ALK squamous?

Portal Forums Lung/Thoracic Cancer ALK Inhibitors ALK squamous?

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December 1, 2016 at 1:02 am  #1289308    

me53

I was told my lung cancer is a mix of adeno and squamous, 50/50 in one lobe and 20/80 in the other. Both tumors tested ALK+, but neither had the adeno and squamous separated out for testing. Is it clear BOTH types of cancer cells are ALK+ (test says 83% response rate)? should I insist on the cell types being separated and tested separately? (the mostly squamous tumor is considered a “metastasis” from the mixed one).

December 1, 2016 at 12:50 pm  #1289315    
catdander forum moderator
catdander forum moderator

Hi me53,

The ratios you’ve given are taken from the biopsy tissue which isn’t necessarily indicative of the whole tumor. genetic testing requires relatively large amount of tissue and so taking a sample large enough to separate is probably not realistic. It’s true that changes in cell type have been seen in people who have been treated with TKIs. Most often and especially when the person is healthy enough continued treatment with TKIs is the treatment of choice until it’s proven not the keep the cancer at bay before moving on to more traditional chemotherapy.
Another treatment option that is gaining momentum after several years of clinical research is to give local treatment (such as radiation) to those who have only one or 3 areas of progression on a TKI then returning to the tki. It even has a new term, oligoprogression. More on that here, the first link is the most recent discussion though more info can be found in older links. http://cancergrace.org/search-results?q=oligprogression

I hope you do very well moving forward.
Janine

December 1, 2016 at 8:46 pm  #1289321    

me53

The ratios I gave were not from biopsy tissue, they were from whole tumors (I had a pneumonectomy). I also was never treated with a TKI, I just had surgery, but there were microscopic cancer cells in a mediastinal lymph node, so I have a high (91%) chance of metastasis. My original question still concerns me, though.

December 2, 2016 at 2:59 pm  #1289328    
catdander forum moderator
catdander forum moderator

me53,

Sorry for the delay. It’s not clear that both types of cells have the ALK rearrangement. We can’t tell you what you should do and in this case it would be an unusual request that may not even be doable. Perhaps question the labs who perform the test you want.

All best,
Janine

December 2, 2016 at 8:03 pm  #1289330    

me53

That’s really my question – is it unusual? The reading I had done seemed to say that it was routine for the squamous and adeno cells to be separated and tested separately, I thought (I think it was at least supposedly routine for them to be broken apart). I wanted to confirm that with a dr. on this site — is it routine, in a mixed cancer cell setting, to have the cells separated and the adeno and squamous separately tested for ALK? Or is that an unusual request. I don’t see why it would be undoable. I wanted to get a sense of what is the norm and possible, before pushing the lab. That’s why I posted here first : )

December 2, 2016 at 9:31 pm  #1289331    
catdander forum moderator
catdander forum moderator

I’ll put in a request for comment in the morning.

December 2, 2016 at 9:44 pm  #1289332    
Dr West
Dr West

Janine’s right that the biopsy doesn’t represent the whole tumor, and we would presume it is nearly certain that the squamous component isn’t ALK-positive. Frankly, even if it was all adenocarcinoma, that doesn’t mean that all of the cells are ALK-positive.

It is not usual to seek testing for both components — in fact, I’ve never heard of that being requested, and it may just be that the lab wants to double the charges. It wouldn’t likely change management, since an ALK inhibitor would be appropriate regardless.

You could never realistically test every cell subtype of a person’s cancer, because a biopsy is only a small sample of the big picture.

Good luck.

-Dr. West

December 3, 2016 at 12:21 am  #1289333    

me53

Thank you. I guess my concern is that if a tumor is 80% squamous, and if the squamous is not ALK+, then a similar metastasis would not respond sufficiently if all that is given targets ALK – only a portion of the cancer would be being treated (I was diagnosed with adenosquamous, which is rare-ish; other opinion very high grade MEC). I worry re losing time if metastasis occurs… Thank you for responding.

December 3, 2016 at 4:56 pm  #1289334    
catdander forum moderator
catdander forum moderator

It’s not clear and therefore difficult to guess what’s behind your questioning. If you’re asking because you’re thinking about having adjuvant treatment (systemic treatment post surgery for curative intent) chemotherapy is still the standard of care. For non curative treatment to prolong life ALK + patients would be given TKI before chemo no matter what histology. If you’re considered metastatic non curable there really wouldn’t be a rush to treat if there’s very little tumor burden; you want all treatment options to last as long as possible.
Hope this helps,
Janine

December 3, 2016 at 5:06 pm  #1289335    

cards7up

And you wouldn’t use a TKI unless you’re stage IV and it doesn’t sound like you are since you had surgery. If you were to have a recurrence in the future, they would re-biopsy and re-test for mutations depending on the type. And as Janine stated, if you do adjuvant treatment, it will most likely be chemo and/ or radiation.
Take care, Judy


Stage IIIA adeno, dx 7/2010. SRS then chemo carbo/alimta 4x. NED as of 10/2011.
Local recurrence, surgery to remove LRL 8/29/13. 5.2cm involved pleura. Chemo carbo/alimta x3. NED

December 3, 2016 at 10:01 pm  #1289336    

me53

Yes, I want to know information BEFORE I am possibly ill and in less of a state to understand and research and decide re it. My concern is a metastasis that is not easily biopsied (due to location), or one like what I already have. B/c my lower tumor was 80% squamous, and Dr. West wrote it can be assumed those cells are not ALK+, then wouldn’t such a tumor still advance if ALK+ meds were all one took? You raise another point, Janine, which is the limited use of these first line drugs (as Dr. West said, such drugs would be used first). I agree, I would want to “save” them until absolutely needed, but most studies show early (CT) metastasis when treated people live longer then “waiting for symptoms” treatment, and if a portion is squamous and the tumor grows, I could suffer when I’ve let it grow hoarding the alk drug (rightly so). So wouldn’t a squamous or general chemo be done? My dr. didn’t think was a point, assumes alk will drive and cure. But he suggested pemetrexed for adjuvant treatment, 2d opinion dr. said due to squamous he would use another (both w/a platinum); I let it go since risk/benefit not worth it, but putting all eggs in alk seems maybe misguided?? I would like to understand the situation as it stands while I am still pre-metastasis, and it is frustrating! Imagine how much more so if I am dealing with reality of diagnosis and possibly symptoms on top of it all! Thanks for reaching out and caring to do this board!!

December 4, 2016 at 7:34 am  #1289337    
catdander forum moderator
catdander forum moderator

Thanks for explaining your situation. We understand your need to know and with the seemingly infinite amount of info needed to make good decisions it’s more important than ever to be a part of decision making.

I have a question. Are you going to be treated for cure? If so the options are very different from treating metastatic nsclc. If you have 2 doctors from 2 different onc groups who want to do adjuvant treatment that means you have 2 opinions that have suggested you can still be cured. That is very different from treatment for mets/stage IV disease. If you’re treated and cured you would finish adjuvant treatment at that point (platinum doublet with or without radiation) and be watched with scans. That would be the end of treatment. I agree a non alimta partner drug would be more reasonable since there is squamous.

If there are clearly mets and cure isn’t an option prognosis changes from cure to treatment only. In that case I’m not sure that sooner treatment is better than waiting. You may be speaking of the studies of maintenance treatment (treatment starting directly after first line treatment of 4-6 cycles of platinum doublet). Today many oncs think that if you watch closely through onc visits and scans (usually every 3 months) you will catch the cancer soon enough to treat effectively. Dr. Pennell and West have stated that the studies probably were one sided in that those who didn’t do well without maintenance treatment were also not watched closely. If 1st line knocks back nsclc significantly it’s believed giving a break until the cancer begins to grow again is not only feasible but practical for giving the patient a break and time to recoup before the next onslot of treatment. In your case you have an actionable mutation and with ALK treatment might give you years of life before you even see an IV infusion type treatment. So yes it would be absolutely # 1 first choice of treatment in the case of metastatic nsclc.

Hope this helps,
Janin

December 4, 2016 at 7:04 pm  #1289345    

me53

Thank you for your reply. Yes, as I wrote, I have not metastasized, had surgery to remove my lung, and decided against adjuvant therapy because the benefit (5-6% chance of cure) wasn’t worth the risks (1% chance of death, 10-20% chance of lifelong disabling and QOL side effects (neuropathy, deafness…) and some 80% chance of ruining QOL in what is still, even with treatment, 85% likely to be my last year or so of full health due to fatigue, nausea…). The first onc. pushed towards the decision I made, the second for chemo but w/illogical reasoning (“the side effects of cancer are worse than the side effects of chemo” – which is true, but doesn’t address the fact that chemo for lung has such a low response rate and the reality of the side effects and experience). If I am cured it will have been from the surgery, and my body/luck not allowing any remaining cells to thrive. It is a 9% chance. At present, radiation is only found to lower local recurrence, but has no effect on overall survival as most met. is distant, and also has serious QOL and health side effects (death, damage to remaining lung, etc), so not doing that was a no brainer for me. I am concerned with the 91% likelihood of met. and wanting to evaluate things while I am still well. I can’t find the study/ies now, but they definitely said people (esp’y with brain met) who are found on scan live some 3-4 months longer than those found on symptoms, which implies earlier treatment helped. First hope, of course, is early detection and surgery possible. But if it’s not, the question of whether to do a chemo before ALK drug due to its short-livedness and lack of symptoms comes to mind — but apparently the response rate to regular chemo is so much lower, I guess they don’t want to bother. Good news re the breaks and returns to ALK drug you wrote, although I thought I’d read that the body can figure out how to endrun it in the interval sometimes.

December 4, 2016 at 8:08 pm  #1289346    
JimC Forum Moderator
JimC Forum Moderator

I will just add a few thoughts to this discussion. I think it’s good to have a clear understanding of the difference in prognosis between Stage IV lung cancer and earlier stage cancers. With stage IV, there are metastases visible on a scan; at lower stages they are not. But in those lower stages scans cannot tell us whether cancer cells have already spread beyond the tumor location into the bloodstream. If they have, the cancer is stage IV even if we don’t realize that it is. The small increase in cure rates for stage III lung cancer attributed to adjuvant treatment is due to the ability of that adjuvant therapy to eliminate circulating cancer cells before they are able to form metastases. The percentage increase in long-term survival is small because chemotherapy usually does not successfully kill all remaining cancer cells, although in those 5-6% of cases it does.

I think the downside of systemic adjuvant chemotherapy can be overstated. Many patients tolerate it quite well, and even if it does not lead to a cure there can be gains in both quantity and quality of life.

Finally, each patient is different and it cannot be assumed that an individual patient diagnosed when already symptomatic will fare worse than a patient whose cancer is found only through a scan, aside from those patients for whom scans reveal a very early stage cancer. As an example, my late wife was diagnosed with stage IV lung cancer after developing a worsening cough, and during her workup her pleural effusion caused her shortness of breath and chest pain. Yet as a result of treatment, she survived three years and four months after diagnosis, well beyond the 10-12 month prognosis for stage IV lung cancer patients. The statistics can only tell so much as far as an individual is concerned.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

December 6, 2016 at 10:20 am  #1289356    

me53

I just want to be clear on a point you made, Jim – you wrote that stage III, if cancer cells are in lymph/blood, = stage IV, just time, with only cure chemo. But my understanding is that you CAN have some cancer cells in blood/lymph and they might die, not take root, not grow, be attacked by body and no metastasis will occur – that is part of the 9% cure (eg, 9% is for cancer cells in lymph node not visible on scan/not bulky; those with bulky nodes have a 7% cure rate) – all of which is more than chemo. Also, stage IV has a higher 5 year survival rate now, largely due to so many people in that group and it encompasses cancers of varying aggressivity (or just numbers – IIIb in study MUCH lower # participants than IV). Of course this question is important, and certainly the more cancer cells left, the higher chance of met. (I read that thousands of cells is not uncommon, with most dying)

December 6, 2016 at 5:29 pm  #1289365    
JimC Forum Moderator
JimC Forum Moderator

The unfortunate truth is that we don’t have a thorough understanding of the process of metastasis, or the specific effects of adjuvant therapy. What is known is that in clinical trials in which half of the patients do not receive adjuvant chemotherapy while the other half do, the long term survival of the chemotherapy group is 5-10% higher. These trials are large enough for clinicians to comfortable conclude that it is the addition of chemotherapy that produces the better survival rates. Having insufficient numbers of remaining cancer cells after surgery or the ability of the body to attack those remaining cells should statistically even out.

But the specifics of that successful therapy are not clear. We don’t know why some cancers recur, while others don’t, or where those remaining cells are/were – in the lungs, confined to the chest, or in the bloodstream – but the additional patients cured after receiving adjuvant chemo almost certainly owe that success to that therapy. My example of an earlier-stage cancer with no visible metastases but individual circulating cancer cells was meant to highlight the gaps in our knowledge. If we knew with some certainty that there are cancer cells in the bloodstream, adjuvant chemo would be easily recommended, absent other limiting factors such as significant comorbidities. Though we don’t know if such therapy will be completely successful, since we see stage IV patients who have been essentially cured, we know that in some cases it can eliminate all remaining cancer cells.

I wish it were a more clear-cut decision process, but it’s not. All we can do is work with the data we have.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

December 6, 2016 at 5:38 pm  #1289366    
JimC Forum Moderator
JimC Forum Moderator

I neglected to add this link to Dr. West’s post on Adjuvant chemotherapy: http://cancergrace.org/lung/2010/05/17/systemic-therapy-for-resected-nsclc-ref-lib/

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

December 6, 2016 at 9:41 pm  #1289369    

me53

Thanks. I understand the fact that chemo adds 5% or so to survival; what I meant was the 9% survival of stageIIIB with nonbulky nodes seems to indicate that even with the likelihood of some cancer cells still in the body after surgery, some of those people do not metastasize, and simply having cancer cells in the blood or lymph, while likely to lead to met, may not — many cells die in that harsh environment, or in their new one — I was trying to confirm that, and say I don’t think, even w/cells in the lymph or blood, one is “stage IV waiting to happen.”

As to chemo, there are reasons not to do it having to do with the numbers — you have a higher chance of having a permanent disabling condition like neuropathy or deafness from it then you do a cure from it, and the greatest probability (94%) is that you will have no benefit from it(I am speaking of chemo before met, as a possible cure). Coupling that with the 1% chance of death from infection and the substantial chance of fatigue, nausea and other factors that decrease QOL for a few months or more, make it something someone needs to decide their priorities and comfort level — it definitely shouldn’t be automatically done (and the fatigue, brain fog… can worsen as time progresses, even after the chemo is over). Out of 100 people taking chemo for cure, 1 will die from it, 6 will live who won’t, and 10-20 will have some form of permanent disability (however long they live), and 70 or so will feel sick during it to some extent, some significantly. 94 of the 100 will have gone through the experience without a cure or any improvement.

December 6, 2016 at 9:43 pm  #1289370    

me53

third line from last I mean wouldn’t, not won’t!

December 7, 2016 at 5:34 am  #1289375    

cards7up

Protocol for treating later stage cancer which includes IIIB and IV, is to do chemo as it’s already in the blood stream and there is no other way to kill it unless you use systemic treatment. It’s everyone’s option whether to do treatment or not at any stage. Your onc will give you the recommendations and you make an informed decision. I personally would not forego chemo if I needed systemic tx and I haven’t. I’ve done it twice, once for original dx and then a recurrence. I don’t have neuropathy and the chemo I used did not affect my hearing as I already have hearing issue and chose a different chemo for that reason. I also suffered very little to no nausea. I’d rather do a few months of treatment to give me a longer time on this earth!
Take care, Judy


Stage IIIA adeno, dx 7/2010. SRS then chemo carbo/alimta 4x. NED as of 10/2011.
Local recurrence, surgery to remove LRL 8/29/13. 5.2cm involved pleura. Chemo carbo/alimta x3. NED

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