Abbreviated Name

LTP2 Results Analysis-Willey-Toledo-2024

Lead Investigator

Willey, James — University of Toledo College of Medicine

Coordinating Investigator

Zheng, Yingye — Fred Hutchinson Cancer Center

Involved Investigators

• Willey, James — University of Toledo College of Medicine
• Zheng, Yingye — Fred Hutchinson Cancer Center

Abstract

Analysis Plan. The planned targeted NGS method enables measurement of TP53/PIK3CA/BRAF variants with VAF as low as 0.0005 (0.05%). In this proposed project, we will assess accuracy of the LFAMB by receiver operator characteristic (ROC) area under the curve (AUC) to identify the cut-off with best positive likelihood ratio for identification of those at high risk for lung cancer diagnosis. The LFAMB is measured as mutation prevalence in units of mutations/base position assessed, mutations/bp. For power analysis, based on preliminary data from the case-control study reported in Craig et al (2019)28 we will test the hypothesis that a cut-off threshold of 0.02 mutations/bp in AEC DNA will identify cancer subjects with >95% specificity and 55% sensitivity, using a two-tailed test for significance and a type-1 error rate of 0.05. We will assume based on preliminary data that the fraction of the study population with a positive biomarker is 32%. Based on these assumptions, analysis of specimens from 60 subjects will have 80% power to test the 0.02 mutations/bp cut-off for 95% specificity and 55% sensitivity, which is associated with a positive likelihood ratio of 11.

Aims

Analysis Plan. The planned targeted NGS method enables measurement of TP53/PIK3CA/BRAF variants with VAF as low as 0.0005 (0.05%). In this proposed project, we will assess accuracy of the LFAMB by receiver operator characteristic (ROC) area under the curve (AUC) to identify the cut-off with best positive likelihood ratio for identification of those at high risk for lung cancer diagnosis. The LFAMB is measured as mutation prevalence in units of mutations/base position assessed, mutations/bp. For power analysis, based on preliminary data from the case-control study reported in Craig et al (2019)28 we will test the hypothesis that a cut-off threshold of 0.02 mutations/bp in AEC DNA will identify cancer subjects with >95% specificity and 55% sensitivity, using a two-tailed test for significance and a type-1 error rate of 0.05. We will assume based on preliminary data that the fraction of the study population with a positive biomarker is 32%. Based on these assumptions, analysis of specimens from 60 subjects will have 80% power to test the 0.02 mutations/bp cut-off for 95% specificity and 55% sensitivity, which is associated with a positive likelihood ratio of 11.

Analytic Method

The planned targeted NGS method enables measurement of TP53/PIK3CA/BRAF variants with VAF as low as 0.0005 (0.05%). In this proposed project, we will assess accuracy of the LFAMB by receiver operator characteristic (ROC) area under the curve (AUC) to identify the cut-off with best positive likelihood ratio for identification of those at high risk for lung cancer diagnosis. The LFAMB is measured as mutation prevalence in units of mutations/base position assessed, mutations/bp. For power analysis, based on preliminary data from the case-control study reported in Craig et al (2019)28 we will test the hypothesis that a cut-off threshold of 0.02 mutations/bp in AEC DNA will identify cancer subjects with >95% specificity and 55% sensitivity, using a two-tailed test for significance and a type-1 error rate of 0.05. We will assume based on preliminary data that the fraction of the study population with a positive biomarker is 32%. Based on these assumptions, analysis of specimens from 60 subjects will have 80% power to test the 0.02 mutations/bp cut-off for 95% specificity and 55% sensitivity, which is associated with a positive likelihood ratio of 11.

Comments

No comments available.

Outcome

Not yet finished

Secure Outcome

No secure outcome available.

Publications

• No publications available at this time for this protocol.

Biomarkers

• No biomarkers available at this time for this protocol.

Data Collections

• No data collections available at this time for this protocol.

Start Date

May 5 2023

Estimated Finish Date

Nov 5 2023

Protocol ID

555

Protocol Type

Reference Set

Fields of Research

• Genomics
• Proteomics

Collaborative Group

Lung and Upper Aerodigestive Cancers Research Group

Cancer Types

• Malignant neoplasm of bronchus and lung

Phased Status

2