ILAs in CT Lung Cancer Screening Population

NCT04503044 | Completed

• 1 other identifier: 1628689
• Study Type: observational
• Target: 1,703
• Locations: 1 country
• Sites: 1

Brief Summary

Interstitial Lung Abnormalities (ILA) have been previously defined as nondependent changes affecting more than 5% of any lung zone on computed tomography (CT) scans of the lung. Several studies suggest that the prevalence of ILA in participants in non-pulmonary research studies ranges anywhere from 7-9%. Work over the last decade has shown that, despite previous characterization as an asymptomatic research finding, ILA has significant clinical and biological consequences. These include reduced exercise capacity, functional limitations, decreased lung volumes, increased mortality, and in some cases histopathology similar to Idiopathic Pulmonary Fibrosis (IPF). ILA have been detected in lung cancer screening cohorts, where the prevalence of ILA is estimated to be between (10%-20%) to those noted in other research cohorts. Given that a significant proportion of those will have progression, CT lung cancer screening (CTLS) cohorts represent an ideal catchment population for future research and clinical trials. Lahey Hospital and Medical Center was one of the earliest clinical centers to develop a CTLS program in the country. Investigators propose to qualitatively characterize ILA in a large clinical CTLS population.

Conditions

Interstitial Lung Disease; IPF

Keywords

Interstitial Lung Disease; Interstitial Lung Abnormalities

Outcome Measures

Primary Outcomes (3)

• Prevalence of ILA at baseline

  Both presence and absence of ILA, as well as phenotypes, will be described for the entire cohort.

  6 months

• Association between baseline ILA (presence/absence) and time to mortality, time to first hospitalization, and time to development of cancer in the full cohort

  Kaplan-Meier plots will be generated to visualize the associations between ILA variables and cancer, hospital admission and mortality. The log-rank test will be used to evaluate for a significant association. Cox regression proportional hazards models will be used to test for this association in both univariate and multivariable models. The multivariable model will be adjusted for age, sex, smoking status and pack years exposure.

  6 months

• Progression of ILA

  Progression of ILA, defined as worsening of existing ILA or incidence of ILA over 5 years, will be described for the subset of patients with T4 imaging at 5 years. Univariate and multivariable analyses using logistic regression will be performed to test for associations between qualitative ILA characteristics (presence and absence, as well as individual phenotypes in separate models) and progression (yes/no). Stable and improved will be considered no progression, while incident ILA and worsening of existing ILA will be considered progression. Models will be checked for influential points. Multivariable models will be adjusted for sex, age, currently smoking, and pack years exposure.

  6 months

Secondary Outcomes (2)

• Association between phenotypes of ILA and outcomes

  6 months

• Association between ILA and time to cause-specific mortality, hospitalization.

  6 months

Study Arms (1)

CT Lung Cancer Screening Patients

All CT Lung Cancer Screening patients at LHMC from January 1st, 2012 to September 30th, 2014 with an in-network PCP that had baseline CT scans will be scored. A subset of these patients with T4 screening scans will be scored for progression.

Other: Retrospective observational study

Interventions

Retrospective observational study OTHER

No intervention to occur

CT Lung Cancer Screening Patients

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All clinical CTLS patients at Lahey Hospital and Medical Center (LHMC), Burlington, MA from January 1st, 2012 through September 30th, 2014 who had an in network primary care physician (n=1703). Patients with T4 screening scans will be scored for progression (n=653). To qualify for our study, patients had to satisfy the National Comprehensive Cancer Network (NCCN) Guidelines® Lung Cancer Screening Version 1.2012 high-risk criteria for lung cancer. Based on the NCCN Guidelines®, individuals eligible for lung cancer screening can be classified into NCCN group 1 and 2 as previously described.21 Patients in both groups were asymptomatic and had a physician order for CTLS, were free of lung cancer for ≥ 5 years, and had no known metastatic disease.

Sponsors & Collaborators

• Lahey Clinic: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

Location

Related Publications (21)

• Moyer VA; U.S. Preventive Services Task Force. Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014 Mar 4;160(5):330-8. doi: 10.7326/M13-2771.

  PMID: 24378917 BACKGROUND

• National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011 Aug 4;365(5):395-409. doi: 10.1056/NEJMoa1102873. Epub 2011 Jun 29.

  PMID: 21714641 BACKGROUND

• Washko GR, Hunninghake GM, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, Ross JC, Estepar RS, Lynch DA, Brehm JM, Andriole KP, Diaz AA, Khorasani R, D'Aco K, Sciurba FC, Silverman EK, Hatabu H, Rosas IO; COPDGene Investigators. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med. 2011 Mar 10;364(10):897-906. doi: 10.1056/NEJMoa1007285.

  PMID: 21388308 BACKGROUND

• Putman RK, Hatabu H, Araki T, Gudmundsson G, Gao W, Nishino M, Okajima Y, Dupuis J, Latourelle JC, Cho MH, El-Chemaly S, Coxson HO, Celli BR, Fernandez IE, Zazueta OE, Ross JC, Harmouche R, Estepar RS, Diaz AA, Sigurdsson S, Gudmundsson EF, Eiriksdottir G, Aspelund T, Budoff MJ, Kinney GL, Hokanson JE, Williams MC, Murchison JT, MacNee W, Hoffmann U, O'Donnell CJ, Launer LJ, Harrris TB, Gudnason V, Silverman EK, O'Connor GT, Washko GR, Rosas IO, Hunninghake GM; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators; COPDGene Investigators. Association Between Interstitial Lung Abnormalities and All-Cause Mortality. JAMA. 2016 Feb 16;315(7):672-81. doi: 10.1001/jama.2016.0518.

  PMID: 26881370 BACKGROUND

• Hunninghake GM, Hatabu H, Okajima Y, Gao W, Dupuis J, Latourelle JC, Nishino M, Araki T, Zazueta OE, Kurugol S, Ross JC, San Jose Estepar R, Murphy E, Steele MP, Loyd JE, Schwarz MI, Fingerlin TE, Rosas IO, Washko GR, O'Connor GT, Schwartz DA. MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med. 2013 Jun 6;368(23):2192-200. doi: 10.1056/NEJMoa1216076. Epub 2013 May 21.

  PMID: 23692170 BACKGROUND

• Doyle TJ, Hunninghake GM, Rosas IO. Subclinical interstitial lung disease: why you should care. Am J Respir Crit Care Med. 2012 Jun 1;185(11):1147-53. doi: 10.1164/rccm.201108-1420PP. Epub 2012 Feb 23.

  PMID: 22366047 BACKGROUND

• Doyle TJ, Washko GR, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, Divo MJ, Celli BR, Sciurba FC, Silverman EK, Hatabu H, Rosas IO, Hunninghake GM; COPDGene Investigators. Interstitial lung abnormalities and reduced exercise capacity. Am J Respir Crit Care Med. 2012 Apr 1;185(7):756-62. doi: 10.1164/rccm.201109-1618OC. Epub 2012 Jan 20.

  PMID: 22268134 BACKGROUND

• Horeweg N, van Rosmalen J, Heuvelmans MA, van der Aalst CM, Vliegenthart R, Scholten ET, ten Haaf K, Nackaerts K, Lammers JW, Weenink C, Groen HJ, van Ooijen P, de Jong PA, de Bock GH, Mali W, de Koning HJ, Oudkerk M. Lung cancer probability in patients with CT-detected pulmonary nodules: a prespecified analysis of data from the NELSON trial of low-dose CT screening. Lancet Oncol. 2014 Nov;15(12):1332-41. doi: 10.1016/S1470-2045(14)70389-4. Epub 2014 Oct 1.

  PMID: 25282285 BACKGROUND

• Horeweg N, van der Aalst CM, Thunnissen E, Nackaerts K, Weenink C, Groen HJ, Lammers JW, Aerts JG, Scholten ET, van Rosmalen J, Mali W, Oudkerk M, de Koning HJ. Characteristics of lung cancers detected by computer tomography screening in the randomized NELSON trial. Am J Respir Crit Care Med. 2013 Apr 15;187(8):848-54. doi: 10.1164/rccm.201209-1651OC.

  PMID: 23348977 BACKGROUND

• Pastorino U, Silva M, Sestini S, Sabia F, Boeri M, Cantarutti A, Sverzellati N, Sozzi G, Corrao G, Marchiano A. Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy. Ann Oncol. 2019 Jul 1;30(7):1162-1169. doi: 10.1093/annonc/mdz117.

  PMID: 30937431 BACKGROUND

• Miller ER, Putman RK, Vivero M, Hung Y, Araki T, Nishino M, Washko GR, Rosas IO, Hatabu H, Sholl LM, Hunninghake GM. Histopathology of Interstitial Lung Abnormalities in the Context of Lung Nodule Resections. Am J Respir Crit Care Med. 2018 Apr 1;197(7):955-958. doi: 10.1164/rccm.201708-1679LE. No abstract available.

  PMID: 28934558 BACKGROUND

• Ash SY, Harmouche R, Ross JC, Diaz AA, Hunninghake GM, Putman RK, Onieva J, Martinez FJ, Choi AM, Lynch DA, Hatabu H, Rosas IO, Estepar RSJ, Washko GR. The Objective Identification and Quantification of Interstitial Lung Abnormalities in Smokers. Acad Radiol. 2017 Aug;24(8):941-946. doi: 10.1016/j.acra.2016.08.023. Epub 2016 Dec 15.

  PMID: 27989445 BACKGROUND

• Ash SY, Harmouche R, Putman RK, Ross JC, Diaz AA, Hunninghake GM, Onieva Onieva J, Martinez FJ, Choi AM, Lynch DA, Hatabu H, Rosas IO, San Jose Estepar R, Washko GR; COPDGene Investigators. Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers. Chest. 2017 Oct;152(4):780-791. doi: 10.1016/j.chest.2017.04.185. Epub 2017 May 12.

  PMID: 28506611 BACKGROUND

• Araki T, Putman RK, Hatabu H, Gao W, Dupuis J, Latourelle JC, Nishino M, Zazueta OE, Kurugol S, Ross JC, San Jose Estepar R, Schwartz DA, Rosas IO, Washko GR, O'Connor GT, Hunninghake GM. Development and Progression of Interstitial Lung Abnormalities in the Framingham Heart Study. Am J Respir Crit Care Med. 2016 Dec 15;194(12):1514-1522. doi: 10.1164/rccm.201512-2523OC.

  PMID: 27314401 BACKGROUND

• Putman RK, Gudmundsson G, Axelsson GT, Hida T, Honda O, Araki T, Yanagawa M, Nishino M, Miller ER, Eiriksdottir G, Gudmundsson EF, Tomiyama N, Honda H, Rosas IO, Washko GR, Cho MH, Schwartz DA, Gudnason V, Hatabu H, Hunninghake GM. Imaging Patterns Are Associated with Interstitial Lung Abnormality Progression and Mortality. Am J Respir Crit Care Med. 2019 Jul 15;200(2):175-183. doi: 10.1164/rccm.201809-1652OC.

  PMID: 30673508 BACKGROUND

• Jin GY, Lynch D, Chawla A, Garg K, Tammemagi MC, Sahin H, Misumi S, Kwon KS. Interstitial lung abnormalities in a CT lung cancer screening population: prevalence and progression rate. Radiology. 2013 Aug;268(2):563-71. doi: 10.1148/radiol.13120816. Epub 2013 Mar 19.

  PMID: 23513242 BACKGROUND

• Whittaker Brown SA, Padilla M, Mhango G, Powell C, Salvatore M, Henschke C, Yankelevitz D, Sigel K, de-Torres JP, Wisnivesky J. Interstitial Lung Abnormalities and Lung Cancer Risk in the National Lung Screening Trial. Chest. 2019 Dec;156(6):1195-1203. doi: 10.1016/j.chest.2019.06.041. Epub 2019 Aug 9.

  PMID: 31404527 BACKGROUND

• Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SLF, Inoue Y, Richeldi L, Kolb M, Tetzlaff K, Stowasser S, Coeck C, Clerisme-Beaty E, Rosenstock B, Quaresma M, Haeufel T, Goeldner RG, Schlenker-Herceg R, Brown KK; INBUILD Trial Investigators. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med. 2019 Oct 31;381(18):1718-1727. doi: 10.1056/NEJMoa1908681. Epub 2019 Sep 29.

  PMID: 31566307 BACKGROUND

• Lynch DA, Sverzellati N, Travis WD, Brown KK, Colby TV, Galvin JR, Goldin JG, Hansell DM, Inoue Y, Johkoh T, Nicholson AG, Knight SL, Raoof S, Richeldi L, Ryerson CJ, Ryu JH, Wells AU. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet Respir Med. 2018 Feb;6(2):138-153. doi: 10.1016/S2213-2600(17)30433-2. Epub 2017 Nov 15.

  PMID: 29154106 BACKGROUND

• Hansell DM, Bankier AA, MacMahon H, McLoud TC, Muller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008 Mar;246(3):697-722. doi: 10.1148/radiol.2462070712. Epub 2008 Jan 14.

  PMID: 18195376 BACKGROUND

• Patel AS, Miller E, Regis SM, Hunninghake GM, Price LL, Gawlik M, McKee AB, Rieger-Christ KM, Pinto-Plata V, Liesching TN, Wald C, Hashim J, McKee BJ, Gazourian L. Interstitial lung abnormalities in a large clinical lung cancer screening cohort: association with mortality and ILD diagnosis. Respir Res. 2023 Feb 14;24(1):49. doi: 10.1186/s12931-023-02359-9.

  PMID: 36782326 DERIVED

MeSH Terms

Conditions

Lung Diseases, Interstitial

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Study Officials

• Lee Gazourian, MD

  Lahey Hospital & Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Quantitative Analysis

Study Record Dates

• First Submitted: August 3, 2020
• First Posted: August 6, 2020
• Study Start: January 30, 2021
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2021
• Last Updated: August 3, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)