利用低劑量電腦斷層篩檢早期肺癌：系統性文獻回顧和統合分析

Use of Low-Dose CT for Early Lung Cancer Screening: A Systematic Review and Meta-Analysis

10.6288/TJPH201534103133

曾健華(Chien-Hua Tseng)；張慧如(Huei-Ru Chang)；邱韶薇(Shao-Wei Chiu)；杜裕康(Yu-Kang Tu)

低劑量電腦斷層 ； 肺癌 ； 篩檢 ； 統合分析 ； 陽性預測率 ； low-dose CT ； lung cancer ； screening ； meta-analysis ； positive predictive value

台灣公共衛生雜誌

34卷2期（2015 / 04 / 15）

156 - 167

繁體中文

目標：近年一個美國政府主導的大型隨機分派研究發現，針對重度抽菸者每年進行低劑量電腦斷層篩檢肺癌，相較於僅接受胸部X光篩檢者，三年內可相對降低20%肺癌死亡率；本文欲探討背後潛在的風險以及應用在台灣本土的適切性。方法：將過去10年針對此議題的研究進行系統性回顧（Systematic Review），蒐集每個研究的相關數據以及可能影響診斷工具效用的因子，再藉由統合分析（Meta-analysis）計算敏感度、陽性預測率等。結果：僅有5篇研究提供較完整追蹤資料，可推估低劑量電腦斷層的敏感度為87.43%（95% CI：72.79%~94.77%）、與特異度為96.45%（95% CI：80.39%~99.44%）；而由19篇文獻提供的資料，陽性預測率估計約為6.4%（95% CI：4.8~8.2%）。結論：雖然美國許多學會根據近年文獻紛紛建議對肺癌高危險群以低劑量電腦斷層篩檢肺癌，但過低的陽性預測率較少被強調，以目前的流程篩檢下來會造成許多的偽陽性個案，這會造成很多篩檢者被迫要面臨結果不確定性的壓力，甚至是接受不必要的侵入性切片或手術。尤其台灣肺癌發生率僅約美國一半，且女性抽菸比率較歐美國家低，而目前也未能確定台灣肺癌的主要危險因子，因此貿然大規模效仿美國指引進行篩檢，會導致更低的陽性預測率。因此，如何發展出適合台灣本土的建議，則是目前這個領域需要克服的難題。

Objectives: Recent studies have demonstrated that low-dose computer tomography (LDCT) screening in place of X-ray screening for lung cancer could reduce relative mortality in heavy smokers by 20%. The aim of this study was to conduct a systematic review and meta-analysis for the performance of LDCT in lung cancer screening and to evaluate the potential benefits and harms of implementing such a screening program in Taiwan. Methods: We searched electronic databases (MEDLINE, EMBASE and Cochrane library) for studies on LDCT screening (1996 to 2014) and conducted meta-analyses of sensitivity, specificity, and positive predictive values (PPV). We also undertook meta-regression to examine the impact of study characteristics on LDCT screening. Results: Only 5 studies provided sufficient information for a meta-analysis of sensitivity (87.43%, 95% Confidence Interval [CI]: 72.79 to 94.77%) and specificity (96.45%, 95% CI: 80.39% to 99.44%). Twenty-one studies provided information for a meta-analysis of PPV (6.4%, 95% CI: 4.8 to 8.2%). Conclusions: Several studies from Western countries recommended the use of LDCT screening for lung cancer in high risk populations, especially for heavy smokers. However, the low PPV of LDCT was seldom discussed. Those false positive cases may suffer from mental stress and harm from unnecessary invasive interventions. Given the low smoking prevalence in Taiwan, implementing LDCT for population screening in lung cancer could represent a significant challenge.

1. 衛生福利部國民健康署： 成年人吸菸行為調查，2010年。http://tobacco.hpa.gov.tw/Show.aspx?MenuId=581。引用2014/12/23。Health Promotion Administration, Ministry of Health and Welfare, R.O.C. (Taiwan). Adult smoking behavior surveillance system (ASBS), 2010. Available at: http://tobacco.hpa.gov.tw/Show.aspx?MenuId=581. Accessed December 23, 2014. [In Chinese]
2. Centers for Disease Control and Prevention (CDC). United States Cancer Statistics (USCS), 2011. Available at: http://apps.nccd.cdc.gov/uscs/toptencancers.aspx. Accessed December 23, 2014
3. 衛生福利部國民健康署：中華民國100年癌症登記報告。http://www.hpa.gov.tw/BHPNet/Web/Stat/StatisticsShow.aspx?No=201404160001。引用2014/12/23。Health Promotion Administration, Ministry of Health and Welfare, R.O.C. (Taiwan). Cancer registry annual report, 2011. Available at: http://www.hpa.gov.tw/BHPNet/Web/Stat/StatisticsShow.aspx?No=201404160001. Accessed December 23, 2014. [In Chinese]
4. CDC. Current cigarette smoking among adults —United States, 2005–2012. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6302a2.htm?s_cid=mm6302a2_w#tab. Accessed December 23, 2014
5. Aberle, DR,DeMello, S,Berg, CD(2013).Results of the two incidence screenings in the National Lung Screening Trial.N Engl J Med,369,920-31.
6. Baaijens, F,Bouten, C,Hoerstrup, S,Mol, A,Driessen, N,Boerboom, R(2005).Functional tissue engineering of the aortic heart valve.Clin Hemorheol Microcirc,33,197-9.
7. Bach, PB,Mirkin, JN,Oliver, TK(2012).Benefits and harms of ct screening for lung cancer: a systematic review.JAMA,307,2418-29.
8. Bastarrika, G,Garcia-Velloso, MJ,Lozano, MD(2005).Early lung cancer detection using spiral computed tomography and positron emission tomography.Am J Respir Crit Care Med,171,1378-83.
9. Blanchon, T,Brechot, JM,Grenier, PA(2007).Baseline results of the Depiscan study: a French randomized pilot trial of lung cancer screening comparing low dose CT scan (LDCT) and chest X-ray (CXR).Lung Cancer,58,50-8.
10. Callol, L,Roig, F,Cuevas, A(2007).Low-dose CT: a useful and accessible tool for the early diagnosis of lung cancer in selected populations.Lung Cancer,56,217-21.
11. Cuzick, J,Clavel, C,Petry, KU(2006).Overview of the European and North American studies on HPV testing in primary cervical cancer screening.Int J Cancer,119,1095-101.
12. Detterbeck, FC,Mazzone, PJ,Naidich, DP,Bach, PB(2013).Screening for lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest,143(5 Suppl),e78S-92S.
13. Diederich, S,Thomas, M,Semik, M(2004).Screening for early lung cancer with low-dose spiral computed tomography: results of annual follow-up examinations in asymptomatic smokers.Eur Radiol,14,691-702.
14. Gohagan, JK,Marcus, PM,Fagerstrom, RM(2005).Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer.Lung Cancer,47,9-15.
15. Harbord, RM,Deeks, JJ,Egger, M(2007).A unification of models for meta-analysis of diagnostic accuracy studies.Biostatistics,8,239-51.
16. Harbord, RM,Whiting, P(2009).metandi: meta-analysis of diagnostic accuracy using hierarchical logistic regression.Stata J,9,211-29.
17. Henschke, CI,Yankelevitz, DF,Libby, DM(2001).Early lung cancer action project: annual screening using single-slice helical CT.Ann N Y Acad Sci,952,124-34.
18. Infante, M,Cavuto, S,Lutman, FR(2009).A randomized study of lung cancer screening with spiral computed tomography: three-year results from the DANTE trial.Am J Respir Crit Care Med,180,445-53.
19. Jaklitsch, MT,Jacobson, FL,Austin, JH(2012).The American Association for Thoracic Surgery guidelines for lung cancer screening using low-dose computed tomography scans for lung cancer survivors and other high-risk groups.J Thorac Cardiovasc Surg,144,33-8.
20. Lopes Pegna, A,Picozzi, G,Mascalchi, M(2009).Design, recruitment and baseline results of the ITALUNG trial for lung cancer screening with lowdose CT.Lung Cancer,64,34-40.
21. MacRedmond, R,McVey, G,Lee, M(2006).Screening for lung cancer using low dose CT scanning: results of 2 year follow up.Thorax,61,54-6.
22. Manser, R,Lethaby, A,Irving, LB(2013).Screening for lung cancer.Cochrane Database Syst Rev,6,CD001991.
23. Menezes, RJ,Roberts, HC,Paul, NS(2010).Lung cancer screening using low-dose computed tomography in atrisk individuals: the Toronto experience.Lung Cancer,67,177-83.
24. Novello, S,Fava, C,Borasio, P(2005).Three-year findings of an early lung cancer detection feasibility study with low-dose spiral computed tomography in heavy smokers.Ann Oncol,16,1662-6.
25. Pastorino, U,Bellomi, M,Landoni, C(2003).Early lungcancer detection with spiral CT and positron emission tomography in heavy smokers: 2-year results.Lancet,362,593-7.
26. Pedersen, JH,Ashraf, H,Dirksen, A(2009).The Danish randomized lung cancer CT screening trial-overall design and results of the prevalence round.J Thorac Oncol,4,608-14.
27. Picozzi, G,Paci, E,Lopez Pegna, A(2005).Screening of lung cancer with low dose spiral CT: results of a three year pilot study and design of the randomised controlled trial "Italung-CT".Radiol Med,109,17-26.
28. Rabe-Hesketh, S,Skrondal, A,Pickles, A.(2004).Generalized multilevel structural equation modeling.Psychometrika,69,167-90.
29. Reitsma, JB,Glas, AS,Rutjes, AW,Scholten, RJ,Bossuyt, PM,Zwinderman, AH(2005).Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews.J Clin Epidemiol,58,982-90.
30. Sobue, T,Moriyama, N,Kaneko, M(2002).Screening for lung cancer with low-dose helical computed tomography: anti-lung cancer association project.J Clin Oncol,20,911-20.
31. Swensen, SJ,Jett, JR,Hartman, TE(2003).Lung cancer screening with CT: Mayo Clinic experience.Radiology,226,756-61.
32. Swensen, SJ,Jett, JR,Hartman, TE(2005).CT screening for lung cancer: five-year prospective experience.Radiology,235,259-65.
33. Tobias, IS,Baum, M(1996).False positive findings of mammography will have psychological consequences.BMJ,312,1227.
34. Toyoda, Y,Nakayama, T,Kusunoki, Y,Iso, H,Suzuki, T.(2008).Sensitivity and specificity of lung cancer screening using chest low-dose computed tomography.Br J Cancer,98,1602-7.
35. van Klaveren, RJ,Oudkerk, M,Prokop, M(2009).Management of lung nodules detected by volume CT scanning.N Engl J Med,361,2221-9.
36. van Rossum, LG,van Rijn, AF,Laheij, RJ(2008).Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population.Gastroenterology,135,82-90.
37. van, Baal, I,Malda, H,Synowsky, SA(2005).Multivalent peptide and protein dendrimers using native chemical ligation.Angew Chem Int Ed Engl,44,5052-7.
38. Veronesi, G,Bellomi, M,Mulshine, J, L(2008).Lung cancer screening with low-dose computed tomography: a non-invasive diagnostic protocol for baseline lung nodules.Lung Cancer,61,340-9.
39. Wender, R,Fontham, ET,Barrera, E, Jr(2013).American Cancer Society lung cancer screening guidelines.CA Cancer J Clin,63,106-17.
40. Whiting, PF,Rutjes, AW,Westwood, ME(2011).QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.Ann Intern Med,155,529-36.
41. Wilson, DO,Weissfeld, JL,Fuhrman, CR(2008).The Pittsburgh Lung Screening Study (PLuSS): outcomes within 3 years of a first computed tomography scan.Am J Respir Crit Care Med,178,956-61.
42. 林森富、吳冠群(2003)。肺癌篩檢使用低劑量多探頭電腦斷層掃描與一般胸部X光之比較。健康管理學刊，1，31-7。
43. 衛生福利部(2013)。中華民國102年版公共衛生年報。

1. 陳嘉允(2017)。肺癌標靶藥物副作用之中醫治療病例報告。中醫藥研究論叢，20(2)，165-173。