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Novel aspects for comprehensive CT screening in smokers

Abstract
Philips CT Clinical Science Philips Healthcare • USA

Prof. Dr. med. Hans-Ulrich Kauczor

Chairman of Radiology

Medical Director

Department of Diagnostic and Interventional Radiology

University Hospital Heidelberg

Im Neuenheimer Feld 110

69120 Heidelberg

Germany

hu.kauczor@med.uni-heidelberg.de

 

On average 28 percent of the European population consumes cigarettes daily, which accounts for around 210 million people. Many of them are heavy smokers, consuming 20 or more cigarettes a day1. There is evidence that tobacco smoking is the key risk factor for lung cancer. Nearly 80-90% of all lung cancers are due to smoking. Lung cancer is the cancer killer number one in Europe and worldwide. Lung cancer is predicted to cause 280.000 deaths in Europe in 2015, corresponding to more than 20% of all cancer deaths2. While the number of deaths in men declined slightly in recent years, more women die from lung cancer as from breast cancer2. In most patients lung cancer is diagnosed in an advanced and non-curable disease stage. Overall 5-year survival is about 16%, however, the 5-year survival rate increases up to 50% for clinical stage IA and up to 100% in tumors smaller than 1.0 cm³. First efforts for early detection of lung cancer with chest-x-ray dates back to the 1950s4. Since then all screening studies and clinical trials using chest-x-ray and sputum cytology failed to prove any benefit of screening. There are different on-going research projects on blood biomarkers for early detection of lung cancer such as circulating tumour DNA (liquid biopsy), non-coding RNAs, cytokines and DNA-hypermethylation. However, up to date no reliable blood biomarker is available. In contrast, there is evidence that CT screening of lung cancer reduces lung cancer mortality. NLST- the National Lung Screening Trial in the US - was the first randomized trial to demonstrate a 20% mortality reduction from lung cancer with three annual rounds of low-dose CT (LDCT) compared to chest- X-ray. According to the NLST 320 patients need to undergo LDCT to save one life5. On the basis of the NLST results, prominent US-medical societies are recommending annual LDCT-screening for high-risk smokers. Since 2015 the major US health care programs reimburse the costs of annual LDCT screening6. In Europe there are no reimbursed screening programs so far. There are several completed and on-going lung cancer screening LDCT-trials in Europe. In all European trials, cancer detection rate at baseline (0.8%- 2.2%) and detection rate of early stage cancers (>60%) were similar to the NLST results (1% and 63% respectively)7,8. The mortality data of the largest European randomized controlled trial NELSON is eagerly awaited.

 

In 2015 the European Society of Radiology and European Respiratory Society published a white paper, recommending lung cancer screening in comprehensive, quality-assured, longitudinal programs within a clinical trial or in routine clinical practice run at certified multidisciplinary medical centres9,10. Being an effective approach for the detection of early lung cancers, the LDCT-screening bears some major challenges. The one with most impact is the high false-positive rate which leads to unnecessary invasive diagnostics and anxiety of participants. The rate of positive screening tests in the LDCT group of the NLST was 24% of which 96% were false-positive5. In contrast, the nodule management approach of the NELSON-trial based on 3D measurement and growth-rate of screen detected nodules showed significant reduction of false-positive results11. Cumulated radiation dose is another issue which shouldn’t be ignored. Although the radiation dose of the LDCT itself is relatively low (<3 mSv), cumulative radiation dose resulting from subsequent diagnostic CT scans for suspicious nodules is still high.

 

There are several considerations to make screening in high-risk smokers more powerful with regard to mortality reduction as well as cost effectiveness. So far calculations of cost-effectiveness of LDCT screening in the USA and UK were within acceptable limits12,13. The integration of risk models complemented by structured classification schemes, such as LungRads, will further reduce the false positive screens. Also, the reduction in lung cancer-specific mortality should be further enhanced by the introduction of smoking cessation as part of the screening program. Researchers of the NLST demonstrated that seven years of smoking abstinence reduces lung cancer-specific mortality at a magnitude comparable to LDCT screening14. Also, CT can do more than just identifying nodules. With the assessment of other smoking-related diseases, such as chronic airway disease, emphysema, interstitial lung abnormalities, vascular calcifications, the lung cancer screening program will transform into a general prevention program in smokers. Although this concept is highly attractive, this will still require some trials to generate the required evidence.

 

References

 

  1. WHO (Webpage accessed in August 2016) http://www.euro.who.int/ en/health-topics/disease-prevention/tobacco/data-and-statistics.
  2. Malvezzi M, Bertuccio P, Levi F, La Vecchia C, Negri E (2013) European cancer mortality predictions for the year 2013. Ann Oncol 24: 792-800.
  3. Shi CL, Zhang XY, Han BH, He WZ, Shen J, et al. (2011) A clinicopathological study of resected non-small cell lung cancers 2 cm or less in diameter: A prognostic assessment. Med Oncol 28: 1441-1446.
  4. Brett GZ (1959) Bronchial carcinoma in men detected by selective and unselective miniature radiography: A review of 228 cases. Tubercle 40: 192-195.
  5. Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, et al. (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365: 395-409.
  6. Chin J, Syrek Jensen T, Ashby L, Hermansen J, Hutter JD, et al. (2015) Screening for lung cancer with low-dose CT--translating science into Medicare coverage policy. N Engl J Med 372: 2083-2085.
  7. Field JK, Hansell DM, Duffy SW, Baldwin DR (2013) CT screening for lung cancer: Countdown to implementation. Lancet Oncol 14: e591- 600.
  8. Shlomi D, Ben-Avi R, Balmor GR, Onn A, Peled N (2014) Screening for lung cancer: Time for large-scale screening by chest computed tomography. Eur Respir J 44: 217-238.
  9. Kauczor HU, Bonomo L, Gaga M, Nackaerts K, Peled N, et al. (2015) ESR/ERS white paper on lung cancer screening. Eur Respir J 46: 28-39.
  10. Kauczor HU, Bonomo L, Gaga M, Nackaerts K, Peled N, et al. (2015) ESR/ERS white paper on lung cancer screening. Eur Radiol 25: 2519- 2531.
  11. van Klaveren RJ, Oudkerk M, Prokop M, Scholten ET, Nackaerts K, et al. (2009) Management of lung nodules detected by volume CT scanning. N Engl J Med 361: 2221-2229.
  12. Black WC, Gareen IF, Soneji SS, Sicks JD, Keeler EB, et al. (2014) Cost effectiveness of CT screening in the National Lung Screening Trial. N Engl J Med 371: 1793-1802.
  13. Field JK, Duffy SW, Baldwin DR, Whynes DK, Devaraj A, et al. (2016) UK Lung Cancer RCT Pilot Screening Trial: Baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening. Thorax 71: 161-170.
  14. Tanner NT, Kanodra NM, Gebregziabher M, Payne E, Halbert CH, et al. (2016) The association between smoking abstinence and mortality in the National Lung Screening Trial. Am J Respir Crit Care Med 193: 534- 541. 59


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Abstract
12th MDCT User Meeting abstracts, Body, calcification, chest, emphysema, low dose, lung cancer, lung nodule, lungs, Oncology, pulmonary imaging, Thorax, tumor, Vascular
 

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