Approach to the Solitary Pulmonary Nodule New Staging System for NSCLC Lymph Node Map-Update

1. Approach to the Solitary Pulmonary NoduleNew Staging System for NSCLCLymph Node Map-Update Bassel Ericsoussi, MD Fellow, Pulmonary and Critical Care University of Illinois Medical Center at Chicago

2. The Peripheral Pulmonary Nodule Small focal radiographic opacities that may be solitary or multiple The term “Coin Lesion” should be discouraged The solitary pulmonary nodule (SPN) Round lesion <3 cm (if > 3 cm called mass) Completely surrounded by pulmonary parenchyma 2 UIC Bassel Ericsoussi, MD

3. Prevalence Prevalence of SPNs in screening trials of populations at high risk for lung neoplasm 8-51% Nodules detected in screening trials are different than those detected in clinical routine practice: Smaller Prevalence of malignancy is lower Tumor volume doubling time is longer Prevalence of malignancy in patients with SPNs: 1.1-12% in screening trials 46-82% in PET trials Wahidi, MM. Chest 2007; 132:94s-107s 3 UIC Bassel Ericsoussi, MD

4. The Dilemma Malignant SPN can represent a potentially curable form of lung cancer Stage I survival: > 60% at 5 years The flip side is unnecessary procedures and surgeries with resultant morbidities Cost implications 4 UIC Bassel Ericsoussi, MD

5. Detection 5 UIC Bassel Ericsoussi, MD

6. Evaluation ? 6 UIC Bassel Ericsoussi, MD

7. Tools Clinical History Chest CT Observation Bronchoscopy Old Films FDG-PET TTNA Surgery 7 UIC Bassel Ericsoussi, MD

8. Goal Likely Benign ? Indeterminate Likely Malignant 8 UIC Bassel Ericsoussi, MD

9. Management Follow Likely Benign ??? Indeterminate Likely Malignant Take Action 9 UIC Bassel Ericsoussi, MD

10. First Steps Obtain old films and compare sizes Determine nodule growth Any evidence of growth should prompt immediate tissue diagnosis In every patient with an indeterminate SPN that is visible on CXR, Chest CT should be performed 10 UIC Bassel Ericsoussi, MD

11. Growth Rate of the SPN Growth rate is usually expressed in volume doubling time (VDT): One doubling in volume of SPN usually represents 26% increase in diameter on chest CT VDT for malignant nodules: 20-300 days Because VDT for malignant SPNs rarely exceed 300 days, a 2–year radiographic stability predicts a benign process For ground-glass nodules, longer follow-up is recommended (>2 years) Gould, MK. Chest 2007, 132:108s-130s 11 UIC Bassel Ericsoussi, MD

12. Adenocarcinoma (3 months) Relatively slow growth 12 UIC Bassel Ericsoussi, MD

13. Infection (2 weeks) Fast growth 13 UIC Bassel Ericsoussi, MD

14. Pure Ground-Glass Nodules More likely to be malignant than solid nodule (59-73% vs. 7-9%) Bronchoalveolar carcinoma is the most common histological subtype Longer VDT Better prognosis Wahidi, MM. Chest 2007; 132:94s-107s 14 UIC Bassel Ericsoussi, MD

15. Ground-Glass Opacities Pure Ground Glass (BAC) Part-Solid (Adenocarcinoma) 15 UIC Bassel Ericsoussi, MD

16. Pre-Test Probability In every patient with SPN, the clinical pre-test probability of malignancy should be estimated either: Qualitatively by clinical judgment Quantitatively by using validated quantitative model The SPN calculator: http://www.chestx-ray.com/spn/spnprob.html This facilitates the selection and interpretation of subsequent diagnostic tests 16 UIC Bassel Ericsoussi, MD

17. Clinical Factors Influence Pre-Test Clinical Probability of Malignancy Size Calcification Margins Morphology 17 UIC Bassel Ericsoussi, MD

18. SPN Size Wahidi, MM. Chest 2007; 132:94s-107s 18 UIC Bassel Ericsoussi, MD

19. Calcification Patterns of SPN SPNs that are calcified in a clearly benign pattern do not warrant additional diagnostic evaluation Benign calcification patterns: Diffuse Central Popcorn Laminated Potentially malignant calcification patterns: Stippled Eccentric 19 UIC Bassel Ericsoussi, MD

20. “Popcorn” Calcification Hamartoma 20 UIC Bassel Ericsoussi, MD

21. Benign Calcifications Diffuse: Benign granuloma Central: Benign disease Laminated 21 UIC Bassel Ericsoussi, MD

22. Markedly Enhancing Nodule Pulmonary Arteriovenous Malformation 22 UIC Bassel Ericsoussi, MD

23. Malignant Calcifications Eccentric Speckled Adenocarcinoma Adenocarcinoma Carcinoid tumor 23 UIC Bassel Ericsoussi, MD

24. Margins Risk of malignancy is 20-30% in nodules with smooth edges Risk of malignancy is 33-100% in nodules with irregular, lobulated, or spiculated borders Wahidi, MM. Chest 2007; 132:94s-107s 24 UIC Bassel Ericsoussi, MD

25. Margins Cavitary SCC Lobulated SCC Spiculated BAC Smooth Granuloma 25 UIC Bassel Ericsoussi, MD

26. Managements Low clinical pre-test probability of malignancy (<5%): serial chest CT at 3, 6, 12 and 24 months High clinical pre-test probability of malignancy (>60%): proceed to surgical resection Indeterminate clinical pre-test probability of malignancy (5-60%): careful consideration of options in conjunction with patient’s preferences 26 UIC Bassel Ericsoussi, MD

27. Talk to Your Patient Discuss the risks and benefits of alternative management strategies and elicit patient preferences 27 UIC Bassel Ericsoussi, MD

28. Choice of Sampling Modality TTNA if nodule is peripherally located Bronchoscopy: Air-bronchogram or bronchus sign are present Experience with advanced tools exists: Electromagnatic Navigation Radial EBUS CT-guided biopsy 28 UIC Bassel Ericsoussi, MD

29. Small Subcentimeter Pulmonary Nodules(<8 mm) For patients with no risk factors for lung cancer: Nodules < 4 mm No further follow up Nodules 4-6 mm Reevaluate with a chest CT at 12 months No further follow-up if unchanged at 12 months Nodules 6-8 mm Reevaluate with a chest CT between 6-12 months and between 18-24 months 29 UIC Bassel Ericsoussi, MD

30. Small Subcentimeter Pulmonary Nodules(<8 mm) For patients with risk factors for lung cancer: Nodules < 4 mm Reevaluate with a chest CT at 12 months Nodules 4-6 mm Reevaluate with a chest CT between 6-12 months and between 18-24 months Nodules 6-8 mm Reevaluate with a chest CT between 3-6, between 9-12 months, and between 18-24 months 30 UIC Bassel Ericsoussi, MD

31. Summary SPN is a common problem and can present a diagnostic dilemma Best strategy is determined on assessment of the risk of cancer in an individual patient Determine patient’s risk of malignancy Low risk: serial chest CTs High risk: surgical resection Indeterminate risk: consider PET scan, diagnostic sampling, or surgical resection Discuss risks and benefits of various strategies and elicit patient’s preferences 31 UIC Bassel Ericsoussi, MD

32. Clinical Scenario: Low Clinical Pre-Test Probability of Malignancy A 44 Y.O. man with history of HTN Had a fall and developed chest pain A chest CT was done and showed a 5 mm nodule in the LUL Patient has never smoked Analysis of case: Likelihood of malignancy is very low Best strategy is observation with serial chest CTs 32 UIC Bassel Ericsoussi, MD

33. Clinical Scenario: High Clinical Pre-Test Probability of Malignancy A 64 Y.O. woman developed an episode of bronchitis RUL nodule was found incidentally on CXR A prior CXR a year ago showed no abnormalities 30 pack-year tobacco use, quit a year ago A chest CT showed a 1.3 cm spiculated pulmonary nodule 33 UIC Bassel Ericsoussi, MD

34. Clinical Scenario: High Clinical Pre-Test Probability of Malignancy Her physician ordered a PET scan which showed increased FDG uptake in the nodule He performed a bronchoscopy with BAL growing klebsiella and negative biopsy He decided to treat patient with antibiotics and to follow with serial chest CTs Analysis of the case: The likelihood of malignancy was very high (100% in the SPN calculator) Smoking history Age Growth of nodule Increased metabolic activity on PET scan Best course of action is surgical resection 34 UIC Bassel Ericsoussi, MD

35. Indeterminate Pre-Test Probability of Malignancy Obtain PET scan Consider management options: Radiographic observation if: Clinical probability is low (30-40%) and no activity on PET Sampling by bronchoscopy or TTNA if: Discordance between clinical pre-test probability and imaging tests (high suspicion but lesion is not active on PET) A benign diagnosis is suspected that requires specific treatment (fungal infection) A fully-informed patient desires proof of malignancy diagnosis prior to surgery Surgery is high risk 35 UIC Bassel Ericsoussi, MD

36. Rational for Staging Aid in planning treatment Indicate prognosis Assist in evaluating results of treatment Facilitate exchange of information between treatment centers Cancer research 36 UIC Bassel Ericsoussi, MD

37. STAGING OF LUNG CANCER HAS CHANGED AS OF JANUARY 1, 2010 37 UIC Bassel Ericsoussi, MD

39. Multiple discrepancies in published literature, particularly with T stage

40. Relatively small database from a single institution series

41. 2,155 patients from the MD Anderson Cancer Center in Houston, TX

42. Mainly surgical based38 UIC Bassel Ericsoussi, MD

43. 39 UIC Bassel Ericsoussi, MD

44. 40 UIC Bassel Ericsoussi, MD

45. International Association for the Study of Lung Cancer (IASLC) 100,869 cases from 45 sources in 20 countries 81,015 cases included in analyses 16% SCLC: 13290 84% NSCLC: 67,725 41 UIC Bassel Ericsoussi, MD

46. Treatment Modalities – 67,725 NSCLC 54% involved surgery Surgery 42% Surgery RT 5% Surgery Chemo 4% Tri-modality 3% RT 8% Chemo 15% Chemo RT 12% 42 UIC Bassel Ericsoussi, MD

47. Stage Groupings The major determinant is the overall survival, based on the best stage Pathologic, if available; otherwise clinical 43 UIC Bassel Ericsoussi, MD

48. Prognosis According to Size Category 44 UIC Bassel Ericsoussi, MD

49. Prognosis According to Additional Nodules, T4 Invasion, and Pleural Dissemination 45 UIC Bassel Ericsoussi, MD

51. T1: (T1a < 2 cm, T1b 2-3 cm) (used to be T1)

52. Not more proximal than the lobar bronchus

53. T2: (T2a 3-5, T2b 5-7 cm) (used to be T2) or

54. In the main bronchus > 2 cm distal to the carina

55. Invades visceral pleura

56. Atelectasis/obstructive pneumonia but not involving the entire lung

57. T3 > 7 cm or

58. Central location: In the main bronchus < 2 cm distal to the carina

59. Invasion: chest wall, diaphragm, phrenic nerve, mediastinal pleura, or parietal pericardium (used to be T4)

60. Atelectasis/obstructive pneumonitis of entire lung

61. Satellite nodules: separate tumor nodules in the same lobe (used to be T4)

62. T4 any size tumor

63. Invades heart, great vessels, trachea, carina, recurrent laryngeal nerve, esophagus, vertebral body

64. Separate tumor nodules in a different ipsilateral lobe (used to be M1)46 UIC Bassel Ericsoussi, MD

65. Special Situations TX: Status not able to be assessed Tis: Focus of in situ cancer T1ss: Superficial spreading tumor of any size but confined to the wall of the trachea or mainstem bronchus 47 UIC Bassel Ericsoussi, MD

66. Prognosis According to the N Category 48 UIC Bassel Ericsoussi, MD

69. The Effect of Skip Metastases Involvement of N2 node station with/without involvement of any N1 nodes have same survival 50 UIC Bassel Ericsoussi, MD

70. M Descriptor M0: No distant metastasis M1a: Separate tumor nodules in a contralateral lobe (used to be M1) Tumor with pleural nodules or malignant pleural dissemination (used to be T4) M1b: Distant metastasis (used to be M1) 51 UIC Bassel Ericsoussi, MD

71. Stage Groups According to TNM Descriptor and Subgroups 52 UIC Bassel Ericsoussi, MD

72. Overall Survival by Clinical Stage 53 UIC Bassel Ericsoussi, MD

73. Overall Survival by Pathologic Stage 54 UIC Bassel Ericsoussi, MD

74. 55 UIC Bassel Ericsoussi, MD

75. 56 UIC Bassel Ericsoussi, MD

76. 57 UIC Bassel Ericsoussi, MD

77. 58 UIC Bassel Ericsoussi, MD

78. 59 UIC Bassel Ericsoussi, MD

79. Lymph Node Map Update The International Association for the Study of Lung Cancer (IASLC) Lymph Node Map 2009 60 UIC Bassel Ericsoussi, MD

80. 61 UIC Bassel Ericsoussi, MD

82. Low cervical

83. Supraclavicular

84. Sternal notch

85. Upper border: lower margin of cricoid

86. Lower border: clavicles and upper border of manubrium

87. The midline of the trachea serves as border between 1R and 1L 62 UIC Bassel Ericsoussi, MD

88. 63 UIC Bassel Ericsoussi, MD

89. Upper Paratracheal(stations 2R/2L) 2R. Right Upper ParatrachealUpper border: upper border of manubriumLower border: intersection of the innominate (left brachiocephalic) vein with the trachea 2L. Left Upper ParatrachealUpper border: upper border of manubriumLower border: superior border of aortic arch 2R nodes extend to the left lateral border of the trachea 64 UIC Bassel Ericsoussi, MD

90. Prevascular and Prevertabral nodes(Stations 3A/3P) 3A anterior to the vessels 3P posterior to the esophagus, which lies prevertebrally 3A not accessible with mediastinoscopy 3P accessible with EUS 65 UIC Bassel Ericsoussi, MD

92. Prevascular 3A (not accessible with mediastinoscopy)66 UIC Bassel Ericsoussi, MD

93. Prevascular 3A node (not accessible with mediastinoscopy) Lower paratracheal 4R nodes 67 UIC Bassel Ericsoussi, MD

94. Right Lower Paratracheal(Station 4R) 4R. Right Lower ParatrachealUpper border: intersection of the innominate (left brachiocephalic) vein with the tracheaLower border: lower border of azygos vein 4R nodes extend to the left lateral border of the trachea 68 UIC Bassel Ericsoussi, MD

96. Station 6 node: aortic node lateral to the aortic arch 69 UIC Bassel Ericsoussi, MD

97. Left Lower Paratracheal(Station 4L) Located left of the left tracheal border, medially to the ligamentum arteriosum Station 5 (AP-window) nodes are located laterally to the ligamentum arteriosum 70 UIC Bassel Ericsoussi, MD

98. Just above the level of the pulmonary trunk 4R/4L lower paratracheal nodes Station 3 node Station 5 (AP window) nodes. 71 UIC Bassel Ericsoussi, MD

99. At the level of the lower trachea just above the carina 4L nodes are between the pulmonary trunk and the aorta, but are not located in the AP-window, because they lie medially to the ligamentum arteriosum The node lateral to the pulmonary trunk is a station 5 72 UIC Bassel Ericsoussi, MD

100. 73 UIC Bassel Ericsoussi, MD

102. 75 UIC Bassel Ericsoussi, MD

104. On the right they extend to the lower border of the bronchus intermedius

105. On the left they extend to the upper border of the lower lobe bronchus76 UIC Bassel Ericsoussi, MD

106. Station 7 subcarinal node to the right of the esophagus 77 UIC Bassel Ericsoussi, MD

107. Paraesophageal Nodes(Station 8) Below the subcarinal nodes and extend to the diaphragm 78 UIC Bassel Ericsoussi, MD

108. Station 8 node to the right of the esophagus 79 UIC Bassel Ericsoussi, MD

110. On the corresponding CT image the node is not enlarged

111. The probability that this is a lymph node metastasis is extremely high since the specificity of PET in unenlarged nodes is higher than in enlarged nodes80 UIC Bassel Ericsoussi, MD

112. Pulmonary Ligament Nodes(Station 9) The pulmonary ligament is the inferior extension of the mediastinal pleural reflections 81 UIC Bassel Ericsoussi, MD

113. 82 UIC Bassel Ericsoussi, MD

114. 83 UIC Bassel Ericsoussi, MD

116. On the right they extend from the lower rim of the azygos vein to the interlobar region

117. On the left they extend from the upper rim of the pulmonary artery to the interlobar regionNodes in station 10 - 14 are all N1-nodes, since they are not located in the mediastinum 84 UIC Bassel Ericsoussi, MD

118. 85 UIC Bassel Ericsoussi, MD

119. Conventional Mediastinoscopy 2R and 2L: right and left upper paratracheal nodes 4R and 4 L: right and left lower paratracheal nodes Station 7: subcarinal nodes (but not 7 posterior) Does not access : 1R and 1L: supraclavicular nodes 3A: prevascular nodes 5-6: Subaortic (AP window), para-aortic nodes 7 posterior 8: paraesophageal nodes 9: pulmonary ligaments nodes 86 UIC Bassel Ericsoussi, MD

120. Conventional Mediastinoscopy Necessary to confirm negative endoscopic biopsies Sensitivity 85.2% Specificity 100% Morbidity 2% Mortality 0.08% Complications Death - Pneumothorax Esophageal perforation - Hypotension Pulmonary artery laceration - IV fluid extravasation Excessive bleeding - Arrhythmia Hammoud et al. J Thoracic Cardiovasc Surg. 1999; 118:894-9 87 UIC Bassel Ericsoussi, MD

122. Mortality < 1%88 UIC Bassel Ericsoussi, MD

124. Station 8: paraesophageal

125. Station 9: Pulmonary ligament

126. 3P: prevertebral

127. Left adrenal gland

128. Left liver lobe89 UIC Bassel Ericsoussi, MD

129. Endobronchial Ultrasound Transbronchial Needle AspirationEBUS-TBNA 90 UIC Bassel Ericsoussi, MD