BRAIN LESIONS - 1269270

kcarn0927
Posts:48

My husband EGFR +, Exon 21, diagnosed in 2013, has had some progression but yet 20%; however, on recent MRI of brain did show small 2-3 lesions and could be more but just too small to see. We will meet with the neuro radiologist tomorrow. Backstory, he did have these lesions back in 2013 when he first was diagnosed; however, it was kind of put back on the backburner so to speak, saying that they thought they were blood vessels plus he had other fires to put out. He is Stage IV w/mets to the bones which have been stable.

When we go meet the neuro radiologist what kind of questions do we ask? They have already mentioned WBRT which we are against due to side-effects (i.e. loss of memory, etc.).

Just wondering if GK or CK would be a better option?

Also, do you know a facility who offers WBR and hippocampal sparing?

Thanks for your help!

K

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JimC
Posts: 2753

Hi K,

I'm sorry to hear of these MRI findings, but I think the first question I would want answered is whether the lesions appear to have changed since they were detected on the original scan. If they haven't, that's pretty strong evidence that either they are not metastases or that they have been controlled with systemic treatment.

When there are 2-3 lesions targeted radiation is often used, so Gamma Knife or Cyber Knife would be options if that is all that is seen. If more lesions are suspected, then whole brain radiation would typically be recommended.

Most patients tolerate WBR fairly well, with cognitive deficits the exception rather than the rule. As GRACE radiation oncologist Dr. Mehta states:

"I have treated a number of patients with WBRT for brain metastases and the side effect can be somewhat variable, but most seem to tolerate it pretty well. The hair loss does not occur in every patient and does not occur to the same degree in the patients that experience this. There is also the sensation that people get "ear stuffiness" and this probably results from some of the ear wax becoming "drier" than pre treatment. There are a few people who experience some nausea after just 1 or 2 treatments. The good news is that this nausea seems to disappear and not return during the remaining treatments. The main complaint that I hear is tiredness or fatigue. This is, of course, difficult to assess because it is such an individual complaint and might be an effect of previous treatments or treatments received after WBRT. I will tell you that in general terms it resolves in most patients approximately 4 weeks after treatment. In terms of late effects, I think that most of the patients seem to function at a normal level more than a year or two out from treatment.

[continued]

JimC
Posts: 2753

[continued from previous post]

"The scientific studies of the incidence of cognitive or functional impairment are very difficult to interpret because of all the other variables that come into play. For example, in one study of patients that had not been treated with WBRT yet, the incidence of cognitive impairment was just as high as another series reported after the patients had been treated with WBRT. The other factors that might have something to do with explaining cognitive decline include general aging, the underlying cancer process, the presence of brain metastases (meaning the existence of clinical or subclinical spread of cancer to the brain), the effect of chemotherapy received before or after the WBRT, and other possible factors (strokes, etc). Unfortunately, there are rare patients who simply don't tolerate any radiation very well. For some of these patients we need to simply quit the radiation all together. There are also rare patients who simply don't recover very well after treatment and the effects of fatigue can be long lasting in this group." - http://cancergrace.org/forums/index.php?topic=80.msg828#msg828

There is also a GRACE FAQ on the subject here, as well as several links to discussions by Dr. West here.

JImC
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dldl94
Posts: 17

Hello- you also may want to discuss with rad onc
whether Namenda could be prescribed, as shown it may have a cognitive protective benefit for WBR patients.
Neuro Oncol. 2013 Oct;15(10):1429-37.
"Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial"

catdander
Posts:

Thanks for the added info. Dr. West discussed this a couple of years ago but I don't recall hearing any updates. It sounded as if the conclusion was why not try it. And it's good to read in more layman terms as well as what practical applications are being used today. http://cancergrace.org/radiation/2013/05/12/can-a-drug-reduce-risk-of-c…

dldl94, is your husband going to take it

dldl94
Posts: 17

Yes, he is on a 9wk course now (began on day 1 of WBR, tapered up over 2 wks.) Well tolerated.

kcarn0927
Posts: 48

Thank you for all your information. Didl94: what type of cancer does he have? Has he had side-effects from WBR?

My husband met with the neuro-radiation physician. We talked about WBRT and GK. She wants to do GK; however, because of the way the cancer cells are presenting the option would have to be WBRT. The reason being is that it's not the location, it's not the size, but the "distribution of the cells". There are 5 altogether, small, no swelling. The cells are coming off of the fluid that surrounding the brain. They are concerned that the GK might not be effective. He has one in his cerebellum area. She said it's presenting like "leptomeningeal carcinomatosis".

She wants to take his case to the Tumor Board and discuss further and have their neuro-radiologist review more in detail. She wants to see him back on Tuesday when she will have the treatment plan. Either way if it is leptomeningeal carcinomatosis it spreads fast so she does not want to wait on this.

She also discussed Namenda which he would be taking for 6 months and also I asked the question regarding pulsing Tarceva.

I did mention hippocampal sparing but there is a risk of not getting it all.

Also, back in my first message (the backstory), in 2013 there was mets appearing, but subsequent MRI's did not show any mets, he was on schedule to get every 3 months, but since the MRI's were clear they decided on every 6 months. She wants to review the MRI back in 2013.

What are your thoughts on this?

K

JimC
Posts: 2753

Hi K,

Most radiation oncologists favor WBR when there are as many as 5 lesions (or more). Also, if cancer cells have entered the cerebrospinal fluid, at least that area will be radiated in an effort to destroy those cancer cells. Truthfully though, WBR does not tend to treat LMC (leptomeningeal carcinomatosis) very well, but unfortunately there isn't really an established, effective treatment for it. Pulsed Tarceva has been effective for some EGFR-positive patients. There are also some new ideas for treating it, which Dr. Weiss discusses here.

JimC
Forum moderator

dldl94
Posts: 17

Hi K
Hoping tumor board discusion/planning goes well and treatment succcessful for your husb!
My husb is 62 with stg iv Lung Adeno-ALK+. Minimal lung lesions, 7 lesions (up to 6 cm) in brain.No LMC. No other options possible and prognosis was poor without WBR. Now one month out from WBR-memory/cognition about same (suspect if lessened, secondary to poor sleep and some anxiety from Dexameth). Fatigue though seems improving. Did go bald, had some burning/peeling which resolved in 2 wks. (Now fashionably bald) Each day is a blessing!
D

kcarn0927
Posts: 48

JimC,

How was your wife Liz diagnosed with leptomeningeal carcinomatosis? Did she have symptoms? Did they do a spinal tap? The reason why I am asking is that my husband has no symptoms at all. Is this difficult to diagnose without a spinal tap? Can you have cells coming off of the fluid and not have lepto? I am getting awful nervous that this is diagnosed correctly?

K

:

JimC
Posts: 2753

Hi K,

LMC was initially suspected due to a small spot within cerebrospinal fluid seen on an MRI. She consulted a neuro-oncologist, who conducted a thorough set of neurological tests, but found no evidence of LMC. He told us what symptoms to watch out for, such as double vision, focal weakness, difficulty swallowing and balance problems, and Liz later told me that when we stepped out of the consulting room she saw a double image of him at the other end of the hall. Her symptoms quickly advanced (each of those mentioned above), so we never did get a spinal tap.

JimC
Forum moderator

kcarn0927
Posts: 48

JimC:

Thank you for explaining. I just received a copy of my husband's MRI and it does not blatantly mention cerebrospinal fluid on MRI. Like I mentioned, he has had no symptoms and the neuro-radiation doctor also conducted a thorough set of neurological test in which he passed with flying colors.

Brain parenchyma: there are rounded enhancing lesions at the right parietal cortex, right posterior lateral cortex, left cerebellar cortex which vary from 5 mm to 7 mm consistent with metastatic disease to the brain. Questionable punctate enhancement at the left frontal white matter and right lateral frontal cortex. A total of approximately 5 lesions seen, These are new findings as compared to the prior study. There is no evidence of acute intracranial hemorrhage or acute territorial infarction. There is no mass effect, midline shift or extra-axial collection. The major intracranial flow voids are preserved. On axial image 19, there is another hyperintensity at the right anterior frontal subcortical region but this does not show abnormal enhancement which measures about 6 mm.

Impression: metastatic disease to the brain with enhancing nodular lesions at the right frontal, parietal lobes and left cerebellum.

So you see there is no mention of LMC. I'm just worried he is going to have symptoms while waiting for our next appointment like double vision while driving.

I'm thinking that what the neuro-radiation sees on MRI when she was reviewing it with us her mention of LMC maybe is an over-call on her part, but she wants to check with the neuro-radiologist to be certain that it is not LMC. If they are still not sure I'm hoping they will do a spinal tap.

What is your thought here?

K

JimC
Posts: 2753

K,

It's impossible to guess for an individual patient, but I think LMC gets overcalled fairly often, especially now that more patients are doing well longer on targeted therapies, giving cancer cells more time to invade the CSF.

In the absence of a positive spinal tap or significant neurological symptoms, I wouldn't assume LMC.

JimC
Forum moderator

kcarn0927
Posts: 48

Diagnosed: September, 2013, Stage IV, EGFR+, EXON 21
Treatment: October, 2013, Radiation to spine x 2 weeks
October, 2013, Carbo/Alimta 1 x infusion while waiting for biopsy
December 2013, Started Tarceva
October 2014, progression
January 2015, progression
April 2014, progression, now with brain mets, increasing size in primary with lungs nodules in both lungs, precarinal lymph node stable, thickening in pleura. Per oncologist, slow-growing.

Hi JimC et al:

My husband is due to get gamma knife for a couple small brain mets. It was determined by the Tumor Board that LMC is not suspected.

Will be meeting with pulmonary for another biopsy; as per the oncologist, "I'm not going to treat you by just looking at you".

Regarding the biopsy... the biopsy will be done on the primary to see if he test + for T790M. Is it possible that the lung nodules could be a totally different mutation... is it possible that the lung nodules could still be EGFR and the primary T790M?

Also, have signed consents for Clovis if he were to be +T790M... does anyone know how Clovis reacts to Exon 21... are there any stats on how long patients stayed on Clovis with an Exon 21?

Your thoughts would be very much appreciated?

catdander
Posts:

It's so good to hear the tumor board didn't find reason to worry about LMC. The gamma knife usually goes quite smoothly.

It is possible to develop differing mutations and histologies among tumors and mets while taking TKIs. There have been discussions on this very topic however there's no answer to this new question only speculation. Following is a link to one of the discussions as well as links under the video box. http://cancergrace.org/lung/2014/10/10/ar_forum_repeat_biopsies_bio-inf…
And this is a slew of links from a Grace search on the subject, http://cancergrace.org/search-results?q=repeat%20biopsy%20acquired%20re…

If you have more question don't hesitate to ask.

Janine

kcarn0927
Posts: 48

Husband had GK yesterday for what was supposed to be on a couple lesions turned out to be "19". Neurosurgeon said will go ahead and take care of the 19, but may have to think about WBRT down the road. The MRI in April only showed a couple (4-5)... could this be part of Tarceva-flare?

Meeting with pulmonologist to schedule a biopsy tomorrow to see what mutation he has. The plan before the GK was to get the biopsy and then determine treatment which they were strongly leaning towards Clovis trial.

My concern is that if the MRI back in April only showed 4-5 lesions and now 19, what must the CT of the lungs look like since April... more progression?

I am very worried about this between treatment phase; although he is still on Tarceva, not sure if this is doing anything at all though.

I'm worried this is going to go down south fast if they don't speed things up and get him on treatment... should we speak with oncologist today... should we wait until we see pulmonology?

JimC
Posts: 2753

K,

I'm sorry to hear of the additional brain mets. As the neurosurgeon said, usually with this number WBRT is performed in order to eradicate any mets or cancer cells to small to see on a scan.

It is not unusual for the brain to act as a "sanctuary site" for cancer cells when a targeted therapy such as Tarceva is successfully controlling the disease in the rest of the body, so I would not assume that the progression in the brain represent Tarceva flare and is replicated elsewhere. If your husband is not feeling significantly worse, that is an indication that the disease is not progressing generally, although a scan could confirm this. It's entirely possible that Tarceva is continuing to control his cancer except in the brain.

My thought would be that if you have concerns regarding cancer issues, it would be better to talk to your husband's oncologist.

JimC
Forum moderator

kcarn0927
Posts: 48

RE: LMC. We obtained the written report of the gamma knife MRI which reads "possible leptomeningeal dissemination of disease, probably progressed when compared with recent prior study". Before the gamma knife the Tumor Board all agreed that my husband did not have LMC so now we are back to square one with this. The oncologist said she still does not think he has this, but is ordering a spinal tap. She also said that 90% of reports read like this.

I am wondering if it would be prudent to request an MRI of my husband's full spine before he does the spinal tap since we hear that the spinal tap is very painful? He has not had a complete MRI of his spine, just sacral area and thoracic.

What is your opinion on this? BTW, he has no symptoms of LMC.

I appreciate your help in this matter?

catdander
Posts:

Unfortunately LMC is difficult to diagnose especially with just an MRI. Dr. West has this to say on the subject,
"Leptomeningeal carcinomatosis (LMC) is discussed all over the discussion boards here, and one conclusion the faculty feel is important is that it is extremely hard to diagnose, sometimes with a clinical picture that strongly suggests LMC but imaging and/or a lumbar puncture negative for cancer cells, and other times imaging being called suspicious for LMC in someone asymptomatic. Because it can be so very difficult to conclusively diagnose LMC even in someone with a picture very consistent with it, the only thing we can say is that anything is possible. Most of the medical oncologists on the faculty don’t take a reading of an MRI like your mothers as proof of LMC — sometimes the course follows what you’d expect for LMC with more time, but definitely not always." http://cancergrace.org/topic/maybe-it-is-not-leptomeningeal-carcinomato…

A second opinion on this would be a fine next step and since there are no symptoms it's difficult to move into invasive procedures without the most excellent of reasons.

Janine

kcarn0927
Posts: 48

To recap, my husband has progressed on Tarceva and is about to begin Clovis trial. Lumbar puncture was ruled out for LMC as the lumbar puncture came back negative. He begins Clovis trial on 6/22. He had to get baseline CT's and also an MRI of the brain before beginning the trial. He was treated on May 12th with Gamma Knife on 19 lesions. The baseline MRI done June 9th showed the 19 lesions + one more which was 2 mm. The neurologist-radiation doctor said he has "microscopic disease" and the baseline MRI showed stable disease/unchanged. She did say that normally an MRI after GK is not usually done until 8 weeks after gamma knife, but we had to get the baseline due to the Clovis trial and prove the mets were treated. She did say that the brain mets have been waxing and waning ever since he was diagnosed back in 2013.

My question...

1) What do you know about microscopic disease?
2) How long does it take to see results from gamma knife?
3) Does Clovis reach BBB?

Kate

JimC
Posts: 2753

Hi Kate,

When the doctor says that your husband has "microscopic disease" he is simply referring to the fact that cancer cells have entered the bloodstream and can show up elsewhere in his body. Since there is a history of brain mets and there are more than were initially seen and treated with Gamma Knife, it is clear that there are cancer cells in the brain, some of which have not combined to form lesions visible on an MRI (individual cancer cells cannot be detected on a scan). This is often referred to as "micrometastatic disease". Whole brain radiation is often favored in treating multiple brain mets because it treats the entire brain, including those individual cancer cells.

It can take weeks or even months to see the full effect of brain radiation, since radiation does not "melt away" the lesions like a laser beam in a sci-fi movie; rather, it disrupts the DNA of the cancer cells, making them unable to continue their uncontrolled growth, so they die off over time like normal cells.

Most drugs cross the blood brain barrier to a certain extent (including Tarceva), but radiation rather than normal doses of chemo or targeted therapy, is the preferred treatment for existing brain mets. As far as trial drugs such as the one in the Clovis trial, there just isn't enough evidence of how well it crosses the BBB. As Dr. West said last November in response to an inquiry regarding penetration of these new drugs into the BBB: "Unknown/unpublished/unreported, on all fronts. None of these approaches is being advertised as a treatment for disease in the CNS." - http://cancergrace.org/topic/blood-brain-barrier-penetration-on-egfr-mu…

JimC
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