BillionToOne, a next-generation molecular diagnostics company with a mission to create powerful and accurate tests that are accessible to all, announced the launch of Northstar Origin, a new liquid biopsy add-on test for tissue-of-origin prediction, along with the expansion of its Northstar Select panel from 84 to 102 genes to cover genes that are included in recent and upcoming FDA approvals.

Northstar Origin is a physician-ordered add-on test to Northstar Select that predicts tissue of origin directly from circulating cell-free DNA (cfDNA) for patients with cancer of unknown primary (CUP) or uncertain cancer diagnosis, reducing the need for additional tissue or separate blood draws. The assay combines methylation profiling with the same single-molecule precision used in Northstar Response with an independent signal obtained from tissue-specific somatic variants detected by Northstar Select.

Northstar Origin addresses a persistent diagnostic challenge for community oncologists: uncertain tumor origin. Roughly 3-5 per cent of new oncologic diagnoses present as CUP, where standard pathology and imaging workup cannot confidently identify a definitive tumor source, complicating therapy selection. Moreover, up to ~10 per cent of patients in community oncology settings without access to detailed pathology work-ups may have uncertain diagnoses. Tissue-based tools for resolving these cases can also be limited by the amount and quality of tissue available.

"Community oncologists are often asked to make the same complex diagnostic decisions as physicians at academic centers, without the same access to tumor boards or subspecialty pathology support," said Ethan Dmitrovsky, MD, Chief Medical Officer, Oncology at BillionToOne. "Northstar Origin is designed to help close that gap. It is a highly accurate, easy-to-use diagnostic aid that can be added to the liquid biopsy a patient already receives for therapy selection. Northstar Origin can extend more equitable access to care."

Northstar Origin’s performance was evaluated in an independent validation cohort of 1,578 patients, after the supervised classifier was developed using 6,025 blood samples from advanced cancer patients previously submitted to BillionToOne's clinical laboratory. In this evaluation, the model identified the correct tissue of origin as its top prediction in 87% of cases, and within its top three predictions in 91 per cent of cases. BillionToOne plans prospective studies to expand the model to additional tumor types and further evaluate its clinical utility.

Allen Chen, MD, Vice President of Oncology Clinical Development and Medical Affairs at BillionToOne and senior author of the study, said the findings underscore the clinical importance of resolving a tumor’s primary site. “Cancers of unknown primary have historically posed a challenge because not knowing where the tumor originated leads to treatment uncertainty and patient anxiety. In these scenarios, conventional workup, including physical examination, imaging, and pathology, is unfortunately often not enough. Northstar Origin provides clinicians with an additional, complementary molecular prediction from the same blood sample used for therapy selection. Studies have consistently shown that uncovering the primary site results in more personalized therapy and better outcomes.”