Radiation for R0? (Page 1 of 2)

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.

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.

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.

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.

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

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.

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

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

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

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

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.