1. The Solitary Pulmonary Nodule Suneel S. Kumar MD

2. The Solitary Pulmonary Nodule “Coin lesion” “Coin lesion” Defined as < 3 cm Defined as < 3 cm Completely surrounded by lung parenchyma Completely surrounded by lung parenchyma Lesions > 3 cm called “masses” and often malignant Lesions > 3 cm called “masses” and often malignant “Coin lesion” “Coin lesion” Defined as < 3 cm Defined as < 3 cm Completely surrounded by lung parenchyma Completely surrounded by lung parenchyma Lesions > 3 cm called “masses” and often malignant Lesions > 3 cm called “masses” and often malignant

3. The Solitary Pulmonary Nodule Incidence of cancer from 10 – 70% Incidence of cancer from 10 – 70% Found on 0.09 to 0.20 % of all CXRs (approximately 1 in 500) Found on 0.09 to 0.20 % of all CXRs (approximately 1 in 500) 90% incidental findings 90% incidental findings 150,000 SPNs found annually 150,000 SPNs found annually Increased with incidental findings on CT Increased with incidental findings on CT Incidence of cancer from 10 – 70% Incidence of cancer from 10 – 70% Found on 0.09 to 0.20 % of all CXRs (approximately 1 in 500) Found on 0.09 to 0.20 % of all CXRs (approximately 1 in 500) 90% incidental findings 90% incidental findings 150,000 SPNs found annually 150,000 SPNs found annually Increased with incidental findings on CT Increased with incidental findings on CT

4. The Solitary Pulmonary Nodule Patients with best prognosis are stage IA (T 1 N 0 M 0 ) Patients with best prognosis are stage IA (T 1 N 0 M 0 ) 61 – 75% 5-year survival following surgical resection 61 – 75% 5-year survival following surgical resection Approximately half of all lung cancers have extrapulmonary spread by time of diagnosis Approximately half of all lung cancers have extrapulmonary spread by time of diagnosis 5-year survival 10 – 15% 5-year survival 10 – 15% Patients with best prognosis are stage IA (T 1 N 0 M 0 ) Patients with best prognosis are stage IA (T 1 N 0 M 0 ) 61 – 75% 5-year survival following surgical resection 61 – 75% 5-year survival following surgical resection Approximately half of all lung cancers have extrapulmonary spread by time of diagnosis Approximately half of all lung cancers have extrapulmonary spread by time of diagnosis 5-year survival 10 – 15% 5-year survival 10 – 15%

5. The Solitary Pulmonary Nodule Most SPNs are benign Most SPNs are benign Primary malignancy found in about 35% Primary malignancy found in about 35% Solitary metastases may account for 23% Solitary metastases may account for 23% Most SPNs are benign Most SPNs are benign Primary malignancy found in about 35% Primary malignancy found in about 35% Solitary metastases may account for 23% Solitary metastases may account for 23%

6. Differential Diagnosis Neoplasm Neoplasm Infection Infection Inflammation Inflammation Vascular lesion Vascular lesion Post-traumatic Post-traumatic Congenital Congenital Lung cyst Lung cyst Pulmonary infarct Pulmonary infarct Amyloidosis Amyloidosis Neoplasm Neoplasm Infection Infection Inflammation Inflammation Vascular lesion Vascular lesion Post-traumatic Post-traumatic Congenital Congenital Lung cyst Lung cyst Pulmonary infarct Pulmonary infarct Amyloidosis Amyloidosis Rheumatoid nodules Rheumatoid nodules Intrapulmonary lymph nodes Intrapulmonary lymph nodes Plasma cell granulomas Plasma cell granulomas Sarcoidosis Sarcoidosis Mucoid impaction Mucoid impaction Hematoma Hematoma Nipple shadow Nipple shadow Rheumatoid nodules Rheumatoid nodules Intrapulmonary lymph nodes Intrapulmonary lymph nodes Plasma cell granulomas Plasma cell granulomas Sarcoidosis Sarcoidosis Mucoid impaction Mucoid impaction Hematoma Hematoma Nipple shadow Nipple shadow

7. The Solitary Pulmonary Nodule Since the SPN by definition is a radiographic finding, radiological imaging is intrinsic to the diagnostic workup Since the SPN by definition is a radiographic finding, radiological imaging is intrinsic to the diagnostic workup

8. RadiologyRadiology Failure to recognize lung cancer on CXR is one of most frequent causes of missed diagnosis in radiology Failure to recognize lung cancer on CXR is one of most frequent causes of missed diagnosis in radiology Rate of failure to diagnose ranges from 25 – 90% in different studies with different designs Rate of failure to diagnose ranges from 25 – 90% in different studies with different designs Error rate of 20 – 50% for radiological detection of lung cancer is generally accepted* Error rate of 20 – 50% for radiological detection of lung cancer is generally accepted* Failure to recognize lung cancer on CXR is one of most frequent causes of missed diagnosis in radiology Failure to recognize lung cancer on CXR is one of most frequent causes of missed diagnosis in radiology Rate of failure to diagnose ranges from 25 – 90% in different studies with different designs Rate of failure to diagnose ranges from 25 – 90% in different studies with different designs Error rate of 20 – 50% for radiological detection of lung cancer is generally accepted* Error rate of 20 – 50% for radiological detection of lung cancer is generally accepted* *Guiss, Cancer 1960;13:91-5

9. RadiologyRadiology Study looked back at CXRs in 259 patients with proven NSCLC* Study looked back at CXRs in 259 patients with proven NSCLC* Found 19% incidence of missed diagnosis Found 19% incidence of missed diagnosis Those missed had significantly smaller nodules (median diameter 16 mm), more superimposing structures, and more indistinct borders Those missed had significantly smaller nodules (median diameter 16 mm), more superimposing structures, and more indistinct borders Study looked back at CXRs in 259 patients with proven NSCLC* Study looked back at CXRs in 259 patients with proven NSCLC* Found 19% incidence of missed diagnosis Found 19% incidence of missed diagnosis Those missed had significantly smaller nodules (median diameter 16 mm), more superimposing structures, and more indistinct borders Those missed had significantly smaller nodules (median diameter 16 mm), more superimposing structures, and more indistinct borders *Quekel, Chest 1999;115:720-32

10. RadiologyRadiology Time of delay in diagnosis was significant at 472 vs 29 days Time of delay in diagnosis was significant at 472 vs 29 days Resulted in 43% of lesions being upstaged from T 1 to T 2 during the delay period* Resulted in 43% of lesions being upstaged from T 1 to T 2 during the delay period* Time of delay in diagnosis was significant at 472 vs 29 days Time of delay in diagnosis was significant at 472 vs 29 days Resulted in 43% of lesions being upstaged from T 1 to T 2 during the delay period* Resulted in 43% of lesions being upstaged from T 1 to T 2 during the delay period* *Quekel, Chest 1999;115:720-32

11. Patterns of Margins Corona radiata sign Corona radiata sign Fine linear strands extending 4-5 mm outward Fine linear strands extending 4-5 mm outward Spiculated on CXRs Spiculated on CXRs 84 – 90% are malignant 84 – 90% are malignant Corona radiata sign Corona radiata sign Fine linear strands extending 4-5 mm outward Fine linear strands extending 4-5 mm outward Spiculated on CXRs Spiculated on CXRs 84 – 90% are malignant 84 – 90% are malignant

12. Patterns of Margins

13. Spiculated lipoid pneumonia

14. Patterns of Margins Scalloped border Scalloped border Intermediate probability of cancer Intermediate probability of cancer Smooth border suggestive of benign diagnosis Smooth border suggestive of benign diagnosis Scalloped border Scalloped border Intermediate probability of cancer Intermediate probability of cancer Smooth border suggestive of benign diagnosis Smooth border suggestive of benign diagnosis

15. Other Characteristics Air bronchograms and pseudocavitation more commonly malignant Air bronchograms and pseudocavitation more commonly malignant Cavitation with thick (>15 mm vs 15 mm vs < 5 mm) more often maligant Air bronchograms and pseudocavitation more commonly malignant Air bronchograms and pseudocavitation more commonly malignant Cavitation with thick (>15 mm vs 15 mm vs < 5 mm) more often maligant

16. Air Bronchograms

17. CalcificationCalcification Suggests benign diagnosis Suggests benign diagnosis With CT the reference standard, CXR has sensitivity 50%, specificity 87%, and PPV 93% for identifying calcification With CT the reference standard, CXR has sensitivity 50%, specificity 87%, and PPV 93% for identifying calcification Suggests benign diagnosis Suggests benign diagnosis With CT the reference standard, CXR has sensitivity 50%, specificity 87%, and PPV 93% for identifying calcification With CT the reference standard, CXR has sensitivity 50%, specificity 87%, and PPV 93% for identifying calcification

18. CalcificationCalcification Laminated or central pattern typical of granuloma Laminated or central pattern typical of granuloma

19. HistoplasmomaHistoplasmoma

20. Popcorn Calcification Classic “popcorn” pattern often seen in hamartomas Classic “popcorn” pattern often seen in hamartomas HRCT can show fat and cartilage in half of cases HRCT can show fat and cartilage in half of cases Classic “popcorn” pattern often seen in hamartomas Classic “popcorn” pattern often seen in hamartomas HRCT can show fat and cartilage in half of cases HRCT can show fat and cartilage in half of cases

21. HamartomaHamartoma

22. CalcificationCalcification Stippled or eccentric patterns Stippled or eccentric patterns Have been associated with cancer Have been associated with cancer Stippled or eccentric patterns Stippled or eccentric patterns Have been associated with cancer Have been associated with cancer

23. CalcificationCalcification

24. Rounded Atelectasis

26. Growth Rate Volume-doubling time for malignant bronchogenic tumors rarely 1 year Volume-doubling time for malignant bronchogenic tumors rarely 1 year If considered spherical, 30% increase in diameter represents a doubling of volume If considered spherical, 30% increase in diameter represents a doubling of volume Volume-doubling time for malignant bronchogenic tumors rarely 1 year Volume-doubling time for malignant bronchogenic tumors rarely 1 year If considered spherical, 30% increase in diameter represents a doubling of volume If considered spherical, 30% increase in diameter represents a doubling of volume

27. Growth Rate Traditionally, stability of SPN on CXR for 2 years suggested benign disease Traditionally, stability of SPN on CXR for 2 years suggested benign disease Bronchoalveolar cell carcinoma and typical carcinoids occasionally appear stable for more than 2 years Bronchoalveolar cell carcinoma and typical carcinoids occasionally appear stable for more than 2 years Hamartomas often grow over time Hamartomas often grow over time Initial studies were retrospective and reviewed only cases which were resected Initial studies were retrospective and reviewed only cases which were resected Traditionally, stability of SPN on CXR for 2 years suggested benign disease Traditionally, stability of SPN on CXR for 2 years suggested benign disease Bronchoalveolar cell carcinoma and typical carcinoids occasionally appear stable for more than 2 years Bronchoalveolar cell carcinoma and typical carcinoids occasionally appear stable for more than 2 years Hamartomas often grow over time Hamartomas often grow over time Initial studies were retrospective and reviewed only cases which were resected Initial studies were retrospective and reviewed only cases which were resected

28. Growth Rate One study examined 156 solitary lesions 1 – 14 cm in size One study examined 156 solitary lesions 1 – 14 cm in size Previous CXR in 74 Previous CXR in 74 Previously documented no growth in 26 Previously documented no growth in 26 9 of these were malignant* 9 of these were malignant* Absence of growth over 2 years on CXR has predictive value of 65% for benign lesions Absence of growth over 2 years on CXR has predictive value of 65% for benign lesions One study examined 156 solitary lesions 1 – 14 cm in size One study examined 156 solitary lesions 1 – 14 cm in size Previous CXR in 74 Previous CXR in 74 Previously documented no growth in 26 Previously documented no growth in 26 9 of these were malignant* 9 of these were malignant* Absence of growth over 2 years on CXR has predictive value of 65% for benign lesions Absence of growth over 2 years on CXR has predictive value of 65% for benign lesions *Yankelevitz, Am J Roentgenol 1997;168:325-8

29. Growth Rate Use of stability predicated on accurate measurement of growth Use of stability predicated on accurate measurement of growth Thus, it is dependent on resolution of imaging technique Thus, it is dependent on resolution of imaging technique Thin-section high-resolution CT has better estimation of nodule size and growth characteristics Thin-section high-resolution CT has better estimation of nodule size and growth characteristics Use of stability predicated on accurate measurement of growth Use of stability predicated on accurate measurement of growth Thus, it is dependent on resolution of imaging technique Thus, it is dependent on resolution of imaging technique Thin-section high-resolution CT has better estimation of nodule size and growth characteristics Thin-section high-resolution CT has better estimation of nodule size and growth characteristics

30. Growth Rate Limit of detectable changes on CXR estimated to be 3 – 5 mm Limit of detectable changes on CXR estimated to be 3 – 5 mm CT has resolution of 0.3 mm CT has resolution of 0.3 mm Reasonable to use two-year stability on CT as a practical guideline Reasonable to use two-year stability on CT as a practical guideline Limit of detectable changes on CXR estimated to be 3 – 5 mm Limit of detectable changes on CXR estimated to be 3 – 5 mm CT has resolution of 0.3 mm CT has resolution of 0.3 mm Reasonable to use two-year stability on CT as a practical guideline Reasonable to use two-year stability on CT as a practical guideline

31. Follow-UpFollow-Up Optimal time not known Optimal time not known Traditionally follow every three months for first year, then six months the second year Traditionally follow every three months for first year, then six months the second year Provided CT is used Provided CT is used Optimal time not known Optimal time not known Traditionally follow every three months for first year, then six months the second year Traditionally follow every three months for first year, then six months the second year Provided CT is used Provided CT is used

32. Nonsurgical Approaches CT Densitometry CT Densitometry Contrast-enhanced CT Contrast-enhanced CT Bronchoscopy Bronchoscopy Transthoracic fine needle aspiration biopsy Transthoracic fine needle aspiration biopsy Positron emission tomography Positron emission tomography CT Densitometry CT Densitometry Contrast-enhanced CT Contrast-enhanced CT Bronchoscopy Bronchoscopy Transthoracic fine needle aspiration biopsy Transthoracic fine needle aspiration biopsy Positron emission tomography Positron emission tomography

33. CT Densitometry Involves measurement of attenuation values Involves measurement of attenuation values Expressed in Hounsfield units, as compared to reference “phantom” Expressed in Hounsfield units, as compared to reference “phantom” Usually higher for benign nodules Usually higher for benign nodules Allows for identification of 35 – 55% of subsequently identified benign lesions Allows for identification of 35 – 55% of subsequently identified benign lesions Involves measurement of attenuation values Involves measurement of attenuation values Expressed in Hounsfield units, as compared to reference “phantom” Expressed in Hounsfield units, as compared to reference “phantom” Usually higher for benign nodules Usually higher for benign nodules Allows for identification of 35 – 55% of subsequently identified benign lesions Allows for identification of 35 – 55% of subsequently identified benign lesions

34. CT Densitometry One large, multicenter trial, only 1 of 66 nodules identified as benign later found to be malignant* One large, multicenter trial, only 1 of 66 nodules identified as benign later found to be malignant* Cutoff used was 264 Hounsfield units Cutoff used was 264 Hounsfield units More conventional cutoff is 185, which yielded a higher false negative rate More conventional cutoff is 185, which yielded a higher false negative rate One large, multicenter trial, only 1 of 66 nodules identified as benign later found to be malignant* One large, multicenter trial, only 1 of 66 nodules identified as benign later found to be malignant* Cutoff used was 264 Hounsfield units Cutoff used was 264 Hounsfield units More conventional cutoff is 185, which yielded a higher false negative rate More conventional cutoff is 185, which yielded a higher false negative rate *Zerhouni, Radiology 1986;160:319-27

35. Contrast-Enhanced CT Degree on enhancement on spiral CT after injection of contrast Degree on enhancement on spiral CT after injection of contrast One study used an increase in attenuation of 20 Hounsfield units as threshold for malignant lesions One study used an increase in attenuation of 20 Hounsfield units as threshold for malignant lesions Sensitivity 95-100%, specificity 70-93%* Sensitivity 95-100%, specificity 70-93%* Awaits further validation Awaits further validation Local expertise varies, and not widely used Local expertise varies, and not widely used Degree on enhancement on spiral CT after injection of contrast Degree on enhancement on spiral CT after injection of contrast One study used an increase in attenuation of 20 Hounsfield units as threshold for malignant lesions One study used an increase in attenuation of 20 Hounsfield units as threshold for malignant lesions Sensitivity 95-100%, specificity 70-93%* Sensitivity 95-100%, specificity 70-93%* Awaits further validation Awaits further validation Local expertise varies, and not widely used Local expertise varies, and not widely used *Zhang, Radiology 1997;205:471-8

36. BronchoscopyBronchoscopy Useful for lesions at least 2 cm Useful for lesions at least 2 cm Diagnostic yield varies in literature from 20 – 80%, depending on size of nodule and patient population Diagnostic yield varies in literature from 20 – 80%, depending on size of nodule and patient population Yield depends on nodule size and proximity to bronchial tree Yield depends on nodule size and proximity to bronchial tree Useful for lesions at least 2 cm Useful for lesions at least 2 cm Diagnostic yield varies in literature from 20 – 80%, depending on size of nodule and patient population Diagnostic yield varies in literature from 20 – 80%, depending on size of nodule and patient population Yield depends on nodule size and proximity to bronchial tree Yield depends on nodule size and proximity to bronchial tree

37. BronchoscopyBronchoscopy Yield 10% for 2 – 3 cm Yield 10% for 2 – 3 cm 70% yield when CT reveals a bronchus leading to lesion 70% yield when CT reveals a bronchus leading to lesion Yield 10% for 2 – 3 cm Yield 10% for 2 – 3 cm 70% yield when CT reveals a bronchus leading to lesion 70% yield when CT reveals a bronchus leading to lesion

38. BronchoscopyBronchoscopy Relatively low risk Relatively low risk Overall complication rate 5% Overall complication rate 5% 3% risk of pneumothorax 3% risk of pneumothorax 1% risk of hemorrhage 1% risk of hemorrhage 0.24% risk of death 0.24% risk of death Relatively low risk Relatively low risk Overall complication rate 5% Overall complication rate 5% 3% risk of pneumothorax 3% risk of pneumothorax 1% risk of hemorrhage 1% risk of hemorrhage 0.24% risk of death 0.24% risk of death

39. Transthoracic FNA Diagnostic yield up to 95% in peripheral lesions Diagnostic yield up to 95% in peripheral lesions Higher complication rate Higher complication rate 30% pneumothorax 30% pneumothorax About 5% of these require chest tube About 5% of these require chest tube Diagnostic yield up to 95% in peripheral lesions Diagnostic yield up to 95% in peripheral lesions Higher complication rate Higher complication rate 30% pneumothorax 30% pneumothorax About 5% of these require chest tube About 5% of these require chest tube

40. Positron Emission Tomography Uptake of 18-flurodeoxyglucose used to measure glucose metabolism Uptake of 18-flurodeoxyglucose used to measure glucose metabolism Taken up by cells in glycolysis but is bound within cells and cannot enter normal glycolytic pathway Taken up by cells in glycolysis but is bound within cells and cannot enter normal glycolytic pathway Most tumors have greater uptake of FDG than normal tissue Most tumors have greater uptake of FDG than normal tissue Due to increased metabolic activity Due to increased metabolic activity Uptake of 18-flurodeoxyglucose used to measure glucose metabolism Uptake of 18-flurodeoxyglucose used to measure glucose metabolism Taken up by cells in glycolysis but is bound within cells and cannot enter normal glycolytic pathway Taken up by cells in glycolysis but is bound within cells and cannot enter normal glycolytic pathway Most tumors have greater uptake of FDG than normal tissue Most tumors have greater uptake of FDG than normal tissue Due to increased metabolic activity Due to increased metabolic activity

41. Positron Emission Tomography Sensitivity for identifying a malignancy is 96.8% and specificity 77.8%* Sensitivity for identifying a malignancy is 96.8% and specificity 77.8%* False negatives can occur False negatives can occur Notable in association with bronchoalveolar carcinoma, carcinoids, and tumors < 1 cm in diameter Notable in association with bronchoalveolar carcinoma, carcinoids, and tumors < 1 cm in diameter Sensitivity for identifying a malignancy is 96.8% and specificity 77.8%* Sensitivity for identifying a malignancy is 96.8% and specificity 77.8%* False negatives can occur False negatives can occur Notable in association with bronchoalveolar carcinoma, carcinoids, and tumors < 1 cm in diameter Notable in association with bronchoalveolar carcinoma, carcinoids, and tumors < 1 cm in diameter *Gould, JAMA 2001;285:914-24

42. Positron Emission Tomography For 450 nodules reviewed in a meta- analysis, mean sensitivity was 93.9% and specificity 85.8% For 450 nodules reviewed in a meta- analysis, mean sensitivity was 93.9% and specificity 85.8% Median sensitivity 98% and specificity 83.3%* Median sensitivity 98% and specificity 83.3%* For 450 nodules reviewed in a meta- analysis, mean sensitivity was 93.9% and specificity 85.8% For 450 nodules reviewed in a meta- analysis, mean sensitivity was 93.9% and specificity 85.8% Median sensitivity 98% and specificity 83.3%* Median sensitivity 98% and specificity 83.3%* *Gould, JAMA 2001;285:914-24

43. Gould, JAMA 2001;285:914-24

45. *Gould, JAMA 2001;285:914-24

46. Positron Emission Tomography For diagnosis of benign nodules, sensitivity 96% and specificity 88% with 94% accuracy For diagnosis of benign nodules, sensitivity 96% and specificity 88% with 94% accuracy False positives usually in association with infectious or inflammatory processes False positives usually in association with infectious or inflammatory processes For diagnosis of benign nodules, sensitivity 96% and specificity 88% with 94% accuracy For diagnosis of benign nodules, sensitivity 96% and specificity 88% with 94% accuracy False positives usually in association with infectious or inflammatory processes False positives usually in association with infectious or inflammatory processes

47. Positron Emission Tomography Resolution is currently 7 – 8 mm Resolution is currently 7 – 8 mm Imaging of nodules < 1 cm unreliable Imaging of nodules < 1 cm unreliable Resolution is currently 7 – 8 mm Resolution is currently 7 – 8 mm Imaging of nodules < 1 cm unreliable Imaging of nodules < 1 cm unreliable

48. Positron Emission Tomography May provide staging information May provide staging information Up to 14% of patients otherwise eligible for surgery have occult extra thoracic disease on whole-body PET Up to 14% of patients otherwise eligible for surgery have occult extra thoracic disease on whole-body PET May provide staging information May provide staging information Up to 14% of patients otherwise eligible for surgery have occult extra thoracic disease on whole-body PET Up to 14% of patients otherwise eligible for surgery have occult extra thoracic disease on whole-body PET

49. PET Images Pieterman, NEJM 2000;343:254-61

50. PET Images Pieterman, NEJM 2000;343:254-61

55. Integrated PET and CT Lardinos, NEJM 2003;348:2500-7

56. Integrated PET and CT Lardinos, NEJM 2003;348:2500-7

57. Positron Emission Tomography Decision-analysis model constructed to assess cost effectiveness showed strategy of CT combined with PET for staging was often superior to conventional approaches Decision-analysis model constructed to assess cost effectiveness showed strategy of CT combined with PET for staging was often superior to conventional approaches Reduced number of surgeries by 15% Reduced number of surgeries by 15% Estimated cost savings per patient ranged from $91 to $2,200 per patient* Estimated cost savings per patient ranged from $91 to $2,200 per patient* Decision-analysis model constructed to assess cost effectiveness showed strategy of CT combined with PET for staging was often superior to conventional approaches Decision-analysis model constructed to assess cost effectiveness showed strategy of CT combined with PET for staging was often superior to conventional approaches Reduced number of surgeries by 15% Reduced number of surgeries by 15% Estimated cost savings per patient ranged from $91 to $2,200 per patient* Estimated cost savings per patient ranged from $91 to $2,200 per patient* *Gambhir, J Clin Oncol 1998;16:2113-25

58. Positron Emission Tomography More expensive than other imaging modalities More expensive than other imaging modalities Medicare reimbursement of $1,912 compared to chest CT ($276) or transthoracic needle aspiration ($560)* Medicare reimbursement of $1,912 compared to chest CT ($276) or transthoracic needle aspiration ($560)* More expensive than other imaging modalities More expensive than other imaging modalities Medicare reimbursement of $1,912 compared to chest CT ($276) or transthoracic needle aspiration ($560)* Medicare reimbursement of $1,912 compared to chest CT ($276) or transthoracic needle aspiration ($560)* *http://cms.hhs.gov, Dec 2002

59. Positron Emission Tomography Question of using PET dependent on when clinical decision making will be changed by its findings Question of using PET dependent on when clinical decision making will be changed by its findings Low-risk patients (pretest probability of malignancy 20%) have posttest likelihood of malignancy with negative PET of 1%* Low-risk patients (pretest probability of malignancy 20%) have posttest likelihood of malignancy with negative PET of 1%* Would support observation in this population with serial CT scans Would support observation in this population with serial CT scans Question of using PET dependent on when clinical decision making will be changed by its findings Question of using PET dependent on when clinical decision making will be changed by its findings Low-risk patients (pretest probability of malignancy 20%) have posttest likelihood of malignancy with negative PET of 1%* Low-risk patients (pretest probability of malignancy 20%) have posttest likelihood of malignancy with negative PET of 1%* Would support observation in this population with serial CT scans Would support observation in this population with serial CT scans *Gould, JAMA 2001;285:914-24

60. Positron Emission Tomography High-risk patients (pretest probability of malignancy 80%) with negative PET still have 14% posttest likelihood of malignancy* High-risk patients (pretest probability of malignancy 80%) with negative PET still have 14% posttest likelihood of malignancy* Those with high risk of malignancy should have tissue diagnosis Those with high risk of malignancy should have tissue diagnosis High-risk patients (pretest probability of malignancy 80%) with negative PET still have 14% posttest likelihood of malignancy* High-risk patients (pretest probability of malignancy 80%) with negative PET still have 14% posttest likelihood of malignancy* Those with high risk of malignancy should have tissue diagnosis Those with high risk of malignancy should have tissue diagnosis *Gould, JAMA 2001;285:914-24

61. Positron Emission Tomography No indication for PET: No indication for PET: Negative lymph nodes on CT if operative intervention definitely planned or if it will otherwise not change management Negative lymph nodes on CT if operative intervention definitely planned or if it will otherwise not change management Known malignancy who has a questionable pulmonary metastasis vs primary lung cancer Known malignancy who has a questionable pulmonary metastasis vs primary lung cancer No indication for PET: No indication for PET: Negative lymph nodes on CT if operative intervention definitely planned or if it will otherwise not change management Negative lymph nodes on CT if operative intervention definitely planned or if it will otherwise not change management Known malignancy who has a questionable pulmonary metastasis vs primary lung cancer Known malignancy who has a questionable pulmonary metastasis vs primary lung cancer

62. Positron Emission Tomography Some gamma cameras can now have PET capability added to them Some gamma cameras can now have PET capability added to them Question if these modified gamma cameras have same ability to detect malignant processes as specific PET equipment Question if these modified gamma cameras have same ability to detect malignant processes as specific PET equipment Requires further study Requires further study Some gamma cameras can now have PET capability added to them Some gamma cameras can now have PET capability added to them Question if these modified gamma cameras have same ability to detect malignant processes as specific PET equipment Question if these modified gamma cameras have same ability to detect malignant processes as specific PET equipment Requires further study Requires further study

63. Diagnostic Strategy Pretest probability of cancer determines most cost-effective strategy Pretest probability of cancer determines most cost-effective strategy Low (< 12%): radiographic follow-up Low (< 12%): radiographic follow-up Intermediate (12 – 69%): CT and PET Intermediate (12 – 69%): CT and PET High (> 69 – 90%): CT followed by biopsy or surgery High (> 69 – 90%): CT followed by biopsy or surgery Very high (> 90%): surgery* Very high (> 90%): surgery* Pretest probability of cancer determines most cost-effective strategy Pretest probability of cancer determines most cost-effective strategy Low (< 12%): radiographic follow-up Low (< 12%): radiographic follow-up Intermediate (12 – 69%): CT and PET Intermediate (12 – 69%): CT and PET High (> 69 – 90%): CT followed by biopsy or surgery High (> 69 – 90%): CT followed by biopsy or surgery Very high (> 90%): surgery* Very high (> 90%): surgery* *Gambhir, J Clin Oncol 1998;16:2113-25

64. Diagnostic Strategy Ost, NEJM 2003;348:2535-42

65. Diagnostic Strategy Determining probability of cancer remains an inexact science Determining probability of cancer remains an inexact science Multivariate model incorporating age, cigarette-smoking status, history of cancer, diameter of nodule, presence of spiculation, and location of nodule proven similar to expert physician judgment in predicting cancer* Multivariate model incorporating age, cigarette-smoking status, history of cancer, diameter of nodule, presence of spiculation, and location of nodule proven similar to expert physician judgment in predicting cancer* Determining probability of cancer remains an inexact science Determining probability of cancer remains an inexact science Multivariate model incorporating age, cigarette-smoking status, history of cancer, diameter of nodule, presence of spiculation, and location of nodule proven similar to expert physician judgment in predicting cancer* Multivariate model incorporating age, cigarette-smoking status, history of cancer, diameter of nodule, presence of spiculation, and location of nodule proven similar to expert physician judgment in predicting cancer* *Swenson, Arch Intern Med 1997;157:849-55

66. Diagnostic Strategy Ost, NEJM 2003;348:2535-42