Promising Liquid Biopsy for Gastric Cancer Recurrence Developed

Epic Sciences plans to accelerate development of its liquid biopsy cancer tests

A blood test to predict recurrence of gastric cancer post-surgery has been developed by researchers at the Johns Hopkins Kimmel Cancer Center in Baltimore and colleagues in the Netherlands. A description of their test, which is still experimental, was published online Jan. 27 in the journal Nature Communications.

Alessandro Leal, M.D., Ph.D., lead author of the paper on the study and former graduate student at the Johns Hopkins University School of Medicine says, “Patients who did not have mutations in the blood after surgery were all cured of cancer, while patients who had mutations in the blood typically recurred. We were able to predict patient outcome about nine months earlier through the blood test than we otherwise could have through clinical evaluation.”

“We performed this study to see if we could predict whether gastric cancers would recur using noninvasive liquid biopsies. Using a deep sequencing approach of cell-free DNA and white blood cells, we found an outstanding prediction of whether the therapy was successful,” says senior study author Victor Velculescu, MD, PhD, professor of oncology, pathology and medicine. Velculescu also is co-director of the Kimmel Cancer Center’s cancer genetics and epigenetics program, and associate director for precision medicine.

The study was performed by Leal and Velculescu, colleagues from Johns Hopkins and with Nicole van Grieken, Gerrit Meijer, Annemieke Cats, and other investigators in the Netherlands. Plans to validate the method in larger clinical trials have begun.

Gastric cancer (GC) remains the fifth most common cancer and the third leading cause of cancer-related death worldwide. Its prognosis is unfavorable owing to aggressive tumor biology, late detection, and high disease progression and recurrence rates. One of the greatest unmet needs in this arena is for biomarkers that can determine which patients are at highest risk of recurrence, and as soon as possible.

In this study, investigators analyzed blood samples from 50 patients with gastric cancer who participated in the CRITICS (ChemoRadiotherapy after Induction chemoTherapy In Cancer of the Stomach) study trial, a phase III, randomized controlled study ofchemotherapy given at about the time of surgery. The researchers performed deep sequencing of both circulating cell-free DNA (cfDNA) and of white blood cells to look for mutations. Subtracting the white blood cells’ information from cfDNA yielded data investigators coulduse to predict cancer recurrence within nine weeks following preoperative treatment and surgery.

After filtering alterations from matched white blood cells, the researchers found that tumor derived DNA (ctDNA) predicted recurrence when analyzed within nine weeks after surgery in patients eligible for multimodal treatment. The authors say these analyses provide “a facile method” for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.

The study included 788 patients from 56 hospitals in the Netherlands, Sweden, and Denmark, and they were randomized upfront to receive three preoperative 21-day cycles of intravenous epirubicin, cisplatin or oxaliplatin, and oral capecitabine followed by three postoperative cycles of intravenous epirubicin, cisplatin or oxaliplatin, and oral capecitabine (chemotherapy group) or to receive the same preoperative regimen followed by radiation combined with daily capecitabine and weekly cisplatin (chemoradiotherapy group).

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