In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 3123-3123
Abstract:
3123 Background: Early detection may reduce cancer mortality. Systematic screening programs are available only for a limited number of cancers (e.g., colorectal cancer). The majority of common cancers are detected after the onset of signs and symptoms, making treatment difficult or less effective. We describe here a multi-cancer epigenetic approach for simultaneous cancer detection of common cancers (̃70% of adult cancers) and determination of tissue of origin (TOO) using circulating cell-free DNA (cfDNA) from plasma. Methods: A total of 2241 cancer cases, including patients with newly diagnosed primary colorectal, gastric, esophageal, liver, lung, and breast cancer (stages I-III or equivalent) and 2289 non-cancer controls were recruited from participating hospitals in China. Study participants were randomly assigned into a training set (70%) and a testing set (30%), and patients were matched for cancer types and stages. Plasma samples were collected before radical treatment or surgery. The 5hmC-Seal, a highly sensitive chemical labeling technique, was used to profile genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA from ̃5mL of plasma per person, followed by the next-generation sequencing, data summarization at gene-level, and normalization. We applied the elastic net regularization to establish a predictive rule based on the multivariable logistic regression model for cancer detection in the training set as well as a multiclass classification model for determining TOO. The final solution for simultaneous cancer detection and TOO determination was established by integrating the 5hmC-based models and protein markers (e.g., AFP). Overall sensitivity and specificity were computed and reported in the testing set of 670 cancer cases and 686 non-cancer controls. Results: For the primary scenario (i.e., stages I-III or equivalent), at specificity of 95%, the overall sensitivity achieved 79.3% for detecting a cancer patient in all six cancer types in the testing set, except stage I lung cancer, for which the multi-cancer detection solution showed a sensitivity of 51%. Notably, for individuals with a negative result from conventional protein markers (e.g., AFP, CEA), the 5hmC-only models showed 67.6% sensitivity at 98.2% specificity in the testing set, representing significant improvement. In the testing set, among the 500 cancer patients who were detected from the multi-cancer detection solution, 435 patients were assigned a TOO; of those, 362 (83.2%) TOO were correctly determined. Conclusions: The 5hmC-Seal in cfDNA shows the potential as a non-invasive tool that could be integrated into a screening program for simultaneous detection of common cancers and TOO localization. This approach can be expanded to additional cancer types and is currently undergoing validation in prospectively recruited cohorts.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2021.39.15_suppl.3123
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2021
detail.hit.zdb_id:
2005181-5
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