A review of novel biological tools used in screening for the early detection of lung cancer

Lung cancer is the most common cancer worldwide and causes more deaths per year than any other cancer. It has a very poor 5-year survival rate of 8–16%, partly because of comorbidity preventing curative treatments but mainly because of the disease presenting with symptoms only when it is at an advanced and incurable stage. When lung cancer is detected earlier and is amenable to radical treatments such as potentially curative surgery and radical radiotherapy, 5-year survival rates are much higher (up to 67%). Therefore reliable detection of lung cancer at this earlier (usually asymptomatic) stage of disease should be an important way to improve outcomes. This review discusses the principles of screening with respect to lung cancer, concentrating mainly on the biological modalities used to detect it. The lack of impact achieved by early studies using sputum cytology (in conjunction with chest radiographs) is described, and then newer technology used to measure other biomarkers in sputum, serum, exhaled breath and bronchial mucosa to diagnose (early) lung cancer is detailed. Many techniques show promise, but debate continues about which population to screen and what is the most (cost) effective modality to use. Moreover, no single biomarker or combination of biomarkers in screening has yet been shown to reduce lung cancer mortality in large prospective randomised studies.

[1]  Hermann Brenner,et al.  Recent cancer survival in Europe: a 2000-02 period analysis of EUROCARE-4 data. , 2007, The Lancet. Oncology.

[2]  A. Hölscher,et al.  Comprehensive expression analysis of retinoic acid receptors and retinoid X receptors in non-small cell lung cancer: implications for tumor development and prognosis. , 2004, Carcinogenesis.

[3]  B Palcic,et al.  Detection and localization of early lung cancer by imaging techniques. , 1993, Chest.

[4]  G. Bepler,et al.  Screening for lung cancer. , 2000, The New England journal of medicine.

[5]  P. Woll,et al.  Circulating DNA and Lung Cancer , 2006, Annals of the New York Academy of Sciences.

[6]  M. Mahoney,et al.  Autofluorescence bronchoscopy for lung cancer surveillance based on risk assessment , 2006, Thorax.

[7]  P. Sebastiani,et al.  Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer , 2007, Nature Medicine.

[8]  J. Jett.  Limitations of Screening for Lung Cancer with Low-Dose Spiral Computed Tomography , 2005, Clinical Cancer Research.

[9]  M. Tsuboi,et al.  [Early lung cancer]. , 1996, Nihon rinsho. Japanese journal of clinical medicine.

[10]  R. Guleria,et al.  Circulating cell-free DNA in plasma/serum of lung cancer patients as a potential screening and prognostic tool. , 2006, Clinical chemistry.

[11]  C. Mountain,et al.  Revisions in the International System for Staging Lung Cancer. , 1997, Chest.

[12]  Douglas C McCrory,et al.  Screening for lung cancer: a review of the current literature. , 2003, Chest.

[13]  S. Belinsky,et al.  Gene-promoter hypermethylation as a biomarker in lung cancer , 2004, Nature Reviews Cancer.

[14]  W F Taylor,et al.  Lung cancer screening: the Mayo program. , 1986, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[15]  R. Cataneo,et al.  Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study , 1999, The Lancet.

[16]  B J Flehinger,et al.  Screening for early lung cancer. Results of the Memorial Sloan-Kettering study in New York. , 1984, Chest.

[17]  A. B. Robinson,et al.  Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[18]  F. O. Fackelmayer,et al.  DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. , 2001, Cancer research.

[19]  O. Miettinen,et al.  Survival of Patients with Stage I Lung Cancer Detected on CT Screening , 2008 .

[20]  Kevin Gleeson,et al.  Detection of lung cancer with volatile markers in the breath. , 2003, Chest.

[21]  W. Rom,et al.  Preneoplastic lesions of the lung , 2002, Respiratory research.

[22]  J Polák,et al.  Lung cancer detection results of a randomized prospective study in Czechoslovakia , 1986, Cancer.

[23]  D. Hürzeler.  Fluorescence Bronchoscopy , 1982, Definitions.

[24]  Graeme P Currie,et al.  Variation in lung cancer survival rates between countries: do differences in data reporting contribute? , 2006, Respiratory medicine.

[25]  J. Herman,et al.  Predicting lung cancer by detecting aberrant promoter methylation in sputum. , 2000, Cancer research.

[26]  Wei Zhang,et al.  Application of serum SELDI proteomic patterns in diagnosis of lung cancer , 2005, BMC Cancer.

[27]  R. Bremnes,et al.  Circulating tumour-derived DNA and RNA markers in blood: a tool for early detection, diagnostics, and follow-up? , 2005, Lung cancer.

[28]  P. Mazzone,et al.  Analysis of volatile organic compounds in the exhaled breath for the diagnosis of lung cancer. , 2008, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[29]  B. E. Peterson.  [Diagnosis of lung cancer]. , 1971, Voprosy onkologii.

[30]  E. Wilkinson.  Cancer Research UK , 2002 .

[31]  Ugo Pastorino,et al.  Computed tomography screening and lung cancer outcomes. , 2007, JAMA.

[32]  E. Bergstralh,et al.  Screening for lung cancer. A critique of the mayo lung project , 1991, Cancer.

[33]  H. J. O’neill,et al.  Volatile organic compounds in exhaled air from patients with lung cancer. , 1985, Clinical chemistry.

[34]  J. Ferlay,et al.  Estimates of the cancer incidence and mortality in Europe in 2006. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[35]  U. Pastorino,et al.  Detecting lung cancer in plasma with the use of multiple genetic markers , 2004, International journal of cancer.

[36]  Tarek Mekhail,et al.  Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array , 2007, Thorax.

[37]  B Rachet,et al.  Trends and socioeconomic inequalities in cancer survival in England and Wales up to 2001 , 2004, British Journal of Cancer.

[38]  F. Khuri,et al.  Autofluorescence bronchoscopy in the detection of squamous metaplasia and dysplasia in current and former smokers. , 1998, Journal of the National Cancer Institute.

[39]  B J Flehinger,et al.  Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Memorial Sloan-Kettering study. , 2015, The American review of respiratory disease.

[40]  L. Bianchi,et al.  Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study , 2005, Respiratory research.

[41]  N. Berlin.  Overview of the NCI Cooperative Early Lung Cancer Detection Program , 2000, Cancer.

[42]  Ja Wilson,et al.  Principles and practice of screening for disease , 1968 .

[43]  Anne-Marie Sykes,et al.  CT screening for lung cancer: five-year prospective experience. , 2005, Radiology.

[44]  L. Crinò,et al.  Plasma DNA, Microsatellite Alterations, and p53 Tumor Mutations Are Associated with Disease-Free Survival in Radically Resected Non-small Cell Lung Cancer Patients: A Study of the Perugia Multidisciplinary Team for Thoracic Oncology , 2008, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[45]  R. Rosell,et al.  Is there a prognostic role of K-ras point mutations in the serum of patients with advanced non-small cell lung cancer? , 2005, Lung cancer.

[46]  B Palcic,et al.  Detection and localization of early lung cancer by fluorescence bronchoscopy , 2000, Cancer.

[47]  E. Glatstein,et al.  CT Screening for Lung Cancer: Five-Year Prospective Experience , 2006 .

[48]  Ming-Sound Tsao,et al.  K-ras mutations in non-small-cell lung carcinoma: a review. , 2006, Clinical lung cancer.

[49]  D. Parkin,et al.  Czech study on lung cancer screening , 2000, Cancer.

[50]  P C Prorok,et al.  Lung cancer mortality in the Mayo Lung Project: impact of extended follow-up. , 2000, Journal of the National Cancer Institute.

[51]  U. Pastorino,et al.  Detection of microsatellite alterations in plasma DNA of non-small cell lung cancer patients: a prospect for early diagnosis. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[52]  A. Kurt,et al.  Microsatellite alterations in plasma DNA of small cell lung cancer patients , 1996, Nature Medicine.

[53]  D. R. Jones.  Survival of Patients with Stage I Lung Cancer Detected on CT ScreeningHenschke CI, for The International Early Lung Cancer Action Program Investigators (Cornell Univ, New York; et al) N Engl J Med 355:1763–1771, 2006§ , 2007 .

[54]  J. Jett,et al.  Screening for non-small cell lung cancer. , 2005, Seminars in oncology.

[55]  G. Bepler,et al.  A systematic review and lessons learned from early lung cancer detection trials using low-dose computed tomography of the chest. , 2003, Cancer control : journal of the Moffitt Cancer Center.

[56]  W F Taylor,et al.  Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. , 2015, The American review of respiratory disease.

[57]  J. Herman,et al.  Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. , 2006, Cancer research.

[58]  W. C. Ball,et al.  Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study. , 2015, The American review of respiratory disease.

[59]  S. Duffy,et al.  The Liverpool Lung Project research protocol. , 2005, International journal of oncology.

[60]  Steven Peace,et al.  Baseline chest radiograph for lung cancer detection in the randomized Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. , 2005, Journal of the National Cancer Institute.