Early Lung Cancer Detection in High Risk Individuals

NCT02837809 | Completed

• 1 other identifier: INT 53/05
• Study Type: interventional
• Target: 4,099
• Locations: 1 country
• Sites: 1

Brief Summary

The MILD project is a randomized lung cancer screening trial whose primary aim is to evaluate the impact on mortality of early lung cancer detection through LDCT (low-dose computed tomography) in 2 groups: a control group undergoing a program of primary prevention with pulmonary function test evaluation and a group undergoing a periodic spiral CT associated with primary prevention and pulmonary function test evaluation. This last one is also randomized in two arms: yearly low-dose CT vs CT every 2 years. MILD trial comprehensive design combines for the first time primary prevention (smoking cessation) with early detection, and molecular risk profile through assessing the value of blood and tissue biomarkers.

Conditions

Lung Cancer

Keywords

low-dose computed tomography; lung; randomized controlled trial; neoplasms; screening; smoking

Outcome Measures

Primary Outcomes (1)

• Lung cancer mortality

  evaluate the impact on mortality of early lung cancer detection through LDCT at annual or biennial intervals versus no screening

  10 years

Secondary Outcomes (3)

• Smoking cessation

  10 years

• Molecular risk profile through assessing the value of circulating DNA in blood samples

  10 years

• Molecular risk profile through assessing the value of microRNA in blood and tissue samples

  10 years

Study Arms (2)

Intervention

EXPERIMENTAL

Low Dose CT, annual or biennial, associated with primary prevention and pulmonary function test evaluation.

Radiation: Low dose CT

Control

NO INTERVENTION

Program of primary prevention with pulmonary function test evaluation

Interventions

Low dose CT RADIATION

annual CT vs biennial CT

Also known as: LDCT

Intervention

Eligibility Criteria

• Age: 49 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Current or former smokers, age ≥50 years or older with a minimum of 20 pack-years smoking history, no history of malignant disease, and adequate performance status (assessed on the basis of the patient's eligibility to undergo thoracic surgery).

You may not qualify if:

• History of malignant disease in the previous years and not adequate performance status (assessed on the basis of the patient's eligibility to undergo thoracic surgery).

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• Associazione Italiana per la Ricerca sul Cancro: collaborator
• Ministry of Health, Italy: collaborator

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Related Publications (23)

• Sozzi G, Roz L, Conte D, Mariani L, Andriani F, Lo Vullo S, Verri C, Pastorino U. Plasma DNA quantification in lung cancer computed tomography screening: five-year results of a prospective study. Am J Respir Crit Care Med. 2009 Jan 1;179(1):69-74. doi: 10.1164/rccm.200807-1068OC. Epub 2008 Sep 11.

  PMID: 18787214 BACKGROUND

• Sozzi G, Pastorino U, Croce CM. MicroRNAs and lung cancer: from markers to targets. Cell Cycle. 2011 Jul 1;10(13):2045-6. doi: 10.4161/cc.10.13.15712. No abstract available.

  PMID: 21623159 BACKGROUND

• Boeri M, Pastorino U, Sozzi G. Role of microRNAs in lung cancer: microRNA signatures in cancer prognosis. Cancer J. 2012 May-Jun;18(3):268-74. doi: 10.1097/PPO.0b013e318258b743.

  PMID: 22647364 BACKGROUND

• Marchiano A, Calabro E, Civelli E, Di Tolla G, Frigerio LF, Morosi C, Tafaro F, Ferri E, Sverzellati N, Camerini T, Mariani L, Lo Vullo S, Pastorino U. Pulmonary nodules: volume repeatability at multidetector CT lung cancer screening. Radiology. 2009 Jun;251(3):919-25. doi: 10.1148/radiol.2513081313. Epub 2009 Apr 20.

  PMID: 19380692 RESULT

• Roz L, Verri C, Conte D, Miceli R, Mariani L, Calabro' E, Andriani F, Pastorino U, Sozzi G. Plasma DNA levels in spiral CT-detected and clinically detected lung cancer patients: a validation analysis. Lung Cancer. 2009 Nov;66(2):270-1. doi: 10.1016/j.lungcan.2009.08.011. Epub 2009 Sep 9. No abstract available.

  PMID: 19744743 RESULT

• Sverzellati N, Ingegnoli A, Calabro E, Randi G, La Vecchia C, Marchiano A, Kuhnigk JM, Hansell DM, Zompatori M, Pastorino U. Bronchial diverticula in smokers on thin-section CT. Eur Radiol. 2010 Jan;20(1):88-94. doi: 10.1007/s00330-009-1515-2. Epub 2009 Jul 14.

  PMID: 19597819 RESULT

• Boeri M, Verri C, Conte D, Roz L, Modena P, Facchinetti F, Calabro E, Croce CM, Pastorino U, Sozzi G. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3713-8. doi: 10.1073/pnas.1100048108. Epub 2011 Feb 7.

  PMID: 21300873 RESULT

• Pastorino U, Rossi M, Rosato V, Marchiano A, Sverzellati N, Morosi C, Fabbri A, Galeone C, Negri E, Sozzi G, Pelosi G, La Vecchia C. Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev. 2012 May;21(3):308-15. doi: 10.1097/CEJ.0b013e328351e1b6.

  PMID: 22465911 RESULT

• Pastorino U. Current status of lung cancer screening. Thorac Surg Clin. 2013 May;23(2):129-40. doi: 10.1016/j.thorsurg.2013.01.018.

  PMID: 23566965 RESULT

• Field JK, van Klaveren R, Pedersen JH, Pastorino U, Paci E, Becker N, Infante M, Oudkerk M, de Koning HJ; European Randomized Screening Trial Group. European randomized lung cancer screening trials: Post NLST. J Surg Oncol. 2013 Oct;108(5):280-6. doi: 10.1002/jso.23383. Epub 2013 Jul 25.

  PMID: 23893464 RESULT

• Pastorino U, Sverzellati N. Lung cancer: CT screening for lung cancer--do we have an answer? Nat Rev Clin Oncol. 2013 Dec;10(12):672-3. doi: 10.1038/nrclinonc.2013.198. Epub 2013 Nov 5. No abstract available.

  PMID: 24189470 RESULT

• Fortunato O, Boeri M, Verri C, Conte D, Mensah M, Suatoni P, Pastorino U, Sozzi G. Assessment of circulating microRNAs in plasma of lung cancer patients. Molecules. 2014 Mar 10;19(3):3038-54. doi: 10.3390/molecules19033038.

  PMID: 24619302 RESULT

• Sozzi G, Boeri M, Rossi M, Verri C, Suatoni P, Bravi F, Roz L, Conte D, Grassi M, Sverzellati N, Marchiano A, Negri E, La Vecchia C, Pastorino U. Clinical utility of a plasma-based miRNA signature classifier within computed tomography lung cancer screening: a correlative MILD trial study. J Clin Oncol. 2014 Mar 10;32(8):768-73. doi: 10.1200/JCO.2013.50.4357. Epub 2014 Jan 13.

  PMID: 24419137 RESULT

• Boeri M, Sestini S, Fortunato O, Verri C, Suatoni P, Pastorino U, Sozzi G. Recent advances of microRNA-based molecular diagnostics to reduce false-positive lung cancer imaging. Expert Rev Mol Diagn. 2015 Jun;15(6):801-13. doi: 10.1586/14737159.2015.1041377. Epub 2015 Apr 30.

  PMID: 25924864 RESULT

• Hu J, Boeri M, Sozzi G, Liu D, Marchiano A, Roz L, Pelosi G, Gatter K, Pastorino U, Pezzella F. Gene Signatures Stratify Computed Tomography Screening Detected Lung Cancer in High-Risk Populations. EBioMedicine. 2015 Jul 8;2(8):831-40. doi: 10.1016/j.ebiom.2015.07.001. eCollection 2015 Aug.

  PMID: 26425689 RESULT

• Sestini S, Boeri M, Marchiano A, Pelosi G, Galeone C, Verri C, Suatoni P, Sverzellati N, La Vecchia C, Sozzi G, Pastorino U. Circulating microRNA signature as liquid-biopsy to monitor lung cancer in low-dose computed tomography screening. Oncotarget. 2015 Oct 20;6(32):32868-77. doi: 10.18632/oncotarget.5210.

  PMID: 26451608 RESULT

• Silva M, Galeone C, Sverzellati N, Marchiano A, Calareso G, Sestini S, La Vecchia C, Sozzi G, Pelosi G, Pastorino U. Screening with Low-Dose Computed Tomography Does Not Improve Survival of Small Cell Lung Cancer. J Thorac Oncol. 2016 Feb;11(2):187-93. doi: 10.1016/j.jtho.2015.10.014. Epub 2015 Dec 23.

  PMID: 26845115 RESULT

• Pastorino U, Boffi R, Marchiano A, Sestini S, Munarini E, Calareso G, Boeri M, Pelosi G, Sozzi G, Silva M, Sverzellati N, Galeone C, La Vecchia C, Ghirardi A, Corrao G. Stopping Smoking Reduces Mortality in Low-Dose Computed Tomography Screening Participants. J Thorac Oncol. 2016 May;11(5):693-699. doi: 10.1016/j.jtho.2016.02.011. Epub 2016 Feb 24.

  PMID: 26921675 RESULT

• Sestini S, Boeri M, Marchiano A, Silva M, Calareso G, Galeone C, Sozzi G, Pastorino U. [Lung cancer screening in high-risk subjects: early detection with LDCT and risk stratification using miRNA-based blood test]. Epidemiol Prev. 2016 Jan-Feb;40(1 Suppl 1):42-50. doi: 10.19191/EP16.1S1.P042.029. Italian.

  PMID: 26951732 RESULT

• Infante M, Sestini S, Galeone C, Marchiano A, Lutman FR, Angeli E, Calareso G, Pelosi G, Sozzi G, Silva M, Sverzellati N, Cavuto S, La Vecchia C, Santoro A, Alloisio M, Pastorino U. Lung cancer screening with low-dose spiral computed tomography: evidence from a pooled analysis of two Italian randomized trials. Eur J Cancer Prev. 2017 Jul;26(4):324-329. doi: 10.1097/CEJ.0000000000000264.

  PMID: 27222939 RESULT

• Venkadesh KV, Aleef TA, Scholten ET, Saghir Z, Silva M, Sverzellati N, Pastorino U, van Ginneken B, Prokop M, Jacobs C. Prior CT Improves Deep Learning for Malignancy Risk Estimation of Screening-detected Pulmonary Nodules. Radiology. 2023 Aug;308(2):e223308. doi: 10.1148/radiol.223308.

  PMID: 37526548 DERIVED

• 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 DERIVED

• Silva M, Sverzellati N, Colombi D, Milanese G, La Vecchia C, Galeone C, Marchiano A, Pastorino U. Pleural plaques in lung cancer screening by low-dose computed tomography: prevalence, association with lung cancer and mortality. BMC Pulm Med. 2017 Nov 25;17(1):155. doi: 10.1186/s12890-017-0506-3.

  PMID: 29178853 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Neoplasms; Smoking

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Behavior

Study Officials

• Ugo Pastorino, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2016
• First Posted: July 20, 2016
• Study Start: September 1, 2005
• Primary Completion: January 1, 2011
• Study Completion: October 1, 2016
• Last Updated: March 7, 2024

Record last verified: 2017-05

Locations

IT (1)