Dr. Goldberg,

This topic is relevant to me; my husband (Age 52, Stage 2B Sq Cell, bilobectomy 10/06, 4 cycles cisplatin/gemzar) was diagnosed with a brain met (about 3cm, occipital lobe) within a few weeks of completing his chemo. This surprised us because he did have a clear brain MRI prior to surgery. His met was fully resected, and he completed WBR 13 months ago. In preparing for the WBR, we met with the radiation oncologist and expressed concern about neurocognitive damage associated with WBR; as a result, he offered us the option of going with 20 sessions rather than the 10 that appeared to be standard. So, 20 sessions and I cannot recall the radiation dose; I know that it was equal to the full dose he was being offered in 10 fractions, just more spread out.

We are now 13 months out from completion of WBR, and all scans since then (last one in March /08)have been clear. My hope is beginning to grow that we will be in the category of Stage 4 patients that simply have an isolated brain met, and no other recurrence.

However, there definitely has been a cognitive and functional cost that I guess is a result of the radiation. My husband can no longer work because of difficulty remembering things, coming up with the right words, and a need to nap a couple of times daily. In addition, he has recently (maybe 3 months ago) developed intermittent periods of significant dizziness. He can function perfectly well doing small jobs around the house and caring for himself, but following a work schedule, using tools, remembering things, just does not seem feasible.) He saw an ENT for the dizziness, but no cause was found there (the oncologist had suggested an ENT consult, since some of my husband’s brain MRI’s since treatment have shown fluid on both mastoids. The ENT did not feel there was an issue there that would cause dizziness.)

I guess I have a few questions:

1. Is this pattern of cognitive difficulty and dizziness something that is often seen at this point after WBR?

2. I assume that since this met was an isolated met, fully resected, followed up with WBR, and there has been
no recurrence, that brain recurrence is unlikely at this point. Is that a correct assumption?

3. Is a patient who is classed in stage 4 due only to an isolated, agressively treated brain met truly stage 4? Since he has no evident cancer in his body, I have a hard time grasping that prognostically. (Maybe that’s just such a gray area it cannot be answered.)

Your presence on the board is greatly appreciated. Thank you!

Hi.

Your questions touch on a number of important topics, so let me see if I can do them justice.

13 months out from radiation, your husband sounds fairly impaired, more so than is common. He did have chemotherapy as well, which was probably leaking into his brain somewhat (the blood brain barrier is leaky in tumors) before the met was diagnosed, so he is had 3 cerebral insults: tumor, chemotherapy and radiation. I obviously don’t know what exactly his radiation oncologist did, but it sounds like he went with small dose per fraction, so that would minimize brain risk. Overall, I would say that some of the effect is definitely from the radiation, but he has had a more significant decline than most. The fluid in the mastoid air cells also doesn’t seem to be related to radiation effects, either, so your husband’s situation raises several questions in my mind — the pieces really don’t fit together.

I would agree that brain recurrence at this point is less likely and a single brain met does have a different (better) prognosis than wide spread mets.

For piece of mind, it might be worth having your husband undergo a complete neurologic and neurocognitive assessment. It will provide a current status and may yield some clues to why he is more incapacitated than one would anticipate (and the dizziness/mastoid fluid question might be solved).

Let us know what happens.

zg

Thanks very much for your reply Dr. Goldberg.

This has been puzzling to me as well. My husband is scheduled in one month for a bi-annual CT and brain MRI. Assuming good results on those, I think I will ask the oncologist for a neuro consult referral, assuming that my husband is willing to see another doctor. My hope is that there is nothing new that would explain the symptoms. As I re-read his most recent MRI report (3/08) this morning, I saw only references to things that had been present since the brain treatment - mild encephalomalacia, mild vasogenic edema - nothing that warranted further comments or follow up. Maybe this is just the result of the multiple factors you cited, and if so, we’ll deal. I’ll let you know how the next MRI looks, and thank you again.

Dear Dr.

My mom was diagnosed with Stage 4 Kidney cancer that metatized to lungs and brain. She just completed 2 weeks of WBRT last friday and she is extremely fatigued now but 2 days ago she started having a lot of pain (headaches) and today she was experiencing some nausea as well. Could these be side effects of the radiation?

Hi.

Yes, your Mom’s symptoms are classic side effects of radiation to the brain. It would be most appropriate to discuss starting or increasing steroids with her doctor. Usually these symptoms are easily managed with short course steriods that can be tapered off. Some patients have to continue low dose steriods, but that is not as common and easily managed in any case.

Please let us know how she does.

zg

Dear Dr.

Thanks for your quick response. My mom is on steroids (methazone or somehting like that) already and that has definitely helped but for some reason these last 2 days have been very tough on her and her oncologist told my dad that her symptoms were not a good sign and it could mean that the tumors in her head may still be growing. Do you have any insight on this?

Thanks a lot

Dear Dr.

I just spoke to my mom and he mentioned that she has completely lost movement on her right arm. Her right arm was already weak since her cancer was detected but now it’s weaker than before.

Thans

Delia

Hi

A change in function, such as complete loss of movement in an arm or leg, is something that your Mom’s treating doctor needs to be informed about. In my practise, I usually want to see the patient, and most often increase the dose of steriods. While symptom progression–from weakness to no movement– can be a sign of tumor progression, it also can be caused by a lot of swelling around the tumor, which can just be a short term side effect of radiation (and can be a good sign as the tumor is responding to the radiation and getting a lot of inflammation around dying cancer cells).

So, bottom line: let your Mom’s doctor know and don’t be surprised if s/he wants to see your Mom, may change her meds, and orders an urgent brain scan to assess.

Please let us know what happens.
zg

Dr. Goldberg (or any other Dr. willing to reply),

How many patients with a resected single brain met will have a new brain recurrence after WBR? The answer to this question seems to be complicated by the fact that there is fairly short median survival after WBR, so maybe not many people live long enough to show recurrence that would occur later. I guess I am asking if a patient does have lengthy survival after resection & WBR (one year so far in our case) do new recurrences become likely?
Does WBR only hold things off for so long? Thank you!

Hi

You have asked a great, and very complicated question. In fact, the only real answer is “it depends”. Useful, isn’t it?

Incidence of brain mets depends on the cancer type, so that is the first specific that drives brain recurrence rates. Another thing that affects it is dose of WBR (this is true in the broadest sense — most schedules used for brain radiation are roughly equivalent, but every once in awhile someone gets much higher doses). Overall tumor control throughout the body can also affect it, but in different ways — more tumor means more potential for spread, but shorter survival and therefore less time for a brain tumor to present. Whether the brain met was diagnosed with the original cancer diagnosis or came later also affects recurrence risk.

I would usually tell patients that a year without a brain recurrence is a good sign. Some people truly only do have a single brain metastasis and their outlook is better and distinguishable from multiple mets.

zg

Thanks, Dr. Goldberg. I figured that the answer would be dependent upon multiple factors. My husband has (had?) 2B squamous cell carcinoma, T2/N1(hilar)until the brain met, of course. I think that he had the most reasonably agressive treatment available (bilobectomy with clean margins, cisplatin/gemzar) and then was diagnosed with the brain tumor 6 months after initial diagnosis and 8 weeks after the end of chemo. That was also fully resected and he had WBR (20 fractions, whatever does that is normally standard in 10 fractions, but instead broken out into 20.) Not knowing much, I considered this to be a pretty short disease free interval, but maybe I’m wrong.

Anyway - as I mentioned in a post a couple of weeks back, he has developed ongoing dizziness and balance issues, and they have become worse very recently, including a near backward fall. He is also now having intermittent headaches that cauase him to briefly lower his head and hold it in his hands as if he cannot respond for a minute.

I am beginning to feel that there is probably reason to believe here that he MAY have a metastatic brain recurrence, and I guess I am just self checking whether that is so unlikely as to be an over reaction on my part. However, I also know that the only right answer is to get to that 9/5 brain scan and find out, so I am not asking you to guess

I appreciate your response and time - thanks so much.

Yes, I agree that rather than speculate, you”ll get a real answer at his next scan. If symptoms are severe enough, it might make sense to move up that timetable. But as Dr. Goldberg indicated, his symptoms are well within the range of believable post-treatment effects, so you wouldn’t have to invoke the dreaded idea of progression in the brain.

-Dr. West

Dear Dr.

My mom still has a lot of pain but she says the pain is more in the front of her head, kind of like pain related to sinus infection. She has suffered from sinus infections in the past and had extreme pain and now she is experiencing that again which it may be related to the tumors she had in her brain but nothing seems to relieve the pain. Is there anything else you can recommend?
She has been laying in bed for the past week or so and does not feel like doing much. I am concern that being in bed all the time will make things worst for her.

Thanks

Hi

You have not mentioned if your Mom has seen or spoken with her treating doctor about these symptoms. I have to most strongly recommend that–especially the arm changes and headaches. Yes, her sinuses may be the cause, but until she is examined, one simply doesn’t know. Under these sorts of circumstances, I really like to get a CT head for my patients to assess what is going on.

From a pain management perspective, the best medications really will depend on what the cause may be. Methadone, which it sounds like your Mom is taking, can be very effective if she is on the best dose for her. If the cause of the increased pain is from swelling around the tumors, though, higher doses of steriods may work better for her. Again–the best answer is dependent upon the cause of the pain. Her doctor would be best able to judge that.

If your Mom is too weak to get into her doctor for an assessment, is there a service that could come to her home? A lot of cancer centers now have good outreach groups–usually nurses who can help sort things out and change medications as needed.

Whatever the source of your Mom’s pain, medications almost certainly can help to manage it better, once an assessment is done.

Please let us know what happens.

zg

Dr. Goldberg,

My mom was finally given a higher dose of steroids for a few days which helped her tremendously. She recovered mobility on her arm and leg and she felt a lot better, unfortunately as soon as they stop that medication and went to a lower dose all the symptoms came back. She even had another seizure and her face also looks swollen (from all the inflammation on her brain I assume). She will get and MRI today and hopefully we will have a better idea of what is going on. Unfortunately, she has also started to tell us that she does not want more medication. She has been feeling disoriented when she takes some of her medication.
Thanks

Delia

Hi

Thanks for the update. Overall, if your Mom improved on higher doses of steriods then at least in the short term, you seem to have a strategy to pursue. While long term steriods have many side effects, short term use rarely leads to much harm. Your Mom’s facial swelling, though, is most probably related to the steriod use, though, since they are known to cause water retention and make people’s faces look rounder.

In my practise, I will often leave people in tumor in the brain on steriods for a fairly long time, and when I do drop the dose, I do so very slowly. Even if your Mom choses to no longer pursue treatment, she may want to consider staying on the steriods just to help her feel better.

Please let us know what the MRI results are.

zg.

Dr. Goldberg,

My mom had an MRI done today and unfortunately it does not look very good. It seems that she has a lot of edema and the the tumors have grown or expanded. She has not seen the oncologist yet to evaluate what is going on but she will later today.
I have read that in cases where WBRT does not work some people have done targeted radiation or something like that and that had better results. Do you have any input on what you would normally do in cases like my mom’s?

Thanks

Delia

Hi:

I am sorry to hear that the MRI results weren’t more promising.

While progression after WBRT can be followed by radiosurgery in some cases, it usually is offered only if there had been a good response previously, there were few lesions that all could be treated, and the patient’s overall performance status was good. Your description of your Mom does not suggest that she would meet these criteria. Clearly your Mom will need to speak with her doctor and see what s/he has to say. In my own experience, overall performance status is the first thing that is considered in the discussion, then the technical issues of re-irradiation can be examined.

Whether your Mom is a candidate for further radiation, and choses to take it, she can be treated for pain with medications and/or steriods for the edema around the tumors. If it is appropriate to end active anti-cancer therapy, then minimally she should be hooked into a good supportive care team to help manage her symptoms.

My best to your family,

zg

Dear Dr.

Thanks for your response again. It’s incredible how somebody online may be more helpful than my mom’s primary doctor. My dad decided to see another doctor and she recommended that my mom takes sutent. Do you know anything about this drug? I have been doing a lot of research and my concern is that this drug may weaken my mom even more.
I saw my mom this weekend and she looked good considering what her brain tests showed. She has been very sleepy since yesterday and even slept from 3 pm until this morning.

Thanks again for all your information. I really appreciate it.

Delia

Hi

I have no personal experience with Sutent, but one of the targets that the drug inhibits is vascular (the VEGF receptors). That is always concerning with known intracerebral brain mets as bleeding is a well recognized side effect of this treatment. Usually, brain metastases is a clinical contraindication for treatment with drugs of this class, so you would need to speak directly to the doctor that your Dad spoke with regarding the specifics of your Mom’s case and get a full consultation.

I would take a slightly different perspective, which is, given your description of your Mom’s sleepiness and her statement of not wanting more therapy, this would be a good time for your family to sit down together and find out what your Mom truly wants people to be doing to help her most right now. It is virtually impossible to know via this forum, but my sense is that she has her own thoughts that will help guide your family during this difficult time.

Please keep us posted and know that we are thinking about you.

zg.

Dr. Goldberg,

First of all, I can’t thank you enough for all the guidance you have provided during this time. I am currently with my mom and she is having a lot of shivers for certain periods of time. She has had 3 incidents since yesterday. Do you have any idea if this is normal under her circumstances?

Thanks

Delia

Hi

I bet that your Mom is incredibly pleased and grateful that you are with her now.

As for the shivers, it is pretty non-specific on its own…..like “cough” or “stomachache” it can be significant or nothing to worry about at all. If she also has a fever and has a low white cell count, then the concern would be infection. Shivers themselves, though, can be from the steriods, from pain medications, from the tumors in the body secreting substances that affect temperature regulation, or other causes. Bottom line: on their own, they are less likely to be something to be concerned about, but if it is in conjunction with some other symptom, a home care nurse (or whichever health care person is involved with your family now) should take a look.

zg

Thanks for your response. BTW, I have been meaning to ask you where you are located and if it’s possible to get an address so I can send a card to you. My family is extremely grateful for all the kind words and support you have provided. My mom, as you said, is very happy that I am here with her. She is definitely amazing and she is fighting hard for her life!
She has been having problems with lack of urination, which I know is a side effect of many of the medications she is taking. She has taken furosamide to help her but I was trying to look for natural ways to help her with that.

Thanks and God bless you!

Delia

Hi

No need for a card, but thanks for the kind thoughts.

Difficulty urinating can be because she isn’t drinking enough, or because of the disease or the medications she is taking. Furosemide is a duiretic, so natural choices would be things like tea, or caffeinated drinks, or just lots of fluids. There are some herbal teas that claim duiretic properties, but any old tea will do it. Furosemide is really effective, though, much more than the natural ways are likely to be. Furosemide does change sodium/potassium balance, so be sure your Mom is also eatting bananas or drinking orange juice or taking potassium suppliments.

zg.

Dear Dr. Goldberg,

My mom’s body has been shaking a lot since this morning (left side since her right is the one that lost mobility). She is very sleepy and couldn’t even eat anything. I am assuming all of this is related to what is happening on her brain, right? It feels as if she is on her last days here with us.

Hi.

As always, it is impossible to answer definitively without seeing someone, but what you describe could well be related to disease progression in her brain. I am hoping that you have hospice or homecare nursing services to check in with to make sure that your Mom’s medications are optimized to keep her as comfortable and relaxed as possible.

My thoughts are with you and your family.

zg.

Is there anything you can recommend for her to eat or IV food so she is not as weak?

Hi

As much as we want to offer comfort in the form of food when we are with a loved person struggling and weak, — and this response is almost universal in families when someone has advanced cancer, in my experience — there are no foods or drink, IV or by mouth that offer anything in particular. What I tell my patients and their families is to make available whatever food or drink the person wants, and if your Mom doesn’t want any food or drink, that is fine, too. She is listening to her body and it is very common for people to not want anything when the cancer is very advanced. If she wants to drink, fruit juices can give her some natural sugars, but often taste ‘wrong’ or bad or too sweet. Again, be guided by her requests.

Let me emphasize that just being with her is a wonderful gift that you are giving to her.

My thoughts are with you.

zg.

Dr. Goldberg,

I visited my mom this weekend and I was devastated to see how her cancer has progressed in just one week. She is not talking that much anymore and she has lost a lot of weight but the most devastating side effect is her state of mind. My mom and my dad have been married for almonst 40 years and have had a pretty good marriage but these last days she does not even want to look at my dad and when he wants to kiss her she moves her face. She was telling me she wanted to come with me and she was so anxious that she even tried to get up as weak as she is she was desperate to come with me. Oh my God, it broke my heart. I want to believe that this is all part of her side effects either from the radiation or all the tumors/lesions on her brain. She seemed very scared and just looking around all the time. Is there something we can do to help her through that phase?
Thanks

Delia

Dear D:

While there are a few things that can be causing this personality change and anxiety, the most common would be either the tumors themselves in her brain (depending on location) or the steriods (depending on the dose). While very difficult for you and your father, if it is any consolation, it is usually harder on the family than the person with the tumors. Your Mom may not recognize who your father is, so when he leans to kiss her it would seem totally inappropriate to her. Obviously, not seeing your Mom, I am only speculating, but I have certainly seen this in other families. Sometimes it helps to ask directly where your Mom thinks that she is and who is around her. It may not make you feel better, but it can yield insight into where her mind is.

There may not be very many good options, other than being there for your Dad, who is probably hurting very badly right now. If she is on high doses of steriods and not having headaches, you can ask her treatment team if they can be reduced — if they are the cause of the problem then that might ease her mind. If the anxiety is very bad, anti-anxiety medications may help, and they can be dissolved under her tongue if swallowing is a problem for her.

If you have not already done so, you and your Dad need to reach out for more help now–be it in the form of a hospice team, friends, extended family and any other social support you can draw on. It sounds like your Dad is the primary care giver and he needs time away to keep him from burning out. This is one of the hardest times in your life and it should not be walked alone.

Keep us posted and know that we are thinking of you.

zg.

Dear Dr.
This Friday will be 8 weeks since my mom completed her wbrt. Things have gotten a little better since last time I e-mailed you. She has not experienced any pain and her steroids have been reduced to only 8 mg every 12 hours. She even walked a little bit and my sister took her out for a ride around the city the other day. She is also talking a little more. Her biggest problem now is chronic constipation which is making her very uncomfortable. Do you know anything that may help?
My dad is not sure about what to do next. Should we try to reduce her steroids even more? I think we will do another MRI to see what has happened to her brain.
Thanks

Delia

Hi

Constipation can be addressed from the top with meds and some foods that stimulate the bowel, and from below with rectal suppositories or enemas. I think that fleet enemas can be obtained from the drug store without a prescription.

There are many meds that stimulate the bowel–I usually prescribe for my patients lactulose (a sweet drink), colace, senokot, and Mg Citrate if it is really bad. And while some may talk about prunes for constipation, I have always found cooked carrots to do the trick for people.

If your Mom has been really backed up for awhile she may need an enema to move out the very dry, hard stool at the very bottom end, as well as bowel stimulants from the top. The other thing to keep in mind is that once constipated, it takes 2 full weeks to clear our a bowel, so she needs to remain on her bowel meds.

Waiting to see what the MRI shows before deciding on the next step in treatment seems very reasonable to me.

zg.

For those who think they need WBR there is hyperbaric oxygen therapy. The University of California, San Diego Medical Center’s Hyperbaric Medicine Center is part of a nationwide effort to compile and evaluate data in order to validate whether cancer patients being treated for radiation-related wounds heal more quickly and more thoroughly with hyperbaric oxygen therapy. For more information on UC San Diego’s Hyperbaric Medicine Center: http://health.ucsd.edu/specialties/hyperbaric

It’s good to see a resurgence of research into this valuable technology. Until the new millenium, the only treatment for patients for radiation-induced necrosis was pentoxifyline or heparin therapy, and it was almost always unsuccessful. Both Duke University for Hyperbaric Oxygen Therapy and the University of Cincinnati previously had successful clinical trials on this science. The most common condition treated at some hyperbaric oxygen therapy centers is tissue injury caused by WBR.

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 healed.

I’ve been unwittingly involved with the subject of whole brain radiation for ten years. The studies performed by Patchell, et al in the early and late ’90s, measured tumor recurrence and not long-term survival. Patchell’s studies convincingly showed there was no survival benefit or prolonged independence in patients who received postoperative whole brain radiation therapy. It never mentioned the incidence of dementia, alopecia, nausea, fatigue or any other numerous side effects associated with whole brain radiation.

The most interesting part of his studies were the patients who lived the longest. Patients in the observation group who avoided neurologic deaths had an improvement in survival, justifying the recommendation that whole brain radiation therapy is not indicated following surgical resection or SRS of a solitary brain metastasis.

Editiorials to the studies by Mintz and Cairncross describe the morbidity associated with whole brain radiation and emphasized the importance of individualized treatment decisions and quality-of-life outcomes. Patients do not remain functionally independent longer, nor do they live longer than those that have surgery or SRS alone.

The Department of Neurosurgery at the University of Texas M.D. Anderson Cancer Center, from their OncoLog (as well as the UCLA Metastatic Brain Tumor Program and University of Pittsburgh School of Medicine), admits that whole brain radiation may still be a standard for four or more brain mets. However, there are a variety of effective “focal” treatment modalities for people who have fewer than four tumors.

Thanks for those “standard” dose-fractions Dr. Goldberg. My wife received 4000 cGy in 20 treatments of whole brain radiation, plus 1000 cGy in 5 treatments of focal radiation to the local tumor bed, to her excised solitary tumor. Four, mm-sized metastatic tumors were found in and around the previously resected cerebeller tumor, 20 months later, via an unenhanced/enhanced MRI, and confirmed by a Pet Scan.

Anonymous,

Thanks for that input. Your point about th data with WBR after surgery or SRS being a measure of recurrence and not very far long-term is particularly well taken. It’s the reason why I remain reluctant to recommend that my patients take concurrent anticancer meds like EGFR inhibitors or chemo with WBR, even when short-term reports reveal no clear increased risk. I think it’s quite possible that evidence from 1-2 years down the road may look less encouraging, and Iprefer to play it safer unless a patient’s back is against the wall and they can’t afford to wait before starting both WBR and systemic therapy.

-Dr. West

Drs:

Summary of previous posts:
Husband, Age 52, Stage 2B Sq Cell, clean brain MRI prior to lung surgery, bilobectomy 10/06, 4 cycles cisplatin/gemzar), was diagnosed with a brain met (about 3cm, occipital lobe) within a few weeks of completing his chemo. His met was fully resected, and he completed WBR 13 months ago.

If you are able to scan my August posts in this section, you will see that my husband has been struggling with continous dizziness, as well as verbal and memory issues since completing WBR 15 months ago.

He recently had quarterly scans, and all was well - NED. The only items of note were elevated liver enzymes and some possible necrosis/infarction around the brain excision area. These have been the case since completing the WBR. Our oncologist did not feel that there were any issues requiring follow up at this time, since these findings are not new.

Needless to say, we were really relieved; however, the dizziness and other issues have not decreased, and now my husband has developed a sudden and apparently complete loss of hearing in one ear.

So…now he has a significantly impaired visual field (occipital tumor), chronic dizziness, a sudden loss of hearing, trouble thinking, yet a “clean” ENT workup, and good scans. Our Oncologist did not see a need to refer him to a neurologist.

I’m sure that you can understand that I’m not really that all is well, in spite of the scans. I understand the visual impairment, but the dizziness, hearing loss, cognitive issues - this seems like a lot going on inside the head of someone with a clean brain MRI and minimal MRI indication of radiation damage.

My husband depends on me to know what to do next, and I’m at a loss. Is all of this likely just our outcome after the trauma of all of the brain events?

Any thoughts would be appreciated - I am out of ideas.

Thanks so much!

I’m afraid I don’t have a good explanation either. Those of us who don’t do radiation are quick to blame the radiation for both short- and long-term complications. My sense is that there is a real possibility of “radiation necrosis”, basically degeneration of tissues after radiation, that may be an increasing problem in longer term survivors of brain radiation. I don’t think we really appreciated this previously, because we didn’t have enough people living a year or more beyond brain radiation to draw any conclusions or really worry about complications in the (relatively) distant future. I’m not sure that this is really an explanation. I’m struggling to come up with something.

As for a neurology consultation, I’d be pleasantly surprised if they could identify a fixable problem. We often seek another opinion for when we just don’t know and need to “buy a vowel”, to use Wheel of Fortune terminology, for lack of a better analogy. A very reasonable thing to do, but I’d bet they’d also find it vexxing and difficult and perhaps impossible to explain.

-Dr. West

Thank you Dr. West. I always appreciate your candor, especially in these grey area situations. I understand that these things are not always a certainty.

I don’t know anything, but my only real guess has been the late-delayed radiation effects I’ve seen in various literature.

I guess I’ve also worried about some sort of neoplastic process not picked up by imaging, but that seems unlikely to be developing slowly over months, correct?

Thank you so much.

Yes, I’d expect to be able to see any visible process if it’s been ongoing for months, especially with an MRI scan, which is quite sensitive.

-Dr. West

Thanks. If it is necrosis, is there a usual outcome? I know that out on the far end of the spectrum there are people who apprently die or become severely disabled as a result. I’m thinking that is unmcommon. Is it more common to just reach some more moderate point of functional decline, then stabilize there? Or maybe even improve over time from this point? The literature on this is kind of murky and disjointed, and I can’t really get a sense of what is common. Thanks very much

I’d believe it’s more likely to stabilize over time, but I think there’s almost no helpful literature on this, and I don’t have enough patients in this situation to say anything definitive about what should be expected.

-Dr. West

I couldn’t help adding my two cents here (I’ve been reading and learning from GRACE for awhile now, but haven’t posted before). My husband is a 56 year old never-smoker, diagnosed in 2/07 with stage IV NSCLC, with mets to the spine (only symptom before diagnosis was vague back & chest pain, misdiagnosed as pneumonia in late ‘06). Initial treatment over the next few months was simultaneous chemo & radiation (to address pain issues), Zometa, and substantial pain meds, which he has been taking ever since. Initial head scan was negative for brain mets.

Almost a year ago, a follow-up head scan showed four tiny spots; they were asymptomatic so far as we could tell, and neither of us could detect any cognitive issues other than his still substantial fatigue from the earlier radiation/chemo. WBRT was recommended, and although we were told that there might be “some” memory and cognitive issues, we got the impression, perhaps because we were listening for good news, that they were likely to be minor and temporary. And perhaps that is the case for most patients, as Dr. Goldberg suggests in her post. He received the treatment in 11/07.

The good news is that the radiation seems to have worked; subsequent scans have shown that the spots shrank away to nothing. There was never any detectable swelling or edema, and he has never had any seizures, headaches, dizzyness, etc. On the other hand, within a month, he developed significant hearing loss, which has never returned, though the radiation oncologist thought at first that it would. Much more distressing, there was a rapid, significant cognitive loss, which has also persisted unchanged for the last ten months. His short-term memory is basically gone, he cannot complete complex, sequential tasks, and he can no longer write a coherent sentence or paragraph. Although he is oriented in time and place, and like Mary’s husband is generally able to care for himself, this has been a terrible and unexpected blow.

Since then, the cancer progressed elsewhere; he began taking Tarceva and, a number of months after the WBRT, when it appeared the brain mets were gone completely, Avastin. The new mets elsewhere in his body (adreanal gland & liver) have now shrunk dramatically as well. Physically, while he certainly shows the effects of all he has been through, he is doing remarkably well. Mentally, it’s another story.

Given the terrible prognosis for untreated brain mets, I suspect that we would still have gone this route even had we fully appreciated what might happen. At least I think I would have recommended it to him; I’m frankly not sure what he would have done. It is also true that his quality of life isn’t terrible by any means; he enjoys his family (though he has withdrawn from friends somewhat, embarrassed by his inability to carry on a conversation), eats well, and enjoys television and movies (though I find talking to him after a show that he often didn’t follow what was happening, and I avoid renting movies with complex plots or subtle story lines). And I well know that still having him here with me 19 months after diagnosis is a rare gift. Bottom line, I guess, is that I wish we had been better prepared for this — and that I hate cancer with all my heart.

Another aspect that may be overlooked here is the possibilities of Leptomeningeal Carcinomatous (LC) or Carcinomatous Meningitis (CM). It is a leptomeningeal metastasis.
Unfortunately, cancer cells are too small to find on any scans unless they have grown into a lump. There can still be cancer cells in the body even though scans may have indicated that all the cancer had gone.

Leptomeningeal metastasis is a condition caused by cancer cells getting into the thin sheets of body tissue that surround and protect the brain and spine. These sheets are called the meninges. Meningitis means inflammation of the meninges.

Carcinomatous just means acting like a cancer. Most people are familiar with the type of meningitis caused by an infection, but with carcinomatous meningitis, it is the cancer cells in the meninges that cause the inflammation, not an outside infection.

Cancer cells do not always develop into an active secondary tumor when they have spread to a new site. Sometimes they stay inactive for many years. Even after a cancer appears to have been successfully treated, some cancer cells may still be elsewhere in the body.

Tumor cells reach the meninges by hematogenous (blood) spread or by direct extension from pre-existing lesions and are then disseminated throughout the neuroaxis by the flow of the cerebrospinal fluid.

Patients present with signs and symptoms from injury to nerves that traverse the subarachnoid space, direct tumor invasion into the brain or spinal cord, alterations in blood supply to the nervous system, obstruction of normal cerebrospinal fluid (CSF) flow pathways or general interference with brain function.

Diagnosis is most commonly made by lumbar puncture, to look for malignant cells or elevated protein levels in the spinal fluid, although the CSF cytology is persistently negative in about 10% of patients with leptomeningeal carcinomatosis.

A MRI of the brain and spine to look for enhancement of meningeal tissue. Radiology studies may reveal subarachnoid masses, diffuse contrast enhancement of the meninges or hydrocephalus without a mass lesion.

The cancer cells in the meninges can cause a range of symptoms, including confusion, headaches and weakness, also head pain, cranial nerve involvement, hearing problems and back pain.

The condition is very difficult to treat. The main aim is to help control symptoms and not cure the disease. Chemotherapy injected into the spinal fluid (via Ommya Reservoir in the brain) or radiotherapy to the brain are both treatments for Carcinomatous Meningitis.

Some patients respond to these treatments, but the prognosis is generally poor. There are no set guidelines for treating this condition as oncologists don’t really know which treatments work best.

Again, I’ve been unwittingly involved with this for ten years. Nine months after my wife’s WBR, she was admitted to the hospital for unexplained falls and light-headiness. To make a very long story short, her spinal fluid was cloudy, meaning some kind of infection.

The cytology test results showed adenocarcinoma nodules in the spinal fluid (Carcinomatous Meningitis). They administered intrathecal Methotrexate along with systemic radiation to the spine. Dr. West mentioned he is reluctant to recommend his patients take concurrent anticancer meds with radiation.

In my wife’s case, when both therapies are performed at the same time, it doubles the therapeutic dosages of each therapy (increasing the neuro-toxic effects on the brain). However, the cancer cells were eradicated completely from her CNS.

Hi All:

First a thanks: to whomever is “anonymous”, you have now written several very comprehensive and comprehensible posts that offer a well thought out response to issues presented.

With regards to the families suffering with long term neurologic decline in the absence of focal imaging changes (MRI or CT) and no clear diagnosis, I would urge you to follow up with your doctors regarding possible leptomeningeal disease, for at least that is treatable.

Radiation necrosis is visible on scans, so that is a “positive diagnosis” rather than one of exclusion.

I am, frankly, a bit perplexed by the reports of abrupt loss of hearing and balance problems. It makes me wonder a bit about where the hot spots on the radiation may have been (a technical issue– depending on how the radiation is delivered, while the overall dose may be standard, there could be a local area that got a higher dose). Clearly, each individual case would need to be reviewed separately (and would only potentially serve to educate, not offer anything on treatment or prediction for improvement.)

I must admit that I have routinely told patients that long term cognitive decline or other brain problems from WBRT are fairly minimal for most people. The long term data from patients with WBRT and small cell lung cancer also shows a remarkable amount of neurocognitive problems before radiation. And, as I said in the original post, surgery/anesthesia/chemotherapy and cancer itself in the brain, are all part of the mix as well as the radiation, so teasing out “who does what to whom” is virtually impossible. That said, once a person is living with the cognitive loss, it is very hard on quality of life, and that is the bottom line of importance. And, our data set on people living for 19 months after WBRT for brain metastases in NSCLC is very small.

I will write more on the latest findings for WBRT vs stereotactic RT for individual mets from ASTRO later today.

zg.

Thanks to all participating in this discussion. To JAF, your situation sounds very similar to mine. When this journey began for us, I saw only 2 long term possiblities - a cure, or illness and death. I didn’t consider this middle ground as a third possiblity. We may have a cure at hand, but there will be no return to life as it was. That comes as a surprise.

To Anonymous, I have considered the possiblity of leptomeningeal disease. My husband was doing so poorly 12 weeks after his final WBR treatment (about a year ago) that he was given a lumbar puncture, which was negative. I realize that a single negative lumbar puncture may not be conclusive, but my impression has been that any malignant leptomeningeal disease would have progressed more quickly and clearly by now.

To Dr. Goldberg: I think it is probably impossible to separate out all of the factors in my husbands history and name a single cause for his issues. To your point about neurocognitive decline in small cell cancer patients, I have to recall that he too had major cognitive issues just before his brain tumor diagnosis. It was one such major incident that forced him into the doctor (he reported his car stolen at a shopping center, forgetting that he had not driven it.) I don’t know that WBR caused his current condition, I don’t know that he would be alive today if we had taken a more moderate treatment course, and I don’t know that we would not make the same decisions today.

We can live with some form of chronic compromised cognitive functioning and make life okay. I worry more urgently (once in a while) that he has cancer in his brain again, but his clean MRI would pretty much preclude a solid tumor, and my impression is that leptomeningeal disease would have made him truly ill by now, not just hung around in some indolent ior chronic form. Is that correct? Overall, he looks well, eats well, and is moderately active around the house.

Thanks to all

Hi

You are absolutely correct that leptomeningeal disease is not expected to be stable over the long term.

zg.

Thank you!

Dear Dr. Goldberg,

Thank you so much for all the advice provided during this time. My mom passed away one week ago, and even though we are devastated by her loss we know she is now resting in a better place. Thanks again and God bless you.

Delia

Delia:

My condolences. May her memory be for a blessing for you and your family.

I am glad that I was able to help during the difficult times.

zg.

Delia,

Thanks for letting us know and for your kind words. Please accept my heartfelt condolences.

-Dr. West

Dr. Goldberg,

My sister who is 56 yrs old was diagnosed Feb 09 with metastatic Pancreastic cancer and has been treated at Sloan Kettering in NJ. In Dec 09, a few days ago, we went to the Pancreas Center at Columbia in NYC for a second opinion on treatment options. We were shocked by the expert there who told us that he wasn’t sure this was pancreatic cancer. He thought it was more consistent with metastatic breast cancer. (We have family history—our mother died of breast cancer at age 59).

The same day we received this news, we got results from the first brain MRI done on my sister since the diagnosis. It showed a .5 CM (1/2 cm) lesion. Today, she was evaluated by a Neurosurgeon who told her he believes it’s a met and is recommending whole brain radiation. It is the only tumor visible on the MRI, but he is recommending whole brain radiation to make sure he gets any other microscopic cells that may not show up on the MRI. He indicated that there was a small amt. of bleeding near the lesion, so he thinks we should not delay the procedure.

Even though we now have questions about the primary cancer, we have not yet been able to get additional testing for breast cancer to consider new treatment options. If my sister does whole brain radiation, she has to stop the chemo treatment (Gemzar) during the two weeks. My questions are: how urgent is the radiation therapy? With only one very small tumor, would it be better to start with cyber-knife procedure first, then track to see if following up with WBR makes sense? Are we better off getting more info on the potential breast cancer diagnosis and starting some treatments geared toward that, even if it means delaying the brain radiation? This is all happening at once so it’s very difficult to process.

This section has been quiet for a while…
My husband, 44yo, finished his chemorad for stage 3a LC the end of June….it didn’t have the desired effect so a pneumonectomy was scheduled for his coming up Thursday. As a part of his pre-op he did another brain MRI and they found 5 lesions(final count not complete) scattered over his brain.
Obviously we’re stunned. WBR is the plan - chemo for his LC will start 2 weeks after (cisplatin/Alimta) 1x wkly for 6 weeks. Followed by Avastin.
They said that after the WBR they will wait for a few weeks and then do another MRI to get new information…if theres a couple stragglers then proton therapy would be done…
What happens if this line of tx doesn’t work? I mean the radiation…all my husband heard, was he’s a goner if radiation doesn’t work…I know he worries because his LC tx didn’t have much of an effect on his tumor…so he’s not hopeful…

Anything that I can pass on would be helpful.

Thank you so much for being here!
Sue

This discussion has been quite old and I wonder if any of the doctors are going to reply.

Dr. Goldberg

Does the daily fraction dose influence cognitive impairment in patients receiving WBRT or Does everyone who underwent WBRT will definitely experience cognitive impairment? Does age also affect the amount of impairment? And will dementia occur to every patient treated with WBRT?

WBRT 30gy/12 fx (2.5gy)+ 30gy/15 fx boost to tumor site (frontal lobe)

Hi,
The daily fraction dose does influence the risk for long term side effects. However, it is only one factor - other key factors are total radiation dose, time course over which the radiation is delivered, and the area receiving the radiation (whole brain vs. partial brain, and which part of the brain - especially whether the medial temporal lobes are boosted to high dose). Also, within a certain range - roughly 1.8 Gray to 3.0 Gy daily, it is difficult to show any significant differences in long term effectiveness or side effects.

Certainly, not all patients experience cognitive impairment and dementia following whole brain irradiation is thankfully a very rare event. The most noticeable potential long term side effects from whole brain irradiation are decreased ability to multi-task, and short term memory recall. Though, for the majority of patients, they are able to adapt and live without these side effects significantly hindering their life. Whether age affects the amount of impairment is difficult to answer, as this too depends on many other factors. For elderly patients that are less mentally and physically active than in prior years, whole brain irradiation may have a more significant and more noticeable adverse effect. However, for the older patient that is young in mind and heart - they often do remarkably well - to the point where they and their family may not notice any difference in their “quickness.”

Best of luck to you.

CL

Thank you for your reply Dr. Loiselle

I had WBRT and 3D boost to the bottom of my frontal lobe (starting from the top of my nosebridge 5cm up) I’ve read bad stuff about people receiving WBRT such as cognitive impairment, dementia and having memory issues but luckily I found this site and you answered my question and saying that cognitive impairment and dementia is a rare even definitely relieved me

Rory

Dr. Loiselle

how about radiation necrosis? what are the chances and factors of developing this complication?

Good question about radiation necrosis. Radiation necrosis is injury to cells (brain cells in this case) with a pattern characteristic of that seen with typically high dose radiation therapy. Radiation necrosis is diagnosed pathologically - that is by biopsy and microscopic examination, although there are MRI findings suggestive of radiation necrosis.

Radiation necrosis is the underlying problem when patients have the long term side effects that we have discussed thus far. Interestingly, radiation necrosis is often minimal, and does not cause symptoms - however it can, and in extreme cases, cause side effects like dementia and cognitive problems. Thus it is the underlying biologic-physiologic process which causes the symptoms for which we are most concerned. I hope that helps clarify…

CL

Thank you for the answer dr. Loiselle. one more question, how often does radio necrosis occur? does it occur to everyone who underwent RT to the brain? or is this a rare complication from RT??

Radiation necrosis in itself, is not a complication. It is only a complication when it causes unwanted symptoms. Most, perhaps close to all patients treated with high dose radiation to areas of the brain have some amount of radiation necrosis in the high dose area where the cancer was situated. This is often a very small area. Sometimes it is large enough to be suggested by MR imaging, often it is not. Concern for extensive radiation necrosis is the reason that we do not treat the whole brain to high radiation doses… but we will treat small areas of the brain to high doses which we know are safe, and when we do so, we understand that there is likely to be a small area of radiation necrosis which is unlikely to cause symptoms. Overall, radiation necrosis suggested by imaging is not a direct concern, but it can cause problems when it extends to larger areas or is in a very important area of the brain.

Dr. loiselle
I have read from articles in the net that cognitive impairment can happen in 50% of patients surviving after 2 years and another study said that when doses below 3gy will result in less neurotoxicities or no late adverse effects at all.. how true are these claims?

In order to address specifically the merits and drawbacks of these studies, one would need to look at them more carefully.
For most patients, the reality (and our expectations) falls in the middle.

It is important to keep in mind the three factors which are going on for patients treated with radiation for brain: the cancer, the treatment, and the fact that we continue to age regardless at the same time.

Neurocognition is in no way straightforward. We are at the tip of the iceberg with regard to our understanding of the complex interplay between cancer in the brain and its resultant effects on things like memory, and ability to multitask. As well, when I say treatment, radiation therapy to the brain is responsible for some side effects, but patients with metastatic cancer are on a number of systemic therapies which may also have some long term neurocognitive side effects… or they may simply be sick and as a result not able to function normally. As well, there elements of depression, anxiety, disappointment, and success which play a strong role in our mood, outlook, and ability. Further, we are all aging all the time… patients who live 5 years between 60 and 65 may not be quite as sharp as they were previously.

My point is - this is a difficult topic to study, and interpretation of studies is complicated by all of these factors. Minor cognitive impairment in a substantial number of patients is not uncommon after whole brain irradiation… mostly in the areas of multi-tasking and short term memory. Fraction size can also be important, but it depends on the total dose, volume, and specific areas irradiated… Hope that helps. CL