Lung cancer inconclusive biopsy - 1249490

Hello Costica,
Welcome to Grace. I'm so sorry your mom is in this position. It isn't unusual to develop lung cancer without a smoking history. Unfortunately it also isn't unusual to not know that.

Again, it isn't unusual to have a non diagnostic biopsy. My husband has had 4. A PET scan would give more information. It will tell what kind of metabolic activity is happening inside the tumor in question. If it isn't active it isn't growing hence not worrisome for causing trouble and probably not cancer and could be watched. If it is active it could be inflammation or infection or cancer and she could try another biopsy. Even if it appears very much like cancer it's possible that it isn't cancer. Until there is tissue in hand there is no definitive dx of cancer.

Surgery would not be out of the question if it is thought that there are no other areas of concern (including MRI of brain) and her health was such that it made surgery feasible for curative intent.

These are all big questions that need to be addressed by her doctors.

I think a good way to help your mom is to learn as much about the dx process as possible, we have that information. Find out who to contact to discuss these options. Your mom may be able to find an advocate for her in the system in Romania. Or you may need to find that out.

More information to have would be the size, has it been watched if so, has it grown? What are the doctors there suggesting.

Below are 3 links to very good discussions about dx

http://cancergrace.org/lung/2011/12/07/yankelevitz-lung-nodules-podcast/
http://cancergrace.org/lung/2010/05/12/general-work-up-and-staging-of-l…
http://cancergrace.org/lung/topic/differential-diagnosis-for-lung-disea…

I hope this is helpful to get you started.
Janine
forum moderator

Yes, really the key is to get tissue that can make the diagnosis, however that can be done. That may be a bronchoscopy, or a CT-guided needle biopsy, but sometimes even a lung surgery is done to get tissue. The links Janine provided offer a good outline of the key issues.

All treatment plans follow the diagnosis that is made by the biopsy.

Good luck.

-Dr. West

Costica, I'm so sorry you are so far away from your mom. It know it's very difficult to put it mildly. Stage 4 lung cancer isn't curable you're right about that but it is very treatable. Many members on this forum are living their lives in stage 4 or they have loved ones they care for who are stage 4. We work daily not to focus on cancer meaning "death" but earnestly work to focus on life. There are lots of things to hope for not all of which include living till we are 80. A dear Grace friend used to remind us we can always hope tomorrow will be a better day. I understand though that today is shocking. I think as you and your mom move forward the shock will wear off or you will learn to live with it, I'm not sure which, but she will move forward with treatment and symptom management and we can help with your understanding of that. And maybe we all we learn something (because we all have difficulty) about living with less depression.

What are the doctors suggesting? Do you have any specific questions, if so let us know. Be sure to use our library and search engine. Some browsers require you to log off before the search works. But it is worth it.

I probably overwhelm people with all the links I suggest reading but here are a few.
http://cancergrace.org/lung/2010/04/16/introduction-to-first-line-thera…

In deciding what treatment to use most nsclc tissue is being tested for markers 2 of which EGFR and ALK have approved drugs to use against. Your mom's liver biopsy tissue can prob be used. This is a primer on the subject. http://cancergrace.org/lung/2010/10/10/overview-of-molecular-markers-in…

Just an FYI, There are some very promising studies being done on drugs in Romania. This is a search result of trials being offered in Romania from clinicaltrials.gov http://www.clinicaltrials.gov/ct2/results?term=nsclc&recr=Open&cntry1=E…

Janine
forum moderator

The biopsy shows a lung cancer that has spread to the liver. This confirms both the diagnosis and stage, so from here it is possible to move forward with a treatment plan. We'd be happy to try to comment on any specific questions you might have after learning what the doctors are suggesting.

Good luck.

-Dr. West

Hi Costica. I am sorry about your mother and the distance between you. It makes it harder when you are not on the spot - I think people actually worry more if they're in another country and can't see the person with cancer close up.
The liver is a common place for lung cancer to spread to. It's true that someone whose cancer has spread to the liver is ultimately going to die, but that doesn't need to be imminent. I have seen people on GRACE with liver metastases live active lives for longer than you would expect.
I thought the link Janine provided was useful, as it shows that clinical trials aren't always in Bucharest but also in TImisoara and Sibiu, for instance (you need to click on the tab for "Geographical locations" to see where the clinical trials are being conducted).
Very best to you and your mother.

In the US, the general recommendation now is to do EGFR mutation and ALK rearrangement testing for all patients with a non-squamous advanced NSCLC, if there is enough tissue available to do such testing. If there isn't sufficient tissue available, it's certainly a debatable point whether to pursue an extra biopsy just to do molecular marker testing -- many oncologists would only recommend additional testing if the patient has a reasonably high probability of having one of these mutations, which tend to be more commonly seen in those with a limited or no smoking history, an adenocarcinoma, and better differentiated cancers. However, this isn't to say that other people can't have one of these mutations, so it's still reasonable to check for a mutation in a pretty broad population.

I'm sorry for all she and your whole family are going through.

-Dr. West

Of course. Everyone here will understand that.
But the test is nothing like as expensive as the treatment. And if your mother did have the EGFR mutation, she could perhaps go on one of the clinical trials Janine linked to, where she would get Tarceva (similar to Iressa) for free. I realise all this depends on her situation and where she lives, but if you can find a sympathetic doctor who would help by ordering the test, it might be worth a try.
Bevacizumab is also known as Avastin, just in case that helps. It is quite a common chemotherapy drug that cuts off the blood supply to the cancer.

I suspect that they didn't get enough information from the liver biopsy... otherwise, you can do all of the same molecular testing from a good liver biopsy that you can do from a biopsy directly from lung tissue.

The plan that is outlined sounds reasonable. EGFR testing is the more readily available test, and ALK testing can be more challenging. Besides being a relatively newly identified molecular marker, the population with an ALK rearrangement is smaller -- about 3-4% of people with NSCLC.

I can't speak to how to obtain treatments outside of the health care system in Romania -- I know there are significant differences from place to place, and I'm sure it can be challenging if treatments aren't regularly available.

-Dr. West

I hope your mom does well with her treatments. Be sure to tell her to do exactly what the doctors and nurses say about taking her nausea meds on time.

Yes, to test for EGFR the tissue has to be sent to a special lab and takes a week or 2. If you are interested let me point back to my post of Nov. 2,
"In deciding what treatment to use most nsclc tissue is being tested for markers 2 of which EGFR and ALK have approved drugs to use against. Your mom’s liver biopsy tissue can prob be used. This is a primer on the subject. http://cancergrace.org/lung/2010/10/10/overview-of-molecular-markers-in… "

Yes, it's somewhat more encouraging to see a better differentiated cancer, but that's just one variable among many. The most important variable is how responsive the cancer is to treatment and how well a person tolerates the therapy. For those variables, you just need to start treatment and see how things go.

Good luck.

-Dr. West

Just an fyi if you haven't already thought about it. If your mom inters into a trial like you noted above the trial would pay for the drugs, who pays and who can afford such costs is often a problem with new drugs.

You don't need to worry that the tissue will "go bad" in the time before testing for EGFR mutations. As long as there's enough tumor tissue to use for testing, it's preserved in paraffin wax and should be fine whether testing is done right after the biopsy, a month later, or 3 years later.

-Dr. West

There is a pretty clear consensus in the lung cancer community that an EGFR tyrosine kinase inhibitor like Iressa (gefitinib) or Tarceva (erlotinib) is quite likely to be more effective than first line chemo in someone who has an EGFR mutation. However, that's in a minority of patients, and those without an EGFR mutation are generally better served by receiving standard chemotherapy as their first line treatment. In the US, the recommendation is to do EGFR mutation testing for patients with an advanced non-squamous NSCLC, but if we don't know someone has an EGFR mutation, chemotherapy is the generally preferred treatment approach. There is no evidence that patients with an EGFR mutation do worse by getting an EGFR inhibitor like Tarceva as second line treatment after chemo, but those without an EGFR mutation do worse if they get first line Tarceva instead of chemo.

-Dr. West

I understand your dilemma and I am not a doctor but I am sure a doctor here will confirm that one should never mix drugs except under a doctor's supervision.
I thought what Dr West said was reassuring for your mother:
"There is no evidence that patients with an EGFR mutation do worse by getting an EGFR inhibitor like Tarceva as second line treatment after chemo, but those without an EGFR mutation do worse if they get first line Tarceva instead of chemo."
On the other hand, I also understand why your mother might not want to have chemotherapy. Does she not own her biopsy material by law?
My guess is that there is someone somewhere in Romania who would order EGFR testing for you. What Janine and I are suggesting is that you might wish to contact one of the clinical trial investigators in a trial involving Tarceva or Iressa. This could be done now or after she has finished her chemotherapy. Then the test would need to be done as part of the trial. Best of luck.

There are studies that show that it is feasible to give chemotherapy together with Iressa or Tarceva, and patients with an EGFR mutation generally do well with that. However, there is no evidence that the combination is better than doing these approaches sequentially. I certainly appreciate your predicament, but we can't make medical recommendations that are based on the social issues in Romania.

-Dr. West

I don't think it necessarily means worse results even if your mother is EGFR positive. Quoting Dr West again (from earlier in your thread):
"There is no evidence that patients with an EGFR mutation do worse by getting an EGFR inhibitor like Tarceva as second line treatment after chemo, but those without an EGFR mutation do worse if they get first line Tarceva instead of chemo."
How is your mother finding the carboplatin/paclitaxel combination so far?
I've never seen anything to say that avastin doesn't work in women. But Dr West recently wrote a post about a trial which looked at adding avastin to carbo/paclitaxel. The researchers concluded that this triple combination did not help prolong life for people over 70. So I think it might be an issue of age rather than gender. Here's his post:
http://cancergrace.org/lung/2012/04/26/zhu-jama-avastin/
I'm sure if you were with your mother you would not feel quite so desolate. It is very hard to be the one who is far away.

I apologise if I am wrong. I am sure Dr West will be knowledgeable about the issue of Avastin and gender - if you search the site you'll see that he was writing about this in 2006, when the NEJM article you cited was published.
I'm sorry it is so hard. But you have your mother now. The future will take care of itself.

Certain Spring is right. On all counts. The info on avastin still stands. I'm very sorry your mom is so sick. We are all in this situation in some way. And speaking as a person who has lived and worried about her husband for the past 3 years I can safely say as difficult as it is for me it is more difficult for the person with cancer than the person who loves them.
this may be helpful, http://cancergrace.org/lung/2012/04/26/zhu-jama-avastin/#more-9468
I hope you continue your cancer education by using our search engine, cancer info links and FAQs.

The question of Avastin (bevacizumab) in women is based on a subset analysis of women and men separately from the ECOG 4599 trial, which happened to show that the significant benefit wasn't seen in women but was seen in men. This is widely considered to be at least a very questionable conclusion, very possibly (probably?) just a random finding that isn't real at all. There is little or no biologically plausible explanation for Avastin working in men but not women, except perhaps for the possibility that more women benefited from enough subsequent therapies in second line and later that the beneficial effect in women washed out with follow up. In fact, since women did get a very clear improvement in response rate and progression-free survival but not overall survival from Avastin, that does appear to be the only explanation -- they did benefit when they were on it, but it didn't make enough of a difference to affect overall survival in the long run.

And that would be my main conclusion: Avastin isn't so impressively valuable that it is something incredibly critical in the treatment plan. If it were that good, it would have been shown to improve overall survival in some other trials after ECOG 4599, but it has failed to do so. I wouldn't want to tell you what to do, but I personally wouldn't consider it a remotely good use of the money it would cost to pay for out of pocket.

If the medical care in Romania is completely unacceptable, do you have the means to move her out of there? I think that might be a better use of the money that you'd otherwise be spending on Avastin.

-Dr. West

Oh that is great news. How did you get the test done, after the opposition from her doctors?
Tarceva and Iressa are similar - Iressa is widely used in Asia, whereas Tarceva is the drug they use in the US. Here in the UK, both are used. They belong to a category of drugs called TKIs - tyrosine kinase inhibitors. One of the GRACE doctors will be able to explain the differences between Iressa (gefitinib) and Tarceva (erlotinib), but from my understanding either drug could be helpful for your mother.
Would she consider one of the clinical trials we mentioned earlier, in which case she could get it free while staying in Romania?

This quote to you from Dr. West is from Nov 12, " ...but if we don’t know someone has an EGFR mutation, chemotherapy is the generally preferred treatment approach. There is no evidence that patients with an EGFR mutation do worse by getting an EGFR inhibitor like Tarceva as second line treatment after chemo,..."

Once a treatment is started a person usually stays with that line of treatment. And as quoted above there is no evidence that a person does any less well having EGFR inhibitor 2nd line instead of first. Regardless your mom will most likely receive both at some point.

As for the "horrors" of chemo, most people find chemo quite doable. There are meds that mitigate most of the side effects that are unpleasant, such as nausea and vomiting. Make sure she keeps the cancer center apprised of side effects and take their directions such a timing of nausea pills verbatim it makes all the difference. She will experience fatigue most likely. If her blood counts drop too low the doctors will allow for that but they usually raise again before the next treatment.

Hoping for the best,
Janine
forum moderator

As Janine noted, there's really no evidence that people with an EGFR mutation who get an EGFR tyrosine kinase inhibitor as second line therapy or maintenance therapy do worse than those who get it earlier. There is certainly no established, "best" way to go, but I think many and perhaps most lung cancer specialists would favor sticking with chemo long enough to clarify its value before rushing into an EGFR inhibitor, as long as we can be confident that the EGFR inhibitor will be given in a timely way when it's needed.

Please also note that it's hard for me to understand what doing EGFR immunohistochemistry testing is going to add if someone has a positive test for an activating EGFR mutation.

-Dr. West

Well, if she moves to Tarceva or Iressa for second-line, her hair may grow back. I lost all my hair from radiotherapy and it came back. I still think the EGFR result is excellent news.

Typically, we repeat scans after 2-3 cycles of chemo. In the US, it's more commonly two cycles, and in many other parts of the world, particularly Europe, going three cycles between scans is quite common.

You're right that serum tumor markers like CEA are not considered to be a reliable indicator of the effect of treatment.

-Dr. West

My husband has gotten scans consistently every 3 months throughout treatment.

This isn't to keep you from asking questions on the forum but to add to your knowledge base,
I want to encourage you to use our FAQ and search engine. The link below is a post that explains treatment assessment with several options for further reading in green live links at the end of the post.

http://cancergrace.org/cancer-101/2010/09/16/cancer-101-faq-assessment-…

Best for your mom,
Janine

Grace can't recommend treatments but can give information. What is it you don't understand about an article. If you highlight and copy the portion you're not sure about and add you questions we will be able to help you get it figured out.

Janine

The concern isn't so much that they interfere with the chemo, but rather that nothing we know of is especially effective against this except stopping the offending agent causing the neuropathy.

-Dr. West

That mutation in exon 21 is a good one to have - it is one of the most common, and it makes your mother a good candidate for Tarceva. The various mutations are explained by Dr Pennell here:
http://cancergrace.org/lung/2009/03/20/np-egfr-muts-demystified/
and Dr West writes here about exon 19 and 21 deletions:
http://cancergrace.org/lung/2011/01/15/are-there-significant-difference…
I think you are doing very well in negotiating the healthcare system, with all its drawbacks!
It might help the doctors to be able to see a forum signature, as described here:
http://cancergrace.org/topic/grace-tips-set-your-forum-signature

You've done brilliantly for your mother. I wish someone had done for me what you have done for her.

I completely agree that if she's getting the best treatment (with appropriate minimization of very debatable small points like cisplatin or carboplatin, or whether the drug the platinum is paired with is a taxane or Alimta or gemcitabine, etc.), there isn't a clear incentive to travel extensively. That said, it's good for you to have a solid understanding of the basic approaches in order to help navigate the system and avoid treatments, such as surgery in advanced lung cancer, that would provide no clear benefit but might be recommended for questionable reasons.

It isn't typical to do MRI scans looking for bone metastases just for surveillance. We'd sometimes do an MRI if someone is describing new back or hip pain, for instance, and has a history of a cancer that could very possibly spread to the bone, but it isn't standard to just do MRI scans to survey for metastases in someone without pain or other localizing signs.

The exon 21 mutation is, as you've now learned, an activating mutation associated with a good probability of a response to an EGFR tyrosine kinase inhibitor like Tarceva (erlotinib) or Iressa (gefitinib). There's certainly an incentive to ensure that it's given, but it would be very reasonable to defer that until after first line treatment has been completed, particularly if there are indicators that she's doing better.

Good luck.

-Dr. West

Yes, it looks like that trial is meant to be evaluating patients receiving Tarceva (erlotinib) as a first line therapy.

Outside of a clinical trial, you don't necessarily need to wait to start Tarceva. Usually we make a decision about the next treatment after someone is already a few weeks out from the last chemo and would potentially be due for more right at the time of a decision to make a change, so I'd say it's most typical that people haven't just received chemo in the last few days before someone starts an EGFR inhibitor.

Good luck.

-Dr. West