Biomarkers in lung cancer screening: the importance of study design

Baldwin, David R; Callister, Matthew; Crosbie, Philip; O’Dowd, Emma; Rintoul, Robert C.; Robbins, Hilary A.; Steele, Robert

doi:10.1183/13993003.04367-2020

Cited by 11 publications

(26 citation statements)

References 22 publications

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“…Various domains of biomarkers have been investigated, but the translation of this research into practice has been slow, partly due to the lack of appropriately designed studies to establish and validate biomarker-based risk prediction models. 17,18 Another setting in which biomarkers could be applied in lung cancer screening is to better distinguish between malignant and benign nodules on LDCT images. Nodules are detected in up to one-quarter of participants, but the vast majority are benign.…”

Section: Motivationmentioning

confidence: 99%

“…23 In validation studies, it is critical that the added contribution of the biomarker, compared with existing tools, can be clearly identified and quantified. 18 In a pilot study published in 2018, members of our team found that a pre-defined set of cancer-related protein biomarkers improved discrimination between lung cancer cases and controls compared to a smoking-based risk prediction model, when the markers were measured in an independent validation study using samples collected within the year before diagnosis. 24 Studies also suggest that protein markers can improve discrimination between malignant and benign lung nodules.…”

Section: Motivationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Recent papers have highlighted common limitations in the design of studies aiming to identify and validate biomarkers for early cancer detection 22 including lung cancer. 18 To avoid common biases resulting from systematic differences between cases and controls, the prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) design emphasizes the use of pre-diagnostic samples, sampling from the same source population, and matching on important factors that impact biomarker measurements and outcome. 23 In validation studies, it is critical that the added contribution of the biomarker, compared with existing tools, can be clearly identified and quantified.…”

Section: Introductionmentioning

confidence: 99%

“…23 In validation studies, it is critical that the added contribution of the biomarker, compared with existing tools, can be clearly identified and quantified. 18…”

Section: Introductionmentioning

confidence: 99%

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Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program

Robbins

Alcala

Moez

et al. 2022

Preprint

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The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1,161 proteins in a nested-case control study within 2 prospective cohorts (n=252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n=479 cases and 479 controls). Eligible participants had any history of smoking and cases were diagnosed within 3 years of blood draw. The Nodule Malignancy project measured 1,077 proteins among participants with a heavy smoking history within 4 LDCT screening studies (n=425 cases within 5 years of blood draw, 398 benign-nodule controls, and 430 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its lung cancer discriminative performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n=1,696 cases and 2,926 subcohort representatives), and in the Nodule Malignancy project within 5 LDCT screening studies (n=675 cases, 648 benign-nodule controls, and 680 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.

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Section: Motivationmentioning

confidence: 99%

Section: Motivationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…23 In validation studies, it is critical that the added contribution of the biomarker, compared with existing tools, can be clearly identified and quantified. 18…”

Section: Introductionmentioning

confidence: 99%

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