Topic: Radiation for R0?

My wife was resected for Intrahepatic CC on 9/12 with great results.  72% of the liver with a 6.4 cm. tumor and a single hilar lymph node with metastatic carcinoma was removed.  The results were great, margins clear, and 6 other lymph nodes benign, classified R0.

We met with the Ochsner oncologist Monday and she recommended the GemCis regiment, which we expected, but she also stated that radiation may be used after around 4 months of chemo.  We did not expect this since my wife's surgeon said that radiation would not be necessary.

Is radiation normal for this type of CC with these resection results and if so, what do they radiate?

Bruce Baird

Please be advised that any advice or information in my posts is my personal opinion only and is not intended nor implied to be a substitute for professional medical advice.  ALWAYS seek the advice of your physician or other qualified health care provider.

2 (edited by eli Wed, 24 Oct 2012 19:09:08)

Re: Radiation for R0?

Hi Bruce,

NCCN Hepatobiliary Cancers Guidelines (the current standard of care in the US) do not recommend radiation for R0 margins.

You need to register for a free account to see the guidelines.

See slide #22 (INTRA-2)
http://www.nccn.org/professionals/physi … iliary.pdf

However, some oncologists take more aggressive approach. This is not entirely unreasonable, given high recurrence rate after resection.

I've been on this board for about a year. Off the top of my head, I recall one other patient who received radiation after R0/N0 resection.

I strongly recommend that you seek 2nd and 3rd opinions about this.

Best wishes,
Eli

Re: Radiation for R0?

Now that I thought about it a bit more, I remember another member who received radiation after a clean resection. That's two in the last year, just going by memory.

As to what they radiate:

Parts of liver, bile ducts, the surrounding lymph nodes.

Re: Radiation for R0?

Thanks Eli.  According to the paper "Intrahepatic Cholangiocarcinom: resectability, recurrence pattern, and outcomes," Journal of the American College of Surgeons, v193, n4, pp 384-391, Oct. 2001, which I found from a link on one of these boards, recurrence in 20 patients, was identified as liver (14), retroperitoneal or hilar nodes (4), lung (4), and bone (2).  I only have the abstract for the paper and it didn't break down the recurrences into how many were R0 and other factors, but the fact that it would show up in the lungs and bone made me wonder if they would radiate those also.

Bruce

Please be advised that any advice or information in my posts is my personal opinion only and is not intended nor implied to be a substitute for professional medical advice.  ALWAYS seek the advice of your physician or other qualified health care provider.

5 (edited by eli Wed, 24 Oct 2012 19:54:44)

Re: Radiation for R0?

No, they would not. They radiate the area surrounding the tumor.

EDIT:

If you want to read medical papers on the subject, search PubMed database. It indexes all articles published in the peer-reviewed medical journals.

http://www.ncbi.nlm.nih.gov/pubmed

EDIT 2:

But...

NCCN Guidelines are based on the published medical papers. The expert panel that writes the Guidelines reviews all new papers twice a year or so. Whenever new evidence comes out, they update the Guidelines.

Re: Radiation for R0?

Thanks Eli.  It appears the NCCN Guidelines don't even recommend chemo for an R0 resection unless it is in a clinical trial.  Am I interpreting that correctly?

Bruce

Please be advised that any advice or information in my posts is my personal opinion only and is not intended nor implied to be a substitute for professional medical advice.  ALWAYS seek the advice of your physician or other qualified health care provider.

Re: Radiation for R0?

Yes, you are correct.

Keep in mind, the evidence to recommend or not recommend chemo/radiation is weak. CC is a rare cancer, so large randomized Phase 3 clinical trials are difficult to conduct. Most CC trials are small and non-randomized (aka Phase 2 trials). The evidence that comes out of such studies is not conclusive.

Also keep in mind, your wife had a positive lymph node. That's a significant risk factor. Take a look at the similar slide for extrahepatic cholangiocarcinoma (Slide #24, EXTRA-2). The patients with positive lymph nodes follow the same path as patients with R1/R2 margins. But note the wording. They say Consider chemoradiation or chemotherapy, rather than Do.

Re: Radiation for R0?

Bruce, one more thing:

If you want to read the discussion behind NCCN recommendations, see slides 59 - 62.

Re: Radiation for R0?

Bruce, I keep finding more reading material for you.

You may want to review two recent papers that I linked in this thread:

Adjuvant treatment in biliary tract cancer: To treat or not to treat?
http://www.cholangiocarcinoma.org/punbb … hp?id=8426

See the links in the first and the last posts.

Re: Radiation for R0?

Hi Bruce.

I had intrahepatic cc with my tumor removed 1 1/2 years ago.  I was R0, negative lymph nodes and clean margin, though one margin was close.
I got 3 cycles gem/cis, 6 wks chemo radiation with Xeloda, 3 more cycles gem/cis.
I went to 3 different hospitals for opinions on the radiation. 
University of Pittsburgh said chemo only, nothing to radiate. (this is where I had my surgery)
Oregon Health and Science at first said only chemo radiation but then went to tumor board and said chemo + chemo radiation. (this is where I live and got the chemo and radiation)
Mayo said chemo and they are not currently recommending radiation for R0 patients, but they are not necessarily opposed to it and if I wanted to proceed with it, they understood because of the close margin.  ( I just went there for another opinion)
Mayo was able to provide me with one study where radiation showed some benefit and another study where it showed no benefit.
I think it is a personal choice.  There is not much data to show any benefit and no benefit was promised to me.
But, the other thing to consider is there are not many R0 patients even out there to study.
I was 31 at diagnosis and otherwise healthy, so I was all for getting as much adjuvant therapy as they would give me.
It is a difficult decision and I wish you the best.
If you have any questions about my radiation experience, please feel free to ask.
Maybe another opinion will help you make the decision?

take care,
Susie

Re: Radiation for R0?

Thanks again Eli.  I checked the NCCN Guidelines Version 2.2012, Extra-2.  It states "Consider fluoropyrimidine chemoradiation {f} (brachytherapy or external beam) followed by additional fluoropyrimidine or gemcitabine chemotherapy or Fluoropyrimidine based or gemcitabine based chemotherapy for positive regional lymph nodes {h}"  I don't know how to interpret that statement.  Does consider apply to both part.  As written it can be interpreted to read that "consider" doesn't apply to the chemotherapy for positive regional lymph nodes and that "consider" only applies to the combination chemoradiation and chemotherapy for R1 or R2 or carcinoma in situ at margin, or positive regional nodes.

The paper you linked to, "Adjuvant treatment in biliary tract cancer: To treat or not to treat?" states the following under Guidelines and Current Clinical Practice. "The National Comprehensive Cancer Network (NCCN) guidelines recommend only observation or adjuvant CRT with concomitant fluoropyrimidine for patients with R0 margins or negative lymph nodes and adjuvant therapy with concurrent 5-fluorouracil-based CRT followed or not by additional fluoropyrimidine or gemcitabin-based regimens in patients with R1 margins or metastic lymph nodes."  So it appears here that the NCCN is recommending CRT with or without chemo for positive lymph nodes.

Also, it appears that the recommendation is to do radiation followed by chemo, whereas what the Ocshner oncologist proposes is to do chemo followed by radiation.

All very confusing to me.

Susie, thank you for your comments.  It makes me wonder about second and additional opinions.  I first ran into this when the Ochsner surgeon and his cancer board said to operate and the Southwest Medical Center and their cancer board said not to operate.  We ended up getting a third opinion from a Baylor surgeon, who was the Ochsner's surgeon's mentor, and he said to operate, which I expected because of the mentor relationship.  When we first met the Ochsner oncologist, she said that Ochsner was agressive and then rattled off about 5 other cancer centers which were either agressive or not.  I kind of got the idea that this is tied in with their "do no harm" vow.  The agressive doctors give me the impression that they will try almost anything to extend your life, even if what they are trying has not been statistically proven, whereas the non-agressive doctors don't seem to want to take the chance that they may cause you harm.

As you say, in the end, it's a personal choice, but I, like you, would prefer to get as much adjuvant therapy for my wife as they will give her.

Bruce

Please be advised that any advice or information in my posts is my personal opinion only and is not intended nor implied to be a substitute for professional medical advice.  ALWAYS seek the advice of your physician or other qualified health care provider.

Re: Radiation for R0?

Hi Bruce,

2000miler wrote:

I checked the NCCN Guidelines Version 2.2012, Extra-2.  It states "Consider fluoropyrimidine chemoradiation {f} (brachytherapy or external beam) followed by additional fluoropyrimidine or gemcitabine chemotherapy or Fluoropyrimidine based or gemcitabine based chemotherapy for positive regional lymph nodes {h}"  I don't know how to interpret that statement.  Does consider apply to both part.

In my (non-expert) opinion, consider applies to both parts.

Chemoradiation is used to treat positive margins and regional lymph nodes. Chemo is used to treat distant spread. Both treatments lack solid statistical evidence provided by Phase 3 clinical trials. Therefore, they have to use weasel words like "consider".

2000miler wrote:

The paper you linked to, "Adjuvant treatment in biliary tract cancer: To treat or not to treat?" states the following under Guidelines and Current Clinical Practice. "The National Comprehensive Cancer Network (NCCN) guidelines recommend only observation or adjuvant CRT with concomitant fluoropyrimidine for patients with R0 margins or negative lymph nodes and adjuvant therapy with concurrent 5-fluorouracil-based CRT followed or not by additional fluoropyrimidine or gemcitabin-based regimens in patients with R1 margins or metastic lymph nodes."  So it appears here that the NCCN is recommending CRT with or without chemo for positive lymph nodes.

The paper is written by Italian doctors. Italy has a strong expertise in treating cholangiocarcinoma. However, I wouldn't necessarily rely on their interpretation of NCCN guidelines. They may be missing some nuances of the English language. (The rest of the paper is still valuable for its discussion of adjuvant therapies)

Did you have a chance to read the second paper I linked?

Adjuvant Therapy Beneficial in High-Risk Biliary Tract Tumors: Meta-Analysis
http://www.medscape.com/viewarticle/762919

They reviewed a very large sample of patients from numerous previous trials. You may need to register for a free Medscape account to read it.

2000miler wrote:

Also, it appears that the recommendation is to do radiation followed by chemo, whereas what the Ocshner oncologist proposes is to do chemo followed by radiation.

There is no definitive standard.

My wife did chemoradiation followed by 6 cycles of chemo. FYI, she had R1 margins and 2 positive nodes after Whipple resection of extrahepatic CC.

Susie did 3 cycles of chemo, followed by radiation, followed by another 3 cycles of chemo.

Derin (another one of our members) did chemo followed by radiation.

13 (edited by betzeegirl Sat, 27 Oct 2012 18:12:47)

Re: Radiation for R0?

my husband, who had an R0 resection for ICC with "close" margins and 1 positive (celiac) lymph node, just completed his adjuvent therapy--gem/xyloda for 4 months, then 5 1/2 weeks of mon-fri radiation. Dr Gassan Abou Alfa of Sloan is his oncologist, though we also consulted with Dr. Abby Siegel of Columbia Presbyterian. Their thinking was that the positive lymph node (even just one), made this the appropriate course of action. Thankfully, my husband tolerated the whole thing pretty well.

Re: Radiation for R0?

Bruce, I am treated at the Cleveland Clinic. I had my first resection in Sept. 2010 with close margins but one lymph node in gallbladder was positive. I had 6 months of chemo(5FU) and no radiation.  The cancer came back and I had another resection, during surgery they radiated the area where the two tumors were removed. I recently had two tumors radiated and it seems my tumors respond to radiation better than chemo. Since there was one positive node, I would take the chemo and radiation, if it was me.....
Lisa

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: Radiation for R0?

Eli - I did read the article about adjuvant therapy in high-risk biliary tract tumors and noticed the authors mentioned the greatest benefit for adjuvant therapy was in those people with positive lymph node disease or mcroscopic positive margins after resection.  For positive lymph nodes, they stated the 5-year odds ratio was 0.49.  I couldn't find what the 5-year survival probability was for an R0 resection with a positive lymph nodes, but if it is 20%, then I calculated the 5-year probability of survival with adjuvant therapy would be 34%.

Well, that's a start.  The researchers searched for studies published from 1960 through 2010 and used 20 of these, but the article didn't say what dates these 20 studies included.  Since they are using 5-year suvival rates, I would assume that resections were done before 2005 although I suppose they may use some sort of algorithm to estimate 5-year survival rates from shorter term rates.  I would think the use of old data would bias their outcomes in favor of older surgical procedures and adjuvant therapies and would hope that newer techniques and adjuvant therapies would increase these numbers.

Audry and Lisa, thank you for your comments.  We just saw the Ochsner radiation oncologist today and it looks like my wife's planned treatment is Gem/Cis for 4 month, then 5 weeks of Mon-Fri radiation with F5U.  Audrey, did your doctors give you a reason for using Xyloda (Capecitabine) instead of Cisplatin?  Lisa, did your doctors give you a reason for using 5FU instead of Gem/Cis?  I understood that Gem/Cis was now the chemo of choice for CC.

Thanks again,

Bruce

Please be advised that any advice or information in my posts is my personal opinion only and is not intended nor implied to be a substitute for professional medical advice.  ALWAYS seek the advice of your physician or other qualified health care provider.

Re: Radiation for R0?

Bruce, there isn't enough research and everyone responds differently. The 5FU worked for me and the Gem/Cis did not. We got the results back from a lab that analyzed a piece of my original tumor that had been frozen. I have two identifiable mutations so next time we should be able to use a more specific chemo that targets those mutations. Did they freeze any of your wife's tumor for research ?
Lisa

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: Radiation for R0?

Lisa- I don't know if they froze the tumor but I'll sure check it out.  Very interesting.  I thought that all cholangiocarcinomas were the same.  I didn't realize that we could be dealing with different mutations.

Bruce

Please be advised that any advice or information in my posts is my personal opinion only and is not intended nor implied to be a substitute for professional medical advice.  ALWAYS seek the advice of your physician or other qualified health care provider.

Re: Radiation for R0?

Bruce...Several mutations have been recognized, Percy compiled the listing for us:
http://www.cholangiocarcinoma.org/punbb … hp?id=7843
I hope this helps.
Hugs,
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: Radiation for R0?

Marion - That link takes me to a list of chemo agents.  I searched the site for mutations and found a lot of information about them, but couldn't find a list of them.  Is there another link?

Bruce

Please be advised that any advice or information in my posts is my personal opinion only and is not intended nor implied to be a substitute for professional medical advice.  ALWAYS seek the advice of your physician or other qualified health care provider.

20 (edited by eli Wed, 31 Oct 2012 16:11:50)

Re: Radiation for R0?

Bruce,

Genetic mutations in CC are poorly researched. I'm not aware of a "master list" of mutations that contains all of them. At present, most clinical decisions are NOT driven by genetics.

CC patients typically receive one of the mainstream chemo protocols, such as Gem/Cis, Gem/Ox, Gem/Cap, etc. Currently there is no reliable way to determine which protocol is the best for the given patient.

21 (edited by marions Fri, 02 Nov 2012 16:04:45)

Re: Radiation for R0?

I have learned that less than 3-10% of all cancers are caused by a genetic mutation and that not all of these mutated cancers can be targeted with drugs.
However, some physicians recommend genetic testing for those at high risk for certain cancers.  We do not have a specific test for our cancer however; I believe that due to the similiarties to ovarian, breast, and pancreatic cancer some people test for the BRCA1, BRCA2 gene.   
We know that cancer is the result of uncontrollable cell growth not following the orderly path of:
1. cell grows,
2. cell division,
3. cell death (apoptosis.)
A breakdown of this normal behavior leads to out of control cell growth forming a mass.
Percy’s in his posting lists the drugs used for our cancer.  Additionally he mentions the specific pathway inhibitors.
I would like to point out that within the last few years researchers have focused on developing drugs that hinder the multiple signaling pathways leading to tumor growth. 
For example: the epidermal growth factor receptor (EGFR) shows significant response to Erlotinib (TARCEVA) and Sorafenib (NEXAVAR.)   
As Percy mentioned, most of the colon and pancreatic cancer studies transfer to our cancer. For example studies on mutations on the gene that encode KRAS may predict whether a colorectal patient will respond to a certain drug therefore, several of the KRAS clinical trials include Cholangiocarcinoma patients. 
As mentioned by Eli few studies have been conducted on genetic mutations, but for our cancer there are none. 
This is an interesting topic, Bruce, and I hope that in time we can continue to build on it.  Better yet, it would be nice to have a researcher explain things in detail.  And, that may very well happen soon.
Hugs,
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: Radiation for R0?

Marion - Very interesting introduction to genetic mutations and cancer for me. I'm going to have to dig into this more fully.

In reponse to Lisa's question regarding whether they have frozen my wife's tumor, we met with the surgeon yesterday and he told me they didn't freeze it, but they did preserve it.

During the meeting, I asked the surgeon for his opinion regarding radiation for my wife's condition (Intrahepatic CC with 1 hilar lymph node (R0)), which was the original question for this topic.  I also inquired about the proposed chemo treatment.  Now this surgeon has a PhD also, so I expected he was pretty much on top of the research in this area.  He told me he didn't think either chemo or radiation would be that helpful for my wife.  He said that a few years ago nothing helped, then a study was done which said that GemCis added a couple of months to a person's life and after that GemCis became the choice of chemo.  He didn't tell me the name of the study, but it appears it was the UK ABC-02 trial which showed that the progression-free survival for advanced or metastatic biliary tract cancer was 8.5 months for GemCis vs. 6.5 months for Gem alone.

However, when asked if my wife should undergo chemo and radiation, he said, "If its offered, take it."

Bruce

Please be advised that any advice or information in my posts is my personal opinion only and is not intended nor implied to be a substitute for professional medical advice.  ALWAYS seek the advice of your physician or other qualified health care provider.

Re: Radiation for R0?

Hi Bruce,

Yes, ABC-02 is the code name of the Phase 3 study done in the UK. Here it is:

http://www.nejm.org/doi/full/10.1056/NEJMoa0908721

Note a couple of things:

1. The study found that GemCis extended survival compared to Gem alone. It did not prove that GemCis is better than any other double-agent chemo protocol such as GemOx or GemCap. GemCis became the unofficial standard of care because it's the only protocol with a Phase 3 study behind it.

2. The study included patients with advanced disease (unresected or metastatic cases). The results of the study do not apply directly to the adjuvant setting (resected patients). Medical community extrapolates the results of ABC-02 to resected cases, but that's really a leap of faith.

Re: Radiation for R0?

Thanks, Eli for your time, effort and well thought out responses (to all questions on this board). Helped me to really understand why there are so few standard protocols with CC treatments, and specifically with adjuvant tx after RO resections. Curious, Are you in the science field?

Willow

Re: Radiation for R0?

Willow, you are welcome. No, I'm not in the science field. I'm a software engineer.