that have not responded to other options. 

Interestingly, a recently published study from five Nordic university medical centers randomized 87 patients with moderately severe radiation-induced cystitis to HBOT or controls. It was known as the RICH-ART trial (Oscarsson N, et al. Lancet Oncol 2019;20:1602-1614.) and it is arguably the first randomized, controlled trial of HBOT in late radiation cystitis to collect data on a diverse array of symptoms associated with this issue.  Approximately two-thirds or 66% of the patients in this clinical trial of cancer patients (cervix, rectal, uterus….) had been previously treated with radiation for PROSTATE CANCER (average age of 64 years). Almost 50% did not have blood in their urine, and the rest had trace amounts or more. It is unethical to withhold HBOT to patients with more serious bleeding as explained by the researchers in this paper, so these patients cannot be randomized to a control group or utilized in this study. The diagnosis of late radiation cystitis was established by a urologist in order for patients to enter this clinical trial. This study took a tremendous amount of effort and, in fact, the enrollment for this trial was over five years because identifying the correct patients and then completing all the treatments for all of the participants also takes a tremendous amount of time. What were the results of this small but important randomized study? Urinary symptoms, and quality of life and a positive impact on the bladder tissue itself significantly favored HBOT over the control group.  Additionally, patients also appeared to experience improvement in radiation proctitis, which is inflammation of the lining of the rectum that can result in some or a variety of symptoms (urge to have bowel movement, bleeding, loose stools, etc.). The patients in this RICH-ART trial had actually experienced some symptoms of RC for approximately three years on average. It is theorized that symptoms could improve even more if HBOT is utilized within 6-12 months of symptoms, and this does make sense. Regardless, the researchers concluded the following from this trial: “Our results suggest that hyperbaric oxygen therapy relieves symptoms of late radiation cystitis. We conclude that hyperbaric oxygen therapy is a safe and well tolerated treatment.” 

Okay, sounds good but what is the real HBOT catch?  The catch is the limited availability of this option in some parts of the U.S./world and also the potential cost and time commitments. For example, it is not unusual to require approximately 20-40 sessions/individual visits to complete the procedure and each session can take anywhere from 30 minutes to 2 hours. Average commitment time for treating some side effects of cancer is approximately 90 minutes a session for 5-7 days a week for a total of approximately 40 treatments over roughly 8 weeks (remember this is just an average so individually you could have more or less). This is usually an outpatient procedure. Although risks or side effects are rare, in general, because patients are usually heavily vetted for whether or not they qualify for HBOT. 

Some of the side effects include:

Additionally, there are other limitations of HBOT for treating side effects from cancer treatment, which includes not enough prospective research or clinical trials completed, but rather retrospective study or looking back in time to determine pros and cons. It is for this reason if you inquire about HBOT, then always ask about the very latest research in this area (for example the recent RICH-ART trial mentioned earlier). A review of past studies just published at the time I was putting together this column found most patients did benefit with HBOT for RC and there is ongoing interest in the retreatment of some patients with more sessions of HBOT if some symptoms returned after initial HBOT treatment (Villcirs L, et al. Int J Urology 2020;27:98-107). Still, the question remains with RC whether it should be utilized after other treatments fail (more of a last resort), or whether it should be used up front with other options? This should never be determined by a column such as this one, but rather with the doctor(s) that you trust with your health and the latest data.

There is also the need to determine more precisely what impact HBOT has on cancer itself since it could encourage blood vessel growth, potentially cause immune changes, but it may also generate free radicals, so is the net impact on your cancer neutral, positive, or negative? Also, HBOT has not received enough research in children (Janisch T, et al. Minerva Pediatr 2020; doi: 10.23736/S0026-4946.20.05741-2.), and it is not a simple option for people suffering from claustrophobia, but health care professionals have options to help with this situation including using a larger HBOT chamber (you know the ones I mentioned earlier with the comfortable chairs, big TV, etc.).

Okay, now it is time to take a break for about 1-2 minutes and then part B will begin. Feel free to grab some water, food, or snacks in the lobby (sorry but I miss going to the movie theater my friends), and please turn your cell phone and TV off so you can enjoy the rest of this information. Thank you.

HBOT-Part B

The future for HBOT looks bright for some other medical conditions, for example it has already been used successfully for some types of sudden and painless vision loss - for example, central retinal artery occlusion (CRAO), which could be from a clot that blocks the normal blood flow to the retina, (Kim SH, et al. Clin Exp Emerg Med 2018;5:278-281.). CRAO is also referred to as a “stroke of the eye.” It is also being utilized and tested for some types of sudden sensorineural hearing loss and has some success in this setting (Bennett MH, Mitchell SJ. Curr Opin Anesthesiol 2019;32:792-798). 

Other areas of medicine are in need of more and higher quality research, or have even been initially disappointing and need to further determine the ideal candidates for HBOT. For example, one RARE and concerning side effect of some osteoporosis prevention drugs, including when they are used for cancer patients, is a condition known as osteonecrosis of the jaw or ONJ. Researchers are always looking for other ways to treat this condition apart from the standard of care. HBOT has not received enough high-quality research but there is interest to see if it can be used as an adjuvant therapy in the future to help improve the prognosis of this condition (de Souza Tolentino E, et al. Head Neck 2019;4:4209-4228.). Right now, the evidence is “inconclusive.” 

Many chronic pain syndromes are being investigated with HBOT, for example fibromyalgia (El-Shewy KM, et al. Biomed Pharmacother 2019;109:629-638.). Currently, exercise is a part of treatment for this condition including traditional aerobic exercise, and even yoga and tai chi has demonstrated success in clinical trials. It is for this reason the combination of some form of exercise with other medical treatments increases the probability of success compared to medical interventions alone (this is true of countless medical conditions). Exercise has been shown to reduce some inflammatory markers, stress hormones, and increase endorphins (natural pain relieving and mood improving compounds produced by the human body) in fibromyalgia patients, which again is also the case for other many other medical conditions. Other chronic pain syndromes are being investigated such as interstitial cystitis/painful bladder syndrome (IC/PBS), which is a fairly common condition (more common in women), and the cause of it is not really known. The wall of the bladder, which is normally protected from urine, becomes thinner over time, or more exposed, and this causes inflammatory reactions and discomfort. However, despite some treatment options, there is a need for more solutions, and very preliminary evidence suggests HBOT should receive more research in this area because it could be of some help (Tanaka T, et al. Int J Urology 2019;26:860-867.).

Furthermore, laboratory studies have suggested HBOT could resolve some of the damage to erectile tissue by providing more oxygen to these injured areas (Muller A, et al. J Sex Med 2008;5:562). However, a recent U.S. double-blind, randomized trial of HBOT with the goal of improving erectile dysfunction (ED) after radical prostatectomy (109 generally healthy patients with 18-month follow-up) found no difference compared to a control group (Chiles KA, et al. J Urol 2018;199:805-11). The HBOT group was given 10 sessions (90 minutes each at 2.2 atmospheres of pressure) beginning day one after being discharged from the hospital.  This does not imply HBOT has no impact on ED after prostate treatment, but rather suggests other types of patients with diabetes or other co-morbidities after cancer treatment could be better candidates for the next clinical trial.  The good news was the preliminary conclusion from this recent ED HBOT clinical trial was that it appeared safe, in general, and did not appear to encourage cancer growth or recurrence. 

In fact, some researchers would like to start testing HBOT against some types of tumors along with conventional treatments. Why? The microenvironment in some tumors appears to be low in oxygen and this is theorized to be just part of the reason cancers are better able to grow. Still, the idea right now that HBOT could enhance the effects of radiation or chemotherapy, for example, in prostate cancer or other cancers is generally weak and clearly needs more research. Perhaps some cancers could respond better than others to HBOT (Bennett MH, et al. Cochrane Database Syst Rev 2018;4:CD005007). 

Finally, since patients with severe COVID-19 have respiratory problems it is not surprising to see multiple clinical studies being initiated to determine if HBOT can help with better oxygen delivery to these patients. One clinical trial at NYU Winthrop Hospital in Mineola, NY appears to already be up and running and recruiting COVID-19 patients. It is being utilized as an “emergency investigational device” for trying to improve respiratory problems. Other clinical trials are setting up in New Orleans (Ochsner Medical Center), Sweden, and France. 

Well, I have been around a long time and I have always wanted to read a lengthy descriptive educational piece on HBOT during my career. I believe it has been provided in this latest large double sized column. HBOT has always fascinated me for so many reasons since it is generally not a part of traditional medical or patient education. And, it clearly has a role in helping some cancer patients, but simultaneously receives too much hype in other situations. It was time to provide an objective overview of some of the pros and cons from my perspective so I really hope some of you enjoyed this piece and can utilize it in order to improve your quality of life.

Thank you for reading my latest installment and I wish you and your family the best of health. I am concerned, of course, but I am also incredibly optimistic! I look forward to modern day science and you of course, kicking COVID-19 and cancer in the gluteus maximus! 

All of my best always,

Mark A. Moyad MD, MPH 

Please pay attention to all of the CDC recommendations that can be found at https://www.cdc.gov/coronavirus/2019-ncov/index.html 

Read my previous COVID-19 articles at:

 

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