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HBOT for Radiation-induced Necrosis


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Not all is lost if one has experienced the insidious side effects of whole brain radiation. The reason for giving whole brain radiation is different between a primary brain tumor patient and a metastatic brain tumor patient. Primary tumors are "invasive" (they are part of the brain tissue and cells), while metastatic brain tumors are "non-invasive" (they are not part of brain tissue and cells). No one with a solitary metastatic brain tumor should ever receive whole brain radiation (perhaps when there are five of more mets, but that has been recently debunked by researchers at the Unitversity of Pittsburgh). Even for primary brain tumors, there are much better protocols these days.

Primary lesions generally involve invasion into adjacent brain tissue and at one time, it made sense to have postoperative whole brain radiation in an attempt to destroy any residual cancer cells. But, like with metastatic lesions, this has been abandoned at leading cancer centers because of the substantial neurological deficits that resulted, sometimes appearing a considerable time after treatment. Metastatic lesions have relative lack of invasion into adjacent brain tissue, making them ideal for radiosurgery or postoperative "focal" radiation.

Radiation can actually result in different types of structural damage to the brain. Necrosis of the endothelial cells can occur 9-24 months after radiation therapy. Necrotizing leukencephalopathy (brain damage) can present itself four to twelve months after radiation doses of just greater than 20Gy. Patients exhibit spasticity, dementia, seizures, and paralysis. Moyamoya syndrome (puff of smoke) is a late vasculopathy involving the distal internal carotid artery, which can lead to infarction.

Radiation-induced necrosis has been estimated to occur in 20% to 25% of patients for cancerous tumors in the brain. Some studies say it can develop in at least 40% to 50% of patients irradiated for tumor following large volume or whole brain radiation and possibly 3% to 9% of patients irradiated focally for brain tumors (in reality, they just don't know). Even with more localized use of radiation, significant neurological deficits can result.

Those at increased risk for long-term radiation effects are generally children less than 2 years of age and adults over 50 years of age. However, whole brain radiation therapy has been recognized to cause considerable permanent side effects mainly in patients over 60 years of age; it can affect up to 90% of patients in this age group.

The diagnosis of radiation-induced necrosis is difficult to confirm. Many patients have a mixture of tumor and radiation necrosis and a biopsy may be necessary to distinguish it. Neither symptoms nor radiographic findings clearly distinguish radiation-induced necrosis from tumor. However, the FDG-PET Scan, PET/CT Scan and T1-SPECT studies are useful in differentiating radiation-induced necrosis from recurrent tumor.

Hyperbaric Oxygen Therapy (HBOT) is now a useful therapeutic option for patients with confirmed symptomatic radiation necrosis. Until the new millenium, the only treatment for patients was pentoxifyline or heparin therapy, and it was almost always unsuccessful. The good news about HBO Therapy is, it works for most patients. I've received numerous letters over the years from loved-ones of cancer treatment victims with radiation-induced necrosis, sometimes HBO Therapy came at a time that was too late. Some, however, have started to come around, and even others have been cured. What is proper timing? I have one respondent that insists not to wait, but to have HBO Therapy immediately after radiation treatments (not to wait and see "if" there will be side-effects).

The most common condition treated at some Hyperbaric Oxygen Therapy Centers is tissue injury caused by brain radiation therapy for cancer. Wound healing requires oxygen delivery to the injured tissues. Radiation damaged tissue has lost blood supply and is oxygen deprived. Chronic radiation complications result from scarring and narrowing of the blood vessels within the area which has received the treatment. Hyperbaric Oxygen Therapy provides a better healing environment and leads to the growth of new blood vessels in a process called re-vascularization. It also fights infection by direct bacteriocidal effects. Using hyperbaric treatment protocols, "most" patients with chronic radiation injuries can be cured.

Hyperbaric oxygen therapy is administered by delivering 100 percent oxygen at pressures greater than atmospheric (sea level) pressure to a patient in an enclosed chamber. Hyperbaric oxygen acts as a drug, eliciting varying levels of response at different treatment depths, durations and dosages, and has been proven effective as adjunctive therapy for specifically indicated conditions.

Oxygen is a natural gas that is absolutely necessary for life and healing. Purified oxygen is defined as a drug but is the most natural of all drugs. Oxygen under pressure is still the same gas but is more able to penetrate into parts of the body where the arterial flow is hindered, producing ischemia (loss of blood flow) and hypoxia (lack of oxygen). When oxygen under pressure is breathed by a patient in a sealed chamber, it is termed a hyperbaric oxygen treatment (HBOT).

In addition to raising the arterial levels of oxygen 10 to 15 times higher than that produced by normal atmospheric pressure, the pressure exerted within the body can and does exert therapeutic benefits on acute and chronically traumatized and swollen tissus.

Who Should Avoid This Therapy?

Avoid these treatments if you have a seizure disorder, emphysema, a high fever, or an upper respiratory infection. Do not undergo them if you have a severe fluid build-up in the sinuses, ears, or other body cavities. Forego them if you've had surgery for optic neuritis, or have ever had a collapsed lung. Avoid them, too, if you are taking doxorubicin (Adriamycin), cisplatin (Platinol), disulfiram (Antabuse), or mafenide acetate (Sulfamylon).

Pregnancy was once considered a contraindication for hyperbaric therapy. However, it's now deemed acceptable if a condition will cause long-term damage to the mother or fetus. For example, the treatments are given to pregnant women with carbon monoxide poisoning, which is toxic to both mother and child.

What Side Effects May Occur?

Seizures, a result of the direct effect of oxygen on the brain, are the most serious side effect associated with hyperbaric therapy. The risk is estimated at one in 5,000. Every chamber is equipped with a quick-release mechanism. If a seizure occurs, the oxygen will be immediately released and the seizure will subside.

Minor side effects include popping of the ears similar to that experienced in a descending aircraft. Sinus pain, earache, and headache are other possible side effects. In fact, pain may occur in any body cavity where air can get in but can't get out. For example, dental pain may occur if a filling has trapped air beneath it. In rare cases, pressurized oxygen may rupture an eardrum.

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GDPawel :

My wife's latest brain MRI radiology report states :

" interval development of a diffuse abnormal signal intensity in the subcortical and deep white matter of the cerebral hemispheres which likely presents postradiation changes ( leukoencephalopathy ) . There is no evidence of acute infarction. "

Based on your research, does the above-referenced terminology, esp. mentioning no evidence of acute infarction, suggest one particular sub-type of this condition as the likely culprit in my wife's case ? And, would this particular sub-type be considered, in your opinion, a candidate for HBOT ? She received WBR ( 11 treatments, don't know the rad dosage ) in late May ~ early June of 2004 for brain mets secondary to NSCLC. I'm estimating that noticeable mental deterioration, as outlined in one of my last posts, began appearing ~ 14 months post-WBR and appear to have stabilized over the last few weeks. Lastly, based on all of this, and if you conclude that she appears to be a candidate for HBOT, any educated guess as to why her rad onc, or rad onc's generally, wouldn't offer HBOT at this stage ?

Thanks much.


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Greg, we have talked, but I wanted to check in with you about this.

My mom's neurosurgeon (who did her stereotactic surgery and confirmed necrosis through PT scan) recommended HBO on October 27th. We are now near mid-December and still no HBO. There are pre-appointments with pulmologists and other Drs. that do not seem to be happening. I am extremely concerned that things are not being handled in a timely manner. As of today, one of the pre-appointments is scheduled for January 30th!!! This would put her at February before he even starts. Is this normal? I am not comfortable with this process at all.

I thought she would start ASAP. Her condition is not better at all, even on 16mg of steroids.

She had 5 seizures Tuesday night. Just looking for your thoughts on this. Thanks for any insight you can provide.

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On an MRI, "diffuse abnormal signal intensity in the deep white matter" is an indication consistent with post radiation and/or chemotherapy changes. A signal abnormality within the white matter may appear increased compared to a prior MRI study, indicating growth. On a Pet Scan, this may be described as "globally decreased radiotracer uptake within the brain," consistent with prior radiation therapy. If it would be a tumor recurrence, it would show "abnormal foci of radiotracer accumulation" (or "lights up").

If there would have been an infarction, you would have seen something like "an area slightly hyperintense on unenhanced T1 weighted images, associated with focal dilatation (stretching)." Her MRI's impression is "there is no evidence of acute infraction." That's a positive indication.

As you know, I could never give you any opinion or conclusions as to what should or shouldn't be done. That's between you, your wife and the doctor(s). I'm sure you can respect that. I can relate my own personal experience, research and information from very valuable physicians in the field. I stay in contact with a number of them.

(For you too Lori on this one) As for doctors not being able to make an educated guess as to offering HBOT at this stage or some other stage, or even suggesting it, would probably be lack of knowledge. I remember asking a neurosurgeon giving my wife Gamma-Knife treatments (extremely high technology), about HBOT (extremely low technology or no-tech) for the side effects of her chemo-radiation treatments. You can imagine his answer. Why push some low-life technology when he is concentrating on a high technology tool?

I was intrigued by one of your posts saying your "wife's usually very accessible rad onc has suddently become unavailable for comment" and "keep in mind that he was 'got-caught' angry and very defensive throughout the entire conversation." Why doesn't that surprise me? I've heard it personally before, and have heard the same reactions from other letter writers.

Professional liability in the field of radiation oncology may result from inadequate explanation to the patient of the intent, risks, side effects and expected results of radiation treatment. A patient must always be fully informed whenever risky (over-aggressive) protocols are followed.

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Just the knowledge that whole brain radiation therapy has been recognized to cause considerable permanent side effects mainly in patients over 60 years of age and that it can affect up to 90% of patients in this age group REALLY upsets me. My father was in his early 60's and had a solitary brain met. We were told it was the next part of his treatment..for preventative reasons... and never told the risks of delayed reactions to the radiation therapy !!! If he had been told these odds, I am pretty certain he would have not had WBR.

Yes, I agree that a patient must always be fully informed whenever risky (over-aggressive) protocols are followed. I know it may sound stupid, but we never fully realized we were agreeing to a risky protocol. When I mentioned radiation induced necrosis to the doctor (after the first CT scan), he treated the whole thing very casually and tried to diffuse the whole thing.


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The radiation onc. where I had Stereotactic Radiation now says he wants to do WBR. He hasn't even seen any of my scans in over a year. Have been followed by my Nuerosurgeon (thank goodness) City of Hope is where radiation onc. is located. I told him Nuerosurgeon wants to do surgery to remove necrosis, Surgeon says acording to my scans no CA or tumor just the necrosis. Scheduled for Pet/CT at Loma Linda, Dec. 30th... I am so angry at the doc at CoH. Insurance had not approved testing, had I kept appt. I would be paying. Rad onc. calls me day after I was supposed to take test and says, I couldn't get approval from your insurence. A day late and many dollars in the hole had I have gone to appt.. Had BAD vibes about appt. scheduled for last Tuesday. I cancelled...

LORI, I'm researching the surgery for Necrosis. Greg, maybe you can help us out here with info about Necrosis removal via surgery...

Thank You,


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Radiation necrosis can occur after radiosurgery (focal radiation) but it is a "focal" problem rather than a "diffuse" problem, as whole brain radiation would be. Long-term effects can be initially managed to some degree with corticosteroids and surgery to remove necrotic tissue. The major complication is the development of symptomatic radiation necrosis requiring prolonged administration of steroids and reoperation. The rate of reoperation is 30 - 40%, usually within six months. Don't think that Decadron can be given forever with virtually no side effects. Steroids have their own insidious side effects!

I would think that the HBOT route for radiation-induced necrosis from whole brain radiation would be preferred. However, for "focal" necrosis (unless it has grown larger), it may be debatable? Look into the HBO Therapy resources that I've just posted. Until the new millenium, the only treatment given for patients with confirmed symptomatic radiation-induced necrosis was Pentoxifylline or Heparin Therapy, however, it was almost always unsuccessful.

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What about necrosis from Stereotactic radiation and NOT WBR, The dosage for long term Decadron is .50 to .75mg, nothing higher.

According to my nuerosurgeon, once the necrosis is removed surgically it will not come back...

What is your take on this information.

Thank you very much for your help.


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My research had delved into HBOT for revascularizing tissue injury, and not surgical removal of necrotic tissue. I was concentrating on "diffuse" necrosis, not "focal" necrosis. The only information I was able to gleam was the rate of reoperation at 30 to 40 percent, usually within six months. I have the utmost respect for surgeons. The surgeon is the most important "first responder" specialist to see a patient before oncologic specialists.

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You have brought up a very, very important point about radiation treatments, "never told the risks of delayed reactions to the radiation therapy." This is what is meant by "informed consent." The patient's right to determine what the patient wants done to their own body was best explained by U.S. Supreme Court Justice Benjamin Cardozo when he said, "Every human being of adult years and sound mind has a right to determine what shall be done with his (her) own body, and a doctor who performs treatment without his patient's consent commits an assault for which he is liable in damages." (Don't bet on any liability on damages)

These days, most cases are not an assault for an intentional act, but rather negligence on the health care provider's part in failing to provide "informed consent." It is not enough for consent for a patient to merely sign their names or say yes to proceed. It needs to be an "informed" consent. That means the patient needs to be told things like the nature of the treatment, the risks of the treatment, their prognosis for after the treatment, the organs that will be affected, etc.

Take the situation with infusional chemotherapy over the last twenty years. Have you considered that all "over-the-counter drugs" you purchase at the pharmacy, have dosage, usage and side-effect declarations on the label. Even prescription drugs that are purchased from a pharmacy have print-out and/or labels. With the infusional drug concession, the oncologist's office (except for some urologists) is the only place where the drugs are purchased for you and you have not been able to read the lable.

This means that "informed consent" is the only thing close to "labeling" of these chemo agents. A number of oncologists have been playing fast and loose with "informed consent," many times ignoring it. Like you said, "it was the next part of (the) treatment." Without the proper administration of "informed consent" or consultation, a patient receiving chemotherapy is less informed than a person purchasing and using a package of Tylenol or Benadryl.

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  • 4 years later...

When brain tumors are treated with radiation therapy, there is always a risk of radiation-induced necrosis of healthy brain tissue. Insidious and potentially fatal, radiation necrosis of the brain may develop months or even years after irradiation.

This poorly understood side effect can occur even when the most stringent measures are taken to avoid exposing healthy tissue to harmful levels of radiation. In most cases, radiation necrosis of the brain occurs at random, without known genetic or other predisposing risk factors. The only treatment options typically available for radiation necrosis of the brain are surgery to remove dead tissue and use of the steroid dexamethasone to provide limited symptom control. But clinicians have not found a way to stop the progression of necrosis, despite having tested a range of therapies including anticoagulants, hyperbaric oxygen, and high-dose anti-inflammatory regimens.

However, recent studies at M. D. Anderson have shown that the monoclonal antibody bevacizumab (Avastin) may be able to stop radiation necrosis of the brain and allow some of the damage to be reversed. Victor A. Levin, M.D., a professor in the Department of Neuro-Oncology and the senior researcher on the studies, said the findings suggest that radiation necrosis of the brain can be successfully managed—and perhaps even prevented—with bevacizumab or similar drugs.

The need for such a breakthrough is as old as radiation therapy for cancers in the brain. “No matter what we do or how good we do it, we know a small percentage of patients who receive radiation therapy to the central nervous system will suffer late-occurring radiation necrosis,” Dr. Levin said. “We used to think it was the dose that was causing problems. Then we did a study and found that there was little to no relation to radiation dose or radiation volume—the necrosis occurred simply by chance. So it is impossible to say which patients will develop this problem; we just have to monitor them and hope for the best.”

Like necrosis, the discovery that bevacizumab has an effect on necrosis can also be attributed to chance. Bevacizumab, a newer drug that prevents blood vessel growth in tumors by blocking vascular endothelial growth factor (VEGF), was originally approved in the United States for the treatment of metastatic colon cancer and non–small cell lung cancer. An M. D. Anderson group that included Dr. Levin decided to test the drug in patients who had VEGF-expressing brain tumors. “Some of these patients also had necrosis from prior radiation therapy, and we were struck by the positive response of those patients to bevacizumab,” Dr. Levin said. “We had never seen such a regression of necrotic lesions with any other drug like we did in those patients.” The observation prompted the researchers to design a placebo-controlled, double-blind, phase II trial sponsored by the U.S. Cancer Therapy Evaluation Program in which bevacizumab would be tested specifically for the treatment of radiation necrosis of the brain.

The trial is small, having accrued 13 of a planned 16 patients, and is limited to those with progressive symptoms, lower-grade primary brain tumors, and head and neck cancers. But the results have been unlike anything the researchers have seen before in radiation necrosis therapy. All of the patients receiving bevacizumab responded almost immediately to treatment, with regression of necrotic lesions evident on magnetic resonance images, while none of the patients receiving the placebo showed a response. The results were striking, and all of the patients who switched from placebo showed a response to bevacizumab as well. So far, responses have persisted over 6 months even after the end of bevacizumab treatment.

Side effects seen in the trial so far included venous thromboembolism in one patient, small vessel thrombosis in two patients, and a large venous sinus thrombosis in one patient. Dr. Levin is unsure whether the side effects were caused by therapy or the radiation necrosis itself. “We’re also not absolutely sure what is causing the positive effects against the radiation necrosis,” he said. “We presume it’s related to the release of cytokines like VEGF, since bevacizumab is very specific and only reduces VEGF levels. We think aberrant production of VEGF is involved with radiation necrosis of the brain, and the fact that even short treatment with bevacizumab seems to turn off the cycle of radiation damage further confirms the central role of VEGF in the process.”

The multidisciplinary research team has also postulated that radiation therapy damages astrocytes, a cell type involved in various brain functions, and causes them to leak VEGF. This leaked VEGF might then cause further damage to brain cells and further leakage of VEGF. “It gets to be a very vicious cycle,” Dr. Levin said. “The question is, is that all that’s going on?”

Dr. Levin hopes that the answers to that question and others may lead to preventive measures against radiation necrosis, beyond what is already done to control the development of radiation itself. Perhaps bevacizumab can be given in low doses before radiation or intermittently afterward to reduce VEGF levels and protect the brain from abnormally high levels of the protein. He hopes such approaches can be tested in future studies. “Just the fact that bevacizumab works has helped us understand so much more about what happens in radiation necrosis,” he said. “Everything we’ve tried up until now has been a brick wall.”

Source: OncoLog, May 2009, Vol. 54, No. 5

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