Lung Cancer IV, brain metastasis - 1290675

Hi jc587,

Welcome to GRACE. I'm sorry to hear of your mom's diagnosis. I'm glad that she's doing well after addressing the effusion issues, as they can have such an impact on daily life.

It's true that Tarceva can cross the blood brain barrier and have some effect on brain metastases; most systemic therapy does cross the barrier to one extent or another. The problem is that the concentration of the drug which reaches those brain mets is often not sufficient to be effective. In fact, it is common for EGFR-positive lung canceer to first show progression in the brain, which becomes a "sanctuary site" for the cancer cells. As a result, the standard treatment for multiple brain mets is whole brain radiation.

It is true that WBRT can have side effects, some of which are more likely to appear over time. The problem with the "“immediate benefit vs delayed deterioration of quality of life" debate is that in many discussions the issue of significant neurological symptoms (and consequent reduction in quality of life) caused by progressing brain mets is not given sufficient consideration.

If the decision is made to forego or delay WBRT, it would be good to closely monitor symptoms and have fairly short interval follow-up scan.

I hope Tarceva is effective for your mom for a very long time.

JimC
Forum moderator

Hi jc587,

I think one month certainly qualifies as a short interval, but I also think that the absence of neurological symptoms might be considered as a factor in lengthening that interval. Typical symptoms of brain metastases include headaches, double vision, balance issues, focal weakness (to a specific body part rather than overall weakness), swallowing difficulty, incontinence/bowel issues.

As far as the timing of Tarceva and WBRT, at times there is a choice to be made between treating brain metastases and treating the disease elsewhere in the body. Most systemic treatments are not effective enough against progressing brain mets, and the growth/swelling of metastases in the brain, where space is limited and damage from lesions can be significant, often makes treatment of those brain mets a priority. On the other hand, if the brain mets are small and asymptomatic but disease elsewhere is significant and progressing rapidly, then systemic therapy may be favored. You haven't described the extent of your mom's cancer aside from the effusions, but it may be that her doctors would like to get the disease outside the central nervous system under control before tackling the brain mets.

A necessity of choosing between systemic therapy and WBRT is based on the problem of systemic therapy acting as a radiosensitizer, effectively increasing the radiation dosage. That's good for killing cancer cells, but it makes it harder to determine the effective radiation dosage, resulting in more damage to healthy cells and more side effects. As a result, systemic therapy is often held during radiation therapy, although there are exceptions made.

JimC
Forum moderator

Being a LC patient myself, IMHO I'd get the brain mets treated. Many onc now give Namenda to help with cognitive issues that may arise due to side effects. With that many mets already, they'll probably just keep progressing and taking up room in her brain. Untreated can affect her quality of life for the long term just as much as being treated. I'd take my chances with the WBR. She's not that old and she can live many years with LC these days. Wishing her all the best.
Take care, Judy

Just one point to add regarding the effect of Tarceva. Although a small percentage of patients can show dramatic improvement after just a few days or a week, it usually takes a bit longer to see efficacy. On the other hand, relief from symptoms such as cough and shortness of breath often show rapid improvement after thoracentesis and pericardial window procedures due to the lessened pressure when the fluid is drained.

The symptoms/side effects you describe do not appear to be neurological in nature, so at this point the brain metastases appear to be small enough to be asymptomatic. I wish we could point you to a decision that is clearly correct, but not only can GRACE not provide actual advice, I don't know that it could be said that either of the proposed treatment plans is unequivocally correct.

JimC
Forum moderator
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The early results on HA-WBRT do look promising, but as far as I can see it's only available in the trial setting, and the full results of RTOG 0933 have not yet been posted, according to clinicaltrials.gov - https://clinicaltrials.gov/ct2/show/NCT01227954?term=RTOG+0933&rank=1 The best information I've seen on that trial regimen is here: https://www.rtog.org/News/tabid/72/articleType/ArticleView/articleId/73…

With regard to the local trial you mention, it is at all not unusual for the trial to be a blind, randomized trial, especially when one of the arms utilizes a proven therapy, in this case traditional WBRT. Nor is it uncommon to hold systemic treatment such as Tarceva during the radiation, which is done to prevent clouding of the results due to varying degrees of radiosensitation.

Brain MRI is the preferred method for monitoring brain mets. New or worsening neurological symptoms may result in moving up the next scheduled MRI to check for progression. The GRACE faculty and moderators can't make specific recommendations regarding treatment or monitoring options; your mom's medical team would best be equipped to do so, having access to all of her medical information and clinical examinations.

I would probably make it a point to ask about a follow-up MRI for the brain mets, the possibility of WBRT and a consult with the radiation oncologist (the doctor who performs radiation procedures). I would leave specific questions about WBRT to the rad onc. You may also want to consider the possibility of getting a second opinion. Not only is that good in general, but when you are facing a major decision (WBRT now or later), it can be invaluable.

JimC
Forum moderator

Hi, new user bmj85 here. My 31-year-old son was diagnosed 4/13/17 with adenocarcinoma, stage iv. Tested positive for EGFR mutation Exon 19 and started Tarceva 150mg/day on 4/25. Moderate rash on face area and rather dramatic response / improvement in pulmonary function since then.

April 13 2017 Diagnosed Stage 4 Adeonocarcinoma lipoidal pattern
April 15 2017 Pericardial window procedure for pericardial fluid
April 25 2017 Started Tarceva after testing positive for EGFR mutation Exon 19
April 28 2017 MRI reveals 20+ brain metastases (BrMs) ranging from barely discernable to 7mm. Asymptomatic thus far with no swelling edema seen on MRI.
May 28/May 1 Consultation with several Radiation Oncologists led to recommendation of "standard treatment protocol of WBRT. Some difference in approach - 2 weeks total of 30 Gu vs 3 weeks total of 37.5 Gu plus Metamantine. Elected to pause WBRT for four weeks to see if Erlotinib can produce response in BrMs. Radiation Oncologists generally supportive of this while Medical Oncologists a bit more nervous.

My local medical providers have very little to no experience in this area. Trying to find out if anyone has experience with centers of excellence such as Duke, Vanderbilt, MD Anderson, etc. who would have better insights into balancing TKIs and possibly immunotherapy (my son tested positive for PDL1 expression as well) with WBRT timing.

This paper from last month was very insightful: https://www.ncbi.nlm.nih.gov/pubmed/28391420

Hi bmj85,

Welcome to Grace. I'm so sorry to know about your son's diagnosis. It sounds as if you've found the general understanding and approach to multiple brain mets w/EGFR mutation. The idea of pulse dosing, giving around 3 or 4 days worth of tarceva (or other TKI) in one dose every 3 or 4 days. The overall amount is the same but it's given in one heavy dose instead of the 3 or 4 normal doses. Many oncologists are finding this regimen helpful for cancer that is in the Cerebrospinal fluid (CSF) known as Leptomeningeal disease though I'm not aware of pulse dosing for brain mets.

A point of timing is also crucial. While your son isn't experiencing symptoms of the brain mets is a good time to let the tarceva have a chance to penetrate the so called blood brain barrier. After symptoms begin aggressive treatment, wbr is the go to treatment for symptom relief.

A 2nd opinion at a large teaching facility such as the ones you mentioned will have information on the most recent thought in this area. There are even some who mat provide telemedicine appointments. If your son lives far from a lung cancer specialist it's common practice to see a specialist at transition times (or with questions like yours) then treated by a local oncologist. Kind of a teaming up of resources.

I hope your son does well. Please keep us posted and don't hesitate to ask if you have more questions.
All best,
Janine

Janine: Thanks for the kind and helpful words. I'm so new to all of this and constantly feel behind the curve, with the stakes so high, this can be overwhelming.

I found this article today on pulsative erlotinib for both lepto and BrMets: https://www.ncbi.nlm.nih.gov/pubmed/28245967 I ended up paying $36 to read the whole article. Was there a better way to get to it?

You speak of a pulse dose / dense dose (are they the same thing) as if its ~ common knowledge, yet here in Knoxville TN I don't think its in their experience set. I'd like to reach out to the folks leading the charge in this area but still a newbie in figuring who that is and how to contact them. e.g. I called the office of one of the authors of this paper today and left a message with her nurse. If they work that way, would that be a possible use of a telemedicine approach? Would I ever expect my oncologist in Knoxville to contact the author and gain helpful insights?

Can you clarify your comment about timing? i.e. his brain mets are asymptomatic at present. Are you concurring with the strategy to see if Tarceva can get a response before resorting to WBRT? And reserve WBRT when you need to address symptoms of the BrMets?

Sorry I've I'm overflowing with questions.

Hi bmj85,

First, let me say that despite your doubts to the contrary, I think you're doing a terrific job of researching and making sense of all the information you've found.

What Janine was saying is that if the brain mets were symptomatic and/or clearly growing, you wouldn't want to delay the best-proven therapy, WBRT. Under the current circumstances, time is not as critical, so you may be able to afford to give erlotinib some time to treat those brain mets.

Other than subscribing to a range of medical journals, I don't know of any better (i.e., less expensive) ways to access these journal articles. During my wife's illness, I worked at a university with a medical school, so my internet access allowed me to view the full contents of such journals. I don't know if going to the library at such a university and using their net connection would give you the same access, but it might be worth a try.

Some oncologists regularly consult with colleagues at other institutions, so it's possible your mother's doctor will do so; it can't hurt to ask. Otherwise, I second Janine's suggestion of a second opinion at a major teaching hospital.

JimC
Forum moderator

I realize that this is a rather late response to the conversation which originated on 5/2/17, but I'd to like share my father's experience in hopes that this may be useful to others who are contemplating WBRT.
At the age of 77 in 2015, he was diagnosed with stage 4 EGFR+ exon 19 deletion NSCLC adenocarcinoma with liver, bone, and brain metastases. He had > 20 brain lesions ranging from few mm up to 10 mm in size, but he was asymptomatic from them. His first oncologist recommended WBRT, which my father was reluctant to do because of concerns about late cognitive effects after radiation, especially in older patients. We requested a second opinion from a lung cancer specialist at a major teaching hospital. Decision was made to defer WBRT in favor of Tarceva. A short-interval brain MRI of 4 weeks was done, and there was a dramatic response after just 4 weeks of Tarceva. All lesions had decreased in size and enhancement, and some were no longer visible on MRI. My father subsequently had consultations with both a neuro-oncologist (who is the author of the aforementioned paper https://www.ncbi.nlm.nih.gov/pubmed/28391420) as well as a neurosurgeon, and all seem to be in agreement that WBRT would be the last resort, at least in my father's case. There are probably many factors that affect the decision to proceed with WBRT, but I wanted to share my father's story since he had a positive response to TKIs without the need for brain radiation.

To Judy, bmj85's son, and jc587's mother, I wish all of you the best, and hope that there is a very good response to treatment for a long time.

Hope

Response to Hope and JC from BMJ85:

Thanks for the insights! My son received a followup MRI after 4 weeks on Tarceva - standard 150mg/day dosage - having postponed the "standard" treatment of WBRT recommended for his 20+ BMets ranging from barely perceptible to 7mm. Wonderful news! All of the BMets are gone with the exception of the formerly 7mm one, which is now reduced by 75%. Wow, you can imagine how thankful we were not to immediately have gone the WBRT route, despite that being the initial suggestion of his general oncologist and two of the radiation oncologists we met with.

I did exchange brief emails with the two authors of the paper you mentioned, Hope, and informed them of the outcome of the "wait and watch" approach, which seemed especially desirable for a 31-year-old. I gathered from your post that you met with them / her at Stanford? Not sure how far that is from your home and if/how you plan to integrate care going forward with perhaps a local general oncologist and one or more specialists at a different institution more distant. Still trying to figure out how to fashion a "team" with my son's physicians.

Not that I want to borrow worries from tomorrow, but was there a discussion of what else to consider should the beneficial effect of the Tarceva on the BMets before re-considering WBRT? For example, my son met with an oncologist in Nashville recently who indicated that he might consider adding Avastin to the Tarceva or seing if he could get Tagrisso approved for him (with or without T790 mutation evident) as that appears to cross the blood/brain barrier more readily.

Finally, JC curious about the use of Allegra and the Elomet cream - my son has a fair amount of the rash on his face and neck and is growing a handsome beard which covers quite a bit. I hadn't heard about the allegra / Elomet - is that considered a common approach? say vs Doxycyline such as is often given to acne patients?

Thanks for the encouragement!

BMJ85 in T

Dear JC and BMJ85,

Glad to hear that your loved ones are doing well on Tarceva.
BMJ85: That's wonderful news that your son's brain metastases have responded so well to Tarceva!

JC:
It sounds like your has mother has a PET-CT scan scheduled as part of the follow up?
The type of imaging may vary by institution, but my father's specialists prefer to use MRI to monitor the brain mets.

My father responded to Tarceva for 9 months. At one point, 1 or 2 of the brain lesions increased slightly by 1-2 mm (oligoprogression), so there was discussion about possible stereotactic radiosurgery (Cyberknife). However, my father again declined brain radiation and decided to stay the course. After 9 months on Tarceva, he developed disease progression in the liver. Therapy was changed to Tagrisso (osimertinib) after he tested positive for the T790M mutation. Tagrisso has worked well for his systemic disease and brain mets, although he has had to take treatment breaks due to a rare but serious side effect, pneumonitis, which occurs in ~3% of patients receiving Tagrisso, and less often with Tarceva.

BMJ85:
Shortly after my father's diagnosis, we transferred his care to Stanford. He is fortunate to have an excellent team of physicians managing his treatment. Since you live near Nashville, has your son seen or will he be consulting with Dr. Leora Horn at Vanderbilt? I believe Dr. Horn is one of GRACE's faculty members.

Avastin or bevacizumab was mentioned as well in my father's case, but his thoracic oncologist was concerned about the possible risk of hemorrhage, as some of the brain metastases had signs of bleeding at the time of diagnosis. While doing some research recently, I came across this article on Avastin.
http://clincancerres.aacrjournals.org/content/21/8/1896.short.

Regarding the skin issues, my father also developed rash/acne after he started taking Tarceva. The rash improved in 2 weeks after treatment with Doxycycline and hydrocortisone.

Best wishes,
Hope