A100-10 Validation of a Multi-Cancer Risk Stratification Blood Test in a Lung Cancer Screening Cohort

Rationale Individuals participating in lung cancer screening (LCS) have increased risks of cancers other than lung cancer, and in LCS trials, non-lung cancer incidence exceeds that of lung cancer. Thus, we sought to evaluate the performance of a new multi-cancer stratification test (MCaST), which can refine risk estimation for 9 common and lethal solid cancers, in an LCS cohort. Methods The MCaST panel consists of immunoassays to 10 cancer-associated biomarkers and is anchored on a 4-protein biomarker panel for lung cancer (4MP) as well as a proprietary algorithms and pre-defined thresholds developed at MD Anderson. The MCaST was initially developed and validated with plasma samples from longitudinal cohorts including the Prostate, Colorectal, Lung, and Ovarian cohort. MCaST improved risk estimation for lung, pancreatic, prostate, colorectal, ovarian, breast, esophageal, liver, and gastric cancers.The LEAP study is an international, prospective, multicenter, longitudinal LCS study that enrolled 2,841 individuals from 10 centers eligible for screening based NCCN guidelines. We assessed the performance of the MCaST using serially collected pre-diagnostic plasma samples from the 73 lung cancer cases and 101 other cancer cases diagnosed during screening as well as 3-times the number of non-case control participants who did not develop cancer during the study follow-up period. Results In the cohort, 74 of 175 cancer diagnoses were lung cancer. The overall sensitivity of the MCaST at a predefined 0.167% risk threshold was 75.7%, capturing 56 out of the 74 lung cancer cases, including, 40 of the 51 early-stage cases. Median (IQR) time from the first positive test to a clinical diagnosis of lung cancer was 12.8 months (1.4 – 28.5 months). Of the 101 other non-lung cancer diagnoses the overall sensitivity for prostate, breast, colorectal, ovarian, pancreatic, esophageal, and stomach was 68.9%. MCaST detected 16 out of 18 prostate, 7 of 11 breast, 6 out of 7 colorectal, 2 of 4 ovarian, 1 of 2 pancreatic, and 2 of 3 upper GI cancers. Median (IQR) time from the first positive test to a clinical diagnosis of any of the above 7 cancer types was 20.7 months (10.2 – 42.8 months). Conclusions LCS with an MCaST could serve as an entry point for multi cancer early detection by stratifying subjects based on their personalized risk for common cancers for their early detection . This abstract is funded by: Lyda Hill Foundation, MD Anderson Moon Shot Initiatives