The Role of PET in Lung Cancer Screening

Transcription

1 The Role of PET in Lung Cancer Screening Michael M. Graham, PhD, MD University of Iowa October 3, 2015

2 Conflict of Interest None FDA Statement No unapproved agents are discussed

3 The Role of PET in Lung Cancer Diagnosis Screening (with or without prior CT) Evaluation of Solitary Lung Nodule Staging Response to therapy Surveillance

4 Kojima S, et al. Cancer screening of healthy volunteers using whole-body 18 F-FDG-PET scans: The Nishidai clinic study. Eur J Cancer. 2007;43:1842. Total N = 4881 Mean age = % current or former smoker

5 Kojima S, et al. Cancer screening of healthy volunteers using whole-body 18 F-FDG-PET scans: The Nishidai clinic study. Eur J Cancer. 2007;43:1842. Total N = 4881 Positive Yield 11.4% 0.7% PPV = 38.7% PPV = 6.86% NPV = 99.67%

6 Minamimoto R, et al. The current status of an FDG-PET cancer screening program in Japan, based on a 4-year ( ) nationwide survey. Ann Nucl Med. 2013; 27: facilities; N= 155,456; Positive = 16,955 (11%) PPV = 11%; Detection yield = 1.2%

7 National Lung Screening Trial Research Team, Aberle DR, et al. Reduced lung-cancer mortality with low-dose CT screening. N Engl J Med. 2011; 365:395.

8 National Lung Screening Trial Research Team, Aberle DR, et al. Reduced lung-cancer mortality with low-dose CT screening. N Engl J Med. Aug 2011; 365:395.

9 American Cancer Society Initial Guideline Clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30 pack-year smoking history and who currently smoke or have quit within the past 15 years. March, 2013

10 Current Recommendation Release Date: December 2013 The USPSTF recommends annual screening for lung cancer with low-dose computed tomography in adults ages 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years.

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16 National Lung Screening Trial Research Team, Aberle DR, et al. Reduced lung-cancer mortality with low-dose CT screening. N Engl J Med. 2011; 365:395. Number screened: % NLST Low-Dose CT Sens=93.1% Spec=76.5% PPV = 3.6% NPV = 99.9%

17 Practical Problems How many subjects will be screened? Will there be reimbursement? How should follow-up studies be done? What is the role of FDG PET-CT in follow-up?

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21 SOLID

22 GGO No Role for PET

23 Multiple GGO No Role for PET

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26 129 Christensen JA, Nathan MA, Mullan BP, Hartman TE, Swensen SJ, Lowe VJ. Characterization of the solitary pulmonary nodule: 18F-FDG PET versus nodule-enhancement CT. AJR Am J Roentgenol Nov;187(5): N= 42 Original dictated report SUV > 2.5

27 132 Fletcher JW, et al with the VA SNAP Cooperative Studies Group. A comparison of the diagnostic accuracy of 18F-FDG PET and CT in the characterization of solitary pulmonary nodules. J Nucl Med. 2008; 49: N = 344 Sensitivity = 92% (95% CI, 87% 95%) Specificity = 82% (95% CI, 75% 88%)

28 Veronesi, G et al. Difficulties encountered managing nodules detected during a computed tomography lung cancer screening program. J Thorac Cardiovasc Surg 2008;136:611 Positive PET definition: SUVmax > 1.5

29 Hypothetical Sequential Low-dose CT followed by FDG PET-CT Incidence = 2.4 % Low-dose CT PPV = 3.6% PET - CT PPV = 32% High risk subjects (24 TP) Low Dose CT Positive CT results (22 TP) FDG PET - CT Positive PET results (19 TP) Note: assumes all positive LDCT nodules are solid and > 8mm + Biopsy/Surgery

30 Definitive PET-CT Guidelines are Needed Emphasis on standardization of patient preparation, image acquisition, image reconstruction and quality control. Interpretation criteria: FDG PET is generally assessed using visual criteria (in the context of oncology, looking for a focally increased uptake that may be compatible with malignancy in the clinical context.

31 NCCN Suggestion

32 Conclusions We are likely to see an increasing number of SPNs for FDG PET-CT imaging. We need consistent methodology and consistent reading criteria. Oncologists, pulmonologists, and radiologists need to work together to define the algorithm (including PET) for work-up of SPNs.

33 Practical Issues Related to Standardization Standardized Uptake Value (SUV) measurements Time of imaging Partial volume effect Pre-test probability

34 Standardized Uptake Value SUV The average SUV in the entire body is 1.0 SUV = = Tissue activity (µci/cc) Administered activity (µci/g) Tissue activity (µci/cc) Administered activity (mci/kg) Body weight or LBM (kg) Tissue activity is determined from attenuation corrected images Administered activity is known from dose calibrator Both activities are decay corrected to time of injection

35 Changing SUV with Time Lowe VJ, DeLong DM, Hoffman JM, Coleman RE. Optimum scanning protocol for FDG-PET evaluation of pulmonary malignancy J Nucl Med :883

36 Patz EF Jr, et al. Focal pulmonary abnormalities: evaluation with FDG PET scanning. Radiology Aug;188(2): N=41 Looking for the simple solution 2.5

37 A somewhat more realistic view Benign 2.5 Malignant

38 Reality: Not very nice Solitary Pulmonary Nodules (Iowa) 217 FDG PET-CT studies for SPNs obtained from 2003 to nodules were benign, 111 malignant. Benign Malignant

39 Solitary Pulmonary Nodules (Iowa) 1 At SUVmax= SUVmax = 2.5 Sensitivity = 71% Specificity = 71%

40 Solitary Pulmonary Nodules (Iowa)

41 Estimating the Risk of Malignancy in a Solitary Pulmonary Nodule

42 Estimating the Risk of Malignancy in a Solitary Pulmonary Nodule

43 Estimating the Risk of Malignancy in a Solitary Pulmonary Nodule

44 Swensen SJ, et al. The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. Arch Intern Med. 1997;157:849. Probability of malignancy=e x /(1+ e x ) N=629 X = ( age) + ( smoke) + ( cancer) + ( diameter) + ( spiculation) + ( location) age = patient s age in years smoke = 1 if the patient is a current or former smoker (otherwise, smoke = 0) cancer = 1 if the patient has a hx of extrathoracic cancer >5 years ago (otherwise =0) diameter = diameter of the nodule in millimeters spiculation = 1 if the edge of the nodule has spicules (otherwise, spiculation = 0) location = 1 if the nodule is located in an upper lobe (otherwise, location = 0) 55yo smoker, no hx ca, 10mm spiculated upper lobe nodule Probability of malignancy = 0.313

45 McWilliams A, et al. Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med. 2013; 369:910.

46 McWilliams A, et al. Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med. 2013; 369:910. 1% 0.1%

47 How big does a lung nodule have to be to see it on PET? It depends...

48 Partial Volume Effect (Iowa) Assumptions: FWHM = 1.0 cm, Background SUV = 0.5

49 The Role of PET in Lung Cancer Diagnosis and Screening Conclusions SUV = 2.5 (or 1.5) is not a magic number High SUV increases probability of cancer Low SUV decreases probability of cancer Pre-test probability is important Histoplasmosis and Low-grade Adenocarcinoma are the problems It makes sense in context of CT screening

50 National Lung Screening Trial Research Team, Aberle DR, et al. Reduced lung-cancer mortality with low-dose CT screening. N Engl J Med. 2011; 365:395. Number screened: % For ground-glass nodules and nodules < 8 mm Repeat f/u LDCT For solid nodules > 8 mm FDG PET-CT

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