Abstract 2243: Diagnostic journey following a multi-cancer early detection test: A retrospective case series of gastrointestinal cancers in the PATHFINDER study
Authors: McDonnell Charles H. , Hudnut Andrew , Jacobs Debbie A. , Ogilvie Patrick D. , Bobolis Kristie A. 
Published: June 2022

Abstract
Introduction: Gastrointestinal (GI) cancers are common, but with the exception of colorectal cancer, are not amenable to population screening. A blood-based multi-cancer early detection (MCED) test is available for use as a complement to existing single cancer screening modalities, however experience deploying such tests is limited. PATHFINDER (NCT04241796; enrollment complete, n=6662) is an ongoing prospective study in asymptomatic adults ≥50 y that returns MCED test results (‘signal not detected’ or ‘signal detected’) with ≥1 cancer signal origin (CSO) prediction to direct diagnostic workup. To better understand challenges and opportunities following a signal detected result, GI case studies are presented.
Methods: Participants who were confirmed with a new Clinical Stage I/II GI cancer from the interim PATHFINDER data set (data cutoff Mar-19-2021) were included. Data were reviewed, and key diagnostic steps from signal detected (Day 1) to resolution were summarized.
Results: Individual 1 was a female &gt;60 y without additional cancer risk factors (CSO=Colon/Rectum, Upper GI Tract). CT abdomen was performed, followed by colonoscopy then upper endoscopy. A 4.0 cm mass identified was further evaluated via endoscopic ultrasound with biopsy and confirmed a Clinical Stage I duodenal adenocarcinoma (Day 60), which was treated with surgery (Pathologic Stage III) and adjuvant chemotherapy. Patient tolerated the treatment and remains disease free. Individual 2 was a male former smoker &gt;65 y with a history of hepatitis C (CSO=Liver/Bile-duct); CT confirmed cirrhotic liver with 6.4cm LI-RADS 5 mass at Day 57 (Clinical Stage Ib). Treatment was declined following surgical referral and participant died &lt;9 months post-test result. Individual 3 was a male former smoker &gt;70 y (CSO=Pancreas/Gallbladder, Lung). Work-up included metabolic panel, CA19-9, CT abdomen and chest, and PET-CT. A CT-guided core biopsy confirmed diagnosis of a Clinical Stage IIb resectable pancreatic adenocarcinoma on Day 38; surgery (Pathologic Stage IIa) and adjuvant chemotherapy followed; patient is disease free to date.
Conclusions: The MCED test detected cancer signals and predicted a GI CSO for three individuals with Clinical Stage I or II GI cancers for which there is currently no single early cancer screening method. All three achieved diagnostic resolution within 2 months and were provided treatment recommendations with curative intent.
Citation Format: Charles H. McDonnell III, Andrew Hudnut, Debbie A. Jacobs, Patrick D. Ogilvie, Kristie A. Bobolis. Diagnostic journey following a multi-cancer early detection test: A retrospective case series of gastrointestinal cancers in the PATHFINDER study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2243.