GRAIL and University of Oxford present results from first prospective study of multi-cancer early detection in a symptomatic patient population at 2023 ASCO annual meeting

The analysis showed strong performance of GRAIL’s MCED methylation-based platform in the symptomatic population of more than 6,000 patients and demonstrated the feasibility of using an MCED test to assist clinicians with decisions around the route of referral from primary care. These results are in press for publication in The Lancet Oncology.

The SYMPLIFY study enrolled 6,238 patients, aged 18 and older, in England and Wales who were referred for urgent imaging, endoscopy or other diagnostic modalities to investigate symptoms suspicious for possible gynecological, lung, lower GI or upper GI cancer, or who had presented with non-specific symptoms. Participants provided a blood sample, from which cell-free DNA was isolated and stored until GRAIL’s MCED test was performed in batches, blinded to clinical outcome. GRAIL’s MCED test’s predictions (cancer signal detected, and if so, cancer signal origin [CSO]) were compared with the diagnosis obtained by standard of care to assess the test’s performance. The most commonly reported symptoms leading to referral were unexpected weight loss (24.1%), change in bowel habit (22.0%), post-menopausal bleeding (16.0%), rectal bleeding (15.7%), abdominal pain (14.5%), pain (10.6%), difficulty swallowing (8.8%) and anemia (7.1%).

Within the study, 368 (6.7%) of the 5,461 evaluable patients were diagnosed with cancer through standard of care. The most common cancer diagnoses were colorectal (37.2%), lung (22.0%), uterine (8.2%), oesophago-gastric (6.0%) and ovarian (3.8%).

The SYMPLIFY study enrolled 6,238 patients, aged 18 and older, in England and Wales who were referred for urgent imaging, endoscopy or other diagnostic modalities to investigate symptoms suspicious for possible gynecological, lung, lower GI or upper GI cancer, or who had presented with non-specific symptoms. Participants provided a blood sample, from which cell-free DNA was isolated and stored until GRAIL’s MCED test was performed in batches, blinded to clinical outcome. GRAIL’s MCED test’s predictions (cancer signal detected, and if so, cancer signal origin [CSO]) were compared with the diagnosis obtained by standard of care to assess the test’s performance. The most commonly reported symptoms leading to referral were unexpected weight loss (24.1%), change in bowel habit (22.0%), post-menopausal bleeding (16.0%), rectal bleeding (15.7%), abdominal pain (14.5%), pain (10.6%), difficulty swallowing (8.8%) and anemia (7.1%).

Within the study, 368 (6.7%) of the 5,461 evaluable patients were diagnosed with cancer through standard of care. The most common cancer diagnoses were colorectal (37.2%), lung (22.0%), uterine (8.2%), oesophago-gastric (6.0%) and ovarian (3.8%).

GRAIL’s MCED test detected a cancer signal in 323 people, 244 in whom cancer was diagnosed, resulting in a positive predictive value (PPV) of 75.5%, negative predictive value (NPV) of 97.6%, and specificity of 98.4%. The overall sensitivity of the MCED test was 66.3%, ranging from 24.2% in stage I cancers to 95.3% in stage IV, and increased with age and later cancer stage. The overall accuracy of the top CSO prediction after a positive MCED test was 85.2%. The mean age of patients in the study was 62.1 years old.

GRAIL’s earlier PATHFINDER study previously demonstrated that adding GRAIL’s MCED testing to standard of care screening more than doubled the number of cancers detected compared with standard screening alone in adults with no symptoms or suspicion of cancer. Now, the SYMPLIFY data confirm the potential benefit of methylation-based MCED blood tests as a diagnostic aid for use in the symptomatic patient population,” said Sir Harpal Kumar, President of GRAIL Europe. “These exciting results will inform our development of an optimized classifier for use in symptomatic patients with a suspicion of cancer.” .