RadTox offers
Personalized Treatment Effectiveness

By comparing conditions before treatment, after treatment, and even during long-term surveillance in the recovery phase

The RadTox™ test monitors tumor treatment responses in patients of different cancer types by measuring the total cell-free DNA (cfDNA) from plasma.

Longitudinal Serial Real-Time Monitoring Tool

Because of the short turnaround time and low cost, the RadTox™ test can serve as a longitudinal serial monitoring tool for tumor responses multiple times during and after treatment, including the transition from disease progression to stable disease, and to recurrence.

Comprehensive Tumor Response Monitoring Tool

Combined with circulating tumor DNA (ctDNA) vertical monitoring deep into clonal evolution and treatment resistance at a treatment point, the cancer management by liquid biopsy becomes more comprehensive and valuable as a complementary tool to imaging.

Although there is no easy way to separate ctDNA from the rest of the cfDNA, specific ctDNA (not the total ctDNA) biomarkers can be identified and quantified by the presence of cancer mutations. The total cfDNA, on the other hand, can be quantified once the plasma is isolated from the rest of the blood.

Liquid biopsy: cfDNA vs. ctDNA

In recent years, liquid biopsy has gained traction for different clinical applications, including early detection, prognosis, and treatment monitoring. cfDNA and ctDNA are the two most essential biomarkers commonly studied and gradually adapted in clinical settings.

Cell-free DNA (cfDNA)

cfDNA is the total DNA released into the bloodstream, consisting of DNA fragments from normal cells and tumor cells.

Circulating Tumor DNA (ctDNA)

Refers to DNA fragments from only tumor cells. At the early stage of cancer development, ctDNA is only a small fraction of cfDNA, as low as 0.01 to 1%. However, with faster tumor cell growth and turnover compared to normal cells, the proportion of ctDNA has significantly increased at the late stage of advanced cancer, reaching even 90% of the total cfDNA.

Cell-Free DNA (cfDNA)

Total cfDNA quantification as a biomarker for prognosis and treatment response

Although total cfDNA varies between individuals, total cfDNA quantification has been found to be a promising biomarker for cancer prognosis and treatment responses in many publications.

Here are some of the findings about the total cfDNA level:

Healthy individuals vs. cancer patients: Cancer patients have much higher cfDNA, even 200-fold more
Early stages vs. late stages: Late-stage cancer patients have much higher levels of cfDNA than early-stage patients
Cancer cell number: Patients with bigger tumor mass has more cfDNA
Prognosis: Patients with more cfDNA has a shorter progression-free survival (PFS) or overall survival (OS)
Treatment responses: cfDNA decreases in progression-free patients and increase in patients with recurrence and metastasis

Due to the lack of specificity of cfDNA quantification in cancer types and limited ctDNA in early-stage cancer, cfDNA quantification is a more favorable predictive and prognostic biomarker in cancer treatment response monitoring than a diagnostic biomarker.

ctDNA Monitoring or Total cfDNA
Quantification Monitoring?

Like total cfDNA quantification, ctDNA quantification has shown great value in prognosis and treatment response monitoring, specific for the individual patient with prior knowledge of the mutation information. In addition, the genomic profiling of the ctDNA provides guidance for target therapy and monitors tumor recurrence or therapy resistance through residual diseases with the known clone evolution mutants, which can’t be done with cfDNA quantification. However, total cfDNA quantification can be used for monitoring treatment responses and cancer recurrence through the total cfDNA level changes over time.

It is true that the cfDNA is a mixture of normal cell DNA and tumor cell DNA. However, studies found that the ctDNA in cfDNA significantly increases over the cancer development, and there is a close to linear correlation between the cfDNA quantification and quantification of a specific ctDNA biomarker such as KRAS or EGFR from non-small cell lung cancer patients. There is also a very good correlation in prognosis between cfDNA quantification and ctDNA quantification monitoring. Most of all, many clinical studies have shown that total cfDNA level is a valuable biomarker for prognosis and treatment response monitoring in many cancer types.

This is partially related to the above myth and partially doubting about the accuracy of cfDNA quantification as a biomarker. Many studies using different cfDNA quantification methods made similar conclusions in identifying the cfDNA differences and clearly reached the same conclusion as ctDNA for prognosis and treatment response monitoring. Therefore, there is no sensitivity issue for cfDNA quantification.

When target therapy is involved, ctDNA monitoring is the choice for monitoring therapy efficacy, therapy resistance, and minimal residual disease.

We recommend using both cfDNA quantification as well as ctDNA monitoring tools to monitor treatment responses as they complement each other and provide different values.

If frequent, overall monitoring without looking into individual tumor clones is desired, cfDNA quantification monitoring can be chosen for faster and real-time monitoring.

The RadTox™ test measures total cfDNA without extracting cfDNA, providing the benefits of accuracy and small plasma sample size (as little as 10 μL plasma used in the test). These benefits allow serial monitoring to become practical in a clinical setting.

Read the white paper for more information

Read the test brochure for case examples

Read RadTox™ test guidelines

Order a RadTox™ for your patients

Questions? Email radtox@diacarta.com

(1) Pantel et al. Liquid biopsy and minimal residual disease—Latest advances and implications for cure. Nat. Rev. Clin. Oncol. 2019, 16, 409–424.
(2) Diehl et al. Circulating mutant DNA to assess tumor dynamics. Nat Med 2008, 14:985-990.
(3) Diaz Jr, LA and A. Bardelli. Liquid Biopsies: Genotyping Circulating Tumor DNA. J Clin Oncol 2014, 32:579-586.
(4) Schwarzenbach et al. Detection and Monitoring of Cell-Free DNA in Blood of Patients with Colorectal Cancer. Ann. N.Y. Acad. Sci. 2008, 1137: 190–196.
(5) Park et al. Quantitative analysis of cell-free DNA in the plasma of gastric cancer patients. ONCOLOGY LETTERS 2012, 3: 921-926.
(6) Gautschi et al. Circulating deoxyribonucleic Acid as prognostic marker in non-small-cell lung cancer patients undergoing chemotherapy. J Clin Oncol. 2004 Oct 15;22(20):4157-64.
(7) Fernandez-Garcia et al. Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer. Breast Cancer Research 2019, volume 21, Article number: 149
(8) Dao et al. Using cfDNA and ctDNA as Oncologic Markers: A Path to Clinical Validation. Int J Mol Sci. 2023, Sep; 24(17): 13219.
(9) Frattini et al. Quantitative Analysis of Plasma DNA in Colorectal Cancer Patients A Novel Prognostic Tool. Ann. N.Y. Acad. Sci. 2006, 1075: 185–190.
(10) Hu et al. Post surgery circulating free tumor DNA is a predictive biomarker for relapse of lung cancer. Cancer Med. 2017 May;6(5):962-974.
(11) Carrasco et al. 2022. Cell-Free DNA as a Prognostic Biomarker for Monitoring Muscle-Invasive Bladder Cancer. Int. J. Mol. Sci. 23, 11732.

FOR PATIENTS

PHYSICIANS FAQ

RadTox offers
Personalized Treatment Effectiveness

By comparing conditions before treatment, after treatment, and even during long-term surveillance in the recovery phase

The RadTox™ test monitors tumor treatment responses in patients of different cancer types by measuring the total cell-free DNA (cfDNA) from plasma.

Longitudinal Serial Real-Time Monitoring Tool

Because of the short turnaround time and low cost, the RadTox™ test can serve as a longitudinal serial monitoring tool for tumor responses multiple times during and after treatment, including the transition from disease progression to stable disease, and to recurrence.