My dad (age: 53; Asian male) was diagnosed with stage IV NSCLC in October 2013. He had all his prior treatments in China since the initial diagnosis, which included 6 cycles of carboplatin/pemetrexed/bevacizumab chemo, 2 months of Tarceva, 2 cycles of Gemzar and 4 cycles of Abraxane. He responded to the initial chemotherapy but not Tarceva (even with positive EGFR mutation), Gemzar and last two cycles of the Abraxane treatment.
As there was no viable treatment option left in China, I decided to let my dad come to Chicago to enroll into a phase-3 Nivolumab clinical trial (BMS-936558). So far my dad has received 4 cycles of the Nivolumab treatment (2 weeks/cycle). Here are the updates since the treatment: (1) 1st cycle: my dad started having much more pain on his left scapula and left chest, and a lump appeared on his left scapula; (2) 2nd cycle: my dad said he started to have less pain and felt better. We all thought that was the sign that the drug might be working; (3) 3rd cycle: my dad felt worse again as the pain increased and the lump on left scapula appeared to be significantly larger. He also started to have new pain at left armpit. I asked the doctor to test my dad's CEA level and it came back with a shocking number: 260 ng/ml (vs 47.91 ng/ml on 09/17; 0-5 normal). I understand that we can't make a conclusion until his CT scan results come back on 12/01. But I have found that his historical CEA level correlated perfectly with his tumor size after the treatment.
My best guess is my dad's increased pain and the lump have been due to true progression instead of peudo-progression. I haven't told my parents about this number as that will be devastating to them, but it's actually extremely important for me to make a decision asap because if his condition starts to deteriorate a lot in the next month, I will not be able to afford the hospitalization bills as my dad doesn't have any insurance in the US. My only hope now is - can this still be a peudo-progression?
Nivolumab treatment for NSCLC - 1267261
linsheng33
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Reply # - November 23, 2014, 08:46 AM
Hello,
Hello,
Welcome to GRACE. As it seems you already know, rising CEA levels are not always indicative of progression, although some patients' levels seem to correlate well with what's going on with the cancer.
Trying to determine whether your father's cancer is progressing would really be guesswork until the CT results come in. Increasing pain from a bone met doesn't always mean that it is progressing; the pain may be from the damage to the bone worsening over time.
Most of us here know the frustration of waiting for results; uncertainty is one of the worst aspects of cancer, but I don't think you'll be able to make any informed decisions until you get those CT results.
Hoping for great results from the scan,
JimC
Forum moderator
Reply # - November 23, 2014, 08:49 AM
Here are some links to
Here are some links to discussions of CEA in lung cancer:
Serum tumor markers in lung cancer, including CEA:
http://cancergrace.org/lung/2007/06/16/tumor-markers-in-lung-cancer/
According to a previous post from Dr. Weiss: “For some patients, CEA correlates well with the amount of disease, but the best data indicate that it’s just not that good a test. There are no clearly good blood markers for monitoring disease in NSCLC.”
http://cancergrace.org/forums/index.php?topic=3950.msg23396#msg23396
Here’s another post from Dr. West with a little more detail about how he interprets CEA.
http://cancergrace.org/forums/index.php?topic=742.msg3874#msg3874
Interpreting Dr. West’s post: the CEA marker doesn’t seem that valuable on its own, but it can be combined with scan results to provide more information. It is of some utility, but not enough to override scan results.
JimC
Forum moderator
Reply # - November 23, 2014, 09:46 AM
Dear Jim,
Dear Jim,
Thank you so much for your answer and the informative links on serum tumor markers in lung cancer.
My dad's oncologist said that even if we see tumor progressions on the CT scan, we might still wants to continue the treatment as long as my dad is feeling okay (i.e. he is not declining very fast). I think what the doctor meant was that it would be very hard to distinguish between "true progression" and "peudo-progression" from the 1st CT scan during immunotherapy, and that's was why I was wondering whether CEA level can help us on this decision given it correlated pretty well with my dad's previous scan results.
Meanwhile, it would be very difficult for my dad to just say "I'm feeling better/worse" after the Nivolumab treatment. On the one hand, he hasn't coughed at all since the 1st Nivolumab treatment which is a positive sign; on the other hand, the lump on his left scapula has been just getting larger every day and his left shoulder now appears to be much lower than the right shoulder, which makes me increasingly worry about the bone met and destruction.
If we were to chose, I would definitely want my dad to stay in the US for this treatment as long as possible. Unfortunately, the reality is that my dad doesn't have any insurance in the US and will not qualify for any financial assistance program as he is not an US citizen. I have been paying all his treatments in China and all the medical bills here in the US so far out-of-pocket (the bills here are insanely high without insurance). I'm willing to continue to support him until my saving drops to $0 because I believe this is the right thing to do. It would be heart-breaking to send my parents back to China if the treatment fails (I still need to continue to work in the US to support their medical bills), but if we have to do that, it's always better to be earlier than later because if my dad does end with hospitalization, the financial burden will be way beyond my capability.
Sincerely,
Sheng
Reply # - November 23, 2014, 01:31 PM
Sheng,
Sheng,
As Jim has conveyed, I'm no great fan of serum tumor markers in lung cancer, but I think when you favor in a clear clinical decline, it's very concerning. I'm not confident about what you learn about disease status from serum tumor markers in the setting of immunotherapy treatment: if disease can look like it's progressing on imaging but be pseudoprogression, I would say it's very possible to see serum tumor markers rise but not really be disease progression. However, I don't think that's likely when a patient is declining clinically. That would make me very concerned that the cancer is truly progressing.
Given his extensive prior treatment and declining clinical condition, I would ask about whether it's necessary to incur major hospital bills here if there are no further good treatment options. Might he be able to receive home-based hospice/comfort care without great cost as an alternative to expensive hospital-based treatments that aren't able to change the trajectory of the disease?
Good luck.
-Dr. West
Reply # - December 4, 2014, 10:04 PM
Dr. West,
Dr. West,
Thank you so much for your advice. My dad just did his 1st CT scan on 11/29 since he started the Nivolumab treatment. Unfortunately, there has been very aggressive progression during the 8-week treatment period:
(1) The left pleura is involved by tumor and fibrosis and there is confluent tissue opacity;
(2) Rib destruction was worse (left ribs 2-5);
(3) Large bulky soft tissue mass which extends through the chest wall and into the axillary space (5.9*6.2 cm vs. 2.8*1.8cm in previous scan on 09/16) - this explains his large lump on left scapula
(4) Expansile soft tissue mass of the left anterior eighth rib: 4.1*3.0 cm (not present in prior scan)
(5) Soft tissue mass near the deep left lateral costophrenic sulcus: 2.6*1.6 cm (not present in the prior scan)
(6) Significant enlargement of a right adrenal nodule (3.3*1.8cm vs. 2.0*0.6cm from prior scan)
(7) small moderate-sized pericardial effusion which is new.
My questions are:
(1) Is it possible for the disease to progress so much in two months even without any treatment? My dad's oncologist has mentioned that there seems to be cystic changes in the soft tissue mass (the center of the mass have darker color than the periphery of the mass). Can this be a sign for pseudo-progression?
(2) My dad's oncologist said that my dad can still choose to stay on the treatment as he is still doing relatively okay given the huge amount of progression we have seen. However, we are taking huge risk if we decide to continue the treatment because if my dad does start to decline very fast and end up with hospitalization, we wouldn't be able to send him back to China through commercial flight. How fast do you think his disease can grow in the next few weeks if Nivolumab turns out to be not working? Is there any treatment option (or clinical trial) we can look for in the US in the immediate future? We cannot afford to wait for too long given the speed of the progression.
We greatly appreciate your guidance.
Sheng
Reply # - December 5, 2014, 07:01 AM
Dr. West,
Dr. West,
We have another two questions on immunotherapy. We apologize for so many questions. But your guidance is very important to us at this crucial stage because even my dad's treating physician cannot make a conclusion now. We understand that at the end of day we are the ones to make the final decision, but we really need some medical evidence and experience to help us make a more rationale decision.
(1) If my dad does decide to discontinue the study and go back to China now, will previous 5 doses of Nivolumab be able to stay in his system and work for a long time? We are still hoping that his immune system has been activated by the drug and eventually all those tumors will go away, but we are just not sure whether additional doses of Nivolumab will make a substantial difference now given the amount of risk we are taking. In the immunotherapy patient forum you organized a couple of weeks ago, I remember you did raise up the question on the "optimal dosage", and I recall one of the speakers mentioned that "4 doses of the drug might already be enough in the immunotherapy setting". Again, we do not need a firm answer as I know we need more data from the trials, but a "best guess" based on theories and experience will be really helpful for us.
(2) Right after my dad returns to China, while he is waiting for the response from Nivolumab, do you think he can receive some other treatments (such as chemotherapy, radiotherapy)? If so, what would be our option at this point given the amount the prior treatments he has already received. We just don't want those other treatments to work against Nivolumab in his system.
Sincerely,
Sheng
Reply # - December 5, 2014, 10:10 AM
Sheng, I'm so sorry you're
Sheng, I'm so sorry you're going through the additional troubles of how best to spend what money you have. How absolutely to the core you must venture.
The researchers have mentioned they’ve seen signs that the immune drugs have lasting effect but no one can say at this time. It's just a possibility. As for starting another treatment regimen the researchers are the best to answer the question of when. They are the ones who are dealing with these new drugs daily and would have the "best guess" at any of these questions.
I wonder if you’ve looked into what the next step could be. There is a saying, “responders respond”, meaning those who respond to one treatment are likely to respond to another, leaving the inference those who don’t respond well to a treatment are less likely to respond to another. Targeted drugs, immunotherapy drugs and chemo all have separate mechanisms of action. One may work where another doesn’t so trying them all is appropriate.
Dr. West mentioned hospice/comfort care. Often it can be very successful given from home. There are very thoughtful and of course extremely difficult conversations on the subject here, http://cancergrace.org/forums/index.php?topic=9519.0 and here, http://cancergrace.org/coping-with-cancer/2010/12/30/transition-to-symp… . I hope I haven't overstepped my bounds but I want to make sure you understand all the options and know comfort care is as important a step as anti cancer treatment.
All best,
Janine
Reply # - December 5, 2014, 03:15 PM
Sheng,
Sheng,
Unfortunately, it is extremely possible for cancer to progress significantly over two months, on or off of treatment.
While there is this entity called "pseudoprogression" that can sometimes occur and cause there to be a growing nodule or new lesion that will later shrink, that's not remotely what this sounds like. This sounds overwhelmingly like progressing cancer.
If he were to go to China, the immunotherapy would potentially still do some good based on what he already received, but I think that all evidence suggests it has done absolutely no good, so I think it is really just not realistic to expect that immunotherapy will provide any benefit.
As for subsequent options, I must confess that I don't know of anything that has a meaningful probability of helping prolong his survival based on the pattern you've described. Having an expertise in lung cancer doesn't mean that there are a new array of treatments that nobody else knows about. You reach a point where treatment is simply more likely to cause harm than to help, and where treatment with a hope or expectation of treating the cancer effectively is just not a realistic situation. I am not evaluating your father directly, but I'm sorry to say that it sounds as if he is at that point.
-Dr. West
Reply # - December 7, 2014, 01:17 PM
Dr. West,
Dr. West,
We really appreciate your honesty. I understand that this is the point where we probably need to cut the loss and accept the reality. However, we are still struggling to to make a final decision on whether we should continue on the Nivolumab treatment when some doctors including my dad's treating physician still think it's hard to determine whether this is "true-progression" or "pseudo-progression" until the next scan.
Below I have summarized the factors we have been considering in our decision:
Positive factors:
- My dad hasn't coughed at all since the Nivolumab treatment (he used to cough for about 10-20 times/day before he came to the US, which caused his serious hoarseness problem);
- He can still manage to walk at least 2 miles every day;
- His breath has been still relatively normal given the amount of progression we see in his left lung;
- His right lung is still relatively clear and well-expanded, without pleural effusion or pneumothorax. If the cancer is spreading aggressively, should we expect to see at least some new lesions in his right lung?
- Based on studies, some patients who initially experienced more "pseudo-progression" actually end up having more durable and profound response later
Negative factors:
- It's very rare to see this level of change in pseudo-progression;
- His pain increased a lot after the 1st treatment and then it has been almost unchanged through the rest of the treatment. It has been still manageable by taking tramadol @ 200mg/day;
- All those new developments in this scan (especially the new pericardial effusion) could be life-threatening if they turn out to be actual progression
Dr. West, I understand that you have already given your clear answer, and I feel like your answer is probably going to be the most likely outcome. However, given that immunotherapy is my dad's last hope to prolong his life, do you think if it's a rational decision for us to give Nivolumab a try for 1-2 months in the US?
Sheng
Reply # - December 7, 2014, 05:10 PM
Sheng,
Sheng,
As Dr. West said in his reply, although no one on the GRACE site is involved in your father's care personally, the scan changes you describe certainly sound like significant progression. It is possible to have such progression without major changes in symptoms, and it's not possible to predict where the cancer will spread. So your father's continuing ability to walk two miles daily and the lack of new lesions in the right lung, while not the norm, do not change the scan findings of progression. However, if the current rate of progression continues, it is likely that his symptoms will increase, perhaps quickly.
I am sorry about the dilemma you face because of the economic factors. My thoughts are with you and your family at this difficult time.
JimC
Forum moderator
Reply # - December 7, 2014, 05:45 PM
I feel that I've said all I
I feel that I've said all I really can say. I don't think that there is any realistic anticipated benefit to continuing immunotherapy beyond this point, though I can't be the person making that decision for you and your family.
Good luck.
-Dr. West
Reply # - December 22, 2014, 05:13 PM
Dr. West,
Dr. West,
Thank you for your honesty. My dad stopped the Nivolumab treatment last week and returned to China on last Saturday. We went to see oncologist at U of Chicago on last Wednesday and below please find the next-step treatment plan they recommended:
1. Bronchoscopy with biopsies: they found that the CT images reveal that my dad's left lower lobe is largely collapsed. They recommend bronchoscopy/additional biopsies to assess for T790M mutation and further molecular markers. Would also consider thoracic radiation therapy pending bronchoscopy results.
2. Palliative radiation therapy for left sided chest wall and rib destruction.
3. Systematic chemotherapy after the bronchoscopy and radiation: would include navelbine, paclitaxel, or irinotecan, among others.
However, my dad's oncologist in China's treatment plan is very different:
Chemotherapy only: Nedaplatin [IV injection for 2 days] + Tegafu (Gimeracil and Oteracil Porassium Capsules) [Oral intake for 14 days]
Given my dad's current disease, how should I decide between those two treatment options? Is radiation necessary before the chemotherapy? (The doctors at U of Chicago said that my dad will need treatment to open up his airway to be able to breath). If so, I will have to convince the Chinese doctor to consider radiation.
I totally understand that there is nothing I can do at this point to save my dad's life back. But I know in my heart that my dad wants to flight this horrible disease until the last minute, so I think the best thing I can do now is to find a reasonable plan with relatively less side-effect.
Your opinion means a lot to us. Thank you.
Sheng
Reply # - December 22, 2014, 05:30 PM
Sheng,
Sheng,
Although the GRACE faculty can't directly suggest what you should do, based on what you've written and the opinions Dr. West has expressed, I think the major factor which should guide your decision would be your father's comfort. For example, if radiation is considered necessary to help him breathe and to alleviate chest pain, I think that would take precedence over any course of action intended to treat his lung cancer.
I hope the path you select helps him find comfort.
JimC
Forum moderator
Reply # - December 22, 2014, 08:21 PM
It sounds as if the radiation
It sounds as if the radiation would be largely directed toward helping to open his airway and improve his performance status. I think there is good reason to be concerned that he may not be able to tolerate a meaningful amount of chemo without radiation providing an improvement in pain management and pulmonary function.
At the same time, a bronchoscopy that provides additional tissue could yield a finding of a T790M mutation, which could make an agent like AZD9291 or rociletinib (CO-1686) the most effective treatment option to consider.
Good luck.
-Dr. West
Reply # - January 5, 2015, 09:12 PM
Sheng, I have a similar
Sheng, I have a similar situation and would like to know more about how you find the clinical trial for your dad. Could you please reach me at zhqian@gmail.com? Thanks so much!!!