Oncologists face a difficult decision after surgically removing a solid tumor. Some patients harbor residual cancer cells, known as minimal residual disease (MRD), and need additional therapy to avoid recurrence, while others are already cured. Determining who falls into each group remains a major challenge in cancer care.
Traditionally, physicians use imaging and protein biomarkers for recurrence surveillance, but these methods often detect relapses only after the tumor reaches detectable levels, highlighting the need for more sensitive MRD testing. Shed by cancer cells into the bloodstream, circulating tumor DNA (ctDNA) has emerged as a promising MRD biomarker but presents its own technical hurdles. “One of the challenges facing ctDNA technologies is, how do we identify ctDNA molecules that are very low abundance in circulation with high accuracy?” said Dan Edelstein, the vice president and general manager of Haystack Oncology at Quest Diagnostics®.
Recognizing the need to detect ctDNA reliably, Haystack Oncology developed Haystack MRD®, a next-generation workflow for ultrasensitive residual disease monitoring. “One of the unique properties of Haystack MRD is its inherent error correction that is built into the workflow, which accounts for any noise that is introduced through the amplification process when we are preparing the DNA or the sequencing instrument,” said Edelstein. The approach uses whole-exome sequencing of a patient’s tumor tissue and white blood cells to identify tumor-specific mutations and design a personalized panel. During postoperative testing, the panel enriches up to 50 ctDNA variants from plasma samples before sequencing, helping overcome background noise that can obscure detection of low-frequency ctDNA.
Using a personalized mutation panel based on the tumor’s genetic signature, Haystack MRD® enriches low-frequency ctDNA from plasma, overcoming background noise for accurate MRD analysis.
Quest Diagnostics/Haystack Oncology
“Our research team leverages Haystack as an investigational tool to optimize the management of patients with head and neck cancer. By integrating the circulating tumor DNA results with our standard clinical and radiographic assessments, we are evaluating how the MRD testing can improve treatment response assessment and adapt treatment,” said Nishant Agrawal, the section chief of Otolaryngology-Head and Neck Surgery at the University of Chicago Medicine. “[Haystack MRD’s] level of exceptional sensitivity gives oncologists around the world the confidence that we need to guide and adapt treatment earlier and more accurately than the current traditional tools that we have at our disposal.”
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