Marwan Fakih: Our large series on Signatera ctDNA surveillance in patients with resected colorectal cancer
Marwan Fakih, Associate Director for Clinical Sciences at City of Hope, shared a post on LinkedIn:
“Today our large series on Signatera ctDNA surveillance in patients with resected colorectal cancer was published in JAMA network.
We were the first to raise concerns regarding the sensitivity of this assay in monitoring curatively resected colorectal cancer.
Our prior paper from years ago was the first to note the poor sensitivity in non-liver metastsatic disease, particularly lung metastases.
In our new series of > 180 patients with resected colorectal cancer, 45 patients recurred by Signatera or Imaging.
14 patients recurred by imaging and were Signatera negative at the first sign of imaging recurrence. 20 patients were signatera and had either no imaging scheduled or negative imaging, 6 of whom on reflex imaging were noted to have disease.
Therefore only 14/45 (~30 percent) were ctDNA positive without recurrence by imaging– out of whom 3 reverted to ctDNA negative spontaneously and NEVER recurred. Among the Signatera+ and Imaging Negative patients, 6 patients eventually recurred and had surgery but only 1 remains NED.
The percentage of curative outcome was higher in the rest of the population.
While this study is hypothesis generating, we clearly show some significant limitations for current ctDNA platforms such as Signatera in the SURVEILLANCE setting.
We are also concerned about spontaneous clearance in the surveillance setting (patients who had finished adjuvant chemotherapy and turned positive after adj to spontaneously become negative).
We do not believe that ctDNA clearance is an adequate endpoint on its own given the spontaneous clearance in some patients.
We also caution against the potential overtreatment of these patients and potentially exposing them to experimental therapies that can be associated with significant toxicities.”
Circulating Tumor DNA Testing in Curatively Resected Colorectal Cancer and Salvage Resection
Authors: Jingran Ji, Chongkai Wang, Ajay Goel, Kurt Melstrom, Yasmin Zerhouni, Lily Lai, Laleh Melstrom, Mustafa Raoof, Yuman Fong, Andreas Kaiser, Marwan Fakih
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