1 (edited by PCL1029 Tue, 08 Oct 2013 07:18:20)

Topic: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi,everyone,
As  the use of  biomarkers will be the vision  of ASCO for  researching and  treating cancers in the next 10 years. I took the liberty to send  the biopsy tissues I had from my 2nd  liver resection to the lab.And 2 weeks later, I got my report  back and I would like to share with you.

The Lab. is Caris Life Sciences.(800-901-5177) in Phoenix,Arizona.
The test report is a"Target Now summary" with about 10 other pages of info. about biomarkers that they had done for me.
The requirement to get this done is either the request from your oncologist or surgeon.
The cost is depends on your insurance.
Is it worth  to have one done? Depends on what your expectation from the report.
Here is how the report looks like.( I have a hard time to copy the scan document and paste here,so I just type it out here.)

Caris Target Now Final Report

Clinical Dx=cholangiocarcinoma based on pathology report;Liver right lobe,wedge biopsy.(3cm)

Agents Associated with                   Agents Associated with* LACK OF*
Clinical Benefit                                         Clinical Benefit
**On NCCN compendium**
cisplatin,oxaliplatin                                  Irinotecan
fluorouracil                                              lapatinib
gemcitabine                                             trastuzumab
                                                               temozolomide
**OFF NCCN compendium**
carboplatin
doxorubicin,liposomal-doxorubicin
epirubicin
erlotinib,gefitinib
cetuximab,panitumumab
calcitriol,cholecalciferol
sunitinib,soranfenib
mitomycin
celecoxib.

The biomarkers they tested are ERCC1,TOP2A,TOP2B,TS,PTEN , EGFR,BRAF,KRAS,RRM2,VDR,VEGFR2,BRCA2 ,TOPO1,Her2/Neu, MGMT and PTGS2,c-kit,RRM1 and a microarray analysis  of  about 60 RNA expressions of the tissue sample(included some of the above biomarkers) This RNA expression  analysis just indicated whether my sample is UNDEREXPRESSED , NO CHANGE OR OVEREXPRESSED on each of the RNA they tested.

The methods they used in the tests included IHC, FISH, Molecular and Microarrayillumina.
The Lab also provided a brief description on the biomarkers they tested;and the references for the agents that show sensitivity to my tumor sample as well as the ones that show lack of the clinical benefits.

I will try to digest the report and report to all of you what I think about this test.
But I have already one complaint.
The "Caris Target Now report" does not give ranking(ie: high to low sensitivity) of the chemo or molecularly targeted agents that  I should use first .Instead they recommended the decision should be  made by the oncologists.
That means one thing I have to be hurry to read up on the biomarkers they tested and try to find the most sensitive agents to use first when I talk with my oncologist. 
MD Anderson uses Foundation life science Lab from the East like the one Mass general  used, you can also ask your tumor tissue sent there too for genome sequence and chemotherapy sensitivity report.

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: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Thanks Percy....
Am I right in thinking that the agents of benefit are based on previous and ongoing studies of all CC patients? 
How much clinical response is expected from treatments focused on the specific biomarkers? 
I can't wait to read your analysis.
Thanks for all the work you do.
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: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi,Marion,

The agents of clinical benefit are based on the  general understanding of the biomarkers used on studies or trials for other forms of cancers,like colorectal and lung cancer not from CCA ;The level of evidence or the criteria of the study validity and design is different  among the  agents.
For example;the level of evidence rated the agent cetuximab and panitumumab as level I/good, II-2/good and II-3/good in five studies.
GOOD means the studies  that my report based on are judged to be valid and relevant as regard to results,statistical analysis,and conclusions and show no significant flaws.(there  are 3 grades of study validity--good,fair and poor)
There are 5  levels of hierarchy of the study design(from I,II-1,II-2II-3 and III)
I means evidence obtained from at least one properly designed randomized controlled trial.
II-2 means evidence obtained from well-designed cohort or case control analytic studies,preferably from more than a single center or research group.
II-3 means evidence obtasined from multiple time series with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.
"How much clinical response is expected from treatments focused on the specific biomarkers? " I do not know yet,I need to read and study more before I can answer if anything at all.
Happy Thanksgiving to yuo all.
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: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi Percy,


Thank you so much for this and I so look forward to hearing more of your thoughts on this. And of course, I hope you had a great Thanksgiving with your family and ate lots of turkey!!


Best wishes,


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.

5 (edited by PCL1029 Fri, 25 Nov 2011 12:28:57)

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi,Gavin,
thanks.
Below is the ASCO message about biomarkers usage.

What to Know: ASCO's Guideline on Tests to Help Choose Chemotherapy

Introduction

To help doctors give their patients the best possible care, the American Society of Clinical Oncology (ASCO) developed evidence-based recommendations on the usefulness of laboratory tests (called assays) to find out if a cancer might be resistant or sensitive to a specific chemotherapy treatment before it is offered to a patient. In 2011, this guideline was reviewed due to new research; this research continued to support the 2004 recommendations. This guide for patients is based on ASCO’s most recent recommendations.

Key Messages

    Chemotherapy sensitivity and resistance assays are laboratory tests that have been studied to help predict how well chemotherapy may work.

    However, these tests should not be used to determine treatment options for an individual patient.

    Instead, the choice of chemotherapy should be based on the research on the drugs being considered and the patient’s health and treatment preferences.

For additional info, go to cancer.net,home,publishing and resources,what to know ASCO guidelines
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.

6 (edited by PCL1029 Mon, 28 Nov 2011 11:43:58)

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi, everyone,
For those who are interested in the bio markers subject,this is the continuation of my research based on my own results.

On the" Target Now" biomarkers report,my ERCC1 is negative by the IHC method but overexpressed by the microarrayillumina method.

This ERCC1 marker is used for  testing the  chemo sensitivity on cisplatin,carboplatin and oxaliplatin.(the platium group).
Usually when ERCC1 is overexpressed,the platin group is not recommended.
but my" Target Now "report said this group(the platium group) is associated with clinical benefit and is ok to use them because I think  my ERCC1 by IHC method is NEGATIVE and  supported by the following study that I dug up from my research.(see below).
God bless.

Different relation between ERCC1 overexpression and treatment outcomes of two platinum agents in advanced biliary tract adenocarcinoma patients.
Meeting:
2010 Gastrointestinal Cancers Symposium
Abstract No:
178
Author(s):
I. Hwang, J. Jang, G.National University, Jinju, South Korea; College of Medicine, Dong-A University, Busan, South Korea;

Abstract:

Background: Several clinical studies have shown that excision repair cross-complementation group 1 (ERCC1) overexpression is associated with resistance to platinum-based chemotherapy and poor prognosis in several tumors. However, these studies have never been tried on biliary tract cancer. The aim of this study was to evaluate the association between ERCC1 expression and treatment outcomes in advanced biliary tract adenocarcinoma (ABTA) patients treated with platinum-based chemotherapy. Methods: 106 patients with histologically confirmed adenocarcinoma of biliary tract were enrolled at 5 institutions between January 2002 and September 2008. Of 106 patients, 93 were assessed by immunohistochemistry from biopsy specimens. 65 patients were treated with cisplatin and the other 28 were treated with oxaliplatin. Results: ERCC1 expression was positive in 47 out of 93 specimens (51%). 20 (22%) of 93 patients showed response (including complete response and partial response). Among 20 patients who obtained response, eleven (55%) were positive for ERCC1 expression and nine (45%) were negative (p = 0.621). In subgroup analysis, ERCC1 expression of oxaliplatin treated adenocarcinomas was 13 of 28 specimens (46%). 6 (21%) of 28 patients achieved response. In patients treated with oxaliplatin, six (100%) were positive for ERCC1 and none (0%) were negative (p = 0.005) among the 6 patients who obtained response. With a median follow-up of 7.3 months (range, 0.8-47.5 months), median progression-free survival (PFS) and overall survival (OS) were 3.6 months and 7.3 months, respectively, and there were no significant differences of median PFS and median OS between ERCC1 negative and positive patients for the total study population (PFS, 4.2 versus 2.9 months, p = 0.116; OS, 7.0 versus 7.8 months, p = 0.143). In patients treated with cisplatin, the median OS was significantly longer in the ERCC1-negative group than in the ERCC1-positive group (9.1 vs 7.3 months, respectively; p = 0.017).
Conclusions: Patients with ERCC1-positive ABTA show a response benefit from oxaliplatin-containing chemotherapy. On the other hand, patients with ERCC1-negative ABTA show a survival benefit from cisplatin-containing chemotherapy.

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 eli Mon, 28 Nov 2011 20:08:05)

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi PCL,

I don't have any medical or bio training. Just trying to understand your last post.

You said:

Usually when ERCC1 is overexpressed, the platin group is not recommended.

Question: Is "overexpressed ERCC1" the same thing as "positive ERCC1"?

If yes, the study you posted doesn't seem to support your statement above.

They wrote:

Conclusions: Patients with ERCC1-positive ABTA show a response benefit from oxaliplatin-containing chemotherapy. On the other hand, patients with ERCC1-negative ABTA show a survival benefit from cisplatin-containing chemotherapy.

If their conclusion is correct, you can't reject the platinum group based on ERCC1 test.

Here's how I read your test results:

If you believe IHT method, cisplatin seems to be better.

If you believe microarrayillumina method, oxaliplatin seems to be better.

Could it be they recommended both cisplatin and oxaliplatin because they don't know which test method is more accurate?

Again, I have zero medical/bio training, so I maybe way off the mark here.

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi,Eli,
thanks to show interest on this bio markers subject.
IHC (Immunohistochemistry) method used "positive" and "negative " and microarrayillumia method used "under expressed","no change" and "over expressed" to describe the result.
The above study of the two platium drugs used the IHC methods and therefore they use the term positive or negative to describe their findings.The study did not use the microarrayillumia method.
So based on the IHC method,you are right that cisplatin is better for me because  of the NEGATIVE RESULT.
On the other hand  from the microarray analysis ,my overexpression  ratio for ERCC1 gene  is only3.11(ie: the ratio  is the difference in expression for this ERCC1 gene between my tumor and the control tissues.) I think my ratio is on the low side of the scale but I need to ask my oncologist for his opinion due to lower nephrotoxicity of oxaliplatin.
For a person has no medical training , and can show such interest and  understanding about the subject matter of CC. I have to tip my hat to you.
Your wife is lucky to have you on her side.
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.

9 (edited by eli Mon, 28 Nov 2011 23:34:52)

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

PCL, thank you for your detailed reply. I will study it tomorrow on a clear head.

Since you mentioned it... medical studies ARE hard to read. I had to learn a whole new language. (Pancreaticoduodenectomy with Lymphadenectomy?? Really??) My background helps a little bit. I'm a software engineer by day. I do research on the Internet all the time.

I must also say this... I'm very impressed by the volume and quality of your research that you post on this site. It's amazing you can pull it off while fighting this horrible disease. Kudos to you!!

I will be back with more questions.

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi PCL,

I re-read your response about ERCC1 results. Thank you for your explanation.

I have unrelated question:

My wife's surgery was 5 months ago. Is her resected block still viable to do the biomarkers test? Or is too late now?

I assume that her specimen was stored somewhere and not destroyed. If it was stored, I have no idea what method was used to preserve it. Need to confirm this.

Best wishes,
Eli

11 (edited by PCL1029 Tue, 29 Nov 2011 22:35:35)

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi,Eli,
You can request the pathology dept. of the hospital your wife had the surgery for the Tissue block and slides. However, it is not the 5month I will worry about but whether the hospital will have ENOUGH of the tissue left for you to do the bio markers chemo sensitivity.But it won't hurt to find out.
BTW,the tissue is preserved in paraffin and is good for years.
One thing is that ,I don't know whether it will be worth it if you have to pay for it 100% by yourself and not by your government. If I were you,I will wait till the next scan to see if the current chemo is working or not. If it works,then You may not need to spend the thousands of dollars.Mine was paid by the insurrance.
The bio markers test are not 100% as  useful as it seems to be partly because it is expensive and   is not widely used by the physicians because of the limitations of the results .(ie: like the CA19-9 is a bio marker for CCA,but the sensitivity and specificity of the test is still debatable; mine CA19-9 never higher than 28.but as you know it is not correlated with the suggested normal range of<37. And it is different from extra hepatic CCA which you can expect a much higher value.)
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: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

PCL, thank you for your response. Very thorough, as usual.

I asked just to figure out how much effort I should put into researching this subject.  If the tissue is not viable, I don't have to study the use of biomarkers.

Sounds like the test might be viable. I will ask our oncologist what he thinks.

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Re CA19-9: I noticed that US patients discuss it a lot. I asked our oncologist if he is going to use it. He said no. Too many false negatives/positives. He actually said that government insurance might not cover the cost of the test for surveillance purposes.

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

eli...that is interesting to hear.  The CA 19-9 is elevated in about 65 % of hepatobiliary cancer. It is taken at onset of chemotherapy treatments in order to monitor response and may be ordered several times throughout treatment.  Often times it will be monitored post treatment and taken in consideration in addition to Ct or MRI' scans.
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: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi, everyone,
Here is another company that can provide  biomarkers lab tests.;and it may be more advance according to this article segment than the "Target Now "report.(please see below)

    Roche’s  cobas EGFR Mutation Test received a CE mark. The regulatory stamp means the test will be commercially available as a companion diagnostic to identify non-small-cell lung cancer (NSCLC) patients with EGFR mutations who may benefit from anti-EGFR tyrosine kinase inhibitors.

    Roche itself has a tyrosine kinase inhibitor for NSCLC, Tarceva. The drug was approved by the EC in September as first-line monotherapy in patients with locally advanced or metastatic NSCLC with EGFR-activating mutations.

    Carried out on a section of tumor, the real-time PCR-based cobas EGFR Mutation Test detects 41 mutations across exons 18, 19, 20, and 21 of the EGFR gene. The firm claims the assay has a higher degree of sensitivity than Sanger sequencing and delivers test results within eight hours.

    The cobas EGFR Muation Test is the third cobas oncology diagnostic to be granted a CE mark this year. It joins the cobas BRAF Mutation Test for metastatic melanoma and the cobas KRAS Mutation Test for advanced colorectal cancer. All assays are carried out on the cobas 4800 system v2.0.

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: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi Percy,

What do you think about Chemo Sensitivity and Resistance Assays testing? Cell Culture Drug Resistance Testing is another name for the same test.

Did you know about this test before your second surgery?

If yes, why did you choose biomarkers test rather than chemosensitivity test?

A short summary of how it works:

When a patient has an infection, doctors often send a sample of infected blood or tissue to a lab where they can grow the bacteria and see which antibiotics are most effective (called Bacterial Culture and Sensitivity Testing). Chemosensitivity testing is an attempt to do something similar for cancer; fresh samples of the patient's tumor from surgery or a biopsy are grown in test tubes and tested with various drugs. Drugs that are most effective in killing the cultured cells are recommended for treatment. It is highly desirable to know what drugs are effective against your particular cancer cells before highly-toxic agents are systemically administered to your body.

More details here:
http://csn.cancer.org/node/145884

The test requires a fresh biopsy sample. It's not an option for many CCA patients, because CCA is hard to biopsy. My guess is it could be an option for two kinds of CCA patients:

- CCA patients with intrahepatic tumor that can be biopsied
- CCA patients who can pre-arrange the test before the surgery, and do it right after the surgery

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi,Eli,
The top message that I posted is the first page of my chemo sensitivity report .I cannot convert the image file to the PDF format for the copied report .that is why I type it out.Any suggestions so I can share the rest of the report on this web site.
Thanks again.
The chemo sensitivity report is called "Target  Now" report by the company.
Depends on where you order the report, you may not need fresh tissue sample for the  new machine that  some lab use to test your sample.
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.

18 (edited by eli Sun, 18 Dec 2011 18:22:44)

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Did they actually test various chemo protocols on your live cell cultures?  If not, your test is not the same as the chemo sensitivity test that I described in my previous post.

My understanding is:

  • "Target Now" is a biomarkers test. It measures a number of known biomarkers in the tumor.  Once biomarkers are measured, they list the drugs that are expected to work best.  They don't actually test those drugs on live cells. This test does not require a fresh biopsy.

  • Chemosensitivity test requires live cells that can be grown in test tubes. Your oncologist tells the lab which drug combinations to test.  The lab tests the requested drug combinations on live cell cultures and reports how well they work. This test requires a fresh biopsy.

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Re sharing your report:

What format is it? Is it an image or a PDF?

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi,Eli,
Your understanding is correct about the "Target Report Now".
And that is what it is as you said they listed the drug that are EXPECTED to work.and that report cost about 8,000 insurance money.
I did it because I want to know exactly what a patient can be expected from the report just in case patient on the web ask me questions about it;and partly also because the vision ofASCO they put out recently.
Unless the patient is very rich and can pay the lab to do the fresh tissue report,I personally think it will be done very often.
BTW,my report is on image format and need to convert to PDF format in order it can be share on the web.
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: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

You don't have to convert the report to PDF.

1. Open the image in Windows Paint
2. Wipe out all personal details such as name, address, etc. Draw solid black rectangles over them.
3. Save the new image
4. Put it on a free file hosting service ***
5. Post the link to the shared file here

*** If you have gmail account, you can use Google Documents as your file hosting service:

1. Log into your gmail account
2. Switch to Documents (a link at the top of the page)
3. Upload your report file from your hard drive
4. Share the file
5. Post the link to the shared file here

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi,eli,

THANKS,THANKS.
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: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi, eli,
Let see how it looks,I hope it works.
Thanks
God bless

https://docs.google.com/open?id=0B9UTQL … YwZjBlMDA3

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: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Percy, I see one report page.  Is that all you wanted to share?  Or are there any other pages?

Since the page doesn't have any personal details, I took the liberty to put it on a free image sharing service: imgur.com

Here's the link:
http://i.imgur.com/QtdsG.jpg

While the image is hosted on imgur, it's also possible to embed it right here:

http://i.imgur.com/QtdsG.jpg

25 (edited by PCL1029 Sun, 18 Dec 2011 21:14:43)

Re: The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Hi,eli,
it works, all I need is click the download button,and then I can adjust the size of the copy.
Thanks,it will help all of us in the future.
BTW yes, this is a general info copy  ,I will share the rest later.
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.