IvyGene Biotechnology Frequently Asked Questions
Section 1: Uses / Accuracy / Sensitivity
Section 2: Commonly Asked Questions about the test
Section 3: Account Set Up / Kit Order / Payment Questions
Section 4: Test Instructions / Logistics – How is the test administered and the sample returned?
Section 5: Where do I get a blood draw?
Section 6: Sample Results
How should the IvyGene test be used and when should I recommend IvyGene?
The IvyGene test can provide additional insight and is supplementary to other standard of care diagnostics. It provides a non-invasive option to aid in the following:
- Confirm specific cancer presence
- Supplement other tests
- Follow-up to other diagnostics and screening tests. Such as: abnormal imaging and BRCA1 and BRCA2.
- Monitor for recurrence
Note: The IvyGene test is not classified a screening test.
The IvyGene® test is an adjunct clinical test that is intended to be based on the independent medical judgement of the ordering physician in conjunction with the patient’s complete medical history and the results of standard of care testing. The IvyGene® Test has been validated with four (4) cancer tissues of origin: breast, colon, liver and lung cancers. The presence of other cancer types may also result in an elevated IvyGene® Score. A large-scale clinical trial to demonstrate the efficacy of the IvyGene® Test as a cancer screening test has not been conducted. Cancer screening is not an approved utility of the IvyGene® test.
Cancers progress at varying rates and therefore, the frequency of diagnostic testing is subject to the ordering Provider’s clinical judgement.
Please, note that the IvyGene test does not “Stage” cancers, but rather provides quantifiable data about disease presence.
What is the Accuracy of the IvyGene test?
Does the IvyGene test provide quantifiable data about disease presence?
Yes. The IvyGene® test measures the methylation status of cell-free DNA extracted from blood samples at target sites that have been demonstrated to be hypermethylated when certain cancers are present. Test results are reported as a quantitative IvyGene® Score, which indicates the methylation status of the target sites. The IvyGene® Score is calculated as a composite average of cell-free DNA that is methylated at the target sites as a fraction of the total cell-free DNA present.
An IvyGene Score of 1-19 is considered normal. An IvyGene Score of 20 or greater is considered elevated.
Certain treatments may affect the Methylation Score with an increase or decrease in cfDNA methylation. Follow up testing should be performed based upon a physician’s medical advice and in combination with the patient’s complete medical history.
What is the science behind IvyGene's cancer detection?
DNA within cells can be modified by the addition of a methyl group (-CH3) to select sites within the genome. Depending on where the site is located within the genome, these DNA methylation sites can be indicators that a particular gene is being expressed (activated) or silenced (inactivated).
Consequentially, normal cells and cancer cells can be differentiated by detecting which of these sites within the genome are methylated. During malignant transformation (the process by which normal cells transform into cancer cells), there are significant changes in gene expression. These changes in gene expression are highly correlated to changes to the methylation pattern of genomic DNA.
The genomic DNA of cancer cells can be shed into circulation, usually due to cancer cell death (apoptosis or necrosis) or release from viable cells. Once the genomic DNA of a cancer cell is shed into the blood stream, it is called circulating tumor DNA (ctDNA).
The IvyGene test measures the methylation status of cell-free DNA extracted from blood samples at specific target sites that have been demonstrated to be hypermethylated when certain cancers are present.
Does the IvyGene test detect the tissue of origin?
No. The IvyGene test does not detect tissue of origin.
Our laboratory has validated the IvyGene test with these 4 cancers: breast, colon, liver and lung. As we complete the validation for additional cancers we will update this list.
Please note that an elevated Score does not necessarily mean that it is due to one of these 4 validated cancers. An elevated Score could be due to methylation associated with other cancers as well.
The IvyGene test does not provide tissue of origin. The IvyGene test analyzes DNA methylation to confirm cancer presence and give measurable information about cancer.
Compared to other Cancer tests, what is unique about IvyGene?
Unlike many genetic tests that use DNA mutations to determine the propensity or possibility of developing cancer over time, the IvyGene test measures DNA methylation at specific target sites that indicates disease presence at the time of testing.
Does the IvyGene test detect Circulating Tumor Cells (CTC Theory)?
No. The analyte of the IvyGene test is cell-free DNA that is present in whole blood samples.
Can the IvyGene test be used for screening?
The IvyGene test is not classified as a cancer screening test.
What is the limit of detection of the IvyGene test?
The IvyGene test has been validated for the detection of cancers as early as stage I.
The IvyGene test has not been investigated for the detection of pre-cancers or stage 0 cancers.
What is the sensitivity of the IvyGene test?
The sensitivity is approximately 86% for patients who have clinically confirmed breast, colon, liver or lung cancer and are not currently undergoing cancer treatment. These numbers are subject to change as the use for the IvyGene test to confirm the presence of cancer for additional cancer types is investigated.
What is the specificity of the IvyGene test?
The specificity is approximately 88%.
What do the test results tell me?
The results 1) identify cancer presence and 2) give quantifiable information about disease presence.
The IvyGene Score is calculated as a composite average of cell-free DNA that is methylated at specific sites as a fraction of the total cell-free DNA present. An IvyGene Score of 19 and below is considered normal. An IvyGene Score of 20 or greater is considered elevated.
An elevated IvyGene Score means that the amount of cell-free DNA in the blood that is methylated at specific sites is consistent with the presence of cancer.
The IvyGene Score itself does not provide an outright measure of cancer presence. Various factors influence the amount of DNA shed by solid tumors (tissue of origin, tumor location, overall tumor burden, etc.). Therefore, the IvyGene Score does not necessarily correlate to a stage of cancer.
Some physicians have advised that an increase or decrease in 2 or more successive IvyGene Tests may be an indicator of treatment effectiveness as it can demonstrate a decline in the methylated cell-free DNA at specific sites.
Cancers progress at varying rates and therefore, the frequency of testing is subject to the ordering provider’s independent clinical judgement.
The IvyGene test does not provide tissue of origin.
For a Sample of the Results form, see “Sample Results” Section in FAQ’s.
Do I need to select a certain test from a Panel?
No, at this time IvyGene Labs has only one test available, the IvyGene test. There may be future versions of the test and additional offerings.
Does the IvyGene test show tumor burden?
The IvyGene test measures the methylation status of cell-free DNA extracted from blood samples at target sites. Test results are reported as a quantitative IvyGene Score, which indicates the methylation status of the target sites. A patient with an elevated amount of circulating tumor DNA would be expected to have an elevated IvyGene Score.
Can the IvyGene test identify metastasis?
No, the IvyGene test does not identify metastasis. An elevated IvyGene Score has been demonstrated to correlate with the presence of cancer.
Can the IvyGene test identify treatment efficacy?
Some physicians have advised that an increase or decrease in 2 or more successive IvyGene tests may be an indicator of treatment effectiveness as it can demonstrate a decline in the methylated cell-free DNA at specific sites.
How soon after treatment can the IvyGene test be administered?
Treatments such surgery, radiation or certain chemotherapies may cause a temporary increase the concentration of cell-free DNA from both normal tissue and cancer tissue.
Cell-free DNA is predicted to have a relatively short half-life (less than 2 hours) within the human body.
How often should the IvyGene test be administered?
Because cancers progress at varying rates, the frequency and necessity of diagnostic testing is subject to the ordering Provider’s independent clinical judgment based upon a patient’s complete medical history and the results of all of the patient’s diagnostic tests.
Can the IvyGene test detect brain cancers?
IvyGene has not been validated for detection of brain cancer.
My sample was rejected. What are the possible reasons?
In the IvyGene workflow, whole blood samples are initially processed to plasma. It is possible that a sample can be hemolyzed during the blood draw, but this will not be known until the red blood cells are removed by centrifugation once the sample is processed in the laboratory. It is also possible for samples to be hemolyzed due to shipping conditions. Please carefully follow the instructions provided in the IvyGene kits in order to prevent this form occurring.
Not all samples have a sufficient amount of cell free DNA (cfDNA) in order to provide accurate results. During the second step of the process, cell free DNA is extracted from plasma samples. If an insufficient amount of cell free DNA is present, then the sample will not pass quality control.
How long has the IvyGene test been commercially available?
IvyGene has been commercially available since January 2018.
What is the cost of the IvyGene test?
Please email customer service at: [email protected] or call us at 844-489-4363.
Is the IvyGene test covered by Insurance?
The IvyGene test is not covered by insurance at this time.
For insurance purposes, the most appropriate CPT code that has been identified is: CPT code 81479 – Unlisted molecular pathology procedure.
Is the IvyGene test FDA approved?
The IvyGene test currently meets FDA requirements to be marketed as a Laboratory Developed Test (LDT). Our laboratory is CLIA Registered (Clinical Laboratory Improvement Amendments) and CAP Accredited (College of American Pathologists).
How do I open an account and order a test kit?
Providers Only: Only Providers and medical clinicians may order IvyGene test kits.
Click on “Order a Test Kit”: This option is on every page–in the menu as well as at the bottom of each page.
New Providers: After clicking on “Order a Test Kit”, you can Register as a New Provider and set up your password and your account. Proceed to ordering a kit.
Existing Providers: After clicking on “Order a Test Kit”, you can Login to your Account. Proceed to ordering a kit.
Timing: We suggest you order kits to align closely with the patient’s appointment. The tubes inside the kits have an expiration date and must be kept at room temperature while stored in your office. Kits should arrive to your office in 4-6 business days.
How do I pay for the test?
Provider Account: Payment is typically through the Provider’s account and will be charged upon receipt of the sample at the laboratory.
Patient Pay: If patient is paying directly, the Provider must include patient’s payment information when filling out the Requisition Form. Patient will be charged upon receipt of the sample at the laboratory.
How do I use the test kit?
The contents of the kit include: Outer shipping box, Styrofoam insulated box, (4) Specialized 10 mL tubes, Biohazard bag, Absorbent material, bubble wrap,Tyvek envelope, 2 or more Temperature Control Paks (2-4 will be sent during summer and winter months), blood draw and shipping instructions, overnight shipping label (pre-paid).
TUBES AND TEST KITS MUST BE STORED AT ROOM TEMPERATURE AT ALL TIMES (59-86 °F).
- ROOM TEMPERATURE GEL PAKS are included in the kit. These Paks must be conditioned at room temperature for 24 hours prior to shipping. Do not refrigerate or freeze the Paks. We suggest you keep the tubes, gel Paks and blood samples at room temperature at all times. We also suggest that you open the Styrofoam holding container to allow room temperature air to reach the Paks. Note: If the gel Paks arrive at your site frozen, you may choose to put them in a water bath of room temperature water to decrease the time required for use.
- DO NOT FREEZE WHOLE BLOOD SAMPLES. Freezing will break open blood cells in whole blood samples and render the sample useless.
- DO NOT USE DRY ICE. Shipping on dry ice is not necessary with the specialized cell-free DNA collection tubes and the Temperature Control Paks.
Use ONLY the tubes which are included in the IvyGene test kit.
- Four (4) specialized 10 mL tubes containing a stabilizing agent for cell free DNA are included in the IvyGene test kit. NO OTHER TYPE OF TUBE may be used. Store the tubes in the kit at room temperature at all times.
Ship the sample overnight.
- Order test kits approximately one week in advance of the blood draw.
- Temperature Control Paks must be conditioned at room temperature for at least 24 hours prior to shipping.
- An overnight pre-paid shipping label is included in the kit.
- SHIP AND DRAW SAMPLES MONDAY-THURSDAY ONLY.
BLOOD DRAW INSTRUCTIONS
- Dietary requirements: No dietary restrictions are required.
- Label EACH TUBE: Label each tube with the unique ID from the Requisition Form and the patient DOB
- Amount of blood needed: 40 mL (10 mL in each of the 4 tubes)
- Collect sample using standard venipuncture technique.
- Invert blood tubes: Per label instructions, the blood tubes need to be inverted by hand multiple times to ensure the blood specimen mixes with the stabilizing reagent.
How long can I keep the blood sample before I ship it?
The sample must be stored in the specialized tubes at room temperature and shipped within 24-48 hours. Temperature Control Paks must be conditioned at room temperature for at least 24 hours prior to shipping. If the Paks arrive frozen to your facility, they may require additional time, or need to be put into a room temperature water bath as needed.
How do I pack the sample in the kit to ship it back?
- Shipping Box. Use the same IvyGene outer shipping box and the Styrofoam insulated box inside.
- Temperature Control Paks. Place one Temperature Pak in the bottom of the Styrofoam insulated container. Make certain the Pak is at room temperature for at least 24 hours before packing.
- Biohazard bag. Place Specialized Tubes with whole blood sample (at room temperature) in the Biohazard bag along with the absorbent material included in the kit. Remove the adhesive tape and seal the Biohazard bag. Note: Make certain each tube is labeled with the UID from the Requisition Form and the patient DOB.
- Bubble wrap. Wrap the Biohazard bag and tubes with the bubble wrap included in the kit.
- Tyvek envelope. Place the bubble wrapped sample into the Tyvek envelope and seal the envelope.
- Requisition Form. The Requisition Form included in each kit MUST BE COMPLETED AND SIGNED and returned. Fold the Requisition form and place it on top of the Tyvek envelope.
- Temperature Control Paks. Place the second Temperature Control Pak that was included in the kit on top of the Tyvek envelope and Requisition Form. Make certain it is at room temperature.
- Additional Temperature Control Paks. Any additional Temperature Control Paks provided (up to 4 depending on the season) should be placed on either side of the Sytrofoam insert.
- Stryrofoam box lid. Place the Styrofoam box lid securely on top.
- Shipping box. Remove previous shipping labels. Close and tape the shipping box.
- Overnight pre-paid label. Place overnight label on the shipping box.
- Shipping Address: The shipping address is on the Overnight Label. It is:
- Mor-NuCo Enterprises Laboratory, 1201 Cumberland Avenue, Suite B, West Lafayette, IN 47906.
- Call FedEx for a pick-up.
May I use a different type of tube or one I already have in my office?
NO. THE SAMPLE MUST BE DRAWN IN TUBES PROVIDED IN THE KIT. These are specialized tubes containing a stabilizing agent for cell free DNA. Any other type of tube will render the sample useless.
What if the specialized tubes have expired or has been stored outside the range of room temperature?
DO NOT USE THE TUBES. Contact IvyGene at 844-489-4363 and we will ship you another kit.
How do I know that the sample was received at the laboratory?
You may check the sample status at [email protected] Please have the following information available and included in your original email to expedite the process:
Results will be returned to the prescribing physician. A result status will only provide the received date and expected result return date.
If the Provider office does not perform blood draws, here are a few options. Please click on the link to their sites to find a convenient location. Or, you may search the internet for a local mobile phlebotomist.
ARCpoint labs www.arcpointlabs.com
LABS TO GO www.labstogo.com
What do the results look like?
What is the turnaround time for test Results?
Results are returned to the ordering physician within 5 business days of the test kit receipt by our laboratory, excluding holidays.
If I have questions about the results, who do I contact?
Providers may send an email to our Provider consultant at [email protected] or call 844-489-4363. We will contact you by noon CST the following business day. If needed, we will be happy to schedule a follow up consult with the Laboratory Director or Chief Medical Officer.