Topic: Surgery not possible, but still hopeful for the future.

As I sit here today, I find myself more hopeful than I have been in a while about the future possibilites.  I am sure it has a lot to do with the fact that my wife is in an ok spot for now (good response to chemo and finally feeling better after IMRT radiation).  However, I think my rationale for hope is more than just her current situation.  After thinking about it a bit, here is what I came up with:

Word of warning if you read this essay.  I am not a doctor nor am I a medical researcher.  The following are my views and could very well be biased, skewed, or flat out wrong.  I did go from a point of virtually no hope to one of being cautiously hopeful.  I believe that having hope is hugely important, so I wanted to write this up in case it helps someone else acquire hope.

Background

My wife was diagnosed on April 1, 2013 with inoperable intrahepatic cholangiocarcinoma (ICC) -- one main 9cm lesion, two medium 4cm lesions and a constellation of smaller lesions all contained in the liver.  While not in the field of medicine, I am a researcher by nature and profession, so of course I dove into the medical research with both feet.  How depressing.  Virtually every research article begins with this type of refrain:  ICC is a rare disease with few treatment options and a poor prognosis.  Most articles will also mention that surgery is the only curative option.  Well, my wife is not a surgery candidate, and probably never will be.  Even so, after helping my wife through treatment and continuing the research effort for the last 13 months, I am actually somewhat hopeful. I wanted to write up why I feel this way to help others that might be feeling hopeless.

Why am I hopeful?  In a word, TIME.

In my opinion, the only way to beat this disease without surgery is to be around for the treatment breakthrough.  Things that improve your odds fall into one of two buckets – they either increase the amount of time you survive, or speed up the process of finding a breakthrough.  To me, both are happening.

Increased survival time – Good response to first line therapy

No way to sugarcoat this.  One of the biggest needs right now from a patient perspective is a better first line therapy option.  Cholangiocarcinoma is usually diagnosed at an advanced stage, and a lot depends on how the patient responds to the initial therapy.  Unfortunately, for many patients, first line therapy does not work very well.

If you are not a surgery candidate, then, to me, a key goal for first line therapy is to buy time to get other options on the table.  When viewed from this perspective, there has been some tangible progress.  For example, suppose you assume you need to survive at least one year to enable other treatment options.  As best as I can tell, it was in the early 2000s when gemcitabine therapy was shown to roughly double the one year survival odds compared to best supportive care.  Later, in 2010, the landmark ABC 02 study was published and established Gem/Cis as the standard first line treatment.  Compared to gemcitabine alone, this study reported that Gem/Cis roughly doubled the one year survival odds again. Other therapies, such as radioembolization and chemoembolization, are being explored as a first line option for locally advanced disease when surgery is not possible.  However, I have not seen data on how these options perform in a first line setting.

Thankfully, my wife cleared that initial hurdle and had a good response to first line chemotherapy (Gem/Cis).  The extra time provided by this response gives me hope because it both improves her shot at being around for a breakthrough, and also gives us more time to explore additional treatment options.

Increased survival time – New approaches, Clinical Trials and the 10%-15%

One thing you will notice if you look at survival curves for many clinical trials is that there is typically a small percentage, say 10%-15%, that have a pretty good outcome (e.g tumor shrinkage and substantial survival).  What’s changing that gives me hope?  I think about it this way: suppose there was only one option available, like traditional chemotherapy.  If that is it, then you better hope that you are in the responsive 10-15%.  Even if there are a lot of different clinical trials available, it may not help much if they all are just different approaches using the same basic mechanism (e.g. traditional chemo)

Things change dramatically if different trials attack the cancer in fundamentally different ways.  Maybe your cancer doesn’t respond to traditional chemo, but perhaps your lymphocytes can be trained to attack your cancer (Trial NCT01174121).  Or maybe your cancer would benefit from a MET inhibitor (Trial NCT 01285037).  You might have a KRAS mutation or could benefit from an Anti-PDL1 agent (Trial NCT01375842).  This list of options is growing.  To me, this is hugely important.  Perhaps you are not super responsive to one, but that doesn’t rule out you being response to a fundamentally different approach.  If you could somehow try four different approaches each with a 15% chance of a good response, all of a sudden, your chances of getting a good response go up to almost 50/50!  A huge improvement.  Moreover, you could be responsive to more than one...even better.

I plan on keeping abreast of all the various clinical trial options.  I am looking for trials that both rely on very different mechanisms and have minimal impact on quality of life.  Quality of life is a very important consideration in general, but I also think good quality of life is critical to increase the number of treatments one can endure.  The idea is if one approach stops working, another is available to quickly shift to.  I think this strategy both helps her maximize her chances and helps others by participating in the clinical trial process.

Shorten the time to a break through – Overcoming rare cancer handicaps

First the bad news – compared to common cancers, rare cancers face two massive hurdles.  First, drug companies often ignore rare cancers.  Obviously, it is hard to make a “blockbuster” drug when total sales are capped in the thousands.  Second, even with a new drug to test, the testing process is exponentially harder with rare cancers.  Suppose you need a minimum of 200 patients to test your new drug.  A breast cancer drug might fill that trial in a matter of weeks.  For cholangiocarcinoma, it could literally take five or more YEARS to accrue that many patients.  Many trials are cancelled or suspended due to lack of patient accrual.   Needless to say, this environment leads to very slow progress.

Well that’s depressing…why is this hopeful?  What is so hopeful is that cancers are more and more being grouped by their characteristics (e.g. genetic mutations and aberrant signaling pathways) and less by their place of origin (e.g. bile duct cells).  For example, my wife has cholangiocarcinoma (small group), but her cancer may also have a KRAS, IDH1 or IDH2 mutation (big groups).  So much of the scientific focus right now is on these mutations and pathways, that I think the odds of research over the next five years helping the typical cholangiocarcinoma patient is much higher than the previous five years.  Going forward, I think it will be increasingly important to know what mutations characterize your cancer because this will help guide your treatment.  While it is not particularly helpful right now, this is a good reason to try and get a next gen genetic test done on your tumor when possible.
 
The research process has made significant progress against many cancers, but rare cancers often are left behind.  The focus on mutations and pathways that affect a large number of different cancers offers real hope that the next round of research will more broadly help rare and common cancers alike.

Conclusion

There is no denying that cholangiocarcinoma is a very bad cancer to have.  Even so, there are reasons to be hopeful.  The variety of treatment options available today provides new hope for extended survival.  Moreover, the evolution of the clinical trial process gives real hope that new treatments will be far more likely to benefit rare cancers compared historical experience.

If you have other reasons why we should be hopeful, I would very much like to hear them.

All the best,

Jason

Re: Surgery not possible, but still hopeful for the future.

Jason,
Thanks for the very thorough, informative post. I know this is all going on, but you've put it down in a clear, concise post. Thanks for all your time and patience in doing so.
My hopeful thoughts are much more simple. I just remember that, upon receiving the diagnosis, I was told to expect less than 2 years, and because of breakthroughs I am still here and "healthy" 3 years later. And every time I turn around, there is another hopeful trial or breakthrough!
BTW, I know gem/cis is the approved first line treatment, but i received gem/Ox, and am glad I did. I believe that gem/Ox should be considered another first line choice... Hopefully soon... As I think it works better for certain mutations.

KrisJ
"Don't just have minutes in the day; have moments in time."
Any opinions I give are based on personal experiences, and are not based on medical knowledge. I strongly suggest receiving medical care and opinions.

Re: Surgery not possible, but still hopeful for the future.

Jason -
Excellent exposition - Beautifully written - I've only been in this game for six months or so and am still struggling to understand it - I am extremely positive by nature and, although I recently celebrated my 81st birthday, I'm convinced I can beat this beast!!!  Your article reinforces my positive outlook and will, I'm sure, do the same for others -
Life is good and we should all do our best to prolong it and enjoy it!!!
Best Regards

Re: Surgery not possible, but still hopeful for the future.

Jason, thank you for your very informative and inspirational post.  I agree 100% that we have many reasons to be hopeful.  Our situations are quite similar in that my wife Lisa is around the same age as Andrea.  Lisa was diagnosed in May of 2013 and we also have small children.

You provided an excellent summary of the treatment options that offer tremendous hope for extended survival and possibly even a cure.

I do not believe that the published survival statistics are very applicable today because they are all based on retrospective studies from the past 10 or even 20 years.  The treatments employed today have definitely extended survival and many patients are living productive lives -- surgical and non-surgical candidates alike.  I think we will see a major shift in the statistics as new studies are published in the future that take the current patient population into account.

Thanks again for being such an excellent resource for this forum.  I personally have learned a lot from reading your posts.  Although this journey is quite challenging, with many highs and lows, I share your optimism about the future.  We will continue to keep your wife in our thoughts and prayers.

-Matt

Re: Surgery not possible, but still hopeful for the future.

Jason-

I appreciate the post!  Although Mom is relatively new to CC (Oct 2013), at first we were given the 1 year average survival and chemo adds another 3 months.  We were not told that after good response to chemo they would do other treatments (radio embo) and then we have chemo and other possible avenues as well.  I am so glad that Mom decided that even if it was only 3 months more, she wanted to fight it. We're at 7 months since diagnosis and just got back from vacation in FL.  In June we will have another scan, but hopefully the radioembo is still working on the tumor.  At our last visit, Mom did put the ONC on the spot and she did say that she does expect Mom to be around past the 1 year mark.  Although we tried to tell her otherwise, Mom was thinking her life would end during or before Oct 2014.

It would be great if the June scan is positive, but if not, we've only been through 3 cycles of the gem/cis and those worked on shrinking the tumor. We also know that since they modified her meds, she can tolerate the chemo.  Additionally, scan two months after SIRT showed we were killing the tumor as well.  So far, no other mets-  just the one stupid tumor in a bad location. 

Amazing to say that I feel blessed.  I read these boards and so many are succumbing so quickly or having bad side effects during their journey.  I'm waiting for the shoe to drop (again), but for now we are thankful for every normal day where you would not realize that Mom is ill. 

I am sorry you and your wife are in this place, but it is evident that she has you there to depend on .  I think that is a big plus for hope.

Take care,

Catherine

Re: Surgery not possible, but still hopeful for the future.

Hi Kris,

Thank you for the comments.  I really appreciate you sharing your experience.  It is very hopeful for unresectable patients and their caregivers.

Good point on the chemo.  My understanding is that the suggested first line therapy (outside of a clinical trial setting) is Gemcitabine + something from the platin family.  It could be cisplatin, oxiliplatin, etc. 

I thought they used different platins based on kidney function (i.e. oxiliplatin was easier on the kidney??)  I didn't realize it could also be that they work better in different situations.  Makes sense though.  Thanks!

Jason