The Radiotherapy Toxicity Measurement Assay is developed to monitor tissue damage-related toxicity from radiation therapy. The measurement fulfils an unmet medical need in cancer radiation therapy by enabling the direct monitoring of side effect severity within days of radiation treatment initiation. The assay would allow dose escalation to tumors in less sensitive patients, aid development of radiotoxicity mitigators, and reduce overtreatment risk for sensitive patients. The radiotherapy toxicity assay provides 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.

VznHealth™ Radiotherapy Toxicity Measurement Assay

Signal detection by a luminometer.

Catalog Number: DC-08-0496R

Pack Size: 96 Reactions

QuantiDNA™ Radiotherapy Toxicity Measurement Assay

Signal detection by Luminex MAGPIX

Catalog Number : DC-08-0296R

Pack Size: 96 Reactions

Instrument Required

Sample Input

10 µl plasma

Advantages of the Radiation Therapy Toxicity Measurement Assay

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 Gold Standard for Radiation Therapy Tissue Damage Estimation 

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

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Is based on population statistics, 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 result in additional medical complications. Low dosage of radiation such as 20 Gy may even cause patient death in some cases.

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: 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, great progress has been made in the development of imaging instruments, but little progress is shown in the development of biological and chemical testing tools. Although new biological or chemical agents are being approved for clinical use, not many of them have been tested for use with a combination of these agents and radiation therapy. Currently, there is no clinical method for determining treatment risk caused by radiation toxicity and for personalizing 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. Development of new biomarkers is necessary for cancer patients and their doctors to understand radiation risks and to determine appropriate dosages.

A Promising Biomarker: cfDNA quantification

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

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 DiaCarta Radiation Therapy Toxicity Measurement Assay provides early detection and 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
DiaCarta Method (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 Repair (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 U.S.)

The Radiotherapy Toxicity Measurement Assay is Powered by SuperbDNA™ Technology

The Radiation Therapy Toxicity Measurement Assay is a SuperbDNA™ technology-based quantitative assay using a luminometer or Luminex MAGPIX instrumentation. The test kits have the potential to scale up or be adapted to automation for high throughput operation by simply integrating into the workflow of radiation therapy centers.

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 Radiation Therapy Toxicity Measurement Assay

The limit of detection (LOD) of the Radiation Therapy Toxicity Measurement Assay was determined by measuring serially diluted genomic DNA at a concentration ranging from 25 to 0.9ng/ml. The low detection limit was calculated to be at 0.9 ng/ml or 1.8 pg DNA in 20 ul assay using Luminex MAGPIX.

Clinical Evaluation of Patient Radiation Therapy Using Radiation Therapy Toxicity Measurement Assay

Among the 54 prostate cancer patients who received radiation therapy in a clinical study, <5% had a large increase in cfDNA. The patients could 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 cfDNA changes 24 hours after radiation therapy. The dataset on the right side shows the correlation of plasma cfDNA concentration with radiation dosage. The biomarker is an indicator for cfDNA before and after radiation therapy.

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
  • DiaCarta Radiation Therapy Toxicity Measurement Assay – 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

Instruments Required for Radiotherapy Toxicity Measurement Assays

VznHealth™ Radiotherapy Toxicity Measurement Assay (Luminometer-based Platform)

Plate Incubator

Requirement: Capable of maintaining a constant temperature between 46–55 °C ±1 °C)

Validated Machine: VznHealth™ Thermal Shaker Incubator

Luminometer

Specification: Read 420nm wavelength, read time of 0.2 seconds/well, linear dynamic range ≥ 5-log (optional) and well-to-well uniformity < ± 5%)

Validated Machine: VznHealth™ Benchtop Luminometer 

QuantiDNA™ Radiotherapy Toxicity Measurement Assay (Luminex-based Platform)

Plate Incubator

Requirement: Capable of maintaining a constant temperature between 46–55 °C ±1 °C)

Validated Machine: QuantiDNA™ Thermal Shaker Incubator

Luminex

Luminex MAGPIX

Manufaturer: Luminex Proudct Name: MAGPIX Catalog #: MAGPIX-XPONENT

Need Help?

Call us: +1 (800) 878-6662

Email us: information@diacarta.com

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