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Lo Screening del Tumore Polmonare: Siamo Pronti?

Lo Screening del Tumore Polmonare: Siamo Pronti?. Mario Silva Section of Radiology, Department of Surgical Sciences University of Parma, IT bioMILD Lung Cancer screening Trial Department of Thoracic Surgery, Istituto Nazionale Tumori, Milano, IT. Objectives.

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Lo Screening del Tumore Polmonare: Siamo Pronti?

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  1. Lo Screening del Tumore Polmonare: Siamo Pronti? Mario Silva Section of Radiology, Department of Surgical Sciences University of Parma, IT bioMILD Lung Cancer screening Trial Department of Thoracic Surgery, Istituto Nazionale Tumori, Milano, IT

  2. Objectives • Lung cancer screening chronology since 1970s: American and European evidence • Controversies • Optimization – Ideal target

  3. Mayo Lung Project chest x-ray 4 monthly vs. control 9211 smokers, 1971-1983 global mortality: + 10% screening control 20 30 10 0 years JNCI 2000; 92:1308-16

  4. ELCAP Project - Cornell NY spiral CT vs. CxR 1000 smokers, median 67 yrs, 45 PY lung cancer detection total: 2.7% vs. 0.6% stage I: 2.3% vs. 0.4% x 6 Cancer 2000; 89:474-82

  5. I-ELCAP conclusion: CT can prevent 80% LC deaths NEJM 2006; 355:1763-71

  6. Randomized Clinical Trials on LDCT ScreeningDetection rates at Baseline & 1stRepeat 90,866 enrolled subjects, 44,629 LDCT arm Thorac Surg Clin 2013; 23:129-40

  7. Randomized Clinical Trials on LDCT ScreeningDetection rates at Baseline & 1stRepeat 90,866 enrolled subjects, 44,629 LDCT arm Thorac Surg Clin 2013; 23:129-40

  8. RCT trials on LDCT screeningsurgical procedures for benign disease Thorac Surg Clin 2013; 23:129-40

  9. NLST: landmark trial Randomized screening trial 53,454 persons 3 rounds of annual LDCT vs CxR 20% reduction of LC mortality 7% reduction all cause mortality 24.2% positive subjects 96.4% of these false positive Need to screen 320 subjects to prevent 1 lung cancer death N Engl J Med 2011;365:395-409

  10. NLST: landmark trial NLST overall survival Randomized screening trial 53,454 persons 3 rounds of annual LDCT vs CxR 20% reduction of LC mortality 7% reduction all cause mortality 24.2% positive subjects 96.4% of these false positive Need to screen 320 subjects to prevent 1 lung cancer death years from randomization N Engl J Med 2011;365:395-409

  11. NLST: overdiagnosis JAMA 2014;174:269-74

  12. Dante trial: 3-year results 2472 males:1276 CT arm, 1196 control arm median follow-up 33 months LCs detected60 (4.7%) vs 34 (2.8%) p=.016 LC deaths:20 vs 20 Other deaths:26 vs 25

  13. DLCST trial: 5-year results Thorax 2012; 67:296-301

  14. EUROPEAN RCTs: 2015 no mortality reduction

  15. + spiral CT MILD trial: design 2005 - 2011 smoking cessation breathing & blood analysis 4,000 smokers ≥ 50 yrs R R CT every CT every year 2 years > 100,000 biologic samples

  16. MILD trial: 5-year results 2005 - 2011 follow-up 17,523 person / year EJCP 2012; 21:308–315

  17. MILD trial: 5-year results 2005 - 2011 Lung cancer incidence LDCT 1 LDCT 2 Control EJCP 2012; 21:308–315

  18. MILD trial: 5-year results 2005 - 2011 All causes mortality LDCT 1 LDCT 2 Control EJCP 2012; 21:308–315

  19. NLST trial: incidence rounds PPV LDCT 2.4%at T1 5.2%at T2 N Engl J Med 2013; 369:920-31

  20. ELCAP trial: optimizing LDCT Ann Intern Med. 2013;158:246-252 Lancet Oncol 2014; 15: 1332–41

  21. NELSON: optimizing LDCT Lancet Oncol 2014; 15: 1332–41

  22. NELSON: optimizing LDCT Lancet Oncol 2014; 15: 1332–41

  23. NELSON trial: optimizing LDCT Eur Radiol 2013; 23:1836–1845

  24. Nodule Characterization J Thorac Imaging 2012;27:230 Eur Radiol. 2015 Mar;25(3):792-9 AJR 2015; 204:281–286

  25. Nodule Characterization J Thorac Imaging 2015;30:139–156

  26. Nodule Characterization - Radiomics J Thorac Imaging 2015;30:139–156

  27. Patient perspective – Positive screen Perceived risk for lung cancer 20% (IQR 10–50%), Actual risk estimated (Mayo model) 7.1% (IQR 4.6– 10.3%) • Surveillance recommended was 2 to 3 years: • 7% of patients willed for about 5 years • 32% for the rest of their lives 35% reported quitting smoking J Thor Oncol in Press JAMA Intern Med. 175(9):1530-7

  28. Incidence round optimization • … CT nodule risk modelling now has a more complex role: • to determine the frequency and duration of screening over 25 years. • Field JK, Lancet Oncology in Press Lancet Oncology in Press

  29. Incidence round optimization Negative low-dose CT prevalence screen had a lower incidence of lung cancer and lung cancer-specific mortality…increasing the interval between screens in participants with a negative low-dose CT prevalence screen might be warranted.

  30. Incidence round optimization Biennial screen may save about one third of LDCT scans with similar performance indicators as compared to annual screening. Stage shift from diagnostic delay? INTERVAL CANCER? European Radiology in Press

  31. Tumor Stage & Interval cancer

  32. Interval cancer 61 subjects with interval cancers (36% retrospectively detectable) • 22 % of missed carcinomas originally presented as bulla wall thickening on CT.• 22 % of missed carcinomas originally presented as endobronchial lesions on CT.• All malignant endobronchial lesions presented as interval carcinomas.• In the NELSON trial subsolid nodules were not a source of missed carcinomas.

  33. LDCT screening: nailing the targets higher individual risk: 5 – 10 fold avoid useless radiation (CT + PET) targeted resection & chemotherapy less surgery for indolent disease primary prevention is a priority

  34. LDCT screening: metabolic profile J Thor Oncol 11:1352-6, 2009

  35. LDCT screening: metabolic profile 76 ground-glass nodules (GGNs) detected in 56 patients at baseline CT followed for 5 years by CT: only one (1.3%) progressed (stage Ia ADC) 3 developed LC in other sites JTO 7:1541, 2012

  36. LDCT screening: metabolic profile LDCT arms: 5/8 LD-SCLC Control arm: 2/2 ED-SCLC Median 82 pack-years No survivor @ 3 years JTO 11;2:187, 2016

  37. Smoking cessation J Thor Oncol in Press

  38. Smoking cessation Log-Rank test P = 0.0572 p-value Log-Rank test: 0.0572 CURRENT FORMER / QUITTER J Thor Oncol in Press

  39. Smoking cessation • Overdiagnosis • Radiation exposure • Cost-effectiveness Ruano-Ravina A. LDCT screen 86.000$/QALY VS Smoking cessation policy 5.000$/QALY …even those who stop at 50 years of age avoid more than half the excess risk… Eur Respir J 2015; 46: 1519–1520 N Engl J Med 2014;370:60-8 Lancet 2013;381:133-41

  40. Traslation to community setting: MediCare • Eligibility: • Medicare benefit for at-risk patients 55-77 years of age • Smoking history: distinct visit for formal shared decision making using dedicated evidence-based decision aids • Multidisciplinary care: primary care, radiology, pulmonology, surgery, and oncology N Engl J Med (2015) 372;22:2083

  41. individual susceptibility (SNPs) COPD & risk of cancer breath analysis (e-nose, exhalate) pre-diagnostic profile (PET-SUV) blood analysis (DNA, microRNA) 2005 - 2011 LDCT screening: biologic profile

  42. 1 - 2 years before CT detection PNAS 2011; 108:3713-18

  43. Complementary Diagnostic Performance of LDCTand MSC to Reduce False Positives1Increased specificity of identifying subjects without lung cancer 594 subjects in LDCT arm without lung cancer 58% had a nodule detected by LDCT This was reduced to 11% by MSC 19.4% had a ≥ 5mm nodule that required clinical action This was reduced to 3.7% by MSC 1Sozzi, Boeri et al JCO, in press

  44. Three-year survival from date of blood sample collection according to miRNA signature classifier (MSC) among all subjects (n=939) 100% 97% 77%

  45. Milan LDCT Trials (pilot + MILD)3411 smokers, 24,000 p/y, 111 lung cancers The overall survival of patients with Low to Intermediate risk MSC was significantly higher than those with High risk MSC Within stage I, the 5-years survival was 100% in Low to Intermediate risk MSC and 77% in High risk MSC. The difference was not statistically significant, possibly due to the small number of events (4 deaths only)

  46. LDCT screening: summary good prospects for screening results of European RCTs are crucial optimize individual selection improve diagnostic algorithm validate biomarkers

  47. Lo Screening del Tumore Polmonare: Siamo Pronti? Mario Silva mario.silva@unipr.it Acknowledgement: Ugo Pastorino Chief of Department of Thoracic Surgery, INT, Milano, IT PI @ bioMILD Lung Cancer screening Trial

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