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January 1987 - March 2016
Publications
Publications (270)
The implementation of low-dose chest CT for lung screening presents a crucial opportunity to advance lung cancer care through early detection and interception. In addition, millions of pulmonary nodules are incidentally detected annually in the United States, increasing the opportunity for early lung cancer diagnosis. Yet, realization of the full p...
The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulatin...
A greater understanding of molecular, cellular, and immunological changes during the early stages of lung adenocarcinoma development could improve diagnostic and therapeutic approaches in patients with pulmonary nodules at risk for lung cancer. To elucidate the immunopathogenesis of early lung tumorigenesis, we evaluated surgically resected pulmona...
Plasma cell-free DNA (cfDNA) is a noninvasive biomarker for cell death of all organs. Deciphering the tissue origin of cfDNA can reveal abnormal cell death because of diseases, which has great clinical potential in disease detection and monitoring. Despite the great promise, the sensitive and accurate quantification of tissue-derived cfDNA remains...
Importance:
Screening with low-dose computed tomography (CT) has been shown to reduce mortality from lung cancer in randomized clinical trials in which the rate of adherence to follow-up recommendations was over 90%; however, adherence to Lung Computed Tomography Screening Reporting & Data System (Lung-RADS) recommendations has been low in practic...
Determining factors influencing patient participation in and adherence to cancer screening recommendations is key to successful cancer screening programs. However, the collection of variables necessary to anticipate patient behavior in cancer screening has not been systematically examined. Using lung cancer screening as a representative example, we...
Objectives:
Discovering airway gene expression alterations associated with radiographic bronchiectasis (BE) may improve the understanding of the pathobiology of early-stage BE.
Methods:
Presence of radiographic BE in 173 individuals without a clinical diagnosis of BE was evaluated. Bronchial brushings from these individuals were transcriptomical...
Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effectiv...
Objective: Screening with low-dose CT (LDCT) effectively reduces mortality from lung cancer. Elective imaging procedures, including lung cancer screening (LCS) LDCT exams, were paused during the height of the COVID-19 pandemic at our institution to conserve healthcare resources and minimize risk as we learned how to mitigate the spread of COVID-19....
With an increasing number of positive lung cancer screening trials and the growing utilization of low dose CT screening, the detection of indeterminate pulmonary nodules is an important clinical problem. A biomarker that will be able to differentiate between benign andmalignant nodules would help to accelerate diagnosis and reduce unnecessary and i...
e21108
Background: RECIST 1.1 can underestimate treatment benefits of immunotherapy, with irRECIST and iRECIST accounting for atypical responses. Inter-reader discordances are known to occur in a dual reader paradigm. Our objective is to compare inter-reader reliability between RECIST 1.1, irRECIST, and iRECIST. Methods: This is a retrospective ana...
Introduction
Lung cancer screening (LCS) is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS). However, patient adherence to recommended intervals varies, potentially diminishing benefit from screening. We conducted a systematic r...
Background:
Randomized controlled trials (RCTs) play a central role in evidence-based healthcare. However, the clinical and policy implications of implementing RCTs in clinical practice are difficult to predict as the studied population is often different from the target population where results are being applied. This study illustrates the concep...
e18592
Background: The National Lung Screening Trial (NLST) demonstrated a 20% reduction in lung cancer mortality when screened with low dose computed tomography (LDCT) as opposed to chest radiography. Notably, participants’ adherence to the screening protocol was 90%. To date, published evidence on the adherence of patients enrolled in clinical lu...
Purpose: Integrative analysis combining diagnostic imaging and genomic information can uncover biological insights into lesions that are visible on radiologic images. We investigate techniques for interrogating a deep neural network trained to predict quantitative image (radiomic) features and histology from gene expression in non-small cell lung c...
Importance
While cholinergic receptor nicotinic alpha 5 (CHRNA5) variants have been linked to lung cancer, chronic obstructive pulmonary disease (COPD) and smoking addiction in case–controls studies, their corelationship is not well understood and requires retesting in a cohort study.
Objective
To re-examine the association between the CHRNA5 vari...
Determining the clinical significance of CT scan-detected subsolid pulmonary nodules requires an understanding of the molecular and cellular features that may foreshadow disease progression. We studied the alterations at the transcriptome level in both immune and non-immune cells, utilizing single-cell RNA sequencing, to compare the microenvironmen...
Background:
Chronic tobacco smoke exposure results in a broad range of lung pathologies including emphysema, airway disease and parenchymal fibrosis as well as a multitude of extra-pulmonary comorbidities. Prior work using computed tomography imaging has identified several clinically relevant subgroups of smoking related lung disease, but these in...
Purpose:
To investigate the use of deep neural networks to learn associations between gene expression and radiomics or histology in non-small cell lung cancer (NSCLC).
Materials and Methods:
Deep feedforward neural networks were used for radiogenomic mapping, where 21,766 gene expressions were inputs to individually predict histology and 101 CT rad...
Crucial transitions in cancer—including tumor initiation, local expansion, metastasis, and therapeutic resistance—involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecede...
We present an interpretable end-to-end computer-aided detection and diagnosis tool for pulmonary nodules on computed tomography (CT) using deep learning-based methods. The proposed network consists of a nodule detector and a nodule malignancy classifier. We used RetinaNet to train a nodule detector using 7,607 slices containing 4,234 nodule annotat...
The original version of this article, published on 24 July 2014, unfortunately contained a mistake. In section "Discussion," a sentence was worded incorrectly.
Globally, lung cancer is responsible for nearly one in five cancer deaths. The National Lung Screening Trial (NLST) demonstrated the efficacy of low-dose computed tomography (LDCT) to identify early-stage disease, setting the basis for widespread implementation of lung cancer screening programs. However, the specificity of LDCT lung cancer screenin...
While deep learning methods have demonstrated performance comparable to human readers in tasks such as computer-aided diagnosis, these models are difficult to interpret, do not incorporate prior domain knowledge, and are often considered as a “black-box.” The lack of model interpretability hinders them from being fully understood by end users such...
Lung cancer is the leading cause of cancer-related death, and lung adenocarcinoma (LUAD) is the most frequent histology. Early diagnosis and treatment are essential; however, there are no targeted diagnostic and therapeutic approaches for early LUAD. An important hallmark of cancer is the increased glucose uptake via GLUT transporters. GLUT activit...
Background: The majority of NSCLC patients do not respond to single agent PD-1/PD-L1 inhibitors, in part due to the lack of cytolytic T cell infiltration at the tumor site. To improve the efficacy of checkpoint blockade, in situ vaccination with functional antigen presenting cells (APCs) is designed to take advantage of the full repertoire of tumor...
Introduction:
In the National Lung Screening Trial (NLST) all cases with a 4-mm nodule (micronodule) and no other findings were classified as a negative study. The prevalence and malignant potential of micronodules in the NLST is evaluated to understand if this classification was appropriate.
Methods and materials:
In the NLST a total of 53,452...
Lung cancer is the leading cause of cancer-related death, and lung adenocarcinoma (LUAD) is the most frequent histology. Early diagnosis and treatment are essential; however, there are no targeted diagnostic and therapeutic approaches for early LUAD. An important hallmark of cancer is the increased glucose uptake via GLUT transporters. GLUT activit...
Background: The majority of NSCLC patients do not respond to single agent PD-1/PD-L1 inhibitors, in part due to the lack of cytolytic T cell infiltration at the tumor site. To improve the efficacy of checkpoint blockade, in situ vaccination with functional antigen presenting cells (APCs) is designed to take advantage of the full repertoire of tumor...
While deep learning methods have demonstrated classification performance comparable to human readers in tasks such as computer-aided diagnosis, these models are difficult to interpret, do not incorporate prior domain knowledge , and are often considered as a "black box." We present a novel interpretable deep hierarchical semantic convolu-tional neu...
Epithelial cells in the field of lung injury can give rise to distinct premalignant lesions that may bear unique genetic aberrations. A subset of these lesions may escape immune surveillance and progress to invasive cancer; however, the mutational landscape that may predict progression has not been determined. Knowledge of premalignant lesion compo...
In a landmark analysis, investigators of the Multicentric Italian Lung Detection (MILD) trial have confirmed 10-year mortality reductions with lung cancer screening using low-dose helical CT (LDCT). These data complement the reduced lung cancer-specific mortality reported in the National Lung Screening Trial and reinforce the rationale for broad im...
Introduction
We performed an external validation of the Brock model using the National Lung Screening Trial (NLST) data set, following strict guidelines set forth by the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis statement. We report how external validation results can be interpreted and highligh...
Background
Lung cancer is the leading cause of cancer-related death due in large part to our inability to diagnose it at an early and potentially curable stage. Screening for lung cancer via low dose computed tomographic (LDCT) imaging has been demonstrated to improve mortality but also results in a high rate of false positive tests. The identifica...
While deep learning methods are increasingly being applied to tasks such as computer-aided diagnosis, these models are difficult to interpret, do not incorporate prior domain knowledge, and are often considered as a "black-box." The lack of model interpretability hinders them from being fully understood by target users such as radiologists. In this...
Objective:
It is crucial for clinicians to stay up to date on current literature in order to apply recent evidence to clinical decision making. Automatic summarization systems can help clinicians quickly view an aggregated summary of literature on a topic. Casama, a representation and summarization system based on "contextualized semantic maps," c...
Computer tomography (CT) imaging plays an important role in cancer detection and quantitative assessment in clinical trials. High-resolution imaging studies on large cohorts of patients generate vast data sets, which are infeasible to analyze through manual interpretation.
In this article we describe a comprehensive architecture for computer-aided...
Rationale:
While epidemiological studies consistently show that chronic obstructive pulmonary disease (COPD) is associated with an increased risk of lung cancer, debate exists as to whether there is a linear relationship between the severity of airflow limitation and lung cancer risk.
Objectives:
We examined this in a large prospective study of...
Objectives:
This study retrospectively analyses the screening CT examinations and outcomes of the National Lung Screening Trial (NLST) participants who had interval lung cancer diagnosed within 1 year after a negative CT screen and before the next annual screen.
Methods:
The screening CTs of all 44 participants diagnosed with interval lung cance...
Each year, more than 1 million persons worldwide are found to have a lung nodule that carries a risk of being malignant. In reality, the vast majority of lung nodules are benign, whether identified by screening or incidentally. The consequences of delaying or missing the diagnosis of lung cancer can be substantial, as can be the consequences of inv...
Lung cancer screening identifies cancers with heterogeneous behaviors. Some lung cancers will be identified among patients who had prior negative CT screens and upon follow-up scans develop a de novo nodule that was determined to be cancerous. Other lung cancers will be identified among patients who had one or more prior stable positive scans that...
(A) Kaplan-Meier Estimates of Progression Free Survival with Number of Subjects at Risk for the Individual Screen-Detected Cancer Cohorts and Prevalence Cancer Cohort. (B) Kaplan-Meier Estimates of Overall Survival with Number of Subjects at Risk for the Individual Screen-Detected Cancer Cohorts and Prevalence Cancer Cohort.
(DOCX)
Schema for the Entire CT-arm of the NLST based on Screening Results and Lung Cancer Diagnoses.
The dashed lines indicate the parts of the schema that were not included in the final analyses.
(PDF)
(A) Kaplan-Meier Estimates of Progression Free Survival of Adenocarcinoma/BAC Cases With Number of Subjects at Risk within the Prevalence and Combined Screen-Detected Cancer Cohorts. (B) Estimates of Progression Free Survival of Adenocarcinoma/BAC Cases With Number of Subjects at Risk within the Prevalence and Combined Screen-Detected Cancer Cohort...
(A) Kaplan-Meier Estimates of Progression Free Survival for Squamous Cell Carcinoma Cases With Number of Subjects at Risk within the Prevalence and Combined Screen-Detected Cancer Cohorts. (B) Kaplan-Meier Estimates of Overall Survival for Squamous Cell Carcinoma Cases with Number of Subjects at Risk within the Prevalence and Combined Screen-Detect...
CT Screening Results at Each Round for the Incidence Cancer Cohorts with Lung Cancer.
Abbreviations: SDLC1 = screen-detected lung cancers cohort 1 with baseline positive screens not associated with a lung cancer diagnosis and a screen-detected incidence lung cancer followed a positive screen at T1; SDLC2 = screen-detected lung cancers cohort 2 with...
Time Intervals Between Events for the Incidence Lung Cancer Cohorts.
(DOCX)
Introduction:
Identifying high-risk lung cancer individuals at an early disease stage is the most effective way of improving survival. The landmark National Lung Screening Trial (NLST) demonstrated the utility of low-dose computed tomography (LDCT) imaging to reduce mortality (relative to X-ray screening). As a result of the NLST and other studies...
Background:
eHealth apps have the potential to meet the information needs of patient populations and improve health literacy rates. However, little work has been done to document perceived usability of portals and health literacy of specific topics.
Objective:
Our aim was to establish a baseline of lung cancer health literacy and perceived porta...
Background:
Annual low-dose CT screening for lung cancer has been recommended for high-risk individuals, but the necessity of yearly low-dose CT in all eligible individuals is uncertain. This study examined rates of lung cancer in National Lung Screening Trial (NLST) participants who had a negative prevalence (initial) low-dose CT screen to explor...
As the volume of biomedical literature increases, it can be challenging for clinicians to stay up-to-date. Graphical summarization systems help by condensing knowledge into networks of entities and relations. However, existing systems present relations out of context, ignoring key details such as study population. To better support precision medici...
Rationale and objectives:
The current paradigm of cancer diagnosis involves uncoordinated communication of findings from radiology and pathology to downstream physicians. Discordance between these findings can require additional time from downstream users to resolve, or given incorrect resolution, may adversely impact treatment decisions. To mitig...
Rationale:
Annual computed tomography (CT) is now widely recommended for lung cancer screening in the United States, although concerns remain regarding the potential harms, including those from overdiagnosis.
Objectives:
To examine the effect of airflow limitation on overdiagnosis by comparing lung cancer incidence, histology, and stage shift in...
In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the Nati...
PET/CT with the glucose analogue (18)F-fluorodeoxyglucose ((18)F-FDG) has several potential applications for monitoring tumor response to therapy in patients with non-small cell lung cancer (NSCLC). A prerequisite for many of these applications is detailed knowledge of the repeatability of quantitative parameters derived from (18)F-FDG PET/CT studi...
Lung cancer screening with low-dose computed tomography (LDCT) has been recommended, based primarily on the results of the National Lung Screening Trial (NLST). The American College of Radiology recently released Lung-RADS, a classification system for LDCT lung cancer screening.
To retrospectively apply the Lung-RADS criteria to the NLST.
Secondary...
The purpose of this study was to quantify the degree of imaging-histologic discordance in a cohort of patients undergoing computed tomography (CT)-guided lung biopsy for focal lung disease.
A retrospective review was performed of 186 patients who underwent percutaneous lung biopsy of a parenchymal lesion at our institution between January and Decem...
This paper describes the information retrieval step in Casama (Contextualized Semantic Maps), a project that summarizes and contextualizes current research papers on driver mutations in non-small cell lung cancer. Casama׳s representation of lung cancer studies aims to capture elements that will assist an end-user in retrieving studies and, importan...
Practitioner guidelines simultaneously provide broad overviews and in-depth details of disease. Written for experts, they are difficult for patients to understand, yet patients often use these guidelines as a source of information to help them to learn about their health. Using practitioner guidelines along with patient information needs and prefer...
Background:
The National Lung Screening Trial (NLST) showed that screening with low-dose computed tomography (CT) as compared with chest radiography reduced lung-cancer mortality. We examined the cost-effectiveness of screening with low-dose CT in the NLST.
Methods:
We estimated mean life-years, quality-adjusted life-years (QALYs), costs per per...
Background:
Computed tomography (CT) screening for lung cancer has been associated with a high frequency of false positive results because of the high prevalence of indeterminate but usually benign small pulmonary nodules. The acceptability of reducing false-positive rates and diagnostic evaluations by increasing the nodule size threshold for a po...
Patient portals have the potential to provide content that is specifically tailored to a patient's information needs based on diagnoses and other factors. In this work, we conducted a survey of 41 lung cancer patients at an outpatient lung cancer clinic at the medical center of the University of California, Los Angeles, to gain insight into these p...
Objectives:
The purpose of this study was to define clinically appropriate, computer-aided lung nodule detection (CAD) requirements and protocols based on recent screening trials. In the following paper, we describe a CAD evaluation methodology based on a publically available, annotated computed tomography (CT) image data set, and demonstrate the...
*Department of Molecular and Clinical Cancer Medicine, Institute of Translational medicine, The University of Liverpool Cancer Research Centre, Liverpool, United Kingdom; †Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, California; ‡Division of Thoracic Surgery, New York Presbyterian-Weill, Cornell, New York, New York...
Importance:
Screening for lung cancer has the potential to reduce mortality, but in addition to detecting aggressive tumors, screening will also detect indolent tumors that otherwise may not cause clinical symptoms. These overdiagnosis cases represent an important potential harm of screening because they incur additional cost, anxiety, and morbidi...
The national cost of cancer care is projected to reach $173 billion by 2020, increasing from $125 billion in 2010. This steep upward cost trajectory has placed enormous an financial burden on patients, their families, and society as a whole and raised major concern about the ability of the health care system to provide and sustain high-quality canc...
Background:
The National Lung Screening Trial was conducted to determine whether three annual screenings (rounds T0, T1, and T2) with low-dose helical computed tomography (CT), as compared with chest radiography, could reduce mortality from lung cancer. We present detailed findings from the first two incidence screenings (rounds T1 and T2).
Metho...
Imaging has become a prevalent tool in the diagnosis and treatment of many diseases, providing a unique in vivo, multi-scale view of anatomic and physiologic processes. With the increased use of imaging and its progressive technical advances, the role of imaging informatics is now evolving-from one of managing images, to one of integrating the full...
Background
Lung cancer is the largest contributor to mortality from cancer. The National Lung Screening Trial (NLST) showed that screening with low-dose helical computed tomography (CT) rather than with chest radiography reduced mortality from lung cancer. We describe the screening, diagnosis, and limited treatment results from the initial round of...
7562
Background: The National Lung Screening Trial (NLST) recently demonstrated that lung cancer screening with low-dose CT reduces mortality. Current protocols use 4–8 mm nodules as positive screens. While there are some computer-aided nodule detection (CAD) systems currently available, they are rarely used in clinical practice because they genera...
7566
Background: Manual tumor measurements for use in diagnosis and longitudinal assessment suffer from intra- and inter-observer variability. In practice they are also limited to 1-dimensional diameter measurements because manual contouring of 3D tumor boundaries is impractical. In this work we evaluated a fully automated tumor assessment system i...
The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. The NLST randomized 53,454 older current or former heavy smokers to receive LDCT or chest radiography (CXR) for three annual screens. Participants were...