CancerIntercept™ Monitor is a blood-based tumor profiling test that provides a non-invasive and less expensive adjunct to traditional biopsy methods. This genomic profiling test provides valuable information that can be used to both personalize and monitor a patient’s oncology care.
What is a liquid biopsy?
With this “liquid biopsy” technology, CancerIntercept™ Monitor can detect specific genomic markers found in circulating tumor DNA (ctDNA) at levels as low as 2 copies of mutant DNA per patient plasma sample.
Why use CancerIntercept™ Monitor?
Tumor Profiling For Precision Medicine
The CancerIntercept™ Monitor test can provide physicians with valuable information about a patient’s tumor profile (somatic mutations present in the tumor), which can be utilized in the development of a personalized treatment plan.
Clinical Utility of Liquid Biopsies
Below are a few clinical examples demonstrating the potential clinical utility of liquid biopsiesThe EGFR inhibitors cetuximab and panitumumab have been proven to be most useful in lung cancer patients whose tumors are KRAS wild type (which means their tumor is KRAS mutation - negative), and whose tumors express the EGFR protein . In metastatic colon cancer cases, a clinical benefit has been demonstrated (progression-free survival) in patients taking regorafenib if their tumor harbors KRAS and PIK3CA mutations . Utilizing ctDNA to identify somatic mutations in tumors has been shown to correlate clinical and radiologic outcomes for a patient as well as, in some cases, to predict the overall survival of the patient [3-7].
Monitor Disease Progression & Tumor Evolution
While patients are undergoing cancer treatment, oncologists can use the CancerIntercept™ Monitor test to check the development of the patient’s tumor progression and/or tumor evolution (changes in the type of mutations within a tumor). It is important to evaluate tumor evolution throughout treatment as it can lend information about potential drug sensitivity and resistance.
Potential Clinical Utility of Liquid Biopsies
Below are a few clinical examples demonstrating the potential clinical utility of liquid biopsies
Metastatic melanoma patients were found to harbor a somatic BRAF mutation (V600E) in their tumor. Subsequently, a liquid biopsy was used to monitor treatment response with BRAF inhibitor dabrafenib .
Serial evaluation of ctDNA is helpful in tracking disease progression, as well as in identifying the appearance of somatic mutations associated with drug sensitivity and resistance in several different cancer types [8-11].
Monitor Residual Disease and/or Recurrence
In instances where patients have undergone a resection of their tumor and/or have gone into disease remission, serial analysis of ctDNA burden utilizing the CancerIntercept™ Monitor test, can help check the development of disease reoccurrence or progression.
Clinical Utility of Liquid Biopsies
Below are a few clinical examples demonstrating the potential clinical utility of liquid biopsies.
ctDNA levels of KRAS and PIK3CA tumors mutations were examined in order to better understand how markers would correlate to the completeness of surgical resection and subsequent treatment. The findings in this study suggested that ctDNA levels were indicative of disease burden and furthermore, that increasing or elevated ctDNA levels post-surgery, seemed to anticipate disease progression even in advance of imaging and CEA levels .
ctDNA levels have been monitored to determine if they could detect distant metastasis in patients diagnosed with primary breast cancer. Scientists have found that ctDNA was highly accurate in determining which patient would have (93%) and would not have (100%) a clinically detected recurrence. ctDNA was able to detect disease recurrence before clinical appearance in 86% of cases, with an average lead time of 11 months .
Clinical Trial Matching
Clinical Trial Matching is an additional feature of the CancerIntercept™ Monitor test, which gives your patient the option to receive personalized information about clinical trials that may be best suited for him or her, based on their tumor’s profile.
Clinical Trial Matching
This option can be utilized with any positive test result, but is best utilized in patients with late-stage disease and where there is specific information about the patient’s disease state. If the physician elects to receive clinical trial information, Pathway Genomics takes the specific genomic information that is derived from the CancerIntercept™ Monitor test and determines what studies might be most applicable for a given patient.
The clinical trial matching results are based both on the genomic markers identified and the site of the tumor; it also takes into account the physical location of the patient (by zip code).
Genomic Markers and Associated Cancers
CancerIntercept™ Monitor tests for 96 different genomic markers in 9 cancer driver genes. A full list of markers included on this tests can be found here. These 9 genes have been associated with different cancer types in somatic mutations studies in the past.
The driver gene frequencies for each of the cancer types below are referenced from the COSMIC database (http://cancer.sanger.ac.uk/cosmic). These values are not necessarily the detection rates found via liquid biopsy or the CancerIntercept™ screen.
CancerIntercept™ Monitor can only be ordered by an authorized healthcare provider. To request a sample collection kit in your office click here.
Test Submission & Required Sample
As a healthcare provider, you will need to register your practice with Pathway Genomics , if you have not previously done so.
After registering your practice, you can request sample kits, which include all required forms and return shipping labels.
Before submitting a sample, you should discuss genetic testing options as well as their benefits and limitations with your patients.
The test requisition form (TRF), informed consent, and clinical history questionnaire must be completed, reviewed, and signed by the patient and/or provider.
A phlebotomist or other qualified professional is required to draw the patient’s blood sample and submit it along with the completed paperwork to Pathway Genomics for processing.
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CancerIntercept™ Monitor Test Description
The CancerIntercept™ Monitor test is a 96-mutation panel designed for the detection of somatic mutations in a set of 9 cancer driver genes (BRAF, CTNNB1, EGFR, FOXL2, GNAS, KRAS, NRAS, PIK3CA, TP53) involved primarily in breast, ovarian, lung, melanoma, and colorectal cancers. The assay requires a blood samples (plasma) for cell-free DNA isolation, which is then used for PCR amplification of both the wild type and mutant DNA. This is followed by a specific enrichment of the mutant and simultaneous removal of the wild type DNA by using a propriety technology. The mutant DNA is sequenced on Illumina’s next-generation sequencing platforms.
Limitations and Warnings
Pathway Genomics’ CancerIntercept™ test is a plasma-based 96 mutation panel to aid clinicians in the identification of plasma mutation tumor burden, monitoring and treatment planning for cancer patients, and preventative surveillance for individuals at high risk for cancer via early detection of disease.
Cancer is heterogeneous disease that can occur as a result of somatic mutations in various driver genes. Pathway’s CancerIntercept™ (Monitor or Detect) identifies somatic cancer derived mutations at 96 hotspots in 9 cancer driver genes. This test is not meant to diagnose cancer, and is only meant to screen for a possible malignancy as an adjunct to other medical examinations and interventions. It will not detect all cancers, and has not been designed to find very small tumors. No test can replace a physician’s examination, imaging studies, and tissue biopsies as the gold-standard for cancer diagnosis. It is possible that mutations in these or other genes not tested in Pathway’s CancerIntercept™ (Monitor or Detect) test may be involved in the patient’s disease. Therefore, a negative test result, where no mutations are detected, does not eliminate involvement of other genes and/or mutations. Furthermore, a positive test result needs to be interpreted in the context of individual’s clinical history including stage of disease, imaging results, therapeutic details, and other laboratory data. Pathway Genomics Corporation strives to provide the most accurate test results. Results could be misinterpreted if clinical information provided is inaccurate or incomplete. Improper blood sampling and handling could result in error. Genetic counseling or medical consultation is recommended for the individual tested.
The performance characteristics for the Pathway Genomics testing services described herein were established and validated by Pathway Genomics according to the requirements of CLIA (Clinical Laboratory Improvement Amendments of 1988). These testing services have not been cleared or approved by the U.S. Food and Drug Administration (FDA).
- Rothschild, S.I., Targeted Therapies in Non-Small Cell Lung Cancer-Beyond EGFR and ALK. Cancers (Basel), 2015. 7(2): p. 930-49.
- Tabernero, J, et al. Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial. Lancet Oncol, 2015. [Epub ahead of print].
- Ascierto, P.A., et al., Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol, 2013. 31(26): p. 3205-11.
- Romero, A., et al., Identification of E545k mutation in plasma from a PIK3CA wild-type metastatic breast cancer patient by array-based digital polymerase chain reaction: Circulating-free DNA a powerful tool for biomarker testing in advance disease. Transl Res, 2015.
- Heidary, M., et al., The dynamic range of circulating tumor DNA in metastatic breast cancer. Breast Cancer Res, 2014. 16(4): p. 421.
- Zill, O.A., et al., Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas. Cancer Discov, 2015.
- Janku, F., et al., Actionable mutations in plasma cell-free DNA in patients with advanced cancers referred for experimental targeted therapies. Oncotarget, 2015. 6(14): p. 12809-21.
- Forshew, T., et al., Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med, 2012. 4(136): p. 136ra68.
- Dawson, S.J., et al., Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med, 2013. 368(13): p. 1199-209.
- Ignatiadis, M. and S.J. Dawson, Circulating tumor cells and circulating tumor DNA for precision medicine: dream or reality? Ann Oncol, 2014. 25(12): p. 2304-13.
- Murtaza, M., et al., Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature, 2013. 497(7447): p. 108-12.
- Kidess E., et al., Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation detection platform. Oncotarget, 2014. 6(4): p. 2549-2561.
- Olsson, E. et al. Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. EMBO Molecular Medicine 2015. [Epub ahead of print].
- Bettegowda, C., et al., Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies. Science Transl Med, 2015. 6(224):pp.224ra24.
- Perrone, F., et al., Circulating free DNA ina screening program for early colorectal cancer detection. Tumori, 2014. 100:pp.115-121.