ALK squamous? - 1289308

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

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

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

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

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

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

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

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

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

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-ns…

JimC
Forum moderator

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