RadTox™ cfDNA Test | DiaCarta, Inc.

Powered by SuperbDNA™ Technology, RadTox™ cfDNA Test is developed for cancer patients’ radiation therapy toxicity monitoring, which is fulfilling an unmet medical need in cancer radiation therapy by enabling the direct monitoring of side effect severity and tumor response within days of radiation treatment initiation. RadTox™ would allow dose escalation to tumors in less sensitive patients, aid development of radiotoxicity mitigators, and reduce overtreatment risk for highly sensitive patients. The assay provides a fast, cost-effective quantitation of liquid biopsy cfDNA sample from cancer patients before and after radiation therapy and provides patient information for estimates of dosage usage and general radiation resistance.

RadTox™ cfDNA Test is CE/IVD-certified.

DiaCarta Received National Cancer Institute (NCI) Funding for Development of RadTox™ cfDNA test.

After successful completion of a NCI Small Business Innovation Research (SBIR) phase I grant of $300,000, DiaCarta recently was awarded a 2-year, $2,000,000 Phase II contract, focusing on the development of RadTox™ cfDNA test into a commercial diagnostic test for early detection of cancer patients at risk for severe radiation reactions. DiaCarta will analyze blood specimens from over 500 patients undergoing radiotherapy for prostate cancer at multiple clinical sites in the US. Once the test is fully validated, the company plans to pursue regulatory approval to sell test kits globally.

Learn More about DiaCarta’s NCI Contract >

Advantages of RadTox™ cfDNA Test

Personalized Radiotherapy Toxicity Monitoring

The first liquid biopsy cfDNA in vitro diagnostics test for real-time assessment of low and high radiation toxicity

Significant Clinical Support

Real-time radiation dose monitoring helps aid doctors to evaluate and optimize radiation dosage and reduce patients’ risk for severe radiation toxicity

Streamlined Workflow

Direct cfDNA measurement without DNA/RNA extraction or cleaning. No PCR or target DNA amplification  

Minimal Sample Requirement

Only 10 µl plasma needed

Drawbacks on the Current Radiation Therapy Tissue Damage Estimation Gold Standard

Radiation therapy to treat cancer patients is widely used worldwide, although doctors and patients recognize potential serious treatment side effects on patients health, either with radiation therapy alone or combined with drugs. The current gold standard for clinical evaluation of tissue damage caused by radiation therapy 

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Is population-based, not personalized

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Relies on the dose volume histogram (DVH) or maximum tolerated dose (MTD) studies of combination of radiation and the drug

Radiotherapy dose is commonly set to achieve remissions or cures in patients without concurrently causing grade >3 toxicity level in over 5 to 10% of patients, based on population statistics correlated with daily dose and dose distributions. However, this standard dose regimen restricts the high-dose tolerating patients from getting curative benefit from radiotherapy and fails to protect the 5% highly sensitive patients with reduced radiation dosage or even no radiation therapy. Some highly sensitive patients may have pre-existing conditions that could increase tissue or organ damage and additional medical complications. However, this standard restricted the high-dose tolerating patients from getting curative benefit and failed to guide the 5% most sensitive patients with reduced radiation dosage or even no radiation therapy as they have pre-existing conditions that could trigger body damage and medical complications. For some of these patients, low dosage of radiation such as 20 Gy may cause patient death.

An Optimal Radiation Biomarker is Necessary

An effective biomarker for radiation therapy safety/toxicity measurement can help

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Reduce risk and cost of life-threatening toxicity

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Avoid unnecessary treatment

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Lower healthcare costs

The ideal biomarker for radiation toxicity monitoring should have the following characteristics

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Early detection: to determine the personalized tolerance of an individual patient’s normal and tumor tissues to radiation therapy

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Quantitative: provides estimate for low, medium or high risk

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Quick and Easy: is performed during a course of treatment to adjust treatments as needed

Radiation treatment is required by 70 percent of cancer patients. However, despite decades of advances in cancer care and technology, there remain many fundamental challenges affecting safe and efficacious delivery of radiation treatment. Currently, there is no reliable method for determining treatment risk caused by radiotherapy.

In the past decades, radiation has made great progress in the development of imaging instruments, but little progress in development of biological and chemical testing tools. Although new biological or chemical agents are being approved for clinical use, there is little experience for use of the combination of these agents and radiation therapy. Currently, there is no clinical method for determination of treatment risk caused by radiation toxicity, which can personalize the radiation dose during the course of treatment. The most closely related technology is non-personalized biodosimetry (TBI), such as lymphocyte counts, chromosomal aberrations, radical traps, cytokine profiles, and H2AX measurements. New development of such biomarkers are necessary for cancer patients and their doctors to understand radiation risks and appropriate dosage usage.

A Promising Biomarker: Alu Repeated DNA Sequences within Circulating Cell-free DNA in Plasma

We discovered that plasma concentration of Alu repeated sequence correlates with radiation doses, and further developed an assay to predict the level of radiation damage to cells by measuring the Alu repeated sequences in circulating cell-free DNA (cfDNA) since the cfDNA is proportionally correlated with circulating tumor DNA (ctDNA) shed from tumor cells from the tumor cells (US patent #8,404,444).

Most cancer patients have a similar baseline level of cfDNA in the blood. Radiation increases cfDNA to different levels for different individuals. By determining the cfDNA level in cancer patients’ blood after radiation, we can identify patients personalized radiation sensitivity and estimate the highest risk for radiation toxicity. Currently, there is no clinical method to determine treatment-induced toxicity. Compared with other technologies that estimate cell death or DNA damage, the RadTox™ cfDNA test provides early detection, is cost-effective and easy to use.

Tumor TypePatient NumberAverage of cfDNA Content (ng/ml)
Colorectal Cancer 13526.43
Malignant Breast Tumor20226.16
Gastric Malignant Tumor15121.94
Malignant Tumor of Esophagus16719.75
Non-Small-Cell Lung Carcinoma 21922.87
Total 874/

Competing Technology (Mechanism)Specimen TypeSpecimen PreparationAnalysisEase of Deployment/AffordabilityTechnical FeasibilityRegulatory Status
RadTox™ (Holistic Measure of Cell Death)Plasma, Strech Tube, Finger StickNone (Plasma Isolation)Quantitative and Reliable HighSimple Implementation and InterpretationCE Marked Europe
Cytokines Arrays (Inflammation)Plasma, Strech Tube, Ice, Platelet Poor Spin, Immediate FreezingVery few Reproducible or Quantitative ELISA Antibodies ExistMediumDifficult QC and ReproducibilityNone
Biomics Array (Acute Response Pathways)RNA Preservation Medium DNA/RNA Purification and PCRProprietary Interpretation (Expected to be Race/Gender Specific)LowProprietary Technology RequiredNone
DNA Repare (e.g. H2AX)Biopsy Irradiated Cells Required DNA/RNA Purification and MicroscopyExtreme Dependence on Time of Specimen AcquisitionVery LowProprietary Technology RequiredNone
DxTdrity (Mechanism Unknown)Leukocytes from Whole BloodDNA/RNA Purification and PCRProprietary Interpretation (Data Mining)Medium (Shipping for Off-Site Analysis)Proprietary Technology RequiredREDI-Dx (CE Marked US)

Powered by SuperbDNA™ Technology

The RadTox™ cfDNA test is a superbDNA™ technology-based quantitative assay on using Luminex instrumentation. The test kits have the potential to scale and simply integrate into the workflow of centers offering radiation therapy.

Branched DNA (bDNA) technology is a widely used clinical platform to quantitatively detect specific nucleic acid sequences directly from the source without DNA/RNA purification or RT-PCR. bDNA quantitative hybridization technology has a wide dynamic range and is sensitive enough for applications intended to reliably detect very few target molecules. bDNA technology has several advantages over PCR technology and is commonly used for applications requiring a high degree of specificity and sensitivity.

Limit of Detection (LOD) for RadTox™ cfDNA Test

The limit of detection (LOD) of the RadTox™ cfDNA Test was determined by measuring serially diluted genomic DN at concentration ranging from 25 to 0.05ng/ml. The low detection limit was calculated to be at 0.05 ng/ml.

Clinical Evaluation of Patient Radiation Therapy Using RadTox™

Among the 54 prostate cancer patient who received radiation therapy, <5% of them have a large increase of cell-free Alu DNA. The patients can be divided into three groups: the low risk, normal and high-risk groups, and radiation therapy dosage suggestions can be given based on the risks determined by the Alu DNA changes 24 hours after radiation therapy. The dataset on the right side shows the correlation of plasma Alu concentration with radiation dosage. The biomarker is an indicator for cfDNA before and after radiation therapy.

Product Specifications for RadTox™ cfDNA Test

Product Catalog Number

CE/IVD Catalog Number: DC-08-0092E
Research-Use-Only (RUO) Catalog Number: DC-08-0092R

Intended Use

For in vitro diagnostic use (CE/IVD) or for research use

Sample Type

Plasma

Input DNA

10 µl plasma

Pack Size

96 Reactions

Instruments Validated

QuantiReader™ Benchtop Luminometer;
Molecular Device SpectraMax L Microplate Reader

Signal Type

Chemiluminescence

Dynamic Range of Quantitation

0.2 to 25 ng/ml

Turnaround Time

8 hours

Stability

Stable for 12 Months at -25°C  to -15°C

Webinar

Title: Creating the Optimal Liquid Biopsy: Post-Radiation Tumor Toxicity Measurement & A Highly Sensitive Early Colorectal Cancer Detection Test

Speaker: Paul Okunieff, M.D. (Professor and Chair, Department of Radiation Oncology, Gainesville and University of Florida Health Proton) and Jinwei Du, Ph.D. (Manager, IVD Development, DiaCarta, Inc.)

Highlight: 

  • Define optimal liquid biopsy and its potential to achieve its promise in personalized medicine
  • Current and proposed implementation of DiaCarta’s SuperbDNA™ and QClamp® technologies
  • RADTOX™ – Implementation & measurement of tumor response and normal tissue toxicity after radiation
  • ColoScape™ – Discuss the future use of early identification of subclinical disease, cancer screening & early measurement of chemotherapy response

Need Help?

Call us: +1 (800) 878-6662

Email us: information@diacarta.com

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