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Lung cancer staging in 2011: use of pet Scan and other modalities

Nicole Bouchard MD FRCPC Pulmonologist April 29, 2011. Lung cancer staging in 2011: use of pet Scan and other modalities. Disclosure. I cannot identify any potential conflict of interest. Objectives. 1) Select the appropriate diagnostic tests to accurately stage lung cancer

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Lung cancer staging in 2011: use of pet Scan and other modalities

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  1. Nicole Bouchard MD FRCPC Pulmonologist April 29, 2011 Lung cancer stagingin 2011: use of pet Scan and other modalities

  2. Disclosure • I cannot identify any potential conflict of interest.

  3. Objectives • 1) Select the appropriate diagnostic tests to accurately stage lung cancer • 2) Understand the strengths and weaknesses of PET Scan for lung cancer staging • 3) Propose a rational approach to optimally stage mediastinal lymph nodes

  4. TNM Lababede O, Chest 2011; 139: 183-189

  5. Diagnostic tests • CT scan: • chest and upper abdomen • PET-CT: • if a radical treatment is considered • Pulmonary function testing • Imaging of the head (MRI): • if symptoms • for small cell lung cancer • maybe in stage 3 disease NSCLC Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27 Alberts WM, Chest 2007; 132; 1S-19S

  6. Diagnostic tests • Bone scintigraphy? PET is more sensitive • to avoid an unnecessary PET-CT • PET: from base of skull to upper thighs

  7. Diagnostic tests • Least invasive approach that provides both the diagnostic and the stage • bronchoscopy, transthoracic CT guided needle biopsy, radial probe EBUS • EBUS, EUS, mediastinoscopy, VATS • US guided needle aspiration: thoracentesis, cervical lymph node, liver • EUS: left adrenal metastasis

  8. Diagnostic tests • → Adequate sample • IASLC/ATS/ERS International Multidisciplinary Classification of Lung Adenocarcinoma NSCLC are to be classified into adenocarcinoma or squamous cell carcinoma • gefitinib, pemetrexed, bevacizumab Travis WD, Journal of Thoracic Oncology 2011; 6: 244-285

  9. Diagnostic tests • Wait times and costs • 2852 patients • provincial cancer registry: Manitoba • ≥ 25% of patients waited more than 55 days Cheung WY, Lung Cancer 2010 Sep [ Epub ahead of print ]

  10. Diagnostic tests • Multidisciplinary team • 1222 patients with NSCLC, 2001-2007 • survival? Freeman RK, Eur J Cardiothoracic Surg 2010; 38: 1-5

  11. PET-CT Scan • Preoperative PET-CT • prospective, randomized study • 189 patients, NSCLC • conventional staging (CT of the abdomen, bronchoscopy) or conventional staging plus PET-CT • PET-CT: reduced the number of futile thoracotomies, had no effect on survival Fischer B, NEJM 2009; 361: 32-39

  12. PET-CT Scan • Preoperative PET-CT • prospective, randomized trial • 337 patients, stage 1-3A NSCLC • PET-CT or conventional (abdominal CT & bone scan) • cranial imaging • PET-CT: spares more patients from inappropriate surgery, but also incorrectly upstaged disease Maziak DE, Ann Intern Med 2009; 151: 221-228

  13. PET-CT Scan • T stage (SUVmax 2,5) • false positive: infectious and inflammatory lesions • false negative: carcinoid, certain adenocarcinomas, uncontrolled diabetes, cavity with necrotic center, lesion < 8 mm Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27

  14. PET-CT Scan • Solitary pulmonary nodule (8 - 30 mm) and an initial SUVmax 2.6 • retrospective study, CHUS, PET-CT • 20 / 65 (31%) patients: diagnosis of cancer; mostly adenocarcinomas • risk factors for malignancy: higher 18F-FDG uptake, spiculated nodule • SUVmax 1: new threshold? Houle MA, Can Respir J 2010; 17, suppl B: 6B

  15. PET-CT Scan • N stage • CT > 10 mm in short axis diameter sensitivity 57-61%, specificity 79-82% • PET sensitivity 84%, specificity 89% false negative: small volume, low metabolic activity false positive: inflammation → sampling size of the lymph node is important Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27 Alberts WM, Chest 2007; 132; 1S-19S

  16. PET-CT Scan • M stage • sensitivity 93%, specificity 96% • detect metastases: 15%, more with advanced stage Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27

  17. PET-CT Scan • Sample of any isolated distant lesion • 350 patients • 21% had a solitary lesion: 46% had a benign lesion or another cancer (second cancer or recurrence) Lardinois D, J Clin Oncol 2005; 23: 6846-6853

  18. Mediastinal lymph nodes (LN) • No lymph node sampling if uptake is within normal limits on PET-CT and < 1 cm • false negative rate: 5-7% for a peripheral tumor • if central tumor, N1 enlargement? • N2 or N3 ≥ 1 cm but PET negative? • Lymph node sampling if PET uptake is positive, to avoid false positive results • EBUS/EUS; +/- mediastinoscopy if negative

  19. Mediastinal lymph nodes (LN) • EBUS: 2, 4, 7, 10, 11 • EUS: 2L, 4L, 7, 8, 9 • mediastinoscopy: 2R, 4R, anterior part of 7 Goldstraw P, IASLC Staging Manual in Thoracic Oncology, 2009

  20. EBUS: meta-analysis (1) • Study caracteristics Adams K, Thorax 2009; 64: 757-762

  21. EBUS: meta-analysis (1) • Study results

  22. EBUS: meta-analysis (1) • Sensitivity 88% • Specificity 100%

  23. EBUS: meta-analysis (2) • Sensitivity 93% • Specificity 100% • Only 2 complications • 2 / 1299 patients (0,15%) • pneumothorax • patient with COPD: hypoxemia during the procedure Gu P, European Journal of Cancer 2009; 45: 1389-1396

  24. EBUS: false negative rate • False negative rates • 20-25% • External validity • other studies have been published

  25. EBUS: learning curve • Learning curves • 500 patients • 5 EBUS operators • no learning from prior experience • operators 3 & 5: still in the learning phase after 100 procedures Kemp SV, Thorax 2010; 65: 534-538

  26. EBUS: cost effectiveness • Cost effectiveness • cost-beneficial in comparison with surgical mediastinoscopy, for a prevalence as low as 30% • negative results confirmed by mediastinoscopy: cost-beneficial according to the prevalence of LN metastases (>79%) Steinfort D, J Thorac Oncol 2010; 5: 1564-1570

  27. EBUS: how many aspirations? • 650 aspirations (163 MLN stations) in 102 patients, ROSE not available • best diagnostic value: 3 aspirations (sensitivity: 69.8%, 83.7%, 95.3%, 95.3%) • 2 aspirations: when at least one tissue core Lee H, Chest 2008; 134: 368-374

  28. EBUS: which needle? • 21-gauge versus 22-gauge aspiration needle • 45 lesions • same diagnostic yield • 21G: better histological preservation but more blood contamination Nakajima T, Respirology 2010 Sep [ Epub ahead of print ]

  29. EBUS: mutations and SCLC • Mutation analysis • EGFR and KRAS mutations can be performed in cytologic specimens (EUS/EBUS) • also EML4-ALK fusion gene • SCLC: high diagnostic yield Schuurbiers OC, J Thorac Oncol 2010: 5: 1664-1667 Nakajima T, J Thorac Oncol 2011; 6: 203-206 Wada H, Ann Thorac Surg 2010; 90: 229-234

  30. EUS: meta-analysis • 18 studies • No major complications; minor complications: 10 cases (0.8%), Micames CG, Chest 2007; 131: 539-548

  31. TBNA, EBUS, EUS • 138 consecutive patients • known or suspected lung cancer on CT Wallace MB, JAMA 2008; 299: 540-546

  32. EBUS & EUS: single scope • 139 consecutive patients, enlarged LN (CT) • EBUS & EUS: single linear US bronchoscope by one operator Herth FJ, Chest 2010: 138: 790-794

  33. EBUS & EUS: single scope • 150 potentially operable patients, prospective study • EBUS +/- EUS used for MLN inaccessible or difficult to access by EBUS • 2 false negative (by mediastinoscopy) Hwangbo B, Chest 2010; 138: 795-802

  34. EBUS versus mediastinoscopy • 66 patients, prospective crossover trial • Prevalence of malignancy: 89% • Diagnostic yield • EBUS: 91% versus mediastinoscopy: 78% (p=0.007) • disagreement: subcarinal lymph nodes (24%; p=0.011) • no difference: true pathologic N stage (per patient) • Ernst A, Journal of Thoracic Oncology 2008; 3; 577-582

  35. ASTER study • Randomized controlled multicenter trial • 241 patients • Lung or mediastinal abnormality on CT, no extrathoracic metastases • EUS & EBUS (systematic sampling) and surgical staging if negative or surgical staging (mediastinoscopy): N2 & N3 Annema JT, JAMA 2010; 304: 2245-2252

  36. ASTER study • Nodal metastases • 62 patients by combined staging (p=0.02) • 41 patients by surgical staging • mediastinoscopy: 11 patients to identify 1 with nodal metastasis • Thoracotomy unnecessary • 21patients in the mediastinoscopy group • 9 patients in the combined group (p = 0.02) • No increase rate of complications

  37. Conclusion • PET-CT: before surgery and radiotherapy • When N2 or N3 is suspected on PET: EBUS; mediastinoscopy if negative • Complete mediastinal staging: EBUS +/- EUS; role of mediastinoscopy? • Further studies are ongoing • preoperative EBUS, EBUS vs mediastinoscopy, surgical staging vs endosonography

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