The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Discussion Board Forums Chemotherapy & More The Use of Biomarkers-A Chemo Sensitivity Report For Cholangiocarcinom

Viewing 10 posts - 31 through 40 (of 40 total)
  • Author
  • #54936

    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,


    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.


    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.


    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.


    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.
    2010 Gastrointestinal Cancers Symposium
    Abstract No:
    I. Hwang, J. Jang, G.National University, Jinju, South Korea; College of Medicine, Dong-A University, Busan, South Korea;


    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.


    Below is the ASCO message about biomarkers usage.

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


    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,home,publishing and resources,what to know ASCO guidelines
    God bless.


    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,




    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.


    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.


    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
    **OFF NCCN compendium**

    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.

Viewing 10 posts - 31 through 40 (of 40 total)
  • The forum ‘Chemotherapy & More’ is closed to new topics and replies.