در مرکز پزشکی هسته ای دکتر دباغ – دکتر صادقی در خدمت شما هستیم

1. در مرکز پزشکی هسته ای دکتر دباغ – دکتر صادقی در خدمت شما هستیم مشهد، ملاصدرا 11 ، پلاک 1/4 www.DSNMC.ir Tel:+98(51) 38411524; +98(51)38472927

2. Molecular Imaging with PET: A Revolution in Medicine 18FDG-PET and PET/CT in Lung Cancer V. R. Dabbagh Kakhki, M.D. Nuclear Medicine Specialist Associate Professor DSNMC Nuclear Medicine Research Center (NMRC; MUMS)

3. 18FDG-PET and PET/CT • Whole-body PET: • Quantities metabolic processes in vivo. • PET images show functional information, however they provide limited anatomical data • PET imaging in oncology-----> PET/CT

5. Lung cancer

9. 18FDG-PET: Analysis • Qualitative (visual) • Quantitative • Semi-quantitative: • Standardized uptake value (SUV) is a semi-quantitative index of glucose utilization • Obtained by normalizing the accumulation in the abnormal lesion to the injected dose and patient body weight.

10. Talk Overview • Background Statistics • Staging Overview • Traditional Staging methods • Clinical Exam and history • CXR • CT Chest • Surgical Staging

11. Background • Lung cancer (of all types) is the second most common malignancy and the leading cause of cancer death • Survival (and management) are closely correlated to stage

12. Background • Lung cancer Four main histologic types; • SCC • Adenocarcinoma (BAC) • Large Cell Carcinoma • Small Cell Carcinoma • Small Cell Carcinoma • NSLC

13. Stages • I T1-2, N0,M0 • II T1-2, N1,M0 T3, N0, M0 • IIIA T3, N1,M0 T1-3,N2,M0 • IIIB Any T4, Any N3, M0 • IV Any M1

14. AJCC-6 Staging • T0 No tumor • Tx Tumor by cytology but no lesion found • Tis Carcinoma in situ • T1 Smaller than 3cm • T2 >3cm or Involves the main bronchus, 2 cm or more distal to the carina or invades the visceral pleura, or with atelectasis extending to the hilum • T3 Extends to chest wall, diaphragm, pericardium, or mediatinal pleura or is a main bronchus tumor <2cm from carina, or causes total atelectasis of the lung • T4 Invades mediastinal structures, trachea, vertebra, or carina or malignant effusion present • Size, Involving main bronchus, pleura, chest wall, diaphragm, pericardium, mediastinal structures, trachea, vertebra, carina or malignant effusion, atelectasis

15. Nodes • NX Cannot assess regional nodes • N0 No regional lymph nodes • N1 Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary nodes (even if directly invaded by primary tumor) • N2 Metastasis to ipsilateral mediastinal and/or subcarinal lymph nodes • N3 Metastasis to contralateral mediastinal or hilar nodes, ipsilateral or contralateral scalene, or supraclavicular lymph nodes • Ipsilateral or contralateral peribronchial, hilar, intrapulmonary , mediastinal , subcarinal, scalene, or supraclavicular lymph nodes

16. Management by Stage • Stage I & II: Surgical (or definitive XRT) • Stage IIIA: being elucidated; • neoadjuvant chemoradiotherapy • Radiotherapy alone • Chemoradiotherapy • Stage IIIB • Chemotherapy or chemoradiation • Stage IV • Chemotherapy

17. Traditional Staging • PE/ clinical exam/ history • CXR • CT scan • Surgical Methods

18. CT Scanning • Criteria for positivity rely on size (short axis greater than 1 cm) • series (by Pieterman, et al) suggest that sensitivity and specificity for detecting lymph node metastases are approximately 75% and 66%; metanalysis by Dwamena is similar

19. CT scanning • All patients should undergo CT scan as an initial staging evaluation Images taken from: http://www.rctradiology.com/ctchest.html

20. Surgical Staging • Possibilities include • Mediastinoscopy • Thoracoscopy • Transbronchial needle aspiration • and endoscopic ultrasound with fine needle aspiration • Final surgical stage often differs from initial clinical stage

21. 18FDG-PET and PET/CTLung Cancer • Solitary pulmonary nodule • Diagnosis of primary lung cancer • Staging • Radiotherapy planning • Therapy Planning • Monitoring of therapy • Detection of recurrence • Ideal site for possible tissue diagnosis • Prediction of prognosis. • PET/CT has the best of both worlds of metabolic and anatomic imaging and may provide optimal disease assessment.

22. Imaging of Non-small Cell Lung Cancer FDG CT

23. Lung cancer

24. 18FDG-PET and PET/CTSolitary Pulmonary Nodule • The crucial objective in the evaluation of the SPN is: • The ability to noninvasively differentiate benign from malignant lesions • In cost-effective manner • Minimizing morbidity and mortality • FDG-PET has proven an accurate, noninvasive method for the work up patients with SPN • Sensitivity; 89-100% • Specificity: 77%-100%

25. 18FDG-PET and PET/CTSolitary Pulmonary Nodule • Visual analysis of the PET images • Semi-quantitative analysis: SUV>2.5 • A few lesions of less than 2.5 are malignant

26. PET in oncology:Solitary pulmonary nodule evaluation A patient with a 1.5 cm left upper lobe nodule. A PET scan was performed but demonstrated no uptake in the lesion (some cardiac activity can be seen more anteriorly). The nodule was resected and found to be a granuloma.

27. 18FDG-PET and PET/CTSolitary Pulmonary Nodule • False-positive results: • Active granulomatous disease (tuberculoma and histoplasmosis) • Certain other inflammatory processes • due to increased glycolytic activity within the active macrophages. • False-negative results: • Low metabolic activity: • Bronchoalveolar carcinoma(BAC), • Pulmonary carcinoids • Lesion is less than 5-7 mm in diameter

28. PET in oncology:Solitary pulmonary nodule evaluation A patient presented for evaluation of an 7 mm right lower lobe pulmonary nodule (white arrow). The PET scan was negative, but because of the lesions small size, the lack of uptake is not definitive for a benign lesion.

29. 18FDG-PET and PET/CTSolitary Pulmonary Nodule • The negative predictive power of PET is sufficiently high to avoid biopsy . • If FDG-PET is negative for lesions > 7 mm diameter, then the process is most likely benign, and may be followed with serial surveillance. • If the lesion is <7 mm diameter then malignancy cannot be excluded with a negative PET • When FDG-PET is positive then diagnostic and definitive treatment may be instituted

30. 18FDG-PET and PET/CTLung Cancer Staging • Survival ---------stage • Stage -------------treatment and prognosis • CT is frequently unable to discriminate between malignant enlarged mediastinal lymph nodes and benign reactive hyperplasia • Conventional imaging limited to the thorax and upper abdomen is unable to detect more distant metastatic disease which can occur in 9% to 11% of all patients with non-small cell lung cancer (NSCLC)

31. 18FDG-PET and PET/CTLung Cancer Staging • FDG-PET: • Can lead to changes in initial staging and treatment plans for lung cancer when used in combination with conventional work-up • One retrospective study; use of PET has an important impact on stage designation and clinical decision making. • PET upstaged 16.2% and downstaged 6.1% of the patients.

32. 18FDG-PET and PET/CTLC Staging: Primary Tumor (T) • CT: excellent in primary tumor for determining • the location • anatomic size • its relationship to surrounding structures • Compared to CT, ‘‘isolated’’ PET offers little additional information in the T characterization of lung cancer • lack of spatial resolution • invisibility of all but the grossest anatomical landmarks • One exception is its usefulness in distinguishing between tumor and post-obstructive atelectasis • In addition, PET can be beneficial in evaluating the cause of pleural effusions. • Accuracy rate of 91% for PET in a study of 35 patients with lung cancer and suspected malignant pleural effusion.

33. 18FDG-PET and PET/CTLC Staging: Primary Tumor (T) • FDG-PET: metabolic activity of the primary lung cancer (cell turnover rate) • May indicate the biologic aggressiveness of the cancer • SUV has prognostic value independent of conventional clinical TNM staging • For example, Higashi et al. demonstrated • A primary tumor SUV greater than 5 was associated with a significant increase in postoperative relapse in early stage lung cancer. • Thereby PET in initial T staging by predicting the likelihood of tumor recurrence after treatment, may help in selecting which patients • are likely to respond to induction therapy before surgery • and which patients should receive adjuvant chemotherapy/radiotherapy .

34. 18FDG-PET and PET/CT LC Staging: Primary Tumor (T) • PET/CT :more useful than PET in determining the T stage and in assessing the presence of mediastinal or chest wall invasion • Accuracy: PET/CT: 97%, PET only: 67%. • Accuracy for T staging with PET/CT: 88% and CT:58% • The reasons for this surprising finding were not fully explored, but it is worth reiterating that PET can have a role in T staging by distinguishing between tumor and distal atelectasis . • Remember: CT component of PET/CT is acquired without IV contrast. • Therefore, a diagnostic contrast-enhanced CT scan of the chest, performed as part of the PET/CT study or independently as a separate scan, is still recommended.

35. Non-small cell lung cancer. PET/CT images show invading the visceral pleura without chest wall invasion while on the CT alone it would be more difficult to determine the chest wall invasion (T2 N0 M0)

36. 18FDG-PET & PET/CTLC Staging: Nodal Involvement (N) • Mediastinal lymph node staging: • Imaging • Sampling • Pooled ROC curves analysis: PET was significantly more accurate than CT or MRI in identifying nodal metastasis with • An accuracy of 81% to 96% • A meta-analysis: nodal stage: • PET: Sensitivity of 79% and a specificity of 91% • CT: 60% and 77%, respectively, • Overall, 20% improvement in accuracy of PET over CT imaging for mediastinal staging of NSCLC. • PET/CT : even higher diagnostic accuracy than either CT or PET alone with a sensitivity of 89% and specificity of 94% and an overall diagnostic accuracy of 93% .

37. PET in oncology:Bronchogenic carcinoma (Staging) A patient with a left lung NSCLC showed a pathologic aorto-pulmonary window node (N2) by CT size criteria (white arrow), and a non-pathologic retrocaval-pretracheal contralateral mediastinal node (N3) (yellow arrow). PET-FDG images revealed increased tracer accumulation within bothnodes, consistent with metastases

38. 18FDG-PET & PET/CT LC Staging: Nodal Involvement (N) • A very well designed prospective study compared CT and PET in the diagnosis of mediastinal lymph node metastases in patients with potentially resectable NSCLC. • NPV was very high, at 98%. • Conclusion: Both imaging methods are complementary • Their strength is powerful NPV. • Thus PET/CT may be more helpful from one of these alone.

40. 18FDG-PET & PET/CT LC Staging: Nodal Involvement (N) • False-positive PET results in the mediastinum: • 13% to 17% • Mainly due to inflammatory lymph nodes (secondary to pneumonia, postobstructive pneumonitis, or chronic granulomatous infection) • May lead to mistaken up-staging of the primary tumor • False-negative rate as high as 8% for the detection of mediastinal metastases by PET imaging.

41. 18FDG-PET & PET/CT LC Staging: Nodal Involvement (N) • It is suggested by some authors that one of the main values of PET is based on its high negative predictive value for nodal disease, (estimated at greater than 90% in several studies)

42. 18FDG-PET & PET/CTLung Cancer Staging: Nodal Involvement • The implication of this is that eligible patients with negative mediastinal nodes on PET examinations may proceed directly to thoracotomy without the need for mediastinoscopy. • False-negatives can occur in this group of patients, with tumour subsequently identified at thoracotomy. These patients are, however, referred to by some as having ‘‘minimal N2 disease’’, which confers a better prognosis.

43. 18FDG-PET & PET/CT LC Staging: Nodal Involvement (N) • De Langen and co-workers have made recommendations based on the fact that the prevalence of nodal disease increases with size on CT. • They concluded that patients with nodes< less than 15 mm on CT and a negative PET examination do not require mediastinoscopy, • whereas those patients with negative PET but large lymph nodes on CT should nevertheless undergo invasive staging. • It is suggested to avoid mediastinoscopy in patients with T1 tumors and negative PET scans .

44. 18FDG-PET & PET/CT LC Staging: Nodal Involvement (N) • The lower PPV makes cytologic or histologic confirmation necessary in case of a positive mediastinum on PET. • In patients with locally advanced but potentially operable tumors based on conventional clinical staging (stages II–IIIA), PET can detect nodal metastases that are inaccessible by cervical mediastinoscopy and that may be missed by conventional staging methods. It can change the work-up of the patient by indicating the need for a different approach to invasive lymph node sampling.

45. Non-small cell lung cancer. PET/CT images show a mass involving the right hilum with extension into mediastinum without extension to the contralateral mediastinum but a separable focus in the right superior mediastinum (stage IIIA)

46. Lung Cancer w/metastasis

47. 18FDG-PET & PET/CTLC Staging: Distant Metastasis (M) • Advantage: FDG-PET versus CT: whole body can be imaged. • In addition to staging the mediastinum, PET has shown promise for identifying distant metastases. • Ability of PET to detect clinically unsuspected distant metastases in 10% to 29% of patients

48. 18FDG-PET & PET/CTLC Staging: Distant Metastasis (M) • PET have an accuracy of 96% and bone scanning, 66%, in the evaluation of osseous involvement in patients with NSCLC. • Although these tests were very similar in high sensitivity for bone metastasis, PET had a much higher specificity for disease than bone scan .

49. 18FDG-PET & PET/CT LC Staging: Distant Metastasis (M) • On PET or PET/CT imaging, the finding of FDG uptake within the adrenal gland greater than that of the liver is a highly sensitive and specific sign of adrenal metastatic disease, with an overall diagnostic accuracy of greater than 92%.

50. 18FDG-PET & PET/CT LC Staging: Distant Metastasis (M) • In brain and genitourinary system, PET is less accurate in identifying malignancy. • The high metabolic activity the brain and concentration and excretion in the genitourinary system, make it difficult to differentiate metastatic disease from normal activity. • As the brain is common site for metastatic lung cancer, CT or MRI recommended.