STAGING OF NON SMALL CELL LUNG CANCER. Slides are not to be reproduced without permission of the author

Transcription

1 STAGING OF NON SMALL CELL LUNG CANCER

2 Characteristics of a Clinically Useful Test Acceptable error rate - Sensitivity, specificity, accuracy Unique information - Patho-physiologic information different than other testing modalities Influences decision making - Management role Cost effective

3 PROGNOSIS SUV > 5 highly associated with poor survival * Pathologic stage 1 projected 5 year disease free Survival = 88% if SUV < 5; 17% if SUV > 5 Higher SUV s generally correlate with increased probability of metastases SUV superior to pathologic stage in predicting relapse in NSCLC * Higashi et al, J Nucl Med 2002; 43:39-45.

4 Lung Cancer Staging

5 HISTORY OF LUNG CA STAGING Developed by the Task force on Carcinoma of the Lung from the American Joint Committee for Cancer Staging (AJCC) in 1974 Classify disease according to extent and severity Define prognostic subgroups Provide a rational for treatment recommendations Facilitate exchange of information between different treatment centers

6 HISTORY OF LUNG CA STAGING Non Small Cell Lung Cancer Multiple revisions of TNM for Lung CA Most recent revision in 1997 Database of 5,319 patients with primary lung ca Rx at MD Anderson from or by the North American Lung Cancer Study Group from 1977 to 1982

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8 T = Primary Tumor Tx Tumor cannot be assessed (x=occult) T0 No evidence of primary tumor Tis Carcinoma in Situ (local, non-invasive)

9 T = Primary Tumor T1 < 3cm in greatest dimension and no proximal invasion T2 > 3cm or invading the pleura or involves the main bronchus > 2cm from carina or partial obstructive pneumonitis T3 Tumor of any size and extension into the chest wall, diaphragm, or mediastinum (or involves main bronchus < 2cm from carina or obstructive pneumonitis of entire lung) T4 Tumor of any size with invasion into mediastinal organs or vertebral Slides are not to body be reproduced without permission of the author

10 N = Lymph Node Nx Lymph nodes cannot be assessed N0 No nodal invasion N1 Nodes on ipsilateral side as tumor ipsilateral peribronchial or hilar

11 N = Lymph Node N2 Tumor spread to lymph nodes on ipsilateral mediastinum Subcarinal or ipsilateral mediastinal N3 Tumor spread to LN s on contralateral side of chest or LN s in neck on either side Contralateral mediastinal or supraclavicular or scalene

12 Nodal Stations

13 M = Distant Metastasis Mx Metastasis cannot be assessed M0 No metastatic extension M1 Disease has spread to distal organs

14 Staging TNM Integration* Occult TxN0M0 Stage 0 TisN0M0 Stage 1A T1N0M0 Stage 1B T2N0M0 Stage IIA T1N1M0 Stage IIB T2N1M0 T3N0M0 Stage IIIA T1N2M0 T2N2M0 T3N1/2M0 Stage IIIB AnyT N3 M0 T4 AnyN M0 Stage IV AnyT AnyN M1 *1997 TNM Classification (5 th edition)

15 Lung Cancer N2+; SUV 9.2 What is the Stage?

16 Stage III-A (B)

17 Lung Cancer; SUV 8.8 What is the Stage?

18 Stage IV

19 Lung Cancer N1+, N2+;SUV 12.4 What is the Stage?

20 Stage III-B

21 CT = N1-, N2-, PET = N1 +, N2 +; SUV 6.8 What is the Stage?

22 Stage III-A (Right Shoulder/ Upper Arm = Trauma)

23 Lung Cancer SUV 11.6 What is the Stage?

24 Stage IV (Bone Mets)

25 SUV 8.2 What is the pathologic staging?

26 Stage 0 Tuberculosis

27 What is the pathologic staging?

28 Stage 1A Primary Lung CA with non caseating granulomas in multiple lymph nodes

29 PET Imaging in NSCLC N Stage Sensitivity Specificity Accuracy PET 85% 94% 92% CT 65% 75% 70% McNemar Test p<0.01 Northern California PET Imaging Center

30 FDG PET of Mediastinum: Sensitivity: 85% Specificity: 86% Accuracy: 85% CT of Mediastinum Sensitivity: 62% Specificity: 43% Accuracy: 52% PET significantly more accurate than CT p<.03 University of Michigan, Wahl et al

31 PET and CT Staging in NSCLC Gould et al Ann Intern Med, 2003

32 PET and CT Staging in NSCLC Slides are not to be reproduced without permission of Gould the authoret al Ann Intern Med, 2003

33 Bx Proven Lymph Node Metastases

34 Lymph Nodes (-) for Tumor

35 CSMC RESULTS (N1, N2 nodes) VISUAL INTERPRETATION Error Rate for FDG-PET for N1, N2 nodes* SENS SPEC PPV NPV Accuracy PET 87% 72% 71% 88% 79% Includes all patients with malignant pulmonary nodule/mass N = 296

36 False-Negative N1, N2 Nodes 17 False-Negative N1 or N2 Nodes 6 = Large central mass 6 = Micromet or single node 1 = Carcinoid (atypical) 1 = Well-differentiated adenocarcinoma 3 = unexplained

37 CENTRAL LESIONS 7 Central lesions - 6 False Negatives - 1 True Positive with distinct N2 focus

38 RESULTS (excluding central lesions) VISUAL INTERPRETATION Error Rate for FDG-PET for N1, N2 nodes* SENS SPEC PPV NPV Accuracy PET (w) 87% 72% 71% 88% 79% PET (w/o) 91% 72% 71% 92% 80% * Includes all patients with malignant pulmonary nodule/mass

39 FDG-PET Issues Criteria for a positive or negative N1 or N2 node by FDG-PET study needs a more rigorous definition than visual observation Any visual detection of focal abnormality above background interpreted as a Tp results in a relatively low specificity. FDG-PET sensitivity for N1, N2 nodes appears limited by tumor burden and tumor location (central tumor as well as micrometastases and single node limited involvement).

40 FDG-PET Issues (cont) Positive mediastinal nodes on FDG-PET and enlarged nodes on CT have a high likelihood for metastases. Negative mediastinal nodes on FDG-PET and normal nodes on CT have a low likelihood for metastases.

41 Does PET Staging Alter Patient Management in Lung Cancer? Mediastinoscopy versus thoracotomy Neoadjuvant therapy Radiation Therapy

42 Impact on Patient Management PET important in determining candidates for mediastinoscopy or thoracotomy. Because of the relative high false-positive rate, mediastinoscopy is advised prior to definitive therapy. A negative CT of the mediastinum alone is not an indication for thoracotomy. Enlarged mediastinal lymph nodes on CT and a negative PET strongly indicates benign disease.

43 Neoadjuvant Therapy Has been shown to improve survival rates by 3-5 % in Stage II-B, III-A, and III-B. Often combined with radiation therapy. Surgery after chemotherapy if PET and CT are favorable.

44 Impact of Image Fusion Fusion of anatomic and functional imaging rapidly increasing Problem solving (mediastinal/ Hilar foci) Aortic inflammation/ plaque Esophageal inflammation Degenerative / traumatic spine lesions Hiatal Hernia / Anatomic deformity Better definition of lymph node levels (localization) Radiation Therapy Planning

45 The Potential Role of PET in Radiation Therapy Planning

46 Fusion Imaging In Lung Cancer Anatomic localization for diagnosis Anatomic localization for Radiation Therapy Planning (RTP)

47 FUSION IMAGING IN RADIATION THERAPY PLANNING (RTP) Contouring by anatomy Contouring by function Combination contouring

48 Case Study: Lung Cancer PET images 12 slices add 4 overlap

49 Radiation Therapy Planning : Lung Cancer (PET/RTP - CT)

50 Staging : Future Directions Quantitation of mediastinal foci Respiratory Gating Elastic transformation

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53 Exam Time This is for your CME Credits Each case represents a typical clinical problem Any case you fail may result in patient injury or death You may also lose your CME status and/or loss of medical privileges Your scores will be kept confidential since you are the only one keeping score

54 HISTORY 79 year old female Smoker with 41 pack year history Routine CXR demonstrated a nodule in the right anterior chest Primary mass and 2 subcarinal LNs were positive for NSCLC

55 PET Scan FC

56 Primary on CT FC

57 Primary on CT FC

58 Primary on CT FC

59 Nodes on CT FC

60 Nodes on CT FC

61 Nodes on CT FC

62 Nodes on CT FC

63 Images aligned FC

64 Triangulated FC

65 Images Fused What is the stage? What is the lymph node station involvement? FC

66 Stage III-A Lymph node stations 4, 7 FC

67 HISTORY 71 year old male Patient presents to the ER with minimal chest discomfort, progressive dyspnea, and a massive left pleural effusion Left pleura demonstrated infiltration by poorly differentiated adenocarcinoma, consistent with a lung primary

68 PET Scan JC

69 CT scan JC

70 CT scan JC

71 CT scan JC

72 CT scan JC

73 Images aligned JC

74 Triangulated What is the Stage? What lymph node stations are involved? JC

75 Stage III-B T4, N0, M0 (Malignant Pleural Effusion) Lymph node stations = 0 JC

76 HISTORY 70 year old male Diagnosed with lung ca in 1983 resected from the RUL Now presents with pain in the right thorax Pathology results confirm poorly differentiated squamous cell ca; no nodes sampled

77 PET Scan BS

78 CT scan BS

79 CT scan BS

80 CT scan BS

81 PET Scan BS

82 CT scan BS

83 Images Aligned BS

84 Triangulated BS

85 What is the Stage? What lymph node stations are involved? BS

86 Stage III-B T3, N3, M0 Chest Wall (R) Lymph node station = 4 (L) BS

87 HISTORY 74 year old female Initially admitted to the ER due to a fall at home; CXR revealed RUL lung opacity Patient noted recent onset shortness of breath Pathology confirms moderately to well differentiated squamous cell ca; negative LNs

88 PET Scan MM

89 CT scan MM

90 CT scan MM

91 CT scan MM

92 CT scan MM

93 CT scan MM

94 Images Aligned MM

95 Images Triangulated MM

96 What is the Stage? What lymph node stations are involved? MM

97 Stage III-A Lymph node station= 7 MM

98 HISTORY 48 year old female Presents with a cough lasting for over one month Abnormal CXR, CT demonstrates a L peribronchial mass, mediastinum negative

99 PET Scan CT

100 CT Scan CT

101 CT Scan CT

102 CT Scan CT

103 CT Scan CT

104 Images Aligned CT

105 What is the Stage? What lymph node stations are involved? MM CT

106 Stage III-A Lymph node station = 5 (AP Window) MM CT

107 FDG-PET in Lung Cancer Staging SUMMARY More accurate than Cross-Sectional Imaging Clinically acceptable error rates Important in selecting patients for mediastinoscopy or thoracotomy Fusion imaging emerging as a clinically useful modality for problem solving and localization of lymph node stations Combined PET/CT now being incorporated into RTP