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screening for lung cancer

Epidemiology: - among 3400 people who received CT scans for lung cancer screening [58] - only 21% met all 3 USPSTF eligibility criteria - 20% met none of the criteria - the rest met only one or two criteria. - among 5800 people who met all 3 USPSTF criteria, only 13% received CT screening [58] Indications: 1) USPSTF & ACA recommend annual screening with low-dose CT (LDLCT) for current or past smokers age 50-80 with a 20-pack-year smoking history [55] - formerly 30 pack-year age 55-74 years who currently smoke or have quit within the past 15 years [20] - formerly insufficient evidence to recommend routine screening [3] - high-risk adults with negative CT screen for lung cancer might not require subsequent annual screening (not standard of care) [38] 2) screening those at highest risk yields highest benefit/harm ratio [21,22,44] a) low-dose spiral CT anually for screening high-risk patients [1,2,4,10,22] b) screen smokers & former smokers age 55-74 with >=30 pack-years of smoking 3) some controvery still exsits, especially in < highest risk patients a) no reduction in mortality in 20 year follow-up analysis [5] b) overdiagnosis & potentially harmful workup of benign lesions is a concern [5,9] 4) screening with low-dose CT reduces risk in older smokers a) *American Lung Association & American Association for Thoracic Surgery, & American Cancer Society (ACA) now recommend screening for high-risk patients [13,15,16] - current or former smoker with >= 20 pack-year history of smoking - age 55-79 years (contrast with CMS proposal) - age 55-77 years (American College of Chest Physicians) [43] - age 50-80 years (USPSTF & ACA) [55] - long-term lung cancer survivors until age 79 [15] b) *number needed to screen to prevent 1 lung cancer related death ~ 320 [11,19] c) substantial uncertainty [14] - harm from overdiagnosis & radiation remain unresolved - positive predictive value of abnormal CT = 4% [19] 5) annual chest X-ray does not diminish mortality from lung cancer [12] * a 55 year old current smoker with a 30 pack-year history of smoking has a higher risk of false positives than a 74 year old current smoker with a 60 pack-year history of smoking, therefore would benefit less from screening [40] Contraindications: - significant medical problems affecting life expectancy - non smokers or former smoked who quit > 15 years ago [26] - asymptomatic smokers & former smokers who do not meet the smoking & age criteria [43] - patients with symptoms suggestive of lung cancer should receive appropriate diagnostic testing not screening [43] Benefit/risk: - sensitivity 93%, specificity 84% [59] - positive predictive value 10%, negative predictive value 99.8% [59] - number needed to treat (screen) to prevent 1 death - 217 [11], 142 [53], 194 [39] (USPSTF guidelines) - models based on risk 162 [39] - 100 [41] - number needed to harm [11] - 4 for false positive CT scan - 2 for false positive CT scan with repeat scanning [41] - 30 for unnecessary surgery - 50 for unnecessary invasive procedures (bronchoscopy, thoracotomy) [41] - 161 for surgical complication - lower quit rates among smokers who have been screened [36] - no statistically significant effects of CT screening on lung cancer mortality [37] - high-risk subgroup analyses showed nonsignificant trends [37] - after 10 years of screening, one radiation-induced cancer for every 108 lung cancers detected [42] - 67% of the screen-detected cancers were overdiagnosis in Danish Lung Cancer Screening Trial vs 19% in U.S.-based National Lung Cancer Screening Trial [47] - indeterminate scans requiring additional imaging 20% [53} - no reduction in overall mortality [53] - early-stage diagnoses & all-cause survival have increased since 2014, after CT screening was recommended for high-risk patients [57] - advances in treatment & lead-time bias may contribute to the increase in survival [57] Procedure: - 4 protein biomarkers for lung cancer screening may identify patients who would benefit from low-dose chest CT [48] - low-dose chest CT * threshold for a positive test is a nodule 4-6 mm in diameter [43] Radiology: - low-dose chest CT (LDLCT) - respiratory bronchiolitis-associated interstitial lung disease found in active smokers with centrilobular micronodules [20] - aortic valve calcification may represent aortic valvular stenosis [56] Adverse effects: - radiation exposure - lifetime risk of radiation-induced cancer from screening is 2.6-8.1 per 10,000 [42] Complications: - 1/3 of patients undergo further imaging [59] - 1/35 patients undergo invasive procedures (biopsy, bronchoscopy, mediastinoscopy ...) - procedural complications - intestinal obstruction [59] - cardiac arrest [59] - acute respiratory failure [59] Management: - see solitary pulmonary nodule Comparative biology: - polymer nanoparticles coated in DNA targeted by protease enzymes linked to stage I lung adenocarcinoma are administered by nebulizer or inhaler - proteases cleave off the DNA which enter the bloodstream & are secreted in the urine [60] - a test strip can detect the DNA, with results ~20 minutes - tested in mice with specificity of 100%, sensitivity 85% [60] Notes: - CMS announces Medicare coverage for lung cancer screening in high-risk patients [30,32] - age 55-77 years - >=30 pack-year history of smoking - current smoker or has quit within last 15 years - a written order from a clinician obtained during a lung cancer screening counseling & shared decision-making visit, which includes information on the procedure's risks & benefits - screening reduces risk of death from lung cancer by 20% in proposed Medicare-covered population [31] - cost per quality-adjusted life-year gained is $81,000 for CT screening in high-risk patients [29] - no mortality benefit of annual low-dose spiral CT in high-risk patients in a community setting [8] - discourse on significance of threshold for positive CT [17] - risk of overdiagnosis [25] - Medicare advisers previously voted against paying for lung cancer screening in high-risk patients [27,28] - higher rate of false positive (27% vs 22%) for patients > 65 vs < 65 years of age [27] - Lung-RADS criteria for classifying lung nodules detected during low-dose computed tomography screening increased specificity at the cost of decreased sensitivty for detecting lung cancer [33] - decline in cases with a 30-pack-year smoking history who had quit within 15 years [34] - contents of lung cancer screening medical websites emphasize potential benefits while downplaying potential harms [54]

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biomarkers for lung cancer screening lung cancer

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screening for cancer

References

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