Wake Forest study – adding liquid biopsy improves cancer diagnosis, treatment

Adding a blood test called liquid biopsy to a standard tissue biopsy could significantly improve the accuracy of diagnosis and treatment for patients with cancer, according to researchers at Wake Forest Baptist Medical Center.

Their recommendation is published in the current online issue of the journal Annals of Oncology.

Cancer management relies on the ability of physicians to accurately “stage” the disease – to determine the size and extent of the primary tumor and whether the cancer cells have spread to the lymph nodes or other organs. Conventional staging of malignant tumors uses the TNM Staging System, which relies on a tissue sample taken from the tumor either through surgery or needle biopsy.

“Although cancer diagnosis and treatment have improved greatly over the past decade, too often the initial results are inaccurate and short-lived and the cancer reoccurs because of limitations of the current staging system and the dynamic and systemic nature of cancer,” said the review’s lead author Wei Zhang, Ph.D., an endowed Hanes and Willis Family Professor in cancer at Wake Forest School of Medicine, a part of Wake Forest Baptist.

Over the last several years, insight into the systemic nature of cancer has emerged from the study of circulating tumor DNAs (ctDNA) that can be detected by powerful sequencing technology through a process known as liquid biopsy.

This expanded capacity to detect cancer-specific mutations, particularly using a noninvasive blood draw that enables resampling over time during cancer treatment, enabled oncologists in the precision oncology program at Wake Forest Baptist to evaluate the value of liquid biopsy in guiding cancer care. Approximately 400 patients at Wake Forest Baptist have been tested by this liquid biopsy. Based on analysis of these results, the team concluded the system of cancer staging should be revised.

“We propose developing a modified staging approach that adds a liquid biopsy to the conventional TNM system,” Zhang said.

“The ctDNA circulating in the blood provides a reservoir of DNA information about cancer status that we simply don’t have using TNM alone. This could dramatically improve cancer early detection, diagnosis, prognosis and treatment, providing real benefits to cancer patients.”

Although the technology is still evolving and many additional steps are needed before widespread adoption and implementation can occur, Zhang and his team hope to raise awareness of the potential of a new, more effective approach to staging and subsequently more precise cancer treatment.

Biological characteristics and clinical applications of ctDNA


(a) Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA) and circulating tumor protein as complementary blood-based biomarkers. Tumor cells release ctDNA into the bloodstream through apoptosis, necrosis and secretion. A subset of aggressive ctDNA enters the bloodstream from the primary tumor or metastatic lesions. (b) Central circle illustrates ctDNA as having multiple classes of genetic and epigenetic alterations. Outer circle presents the potential clinical benefits of ctDNA monitoring in cancer management. CNV, Copy Number Variation.

Source – Wake Forest Baptist Medical Center

Yang M, Forbes ME, Bitting RL, O’Neill SS, Chou PC, Topaloglu U, Miller LD, Hawkins GA, Grant SC, DeYoung BR, Petty WJ, Chen K, Pasche BC, Zhang W. (2017) Incorporating Blood-based Liquid Biopsy Information into Cancer Staging: Time for a TNMB System? Ann Oncol [Epub ahead of print]. [article]

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