SAGA shows ctDNA lead time detection

Why it matters

SAGA Diagnostics said on May 26 that a newly published NeoCircle study found its Pathlight circulating tumor DNA test detected relapse in early breast cancer up to four years before clinical progression. The company said the paper was published in *EMBO Molecular Medicine* and evaluated tumor-informed ctDNA monitoring in patients receiving neoadjuvant therapy. (biospace.com) The study adds to a growing body of work on whether molecular residual disease testing can identify recurrence risk earlier than imaging or symptoms. SAGA said the results also showed Pathlight outperformed pathologic complete response as a prognostic marker in this setting. ### What exactly did the NeoCircle study test? NeoCircle is a prospective real-world clinical study nested within the SCAN-B study, identified as NCT02306096, according to SAGA Diagnostics. The company said the trial enrolled patients with early breast cancer who were eligible for neoadjuvant therapy and used structural-variant-based ctDNA detection to assess treatment response and residual disease. (biospace.com) The analysis covered 136 neoadjuvant-therapy-eligible patients across all breast cancer subtypes, SAGA said. The company said 85.3% of the analysis cohort had Stage I or Stage II disease, a group in which treatment is typically given with curative intent. ### How far ahead of clinical relapse did the blood test signal trouble? (biospace.com) SAGA Diagnostics said Pathlight detected relapse months to years before clinical progression, with lead times of up to four years. The company said those findings came from ctDNA monitoring across neoadjuvant and adjuvant treatment, where persistent or re-emerging ctDNA signaled molecular residual disease and a high risk of recurrence. Lao Saal, head of translational oncogenomics and co-director of the CIRCE Women’s Cancer Research Center at Lund University, said in the company release that Pathlight can detect structural variants at levels as low as 1 part in 10 million. (biospace.com) Saal said the study, with up to 9.7 years of clinical follow-up, offered a view of the durability of structural variants and their potential clinical use in patient care. ### How did ctDNA compare with pathologic complete response? SAGA Diagnostics said the publication found Pathlight outperformed pathologic complete response, or pCR, as a prognostic marker in early breast cancer. The company said pCR remains an established marker, but has limited ability to stratify the larger group of patients who do not achieve pCR after neoadjuvant treatment. (biospace.com) The company said complete or partial ctDNA clearance during neoadjuvant therapy was a significant predictor of favorable outcome. SAGA reported that 10.4% of patients in the ctDNA clearance group experienced recurrence, compared with 56.3% in the ctDNA non-response group. ### Why does sample handling matter in a result like this? (biospace.com) Circulating tumor DNA testing depends on detecting very small amounts of tumor-derived DNA in blood, and SAGA said its assay is designed for ultrasensitive molecular residual disease detection. That makes pre-analytical steps such as blood collection, stabilization, transport, storage and extraction part of the workflow that laboratories must control if they want reliable results from low-abundance samples. This is an inference based on the assay sensitivity and the study’s focus on early molecular detection. (biospace.com) Medical Xpress, citing Lund University researchers, separately reported on May 27 that the blood test detected signs of recurrence long before imaging or symptoms. That report described the work as a method for identifying extremely small amounts of tumor DNA in blood with high precision and specificity. (biospace.com) ### What happens next for the findings? The publication is now in *EMBO Molecular Medicine*, and SAGA Diagnostics has tied the results to its Pathlight molecular residual disease platform. The next milestones are likely to come from additional clinical validation, adoption studies and any future use of the SCAN-B sub-cohort data by SAGA, Lund University researchers and other named study participants. (medicalxpress.com) (biospace.com)

Key numbers

• SAGA Diagnostics said on May 26 its NeoCircle study publication showed Pathlight detected relapse in early breast cancer up to four years before clinical progression.
• (biospace.com) The study analyzed 136 neoadjuvant-therapy-eligible patients, and SAGA said ctDNA non-response was linked to 56.3% recurrence versus 10.4% with clearance.
• (biospace.com) SAGA Diagnostics said on May 26 that a newly published NeoCircle study found its Pathlight circulating tumor DNA test detected relapse in early breast cancer up to four years before clinical progression.
• NeoCircle is a prospective real-world clinical study nested within the SCAN-B study, identified as NCT02306096, according to SAGA Diagnostics.

What happens next

• SAGA Diagnostics said on May 26 that a newly published NeoCircle study found its Pathlight circulating tumor DNA test detected relapse in early breast cancer up to four years before clinical progression.
• (biospace.com) Medical Xpress, citing Lund University researchers, separately reported on May 27 that the blood test detected signs of recurrence long before imaging or symptoms.
• (biospace.com) What happens next for the findings?

Sources

• biospace.com
• medicalxpress.com

Quick answers