What is germline testing?

Germline testing is done with a routine blood sample. If your oncologist decides that germline testing could be beneficial for you, you will get a referral for genetic counseling.

The genetic counselor will order the test, help you interpret the results, and give you cancer screening recommendations for you and your immediate family members.

Who should get germline testing?

Most colorectal cancer cases are not caused by heritable genetic mutations. Also, some insurance plans do not cover this type ot testing. Because of this, germline testing is usually only recommended for some patients, such as those diagnosed at a young age or at an advanced stage.

If you have questions about whether germline testing is right for you, ask your oncologist. If you have questions about how to cover testing costs, contact your insurance company or speak to the genetic counselor at your cancer center. Some testing companies have financial assistance programs for patients whose insurance does not cover test costs.

How do I interpret my results?

It’s important to discuss the results of your test with your genetic counselor to make sure you’re getting the most accurate and complete information.

To make things a bit easier, here’s a sample report:

If you look at the “results” section, this patient does not have any specific mutations that makes them more likely to get cancer.

However, this patient has a mutation in the BRIP1 gene. This is classified as a variant of unknown significance — which means it is a gene mutation that has not yet been definitely associated with cancer.

In the “interpretation” section, the report explains that there were “no known clinically actionable alterations,” which means that there is nothing for the patient to take action on at this time.

Because gene lists are constantly being updated, it’s a good idea to contact your genetic counselor annually to see if there are any changes that may affect your report.

Your report may also come with a list of screening recommendations for you and your immediate family members. The report may look something like this:

Want to learn more about germline testing?

Check out this link from the National Cancer Institute, where you can find more information.

Do you have a heritable mutation? Want to chat with other patients with a similar diagnosis? 

Come join us in COLONTOWN!

  • Tom’s Inherited Mutation Clinic is for patients with heritable mutations such as Chek2 or BRCA
  • In Lynchville, you can chat with patients and survivors with Lynch Syndrome

Interested in joining? Fill out the registration form here.

COLONTOWN University has so much more to offer, from DocTalk videos with CRC experts to easy-to-understand biomarker test breakdowns. We’re here for you! See our list of Learning Centers here.

Last updated: May 18, 2022

What are liquid biopsies?

A solid tumor is made of cells that are constantly turning over. This means that while some cells are dying, others are growing and dividing to replace these dead cells. A tumor grows if there is more cell division then cell death. A tumor shrinks if more cells in it die than divide. Therefore a tumor is stable when cell death rates are the same as cell division rates. 

When cells die, they shed fragments of their DNA into the bloodstream. This is called circulating cell-free DNA, or cfDNA.

The same thing happens with tumor cells — and we call this circulating tumor DNA or ctDNA. We can think of this as “tumor trash” in the bloodstream.

ctDNA makes up only a tiny portion of the cfDNA found in your blood — but we can detect it. That’s because tumor DNA is different from healthy cell DNA due to the presence of specific mutations.

A blood test to detect ctDNA is often called a liquid biopsy, or a blood biopsy. Some tests require just a blood sample, others require a tumor sample as well.

If just a blood sample is used, we call this a tumor-naive test — meaning that the test checks for the same things for every patient with a standard panel. In a tumor-informed test, the company first evaluates your tumor, then creates an individual tumor-specific panel for screening your blood.

Tumor-naive ctDNA tests give results faster, while tumor-informed tests may have slightly better sensitivity. 

How can liquid biopsies be used?

In general, there are two ways to use ctDNA tests:

1. Minimal residual disease (MRD) testing

MRD testing is frequently used for monitoring and surveillance. That means if they come back positive, you most likely have a tumor growing somewhere in your body.

The good news is these tests can often detect tumors before they are visible on scans, and prompt more frequent imaging tests to figure out where the tumor is.

These tests are most often used in early stage CRC, after patients have undergone treatment for their cancer. They may also be used in limited (often called oligometastatic) stage IV cancer, after patients have finished treatment.

Examples of this kind of testing include Signatera and Guardant REVEAL. 

2. Mutation detection

The other kind of ctDNA test is aimed at detecting specific mutations in patients with growing tumors. These tests can also provide information on your tumor mutational burden (TMB) numbers.

Examples of this kind of test include Guardant 360 and Foundation One Liquid. 

Pros of liquid biopsies:

These kind of tests can give you a glimpse at your disease in real time, because blood samples can be taken regularly. Blood samples are also less invasive than tumor tests, which require a tissue sample.

Cons of liquid biopsies: 

Chemotherapy may suppress the release of ctDNA and affect your results. Also, these types of tests are relatively new — so doctors are still learning about accuracy, limitations, and the best ways to use them for surveillance.

Want to learn more about ctDNA tests for colorectal cancer? Check out this video:

 

What kind of liquid biopsies are there?

Let’s take a look at some of the common liquid biopsy tests that are being used at the moment. 

Guardant360 CDx

The Guardant360 CDx test covers every guideline-recommended biomarker for those with advanced colorectal cancer, including MSI, expanded KRAS/NRAS, and BRAF mutations.

It’s important to note that Guardant360 CDx is different from Guardant360 — which provides extensive panel testing beyond the guideline-recommended biomarkers.

This video is a good introduction to the Guardant360 CDx test:

For more information on the test, as well as a copy of a sample report, check out this section of our Diagnosic and Surveillance Tests learning center

Guardant REVEAL

Guardant REVEAL is the first ctDNA test for minimal residual disease (MRD) and recurrence monitoring that does not require tumor tissue. It only requires a blood sample. 

The Guardant REVEAL test can be ordered approximately one month after surgery to determine if there is any cancer left in the body — or as regular surveillance at the end of treatment to help your doctor spot cancer recurrence early.

The results from Guardant REVEAL are available approximately one week after the sample is received. 

What’s the difference between Guardant360 and Guardant REVEAL?

The Guardant REVEAL test is for patients with early-stage colon or rectal cancer (stage II-III). It looks for evidence of residual or remaining cancer after surgery or systemic treatment.

Guardant360 is a liquid biopsy test for patients with advanced colon or rectal cancer (stage IV). It provides comprehensive genotyping of an extended panel beyond the guideline-recommended biomarkers.

Learn more about the REVEAL test with Guardant’s Medical Science Liason Leslie Bucheit and PALTOWN’s Scientific Director Dr. Manju George:

 

For even more information, as well as a copy of a sample report, check out this section of our Diagnostic and Surveillance Tests learning center

Signatera

Signatera is a new blood test that can identify molecular residual disease (MRD) or cancer recurrence by detecting ctDNA. This test also requires a tumor sample.

Signatera is a custom-designed test that is generated based on each patient’s unique set of tumor mutations. Knowing earlier if your cancer is likely to recur — or has progressed after treatment — can help you and your doctor have a more informed discussion on how to treat your disease.

Here’s a short introduction to Signatera, from Natera Oncology:

 

When should you consider Signatera?
  1. At initial cancer diagnosis, to establish a baseline before surgery or treatment
  2. After surgery, before starting chemotherapy
  3. During treatment, to evaluate how well you’re responding to therapy
  4. After treatment, to monitor for tumor response or molecular residual disease (the presence of ctDNA in your blood)
What’s the difference between Signatera and other ctDNA tests?

As we mentioned earlier, a Signatera test requires both tumor tissue and a blood sample to create a customized test. 

Signatera can be ordered multiple times over the course of treatment or during follow-up visits to look for signs of recurrence. Once created, your doctor can asses whether there is any cancer left in the body with just a simple blood draw.

Want to learn more about these tests?

Visit COLONTOWN University’s Diagnostic and Surveillance Tests learning center. 

Or come join us in Colontown Downtown, where you’ll find an active discussion on all types of testing and opportunites to ask questions!

Interested in joining? Fill out the registration form here.

COLONTOWN University has so much more to offer, from DocTalk videos with CRC experts to easy-to-understand biomarker test breakdowns. We’re here for you! See our list of Learning Centers here.

Last updated: May 18, 2022

What is tumor testing?

Tumor testing requires a biopsy — a small tissue sample of your tumor. Tumor samples can be collected during a colonoscopy, taken from surgically removed tissue, or biopsied as an outpatient procedure.

A variety of tests can be done on your tumor sample. Technicians can examine tumor proteins (by immunohistochemistry) or isolate and sequence tumor DNA (by a mutation panel). DNA sequening is usually done by testing companies that check for concerning changes in a selection of CRC-relevant genes.

A tissue test can tell you if your tumor is MSS or MSI-H, which can influence whether or not you qualify for immunotherapy treatments. It can also identify biomarkers such as KRAS and BRAF, which may influence chemo decisions in later-stage patients. Some examples of this kind of testing include Foundation One, Caris, and Tempus.

If no mutations are identified, a gene will be described as “wild,” “wild type,” or “WT.” This means that the gene tested is normal, or unmutated.

There are also some tumor tissue tests for stage II and III patients that can determine the likelihood of recurrence. This can help your doctors choose what chemo protocol is most appropriate for you. Some examples include Oncotype DX and Immunoscore. It’s always a good idea to research how accurately these tests can predict recurrence.

Pros of tumor testing

Chemotherapy will not affect the accuracy of this kind of test. Some mutations that tumor testing can identify are very rare — such as POLE, POLD, or NTRK fusions — but there are effective treatments for patients in these groups. Therefore it’s important that you find out if your tumor has them.

Cons of tumor testing

Tests requiring tumor tissue are more invasive than blood tests — making them inconvenient to repeat regularly. If your tumor biopsy was taken when you were first diagnosed, your genomic profile may have changed slightly after months or years of receiving treatment. Therefore the results of an older tumor test may not give you the most up-to-date information. However, it’s unlikely that these mutation changes would significantly affect your treatment plan.

Want to learn more about testing?

Come join us in Colontown Downtown, where you’ll find an active discussion on all types of testing and opportunites to ask questions!

Interested in joining? Fill out the registration form here.

COLONTOWN University has so much more to offer, from DocTalk videos with CRC experts to easy-to-understand biomarker test breakdowns. We’re here for you! See our list of Learning Centers here.

Last updated: May 18, 2022

What kind of biomarker tests are available?

If you’ve just been diagnosed with colorectal cancer, you’ll likely be given a variety of different tests based on your specific diagnosis and circumstances.

Some of the tests you may take include:

In this video, COLONTOWN’s Scientific Director Manju George gives an excellent overview of the first three types of testing:

 

Still confused? Don’t worry! We’ll go into each type of testing in more detail in the following sections.

Want to learn more about testing?

Come join us in Colontown Downtown, where you’ll find an active discussion on all types of testing and opportunites to ask questions!

Interested in joining? Fill out the registration form here.

COLONTOWN University has so much more to offer, from DocTalk videos with CRC experts to easy-to-understand biomarker test breakdowns. We’re here for you! See our list of Learning Centers here.

Last updated: May 18, 2022

Cancer and my genes

Genes are instruction manuals for your cells. What can testing your genes tell you about your cancer?

First off, let’s talk about the words we use to describe testing. Tumor genomic testing and genetic testing are often used interchangably, but they actually refer to two different things.

  • Tumor genomic testing is used to find DNA mutations in your tumor cells
  • Genetic or germline testing is used to find out if you have heritible gene changes that you have inherited from your parents and can pass on to your children

Genomic testing

As you grow and age, your cells have to replicate trillions of times — and sometimes, mistakes are made. An error in replication is known as a somatic mutation, as it happens to just one cell in your body.

Most of the time, these somatic mutations are completely harmless. Other times, like when mutations happen in oncogenes — important genes that contain instructions for cell division, programmed death, and other essential functions — you might end up with cancer.

Studying the specific mutations in your tumor’s DNA is known as genomic testing. This is also referred to as molecular testing.

Germline testing

If you were born with a specific gene variation (such as a variant that makes cilantro taste like soap!), this variation can be found in the DNA of every cell in your body.

This is what we call a germline mutation.

These mutations are inherited from your parents, and can be passed down to your children. Checking for such heritible mutations in your DNA is called germline testing. In the context of CRC, this would be done with the help of a genetic counselor. Your genetic counselor can explain how the test works, interpret the results, and tell you what you need to know about your family’s cancer risk. This information can help your oncologist and primary care physician decide what cancer screening recommendations are right for you and your family.

This is confusing, right? Let’s go over all that one more time.

Genomic testing refers to testing for somatic mutations in your tumor’s DNA. This is also called molecular testing.

Genetic testing refers to studying germline mutations you’ve had since birth.

Who should get genomic testing done?

Not everyone needs to be concerned about their tumor’s genomic profile.

For most people in stages I and II, the most important and successful therapy is surgery. For people who have stage III CRC, a combination of surgery and chemotherapy can be curative.

Getting extensive genomic testing may be a good idea for some stage III patients, especially if you have a family history of CRC (or any other kinds of cancers), are young (under 45 years old at diagnosis), or have a particularly aggressive cancer. Tumor genomic testing may not be covered by insurance for stage III patients.

About 30% of people with stage III CRC will progress to stage IV. For those with stage IV cancer, it’s very important to understand the genomic profile of your tumor. This helps you and your doctors figure out the nature of your tumor and see what else — in addition to first and second line chemotherapy — might be effective for you.

Who should get genetic or germline testing done?

Around 95% of colorectal cancers come from spontaneous somatic mutations, and around 5% come from inherited germline mutations. This means that for the majority of patients, germline testing is unlikely to turn up anything significant.

Your oncologist might order a germline test if you were diagnosed with cancer at a young age, or if you have a family history of colorectal cancer.

It’s important to know that about 30% of colorectal cancers have hereditary components — which means that your family may have an increased risk of CRC. However, the specific gene mutations responsible for your increased risk might not yet be known — and therefore not included in commonly available germline testing panels. So you may test negative for germline mutations even though there is a history of colorectal cancer in your family.

In these cases, it’s very important to bring up your family history of CRC with your care team and discuss how you can stay updated on research in this area. Newly discovered gene mutations are likely to be identified and added to the list of known inherited mutations, so germline panels will likely get updated as time passes.

It’s a good idea to save your germline testing results and reach out to your genetic counselor periodically to see if your panel has been updated to include new mutations. This information may be important for your kids and siblings.

Do you have a heritable mutation? Want to chat with other patients with a similar diagnosis?

Come join us in Colontown!

  • Tom’s Inherited Mutation Clinic is for patients with heritable mutations such as Chek2 or BRCA
  • In Lynchville, you can chat with patients and survivors with Lynch Syndrome

Interested in joining? Fill out the registration form here.

COLONTOWN University has so much more to offer, from DocTalk videos with CRC experts to easy-to-understand biomarker test breakdowns. We’re here for you! See our list of Learning Centers here.

Last updated: May 18, 2022

What are biomarkers?

When discussing testing and surveillance, you’ll likely hear people talk about biomarkers. But what are they?

In the context of colorectal cancer, biomarkers are typically proteins found in and released by the tumor or metastases. They can be detected using blood, other bodily fluids, or tissues.

What information can biomarker testing provide?

Biomarker testing can be prognostic or predictive. What does that mean?

  • Prognostic biomarkers provide information on the overall cancer outcome, regardless of specific therapy
  • Predictive biomarkers provide information on the effects of a potential intervention or treatment

Biomarker testing can provide personalized information, which can be used to:

  • Gain a better understanding of the prognosis of your cancer
  • Help predict how your cancer may or may not respond to a particular treatment
  • Guide treatment decisions
  • Predict potential severe side effects (toxicities) of treatment
  • Monitor cancer for recurrence

Still a bit confused? Take a look at this video from our friends at the Cholangiocarcinoma Foundation:

 

What are some common biomarkers?

MSS/MSI-H

All colorectal cancer patients should have their tumors tested for MSS/MSI-H status. This test is usually done on tumor tissue obtained from a biopsy during a colonoscopy, or from tissue removed during surgery. Approximately 85% of colorectal cancers are MSS, and about 15% are MSI-H. 96% of metastatic CRC is MSS, while 4% is MSI-H.

Even though MSI-H is relatively uncommon in stage IV CRC, it’s important to know this about your tumor, because patients with MSI-H CRC qualify for immunotherapy — which can result in a cure for a subset of these patients.

MSI-H tumors are much rarer in rectal cancer (found in 0.5-1% of patients). However, if the tumor is MSI-H, these patients are eligible for first-line immunotherapy trials.

For more information on MSS/MSI-H, click here.

RAS

All patients who are diagnosed with stage IV metastatic CRC should have their tumor tested for RAS status. There are three different RAS family members (KRAS, NRAS and HRAS) that can be mutated in colorectal cancer. However, HRAS is very rarely mutated. Approximately 40% of CRC patients have tumor mutations in the KRAS gene, and about 5% have mutations in the NRAS gene. If you do not have a RAS mutation, your report may say your tumor is “wild type” or “WT” — meaning your gene is normal and unmutated.

Not only is RAS mutation status important, but the specific variant should be identified, because treatment can be targeted to specific variants. Some common KRAS mutation variants are: KRAS G12C, G12D, G13C and AI46T.

For stage IV patients, your tumors’ RAS status is important for treatment decisions. Tumors with RAS mutations do not respond well to EGFR inhibitors, such as panitumumab and cetuximab, so if you have one of these mutations, you are not eligible to receive these drugs.

RAS mutations can also be acquired over time as a resistence mechanism to therapies such as EGFR inhibitors — so repeating RAS testing at disease progression or recurrence can be useful.

There are also clinical trials targeting specific RAS mutation variants, such as KRAS G12C, so knowing your RAS status can help you figure out which clinical trials you qualify for. 

Want to learn more about RAS mutations?

Join one of our COLONTOWN Facebook groups:

  • Check out the RAS Clinic to learn about patient and caregiver experiences about dealing with RAS-mutated CRC

Want to join? Fill out the registration form here.

BRAF

All patients diagnosed with colorectal cancer should have their tumors tested for BRAF status. BRAF mutations are found in 10-15% of CRC. If you do not have a BRAF mutation, your report may say your tumor is “wild type” or “WT” — meaning your gene is normal and unmutated.

One particular mutation — BRAF V600E in MSS CRC — can cause a much faster-growing cancer. Tumors with BRAF V600E mutations generally do not respond to EGFR inhibitors, such as panitumumab and cetuximab, alone or in combination with chemotherapy. However, these patients do respond to what is called a “Beacon doublet,” which combines an EGFR inhibitor (panitumumab or cetuximab) with a BRAF inhibitor (encorafenib).

Want to learn more about BRAF mutations?

Join one of our COLONTOWN Facebook groups:

  • Check out the BRAF Clinic to learn about patient and caregiver experiences about dealing with BRAF-mutated CRC

Want to join? Fill out the registration form here.

In this video, Dr. Kopetz gives an overview of the treatment options available for patients with BRAF mutations:

HER2/ERBB2

HER2 (also called ERBB2) amplifications/mutations are present in about 8% of rectal cancer and 3% of colon cancer, so it can be useful to test all CRC patients for HER2 gene alterations. HER2 gene alterations can also be acquired over time as a resistance mechanism to therapies such as EGFR inhibitors — so repeating HER2 testing at disease progression or recurrence can be useful.

If you have a HER2 amplification, there are drug treatments you qualify for. These drugs include trastuzumab with pertuzumab or lapatinib, either alone or alongside chemotherapy. In addition, you may be eligible for first-line clinical trials — but these trials are only available for people who have not started chemotherapy yet. So it’s very important that you ask your oncologist about HER2/ERBB2 testing and trials.

Want to learn more about HER2 mutations?

Join one of our COLONTOWN Facebook groups:

  • Check out the HER2 Clinic to learn about patient and caregiver experiences about dealing with HER2-mutated CRC

Want to join? Fill out the registration form here.

TMB

Tumor mutational burden (TMB) is a measure of gene mutations found in the tumor DNA. It is expressed as number/megabase (Mb). In general, MSI-H tumors have a higher TMB (greater than 20/Mb), while MSS CRC has a much lower TMB on average (around 4-6/Mb).

Many patients with MSI-H CRC are eligible for immunotherapy. Very rarely, MSS CRC patients with POLE or POLD mutations may have a very high TMB (greater than 100/Mb), and these patients are also likely to respond to immunotherapy. More commonly, a small subset of MSS CRC patients may have a TMB closer to 15/Mb, and these patients may respond to combination therapies with immunotherapy. Therefore it’s important for all patients with metastatic CRC to learn the TMB of their tumor and discuss options with their care team.

TMB testing is part of tumor genomic testing, and a variety of panels that include TMB are now available. TMB is usually determined from testing tumor tissue. This is called tissue TMB. TMB can also be calculated using a blood sample, and this is called plasma or blood TMB. The numbers above are tissue TMB numbers, and are not directly comparable to plasma TMB numbers.

More information about tumor genomic testing can be found in the Diagnostic & Surveillance Testing Learning Center.

CEA

Carcinoembryonic antigen (CEA) is a common tumor marker found in the blood. Testing for CEA levels can help determine if your cancer is growing, or if the cancer has returned. It’s usually included in regular blood tests CRC patients take during treatment and surveillance.

It’s important to note that not all colorectal cancers will express high levels of CEA, and it may not be a useful biomarker for all patients. Your cancer may be visible through scans, but your CEA levels may be within normal ranges. In these cases, other markers such as CA 19-9 (used less commonly for CRC) or circulating tumor DNA (ctDNA) may be additionally used to keep track of your cancer.

Individual CEA levels can vary remarkably between people. All it may reflect is whether or not your tumor is a high CEA expresser. For example, one person with stage IV CRC can have a CEA value of 8, while another patient with stage IV CRC may have a CEA of over 500 — or 50,000!

That’s why it’s important to notice the trend of CEA changes — how your CEA values change from diagnosis to after surgery to recurrence to stable disease. This can give you much more valuable information than a one-time number. Simple graphic tools can be used to figure out this trend, and they’re often available on online patient portals.

CA 19-9

CA 19-9 is not a commonly used biomarker for colorectal cancer patients, but it can be useful for people who have normal CEA at diagnosis. CA 19-9 is sometimes elevated with peritoneal metastases, and may be an additional biomarker for patients with BRAF mutations. Since this biomarker is not so commonly used in CRC monitoring, it’s a good idea to discuss whether or not it might be useful for you with your care team.

Sidedness

Sidedness is considered as a newer biomarker for CRC. Colorectal cancer that arises from the left and right sides of the large intestine have differences in their molecular makeup — which makes them more or less responsive to certain drug combinations.

Broadly, tumors in the cecum, ascending colon and transverse colon are referred to as right-sided CRC, while tumors in the descending colon, sigmoid colon, and rectum are referred to as left-sided CRC. 

Approximately 70% of tumors are located on the left side, and 10% are on the right. EGFR inhibitors (panitumumab and cetuximab) seem to be more effective in left-sided tumors. Right-sided tumors are more likely to be MSI-H, and patients with MSI-H tumors may qualify for immunotherapy.

ctDNA

Circulating tumor DNA (ctDNA) is a very recently identified biomarker that has attracted the attention of patients — and is the topic of discussion in many CRC support groups since 2019!

Simply put, ctDNA is tumor trash in the blood stream. If there is a tumor that’s growing in the body, the cells of the tumor turn over continuously. This means that at any given time in a growing tumor, more cells are dividing than dying. In a shrinking tumor, in contrast, more cells are dying than dividing. Dead cells shed pieces of their DNA into the blood stream. Tumor cells have mutated DNA, and ctDNA tests look for this mutated tumor DNA in the blood stream.

ctDNA can be thought of as an “ultra sensitive” CEA test, and can give you more information about cancer in your body. Since this is a very new biomarker, there are many uncertainties about its use — and it’s not widely accepted in the US or other countries. Whether ctDNA is useful for you is something to discuss with your care team.

The Diagnostic and Surveillance Test Learning Center has a lot of information on ctDNA testing and covers 3 commonly used tests. Dr. Stacey Cohen talks about the use of ctDNA in CRC in a very informative talk available in the Lecture Hall

Pharmacogenomic testing

Pharmacogenomic testing looks for mutations or polymorphisms that affect the function of enzymes involved in the metabolism or breakdown of drugs in the body. There are two main gene tests that are relevant to CRC patients undergoing chemotherapy. These are not usually done in the US, unless the patient develops severe side effects that warrant these tests.

DPYD

The DPYD or DPD gene codes for an enzyme that’s important in the metabolism (breakdown) of the drug 5FU (5 Fluorouracil) in the body. 5FU is the major component of chemotherapy for CRC. All patients who experience specific severe side effects like uncontrolled diarrhea, chest pain or discomfort, or dehydration after the first 1 or 2 cycles of Folfox, Capox, Folfiri or Folfoxiri can request a test for DPYD deficiency to rule out this rare condition. The test uses blood to look at genomic DNA for DPYD mutations.

Without this enzyme, your body can’t break down 5FU — so the drug builds up in your body. This causes severe side effects and toxicity. Complete DPYD deficiency is very rare (about 1 in 1000 people) but it can be life threatening if not managed immediately. Partial DYPD deficiencies are much more common, and need more extensive pharmacogenomic testing panels to identify all the gene changes that could cause it. If your team suspects you have a partial DPYD deficiency, they will likely manage it with a reduced dose and extra fluids. Always report your side effects promptly to your care team, so they can make sure your treatment is most appropriate — and most comfortable — for you!

UGT1A1

The UGT1A1 gene codes for an enzyme that is important in breaking down the chemotherapy drug irinotecan. Gilbert’s syndrome is a benign condition associated with variants of the UGT1A1 gene, and is present in 3-7% of the US population. Routine testing for UGT1A1 variants are not done in the US. When patients experience increased toxicity with chemotherapy containing irinotecan — such as Folfiri or Folfoxiri — irinotecan doses are often reduced.

Rare yet important mutations

While the above mutations are most common, there are a few other tumor mutations that are important for stage IV patients to know. These are very rare for CRC, but there may be effective treatments in later lines of therapy for these patients. These mutations are commonly included in multi-gene testing panels, like next-generation sequencing (NGS) panels — so these mutations will not likely be tested for individually. If your tumor does not have these mutations, you may not see them on your results. However, you can confirm with your doctor, or look for a list of “mutations tested” in your NGS report to confirm they were included in the analysis. If they weren’t there are additional kinds of tests that your oncologist can order that can detect these mutations.

The following mutations or fusions are typically found in less than 1% of CRC, and most often occur in tumors that are also MSI-H. For MSI-H patients, knowing the status of these mutations is critical, especially if immunotherapy isn’t effective. For MSS patients, it’s very rare to have these mutations — but when they do exist, there may be additional treatment options available to patients.

NTRK

NTRK fusions are found very rarely in colorectal cancer, in less than 1% of patients. Usually, they occur in MSI-H tumors. There are very effective drugs available that target NTRK fusions, such as larotrectinib and entrectinib. These drugs can result in a cure for patients with NTRK fusions — therefore it’s important that metastatic CRC patients, especially those who have MSI-H tumors, get tested for NTRK fusions.

It’s important to note that NTRK mutations are different than NTRK fusions, and the drugs mentioned above may not work against NTRK mutations.

RET fusions

There is a drug that effectively targets RET fusions called selpercatinib. It’s important to note that RET mutations are different than RET fusions, and the drug mentioned above is only indicated for RET fusions.

POLE/POLD

POLE/POLD mutations are often associated with a higher tumor mutation burden. While there aren’t specific targeted drugs for these mutations, immunotherapy agents can be effective at treating these tumors. If you are an MSS patient with one of these mutations, discuss whether immunotherapy might be an option for you with your oncologist.

Want to learn more?

This table from the Global Colon Cancer Association gives a good overview of what we currently know about CRC biomarkers, who should get tested, as well as what the consequences are for treatment. It goes over all the biomarkers listed here, as well as some of the less common and less actionable biomarkers such as P1K3CA. Click here for a full-sized PDF version, which you can download!

So what does all of this mean for treatment?

Knowing your biomarkers, particularly if you are stage IV, is really important! They give you and your team useful information which can help determine which treatments will be most effective for you. They can also give you information that can help you figure out if you qualify for clinical trials.

In this video, Dr. Kim and Dr. Kopetz discuss the importance of biomarker testing for stage IV patients:

Unfortunately, data suggests not all stage IV patients receive the recommended biomarker testing.

To help, we’ve put together a biomarker worksheet that you can print out and give to your oncologist to fill out for you!

Want to learn more about biomarkers and what they mean for treatment?

Join one of our COLONTOWN Facebook groups:

  • In Tom & Con’s BRAF + Clinic, you can chat with other patients who have the BRAF mutation.
  • In Tom’s RAS Clinic, you can ask all your questions about treatment options for patients with the RAS mutation.
  • Tom’s HER2 Clinic is for patients with HER2 mutation/amplification.
  • On the Right Side is a group for patients with right-sided tumors to discuss experiences and treatment options.

Want to join? Fill out the registration form here.

COLONTOWN University has so much more to offer, from DocTalk videos with CRC experts to easy-to-understand biomarker test breakdowns. We’re here for you! See our list of Learning Centers here.

Last updated: January 5, 2023

What routine blood work will I have done?

If you’re getting chemotherapy, you’ll become accustomed to having regular lab work done before each chemo session. This is to make sure you’re healthy enough to receive your treatment that week.

In this post, you’ll learn how to understand and interpret your basic lab results. Let’s get started!

What tests will I get?

Most centers run a complete blood count (CBC), complete metabolic panel (CMP) and tumor marker tests, such as CEA and CA 19-9.

Complete blood count (CBC)

The complete blood count measures your white blood cell, red blood cell and platelet counts. Since chemotherapy can lower your blood counts, it’s important to make sure they’re high enough to receive chemo safely.

If your counts are too low, your oncologist may delay your chemo treatment to give them a chance to recover. If your white blood cell counts are consistently low, your oncologist might recommend an injection such as Neupogen or Neulasta to help prevent treatment delays. If your red blood cell counts dip too low, your oncologist might recommend a blood transfusion.

Complete metabolic panel (CMP)

The complete metabolic panel checks your kidney and liver function. Your kidneys and liver need to be working properly in order to process the chemo drugs. Liver enzymes can often become elevated when on chemo drugs, as your liver is working extra hard to process them.

If your numbers are too high, or too low, your oncologist may need to delay chemo in order to give your organs a chance to recover. If kidney and liver function is a consistent problem, your oncologist may consider various interventions to prevent treatment delays.

Tumor markers

CEA — and less commonly, CA 19-9 — are blood markers that can become elevated in people with colorectal cancer. These tumor markers are not a good predictor for everyone, as some stage IV patients have CEA and CA 19-9 levels within normal range — despite having widespread disease! However, for many patients they can be a good predictor of whether cancer is progressing or not — and how you are responding to treatment.

It’s also important to remember that tumor markers can become elevated for a variety of other reasons, particularly related to inflammation. For example, several COLONTOWN Community members have reported receiving elevated CEA results shortly after a COVID vaccine. For this reason, it’s very important to have your oncologist help you interpret these results in context with other surveillance methods you may be using. 

How often will I get tested?

Most infusion centers require these tests prior to every chemo infusion. For most chemo regimens, that means once every two weeks (but in some cases, like the Capox regimen, would be every 3 weeks). Some oncologists will order the tumor marker tests less frequently, such as once a month — or not at all, if they’re not good predictors for you.

How are the tests done?

You will usually be given an appointment to come in an hour or so before your infusion starts, or sometimes on the day before. A nurse will access your port or PICC line, and draw vials of blood. Then, the nurse will leave the needle in your port and apply a dressing. If you don’t have a port or PICC line, they will draw blood from a vein in your arm. Now you’re ready to receive chemotherapy!

The image below shows how your port is accessed for routine blood draws:

National Cancer Institute

After your blood draw, the results will take about an hour to come back. Before starting your infusion, your oncologist will check your results to make sure it’s safe for you to get your treatment.

How do I interpret the results?

To make this a bit easier to understand, below is a sample copy of what your routine labs might look like. Let’s call this patient Sara.

These are screenshots from an online portal. If your cancer center has a portal, it’s a great idea to set up an account. It makes it much easier to access your medical records, and keeps them organized in one place. If your cancer center doesn’t have an online portal, remember to get printed copies of all of your tests and scans for your records. You never know when you may need them later on while searching for a second opinion!

Now, let’s get into the details.

The first four images show the CBC, which are blood cell counts. Sara’s numbers are at the top, and the normal values (called the reference range) are at the bottom. Remember, this reference range is for the general population — not specifically for people with cancer or people going through treatment.

Your oncologist will use different parameters for your results, based on your personal situation. If you have any concerns about your test results, it’s a good idea to speak to your oncologist.

CBC: Key things to look for

WBC: This stands for white blood cell count. Sara’s WBC count is elevated, probably due to a Neulasta injection. For patients who don’t receive these injections, WBC counts are often lower. If your levels drop too low, it can compromise your body’s ability to fight off infection — so chemo might be delayed to keep you safe. There are several conditions that increase WBC counts in people who don’t have cancer and who are not undergoing chemotherapy — but we won’t cover that here.

RBC: This stands for red blood cell count. Sara’s RBC is a little low, which is very common for patients undergoing chemotherapy. At this level, most patients should be able to receive chemo safely, but it’s always important to follow your care team instructions. Several conditions can affect RBC counts in the general population, but are not discussed here.

HGB: This stands for hemoglobin. Sara’s hemoglobin is also low, which is very common during chemo. At this level, most patients should be able to receive chemo safely, but each individual case is different.

HCT: This stands for hematocrit. Sara’s levels are low, which is a common side effect of chemo. At this level, most patients should be able to receive chemo safely, but each individual case is different.

Neutrophils: Sara’s neutrophil levels are elevated, probably due to Neulasta injections. If these levels get too low, your care team might delay chemo to give your body more time to recover.

Lymphocytes: Sara’s lymphocytes are within normal range. If they get too low, chemo might have to be delayed.

CMP: Key things to look for

The following four images show Sara’s complete metabolic panel (CMP) — which gives your oncologist information about your kidney and liver function.

Sodium, potassium and chloride: These are key electrolytes. If a patient’s levels get too low while undergoing chemotherapy, it may indicate dehydration — usually from vomiting or diarrhea. Your team will probably recommend supplemental fluids, at least for a little while, to bring your levels back up. For patients with ileostomies, it’s very important to keep a close eye on these numbers, as you’re more prone to getting dehydrated.

AST, ALT, alkaline phosphatase: These are liver enzymes that often become elevated with chemotherapy. This is because your liver is working overtime to process the chemo drugs! Sara has a slightly elevated ALT and alkaline phosphotase, but she should still be able to receive chemo at these levels. If your numbers get too high, your team may need to delay chemo to give your liver more time to recover. Bilirubin is another marker that indicates normal liver function, and can increase in cancer patients on chemo.

CEA: The last result on the list is carcinoembryonic antigen (CEA), a tumor marker. Sara’s is slightly elevated based on the normal range. However, this result needs to be interpreted by an oncologist in the context of Sara’s history, diagnosis, and other surveillance tools such as scans and liquid biopsies.

So what do these results mean for treatment?

Your team will be regularly checking your blood work to make sure it’s safe for you to receive chemo. They will be looking very closely at your white blood count, red blood count, hemoglobin, hematocrit, platelet, neutrophil, and lymphocyte counts. They will also check your liver and kidney function. If you are receiving Avastin, it can affect kidney function — so you may also be required to take a urine test to ensure there’s no protein in your urine and your kidneys are working well.

The exact cutoff levels can vary slightly based on your infusion center, treatment protocol and specific situation. However, if your blood counts are too low, liver enzymes are too high, or your kidney function is off, your team may delay your treatment.

This can be a huge source of anxiety for patients, but know that an occasional delay in treatment is unlikely to significantly affect your overall outcome or prognosis. If you have questions about your cancer center’s policy, talk to your oncologist. If delays become a consistent problem, there are some things your team can recommend to help prevent this!

Want to learn more about routine bloodwork?

Come join us in Colontown Downtown, where you’ll find an active discussion on all types of testing and opportunites to ask questions!

Interested in joining? Fill out the registration form here.

COLONTOWN University has so much more to offer, from DocTalk videos with CRC experts to easy-to-understand biomarker test breakdowns. We’re here for you! See our list of Learning Centers here.

Last updated: January 5, 2023