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Noninvasive Test of Cell-Free Methylated DNA Markers Shows High Sensitivity and Specificity in Detection of Nasopharyngeal Carcinoma (NPC); Early Study Results Presented at ASCO 2019 by Laboratory for Advanced Medicine (LAM)

(by Michael D. O’Neill, Editor & Publisher of BioQuick News, based on interview of, and materials provided by, Dr. Dhruvajyoti Roy)--One of the highly significant abstracts presented at the recent American Society of Clinical Oncology (ASCO) Annual Meeting 2019 in Chicago (May 31-June 4) described impressive preliminary data on the liquid biopsy detection of nasopharyngeal carcinoma (NPC), which is one of the most prevalent malignancies in Southeast Asia, the Mediterranean, and the Arctic. Using a proprietary test of cell-free DNA methylation markers, the Laboratory for Advanced Medicine (LAM), headquartered in Irvine, California, showed preliminary data demonstrating high sensitivity and high specificity in the early detection of NPC using its DNA methylation test (the IvyGene test). The LAM study was conducted using samples obtained from 168 subjects, including 59 subjects diagnosed with NPC (Stages I to IV), 14 subjects diagnosed with benign nasopharyngeal disease and 43 healthy subjects. From the 59 subjects diagnosed with NPC, a total of 57 subjects were correctly identified (sensitivity of 97%), with little difference between the sensitivity of detecting Stage I to Stage IV NPC (range 92% to 100%). Additionally, for subjects diagnosed with other cancers, a total of 86% of subjects were correctly identified as negative for NPC. Finally, all 43 samples drawn from healthy donors and all 14 samples drawn from subjects diagnosed with benign nasopharyngeal disease were correctly identified as negative for NPC (combined specificity of 100%). The LAM ASCO abstract was number e14537 (https://meetinglibrary.asco.org/record/177028/abstract) and titled “Cell-Free DNA Methylation Markers for Noninvasive Early Detection of Nasopharyngeal Carcinoma.” Commenting on the significance of these results, Dhruvajyoti Roy (photo), PhD, Director of Technology at LAM, said the following. “Due to often minimal or non-specific local symptoms and the relative inaccessibility of the nasopharynx for routine examination, an early diagnosis is challenging and most NPC patients are diagnosed at advanced stage, resulting in poor prognosis and low survival rate of these patients. Therefore, implementation of a non-invasive assay for early detection of NPC will greatly increase the chances of effective treatment and appropriate monitoring of the disease. Our test provides the hope to detect nasopharyngeal cancer at an early stage when the treatment options available to the physician are more manifold. The patients’ health outcomes can be improved at lower cost. We plan additional validation of a large cohort NPC population with the objective of making an accurate test commercially available to the at-risk population.”

NASOPHARYGEAL CARCINOMA (NPC)

Nasopharyngeal carcinoma (NPC) is a non-lymphomatous squamous cell carcinoma which is a distinct form of head and neck cancer that occurs in the epithelial lining of the nasopharynx. NPC is the third most prevalent malignancy among men in Southern China and the fourth most common cancer in Hong Kong, constituting one of the most prevalent malignancies among populations native to Southeast Asia, the Mediterranean Basin, and the Arctic.

The nasopharynx is hard to examine, and traditional examination of NPC requires an invasive nasal endoscopy (which is not practical for early detection) screening and post-therapy disease monitoring. “Therefore,” Dr. Roy says, “Early diagnosis of NPC from non-invasive liquid biopsy samples will improve the overall survival. In this context, the identification of cancer-specific DNA methylation patterns of cell-free DNA (cfDNA) isolated from blood samples has great potential for early diagnosis and can improve survival rate.”

LIQUID BIOPSY FOR EARLY DETECTION OF CANCER; BIOMARKER SELECTION IS KEY

Cancer is often detected in the later-stages of the disease, when the tumor is larger, and metastasis has occurred, and this significantly worsens overall survival rates. According to LAM, early cancer detection would help physicians diagnose patients in the beginning stages of the disease and greatly increases the chances for successful treatment. In this context, “Liquid Biopsy”-based analysis of tumor cells and tumor-derived circulating cell-free DNAs (circulating tumor DNAs--ctDNAs) that are detectable in the blood and other body fluids have been well investigated and implemented into new clinical trials designed to cure cancer patients before overt metastasis. However, the choice of biomarkers for early detection is crucial and liquid biopsy based on cfDNA or ctDNA analyses have provided new avenues for early detection of various cancer types.
Both genetic and epigenetic alterations have been found to be involved in the process of cancer development. In particular, alterations in DNA methylation play a key role in tumor initiation, and methylation markers are well established for detecting various cancer types at early stages of tumor development. Furthermore, cancer-specific DNA methylation patterns of cfDNA isolated from blood samples is a non-invasive method to obtain representative epigenetic information from solid tumors, thus constituting a source for promising cancer detection biomarkers.

LAM ALREADY HAS TWO COMMERCIALLY AVAILABLE METHYLATION-BASED TESTS FOR EARLY CONFIRMATION OF MULTIPLE CANCERS

LAM has developed highly sensitive and specific methylation-based tests for the early detection of various cancer types. The company believes that methylation is the next big cultural shift in cancer detection because large-scale epigenetic alterations potentially have greater ability than somatic mutations for use in the detection and classification of cancers at early stages.

By analyzing methylation, which is an epigenetic process and is predictable in cancer and healthy patients, LAM is able to shift the industry from analyzing mutations, which, by nature, are harder to accurately predict. LAM notes that it has been analyzing methylation for years, while many other companies have only just recently identified methylation analysis as the key for early cancer detection and differentiation.

The IvyGene (https://www.ivygenelabs.com) is the product name for LAM’s early cancer confirmation tests. Currently, LAM has two commercially available products, IvyGene CORE and IvyGene Liver, that confirm the presence of multiple cancers, as early as stage I, and provide measurable information about the cancers. These are just the first of many products coming down LAM’s product pipeline, the company asserts.

LAM’S FUTURE EFFORTS ON NPC

As noted earlier, with respect to NPC, LAM plan additional validation of a large cohort NPC population with the objective of making an accurate test commercially available to the at-risk population.

[ASCO abstract] [ASCO 2019] [Laboratory for Advanced Medicine web site]

IMAGE

Dhruvajyoti Roy, PhD, at Laboratory for Advanced Medicine Inc., Irvine, California; is working on cell-free DNA (cfDNA) methylation-based platform for early detection of cancer. (Credit: Laboratory for Advanced Medicine).