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CASE REPORT article

Front. Oncol.

Sec. Cancer Genetics

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1637999

Multi-cancer early detection utilizing blood-based genomics: Single-institution case series of novel cancer screening

Provisionally accepted
Somya  KhareSomya Khare1Jason  C BurtonJason C Burton1Francis  De AsisFrancis De Asis2Saron  MekonnenSaron Mekonnen2Mason  Stewart- MclellanMason Stewart- Mclellan2Diana  PottsDiana Potts2Tiffani  HowardTiffani Howard3Nima  NabavizadehNima Nabavizadeh1*
  • 1Department of Radiation Medicine, Oregon Health and Science University, Portland, United States
  • 2Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, United States
  • 3Community Outreach and Engagement, Knight Cancer Institute, Oregon Health and Science University, Portland, United States

The final, formatted version of the article will be published soon.

Cancer screening continues to be a major challenge, with reliable tests only being available for very few cancers. Multi-cancer early detection (MCED) genomic tests are being developed that allow for blood-based screening of multiple cancers simultaneously. The PATHFINDER study was a multi-institution prospective cohort study in healthy participants over the age of 50 years (no cancer history, or history of treated cancer > 3 years prior), investigating the feasibility of the Galleri (GRAIL, LLC) cfDNA methylation MCED blood test. For participants in which the Galleri MCED test revealed methylation signatures indicative of cancer, predicted cancer signal origins were provided to the clinicians to assist with further diagnostic workup. Our institution was the highest accruing site nationally. Here, we describe our institutional test performance and provide informative case vignettes.Under IRB approval, a retrospective chart review of participants enrolled in the PATHFINDER study was performed. Cancer risk factors, outcomes of tests and studies performed due to MCED signal positive, time to diagnostic resolution, and treatment outcomes were obtained from chart-review.From January 2020 to December 2020, our institution enrolled 1735 participants (26% of total study enrollment), 27 of which returned a signal positive for cancer suspicion (1.6%), and ultimately 12 diagnosed cancers (true positives) for a positive predictive value of 44%. Four of 12 were recurrent cancers in participants more than three years from cancer therapy. There were 15 signal positives without cancer diagnoses (false positives), with one patient receiving extensive work-up for possible uterus, breast or lung cancer origin. Six of 15 false positive results correlated to monoclonal B-cell lymphocytosis (chronic lymphocytic leukemia precursor). During the course of 12-month follow-up for signal negatives, 19 additional participants were diagnosed with a cancer (sensitivity: 39%, specificity: 99.1%).Our institutional experience demonstrates the feasibility of MCED testing. Additional prospective randomized clinical trials are needed before widespread adoption.The information and data included in this manuscript was previously presented as a poster (e612 Poster Q&A Sessions) at the 2024 American Society for Radiation Oncology Annual Meeting.

Keywords: cancer early detection, pathfinder, Cancer genomics, Retrospective study, cancer screening, precision oncology, Blood-based screening

Received: 30 May 2025; Accepted: 31 Jul 2025.

Copyright: © 2025 Khare, Burton, De Asis, Mekonnen, Stewart- Mclellan, Potts, Howard and Nabavizadeh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Nima Nabavizadeh, Department of Radiation Medicine, Oregon Health and Science University, Portland, United States

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