Topic: Adjuvant chemo- or radiotherapy?

For a patient, after a Whipples-resected distal bile duct tumor, is there any evidence to show whether adjuvant chemotherapy or radiotherapy is more effective post-op (i.e. when no sign of recurrence) or when (and if) recurrence occurs?

In other words, with recurrence, is a patient less likely to achieve a cure after a period (months/years) of active surveillance compared with immediate chemo or radiotherapy?

We can't find any research which shows a difference.

Many thanks.

Re: Adjuvant chemo- or radiotherapy?

Dear Richard, unfortunately there has been no set standard whether to chemo/rad after a Whipple. My husband had one in August of 2005 and since he had all clean margins, 5 different Doctors (ONCs, Surgeons, Radiologists) all decided no Chemo, that only surgery would take out the CC. His was located in the bile duct valve where it connects to the Pancreas. To chemo or not to chemo is one of the biggest discussions on this Board and I have never seen any statistics on chemo after a Whipple. They have used chemo if nodes were involved. Teddy's did return 3 years post surgery where his duodenum used to be and it was small enough to use Cyber Knife and that worked well for 2 years when it returned to the same place. Now, that is not to say things have not been upgraded in those 5 years but again, I have not read or heard about any changes. Post Whipple Teddy had ONC visits every 3 months with PET Scans every 6 months to keep watch. Wishing you the best of luck and I know it sounds trite but the decision you make will be the right one. Wishing you the best of luck.

Teddy ~In our hearts forever~ATTITUDE is EVERYTHING
Any suggestion I offer is intended as friendly advice based solely on my own experience. Please consult your doctor for professional guidance.

Re: Adjuvant chemo- or radiotherapy?

Hi,
there are retrospective series and small phrase Ii studies suggest superior outcomes for patients who receive EBRT radiation with or without concomitant chemotherapy  or the combination  of  post-op 5FU plus brachytherapy after resection of cholangiocarcinoma.
for patient who are left with microscopically positive margins after resection,the main benefit of postoperative radiation therapy is a reduction in the rate of  local recurrence.
in one study, margin positive resection patients increase their 5 year survival
rate  if they received postoperative adjuvant EBRT (34 vs 14%).
In another study,46 cholangiocarcinoma patients(total pop.=128 patients of hepatibiliary ca) had 3D-CRT radiation plus FUDR intrahepetic artery infusion;60% of all patient were free of hepatic progreesion at 3 years.
In short ,receive postoperative adjuvant radiation treatment with or without chemo may prolong survival.

I know the above response may not answer the actual question that you had.
Should i wait until the CCA recur or do the preventive adjuvant radiation treatment as soon as possible?
MY answer is at least ,up to now, there are NO CURE for this disease;all the treatment plans are use to prolong or for palliative purposes;Recurrence  is high in this disease(>65%). whether you monitor the disease progress every 3 months  with scans like me or wait until the recurrence hit home. it is always a very difficult decision to make. Because there are no guaranteed for either way. But if you,like me, try the best we can, there will be no regrets when the time comes.
God bless

Please know that my personal opinion is not intended nor implied to be a substitute for professional medical advice. If  provided, information are for educational purposes.Consult doctor is a MUST for changing of treatment plans.

Re: Adjuvant chemo- or radiotherapy?

Richard...The issue of adjuvant therapy vs. observation post resection is a hot topic within the medical community and there are some clinical trials conducted; some have completed. 
Here are a few of the ongoing studies:
http://clinicaltrials.gov/ct2/show/NCT0 … amp;rank=4

http://clinicaltrials.gov/ct2/show/NCT0 … amp;rank=3

http://clinicaltrials.gov/ct2/show/NCT0 … amp;rank=6

http://clinicaltrials.gov/ct2/show/NCT0 … amp;rank=6

http://clinicaltrials.gov/ct2/show/NCT0 … amp;rank=6   

I hope this helped.
All my best wishes,
Marion

THIS INFORMATION IS NOT INTENDED NOR IMPLIED TO BE A SUBSTITUTE FOR PROFESSIONAL MEDICAL ADVICE. YOU SHOULD ALWAYS SEEK THE ADVICE OF YOUR PHYSICIAN OR OTHER QUALIFIED HEALTH CARE PROVIDER

Re: Adjuvant chemo- or radiotherapy?

Hi Richard,
I believe that the evidence is in the process of being compiled but unfortunately in this case the internet is not a fount of all knowledge.
You will notice that mostly the trials Marion mentioned are phase III.  My dad's oncologist points out that to get to that phase they must be based on some evidence, and has a strong conviction that the results will be positive.
Treatment varies wildly depending on where you live - in the UK we have a fairly strict protocol with few deviations.  In the US there seems to be much more flexibility for doctors to make their own recommendations.
Kate

6 (edited by PCL1029 Sun, 06 Nov 2011 10:18:12)

Re: Adjuvant chemo- or radiotherapy?

Hi,
Kate is right. I f you live in UK, try to get into the BILCAP trial which still need patients to attain the goal  to report to the world their finding on 2013 ASCO meeting in Chicago. Provided you had resection done and nothing recur when join the trail.
I wll talk to the author when I see him on the ASCO 2012.  And repot to all of you his findings up to that point.I did discussed with his interim  findings at aSCO2011.and he indicated it is difficult to get more resected  patients in UK since CCA is a rare disease.. And posted the main findings last June.they need more patients to achieve  their goals
God bless

Please know that my personal opinion is not intended nor implied to be a substitute for professional medical advice. If  provided, information are for educational purposes.Consult doctor is a MUST for changing of treatment plans.

7 (edited by marions Sun, 06 Nov 2011 12:16:49)

Re: Adjuvant chemo- or radiotherapy?

Richard

THIS INFORMATION IS NOT INTENDED NOR IMPLIED TO BE A SUBSTITUTE FOR PROFESSIONAL MEDICAL ADVICE. YOU SHOULD ALWAYS SEEK THE ADVICE OF YOUR PHYSICIAN OR OTHER QUALIFIED HEALTH CARE PROVIDER

8 (edited by marions Sun, 06 Nov 2011 14:11:40)

Re: Adjuvant chemo- or radiotherapy?

Here is the clinicaltrials.gov link for this trial:
http://clinicaltrials.gov/ct2/show/NCT00363584
It is a bit more expanatory and lists the centers involved of the requirements needed.

THIS INFORMATION IS NOT INTENDED NOR IMPLIED TO BE A SUBSTITUTE FOR PROFESSIONAL MEDICAL ADVICE. YOU SHOULD ALWAYS SEEK THE ADVICE OF YOUR PHYSICIAN OR OTHER QUALIFIED HEALTH CARE PROVIDER

Re: Adjuvant chemo- or radiotherapy?

Kate...I agree there are numerous differences in re: to clinical trials conducted in the UK vs. the US.  There are some advantages in the UK over the US system though. In the UK medical institutions are required to conduct clinical trials hence you see quite a few studies initiated.
Accrual is relatively easy as numerous centers participate and considering the size of the UK vs. the US patients access to the medical facilities is easy and always cost free to the patient. 
The above trial is conducted in 47 different centers in the UK.  This is pretty significant.  A similar trial conducted in the US would involve the majority of patients to incur travel expenses for which they are not reimbursed. And, more significantly US patients have to bear the cost of additional scans and testing not covered by their insurance carrier. (Medicare recipients excluded.) This however, is supposed to change as the government is requiring insurance companies to include clinical trial expenses.  It can

THIS INFORMATION IS NOT INTENDED NOR IMPLIED TO BE A SUBSTITUTE FOR PROFESSIONAL MEDICAL ADVICE. YOU SHOULD ALWAYS SEEK THE ADVICE OF YOUR PHYSICIAN OR OTHER QUALIFIED HEALTH CARE PROVIDER

10 (edited by RichardL Sun, 06 Nov 2011 17:27:11)

Re: Adjuvant chemo- or radiotherapy?

Many thanks for the information and links everyone. I need to read thoroughly before replying.

We've noticed one interesting set of information to have come out of BILCAP: an interim analysis commented on survival of patients on the trial. 12-month survival rate was 86.4%, and 24-month rate was 82%. Not easy figures to interpret, as this includes both arms of the trial - those on Capecitabine and the control group who are not.

Does it imply that the live arm figures could be even higher? Do studies like this, even at interim stages ever break down the live arm and control arm differences?  Is there data to show survival figures for resected patients who've not had adjuvant treatment? If so, it would be interesting to compare with the interim data.

Those survival figures above come from the BILCAP poster ( see: http://goo.gl/0QPsY ) under the heading of Survival and Toxicity.

Re: Adjuvant chemo- or radiotherapy?

Richard.......Studies vary greatly.   This particular study is focusing on overall survival of control arm (observation) vs. study arm (treatment) and the effect on 2-year survival. We can expect data to be released 2 years after begin of study.
The secondary study focuses on survival, relapse-free survival, toxicity, quality of life, and health economics.
We have seen studies to be halted in cases where the study arm demonstrates significant benefit over the control group.  In such case the treatment will be applied immediately to the entire patient population.  I don

THIS INFORMATION IS NOT INTENDED NOR IMPLIED TO BE A SUBSTITUTE FOR PROFESSIONAL MEDICAL ADVICE. YOU SHOULD ALWAYS SEEK THE ADVICE OF YOUR PHYSICIAN OR OTHER QUALIFIED HEALTH CARE PROVIDER

Re: Adjuvant chemo- or radiotherapy?

Hi,Richard,
I looked over my info.(the poster I got from the 2011 ASCO)and your poster. Based on the graph(overall survival % vs months of survival) ;You can get according to the graph, a 12 month survival rate of 86.4% as the poster had indicated or 75% of the patients had survived at least 18.6months.(projection only for the 75%)
I could not arrive the same conclusion of  24 month survival rate at 82% like you indicated.
As you may notice the graph is just short of the 24 month mark when they plotted the graph.They had indicated on the interim report that due to the MEDIAN follow up of alive patients is only 9.3months and as such the survival curves are not STABLE beyond this time point.(when this interim report was done.)
The primary goal for the BILCAP study is to measure the overall survival,try to detect an increase in 2 year survival from 20 to 32% from 360 patients using adjuvant therapy of capecitabine only.
God bless.

Please know that my personal opinion is not intended nor implied to be a substitute for professional medical advice. If  provided, information are for educational purposes.Consult doctor is a MUST for changing of treatment plans.

13 (edited by Katja Mon, 07 Nov 2011 13:39:16)

Re: Adjuvant chemo- or radiotherapy?

Hi all,
I find a lot of the poster vague and a bit confusing really.  Richard points out that the poster states '41 (18%) patients had died within 24 months' which should logically lead us to assume that 82% had not died within that time.  This does not tie in with the graph.
I also find the statement 'To detect an increase in 2 year survival from 20 to 32%' confusing.  I wonder where this evidence comes from - I have never read anywhere that 2 year survival of resected patients having no adjuvant therapy is 20%.  It sounds more like the current 5 year survival for resected patients?

Not to put too fine a point on it, but I do not think the 2 year survival is as significant as 'relapse free survival'.  Richard is right, it would be interesting to compare the data but it cannot be considered significant at this point.  It is important to remember that all patients have undergone a macroscopically complete resection - so we would really hope that a good proportion of these are still alive within 2 years - if they are cancer free is a very different question.

I suppose what Percy is saying is true of all cancer 'there is no CURE' - just more and more effective ways of removing it and minimising the likelihood of it returning.  My personal attitude would have been to encourage my dad to take or do everything possible to stop it coming back.  We were never offered radiation and the doctor said 'what would we radiate? There's nothing there'.  Certainly the evidence Percy found would suggest the efficacy with margin positive patients.

Marion, thanks for that info about UK v US - I've sometimes wondered how different things would be if we could effectively just ask a doctor to prescribe something we wanted rather than being at the mercy of the NHS, but I just find it so difficult to imagine the accompanying financial/travel considerations that so many US patients encounter.

Kate

14 (edited by PCL1029 Mon, 07 Nov 2011 14:24:36)

Re: Adjuvant chemo- or radiotherapy?

Hi,Kate,
Thanks to Gavin andHelen,please read my response message ofBILCAP under chemotherapy forum on this web site.
This study is different in a way that the patient population is not fix (close off),but rather is on going.
I  agree with you,for this cholangiocarcinoma cancer,since good and bad cell in the liver both can be regenerated themself,unlike other cancer,(ie:breast ca,once you took it out,the chance of recurrence is far less thanCCA);there is no cure at this point,that is why we have to find treatments to improve the chance of survival more or less by ourselves until otherwise.
God bless.

Please know that my personal opinion is not intended nor implied to be a substitute for professional medical advice. If  provided, information are for educational purposes.Consult doctor is a MUST for changing of treatment plans.

Re: Adjuvant chemo- or radiotherapy?

Thanks Percy - I had seen the BILCAP poster when Helen first posted it.  I have read pretty much everything that is found on the internet about BILCAP - I just have to presume there is more evidence within the medical community which is not available for us laypersons to read!

Re: Adjuvant chemo- or radiotherapy?

PCL 1029, you're absolutely correct  about the 2-year figures.

Kate, I think you'll find this interesting: http://goo.gl/xE8lg

If you tweak it to give Bile Duct / Resectable Disease, there's some useful info on survival rates for 5 years, and there are enough references to keep me quiet for a day or so - I'm still wading through them.

Also, have you got the full BILCAP protocol? It's about 75 pages, and I've got it on PDF if you haven't.

Re: Adjuvant chemo- or radiotherapy?

Thanks Richard, it's been nearly two years since I did my research but I think I had read most of those-I can still see why our oncologist said'what would we radiate?'.  Margin status seems to play a more significant role in RT .

I had not found a Bilcap protocol of 75 pages though-would be very interestedto read that.
What chemo/radiation has your wife been offered?
Kate

18 (edited by RichardL Tue, 08 Nov 2011 00:55:29)

Re: Adjuvant chemo- or radiotherapy?

Kate, I'll send the BILCAP as an attachment (and anyone else is welcome to have a copy); as far as I can see it's not on the web.

2nd opinion recommendation for my wife was immediate GemCIS followed by radiotherapy, but our 2nd opinion hospital onco requested repeat exam. of the histology/slides and have (radically) revised the original histo report, so this advice may change. It just happened yesterday. Ist opinion was choice of either BILCAP or active surveillance (expectant management?).

Re: Adjuvant chemo- or radiotherapy?

Hi,Richard,
If your wife's histology reported indicated positive margin;do what the 2nd opinion recommended;that is Gem/cis and radiation. If your wife's CCA is extrahepatic CCA,Gem/Cap , radiation with or without FUDR  or Capecitabine may be a better choice since 5FU or capecitabine for some unknown reason works better for extrahepatic CCA than intrahepatic CCA unless your wife have done some chemo sensitivity test for choosing the  proper agents.and it is much easier to take the Capecitabine than the cisplatin.(less toxic to the kidney and hair loss.)
I love to see a copy of the BILCAP procotol if you can e mail me one.
God bless.

Please know that my personal opinion is not intended nor implied to be a substitute for professional medical advice. If  provided, information are for educational purposes.Consult doctor is a MUST for changing of treatment plans.

20 (edited by RichardL Tue, 08 Nov 2011 15:37:33)

Re: Adjuvant chemo- or radiotherapy?

Many thanks for the advice. We're still waiting for the revised histology - should have it tomorrow, but suggested chemo now looks like Gem on its own.  BILCAP en route.

Re: Adjuvant chemo- or radiotherapy?

Percy......did you see some studies on the extrahepatic vs. intrahepatic and response to above mentioned?

THIS INFORMATION IS NOT INTENDED NOR IMPLIED TO BE A SUBSTITUTE FOR PROFESSIONAL MEDICAL ADVICE. YOU SHOULD ALWAYS SEEK THE ADVICE OF YOUR PHYSICIAN OR OTHER QUALIFIED HEALTH CARE PROVIDER

22 (edited by PCL1029 Wed, 09 Nov 2011 17:49:35)

Re: Adjuvant chemo- or radiotherapy?

Hi,Marion,
That was mentioned in the article written by Tushar Patel-"Cholangiocarcinoma-controversies and challenges" on Gastroenterology & Hepatology vol.8 apr.2011.
The exact quote is,"In contrast to patients with intrahepatic cholangiocarcinoma ,the combination of gemcitabine with cisplatin does not seem to offer an advantage for those with ductal cancers."
And in uptodate.com ,when they review 'Systemic therapy for Advanced cholangiocarcinoma",they mentioned,base on the review of the article by Patt YZ,HassanMM etc"Oral capecitabine for the treatment of hepatocellular carcinoma,cholangiocarcinoma and gallbladder carcinoma.Cancer 2004;101:578",for some unclear reasons capecitabine as a single agent appears relatively less active for cholangiocarcinoma than for gallbadder caner.But here is the tumor biology of gallbladder cancer come into place.The gallbladder lymphatics drain FIRST to the cystic  and the common duct nodes first and in some cases to the lymphatic nodes posterior to the pancreas or portal vein.If so,the gallbladder cancer is more related to the ductal(extrahepatic) CCA than intrahepatic CCA(which mainly involved the liver.) and therefore I think Patel's observation is correct.
Futhermore,and here is the difficulty for chosing the BEST chemotherapy for the specific type of cholangiocarcinoma (intra or extrahepatic) according to up to date.com and what I read so far is this.
By no means that the Gemzar/Cis is the REFERENCE standard . Ramdomized trials will be needed toCOMPARE if Gem/Cis is more active regimen  and less toxic than gem/cap(Xeloda);GEMOX(oxaliplatin);CAPOX(capecitabine/oxalipiatin);Gem/irinotecan;not to mention to compare Gem/cis using one of  the above regimen  with one of the molecularly targeted therapy like erlotinib(Tarceva) or bevacizuman(Avastin).
The only thing that is clear is that Gem/cis in combination provides better overall response than using Gemzar alone. but than again,using Gemzar alone is not a bad choice too, it works for me for 14 months and I think after 2nd opinion,I think I will be on it again. I will present myself as an experiment and see what can come out with it to benefit to all of us. So far I know for sure one thing; that it takes exactly 12 months for an intrahepatic CCA to grow from 0 to 3cm(a size like a large grape inside the bile duct without vascular involvement.)
I will report  the results and decisions made as the ride continuing thru this long and winding journey.
God bless.

Please know that my personal opinion is not intended nor implied to be a substitute for professional medical advice. If  provided, information are for educational purposes.Consult doctor is a MUST for changing of treatment plans.

23 (edited by Gavin Wed, 09 Nov 2011 12:55:11)

Re: Adjuvant chemo- or radiotherapy?

Here's a link to the Journal that you mention Percy -

http://www.nature.com/nrgastro/journal/ … 11.20.html

Thank you Percy for everything.

Gavin

Any advice or comments I give are based on personal experiences and knowledge and are my opinions only, they are not to be substituted for professional medical advice. Please seek professional advice from a qualified doctor or medical professional.

Re: Adjuvant chemo- or radiotherapy?

Thanks Gavin and Percy.

THIS INFORMATION IS NOT INTENDED NOR IMPLIED TO BE A SUBSTITUTE FOR PROFESSIONAL MEDICAL ADVICE. YOU SHOULD ALWAYS SEEK THE ADVICE OF YOUR PHYSICIAN OR OTHER QUALIFIED HEALTH CARE PROVIDER

Re: Adjuvant chemo- or radiotherapy?

Hi,Gavin and Marion,
you are always welcome.

Gavin, with last nite's win ,the Bear may actually have a chance for playoff.
If they will beat the Lions this Sunday ,then I may ask your mum to borrow 20 pounds from her and bet on the Bears to win the NFC at least;.Again the 49ers looks so good this year under Jim Habrough -a former Bear QB from the Golden era.  Make sure you say hi to your mum for me.

And to Marion, sometimes I feel bad that I cannot comfort those patients and caregivers like you and Lainy or Gavin did. I know as patients,some of them just don't want to know.
and therefore sometimes I choose not to answer ALL the messages I saw on the board but selectively in fear of upsetting  them more.It is a difficult choice;plus I am not good at that anyway emotionally.
God bless.

Please know that my personal opinion is not intended nor implied to be a substitute for professional medical advice. If  provided, information are for educational purposes.Consult doctor is a MUST for changing of treatment plans.