An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage

Aaron M Newman ¹, Scott V Bratman ², Jacqueline To ³

¹1] Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. [2] Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California, USA. [3].
²1] Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. [2] Department of Radiation Oncology, Stanford University, Stanford, California, USA. [3].
³Department of Radiation Oncology, Stanford University, Stanford, California, USA.
⁴1] Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. [2] Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California, USA.
⁵Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California, USA.
⁶Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford School of Medicine, Stanford University, Stanford, California, USA.
⁷1] Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. [2] Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California, USA. [3] Division of Hematology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California, USA.
⁸1] Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. [2] Department of Radiation Oncology, Stanford University, Stanford, California, USA. [3] Stanford Cancer Institute, Stanford University, Stanford, California, USA.

⁰1] Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. [2] Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California, USA. [3].

Summary

Cancer personalized profiling by deep sequencing (CAPP-Seq) offers an ultrasensitive method for detecting circulating tumor DNA (ctDNA). This approach shows high sensitivity and specificity for non-small cell lung cancer, enabling early detection and monitoring.

Area Of Science

Oncology
Molecular Biology
Genomics

Background

Circulating tumor DNA (ctDNA) shows promise for noninvasive cancer burden assessment.
Current ctDNA detection methods lack the sensitivity and patient coverage for widespread clinical use.

Purpose Of The Study

To introduce Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq), an economical and ultrasensitive ctDNA quantification method.
To evaluate CAPP-Seq's efficacy in non-small cell lung cancer (NSCLC) detection and monitoring.

Main Methods

CAPP-Seq utilizes deep sequencing for personalized profiling of circulating tumor DNA.
The method was designed to cover multiple classes of somatic alterations in NSCLC.
Sensitivity and specificity were assessed for detecting low-fraction ctDNA mutations.

Main Results

CAPP-Seq identified mutations in over 95% of NSCLC tumors.
ctDNA was detected in 100% of stage II-IV and 50% of stage I NSCLC patients with 96% specificity.
ctDNA levels correlated with tumor volume, differentiated residual disease, and enabled earlier response assessment than imaging.

Conclusions

CAPP-Seq is an ultrasensitive, economical method for ctDNA quantification with broad clinical potential.
The technology facilitates biopsy-free tumor screening, genotyping, and personalized cancer therapy.
CAPP-Seq could be routinely applied for detecting and monitoring various malignancies.

An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage

Summary

Area Of Science

Background

Purpose Of The Study

Main Methods

Main Results

Conclusions

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An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage

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Summary

Area Of Science

Background

Purpose Of The Study

Main Methods

Main Results

Conclusions

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