Surgery and Sarcomatoid carcinoma - Scan frequency and nivolumab trials - 1262307

With regard to frequency of surveillance scans after surgery, Dr. West has previously stated:

"There really isn't an established protocol, which is why there is such variability. We don't have any real evidence that routine surveillance even improves outcomes -- for the clear majority of people with a recurrence after surgery, they are going to have metastatic disease, for which there isn't really an expected benefit to diagnosing it a few months earlier instead of a few months later. The truth is that most of our practice is guided by ritual and expectation -- and anxiety. A rare patient may be found to have a cancer that can be treated with curative intent, but there's no evidence that outcome are better for doing surveillance scans every 3 months vs. every 4 or 6 months. Frankly, I think it's almost unimaginable that there would be a difference between a recurrence detected after 4 months vs. one 6 months after the last scan." - http://cancergrace.org/forums/index.php?topic=1639.msg9687#msg9687

As far as trials, the inclusion criteria you describe certainly do not seem to exclude pre-treated patients, and that is usually pretty clearly stated. Recruiting trials may change between now and when your dad needs them (hopefully a very long time from now!), so you'll want to contact the trial investigators to be certain of their specific criteria. In my experience, trial staff tend to be very helpful.

JimC
Forum moderator

Yes, I agree with all of my prior comments unearthed by Jim about surveillance after surgery.

As for the trials, it may even be that one or more of the immune checkpoint inhibitors currently in clinical trials are commercially available by the time your father needs them -- if that's ever the case (and I hope not). The trials for metastatic disease don't disqualify patients who have received prior chemo, as long as they demonstrate distant recurrence later. In that case, it's the same situation as presenting with metastatic disease from the beginning, though the patients who recur after initial surgery tend to have a longer survival, likely because the time line of progression is naturally slower than it is in patients who never have an interval between initial diagnosis and identification of metastatic disease.

Good luck.

-Dr. West

Since there's no practical way to find micrometastases in the body, I think the answer to your question about them being curable is that although it is known that more patients are cured with adjuvant therapy than without it, how and why that happens is not known. Is adjuvant chemo killing the remaining cancer cells in the lung before they have a chance to spread? Or is it successful in eradicating those cells which have already reached the bloodstream?

JimC
Forum moderator

Several large trials have shown that 4-5 year survival is higher after 3 or 4 cycles of platinum doublet chemotherapy in the post-operative setting, at least in patients with node-positive cancer and/or a tumor at least 4 cm. Smaller node-negative tumors are at low enough risk for recurrence that the risk of treatment, though small, is in the same ballpark as or worse than the improvement in risk profile after chemotherapy.

Here's a very good summary of the field:

http://cancergrace.org/lung/2010/05/17/systemic-therapy-for-resected-ns…

Jim is quite right in saying that we can't be authoritative about the mechanism, but we tend to think of is as a model in which chemotherapy can potentially kill off a few stray micrometastases we can't see. The issue you bring up of creating resistance early is more for the setting of a cancer that isn't curable, and I think you may also be referring to my recent post about targeted therapy post-operatively, which is really not well enough studied to really know what to expect or how it might be working.

Good luck.

-Dr. West

Cisplatin/vinorelbine is the best-studied regimen, although both cis/gemcitabine and cis/docetaxel appear on the NCCN guidelines page for adjuvant chemo. Dr. West gave his thoughts on adjuvant chemo regimens here:

"There are three regimens that are included right now in a large adjuvant trial of chemo alone or with avastin, being run across North America: cisplatin/navelbine, cisplatin/gemcitabine, and cisplatin/taxotere. Cisplatin/navelbine is the best studied, the one that has been part of far more of the positive studies than other regimens, but it had largely fallen out of favor in the US for advanced NSCLC and was actually inferior to cisplatin/taxotere in one trial in advanced NSCLC (abstract here). Despite that, I’ve been impressed that so much of the evidence is with this regimen and have often used cisplatin/navelbine. I’ve found it to be feasible for many patients, although I’ve modified the schedule to another commonly used way of giving cisplatin/navelbine as two weekly doses every three weeks, rather than giving weekly treatments with no break (most oncologists I speak with find that schedule to be remarkably difficult or impossible to actually administer as intended). I’ve sometimes used cisplatin/gemcitabine, a regimen I’m also perfectly happy with. Both cisplatin/navelbine and cisplatin/gemcitabine cause little or no hair loss in most patients and don’t require steroid premedication, so that’s helpful. I haven’t favored cisplatin/taxotere, even though it’s certainly a very active combination. I find it hard for many patients to tolerate even if they haven’t just undergone major chest surgery, and the folks at Memorial Sloan Kettering actually reported that they found it to be very difficult to administer post-operatively as they had intended (abstract here)" - http://cancergrace.org/lung/2008/09/03/wird-adjuvant-chemo/

JimC

I ran out of space in the previous post, but wanted to add that you can find the NCCN guidelines for adjuvant chemo here: http://cancergrace.org/lung/files/2009/07/dr-dubey-interview-chemo-for-… (second slide).

JimC
Forum moderator

Just an amendment that the ECOG 1505 trial of adjuvant chemo +/- Avastin (bevacizumab) added (for non-squamous NSCLC only) cisplatin/Alimta (pemetrexed) to the other three mentioned in my prior quote, but the idea is still the same: these are all comparable, very acceptable chemo choices in my mind and the minds of most lung cancer specialists. We may all have our preferred regimen, but I think nearly all of us think they have very comparable activity and are all acceptable, though cisplatin/Navelbine happens to be the best studied, in part because it was among the older and least expensive agents, which is important in many parts of the world where these studies were done.

Thanks for your kind words about GRACE!

-Dr. West

Just an amendment that the ECOG 1505 trial of adjuvant chemo +/- Avastin (bevacizumab) added (for non-squamous NSCLC only) cisplatin/Alimta (pemetrexed) to the other three mentioned in my prior quote, but the idea is still the same: these are all comparable, very acceptable chemo choices in my mind and the minds of most lung cancer specialists. We may all have our preferred regimen, but I think nearly all of us think they have very comparable activity and are all acceptable, though cisplatin/Navelbine happens to be the best studied, in part because it was among the older and least expensive agents, which is important in many parts of the world where these studies were done.

Thanks for your kind words about GRACE!

-Dr. West

I think with the short interval between surgery and this brain metastasis, it's not likely to represent recurrence as much as pre-existing stage IV disease that wasn't looked for in the brain until after surgery. On the other hand, if you tell me he had a brain MRI before surgery that showed no cancer and now there's a new metastasis 2-3 months later, I'd be surprised, but that would represent a very early recurrence.

The term adjuvant therapy doesn't apply for patients with metastatic spread. While you might consider this to be "oligometastatic" or even "precocious metastatic" disease (as described in this link), that concept really applies better for what would otherwise be stage I disease than stage IIIA disease except for the metastasis. The presence of stage IIIA disease elsewhere unfortunately makes it far more likely that there is disease that is invisible and micrometastatic, likely to appear in new places over time.

In such a situation, many experts and general oncologists would favor waiting to initiate treatment until you have something to treat. However, some would make an argument that if you've removed (and/or eradicated with Gamma Knife) all evidence of disease and can think about treating for cure, you might want to try giving post-operative chemotherapy with an understanding that the risk of recurrence is very high.

Good luck.

-Dr. West