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1. Using PET in Esophageal Cancer Place your logo here

2. Oncology Imaging

3. Plasma Cell Glucose Glucose Glucose-6-P FDG FDG FDG-6-P FDG participates in the first step of glucose metabolism, but cannot be further metabolized and is trapped inside the cell where it is retained in proportion to the rate of glycolosis. 18F-FDG Pharmacokinetics

4. Normal distribution pattern of 18F-FDG • After IV injection, FDG is distributed to all organs of the body in proportion to cellular glucose metabolism. • Normal biodistribution will demonstrate uptake in the brain, evidence of excretion via the urinary and GI systems, faint hepatic uptake, some bone & soft tissue uptake, and variable cardiac uptake • Cancer cells are highly metabolic and utilize glucose at 3-5x the rate of normal cells.

5. Oncology Imaging Clinical Applications of PET • Characterization of radiographic abnormalities • Detection of radiographically occult lesions • Staging – initial evaluation of the extent of disease • Restaging - evaluation of the extent of recurrent disease (resectability) • Evaluation of response to therapy

6. Characterization of Radiographic Abnormalities • 66 yr old w/ ovarian cancer & brain mets treated w/stereotactic radiosurgery & chemotherapy; developed right hemiplegia 2 wks prior to PET. Treated w/steroids, symptoms resolved. • A new mass or nodule is identified by conventional imaging (x-ray, CT, MRI, US) and the physician needs to determine what it is.

7. 61 year old woman with ovarian cancer and brain metastases treated with whole brain and stereotactic radiation Characterization of Radiographic Abnormalities

8. Characterization of Radiographic Abnormalities • 66 year old man with pancoast tumor of the right lung – new adrenal mass. • CT shows enlargement of the right adrenal gland, adenoma vs metastasis.

9. Accuracy of PET in characterizing adrenal masses Differentiation of Benign from Malignant Adrenal Masses SensitivitySpecificity Yun 2001 100% (18/18) 94% (30/32) J Nucl Med 2001;42:1795 Erasmus 1997 100% (23/23) 80% (8/10) Am J Roentgenol 1997;168:1361 Maurea 1996 100% (7/7) 100% (6/6) Radiol Med 1996;92:782 Boland 1995 100% (14/14) 100% (10/10) Radiology 1995;194:131

10. Detection of a radiographically occult lesion • 61 yr old man s/p partial colectomy for sigmoid cancer, rising CEA level to 44.8. Negative CT, CEA scan, bone scan, colonoscopy. PET demonstrates FDG uptake; biopsy = adenocarcinoma. • Abnormal lab values or physical symptoms indicate possible cancer or cancer spread, but conventional imaging is normal

11. Staging after initial diagnosis of cancer • To determine extent of disease and select the most appropriate treatment course • Surgery • Induction chemo and/or radiation therapy prior to surgery • Systemic therapy • Palliative therapy Images courtesy of Macapinlac, UT MD Anderson Cancer Center

12. Restaging a known or suspected recurrence • 76 yr old with locally recurrent cervical cancer, CT shows pelvic adenopathy, scheduled for pelvic exenteration. PET positive for disease beyond pelvis. • To determine extent of disease, particularly if planned treatment is local/regional surgery or radiation therapy to confirm suspicion of recurrence

13. Restaging a known recurrence • Repeat positive right breast excisional biopsy. • Conventional imaging negative and pt scheduled for right mastectomy • PET results: Widespread liver metastases • 7 cm abdominal mass (!) • Unsuspected left breast tumor • Bone metastases, left acetabulum • Impact: Mastectomy cancelled and chemotherapy initiated Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

14. Restaging a known recurrence Restaging a known recurrence Restaging at completion of therapy Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

15. To determine effectiveness of treatment and whether additional treatment is necessary • Testicular cancer patient with apparent complete response to chemotherapy Evaluating response to therapy Images: Northern California PET Imaging Center

16. Esophageal Cancer Problem • Relatively uncommon cancer (1.5% of all malignancies) • 16,470 new cases annually in the U.S. (12,900 in men, and 3500 in women) • 14,280 estimated deaths per year • Prognosis is poor, five-year survival is only 5-20% in patients with operable disease Source: American Cancer Society. Cancer Facts & Figures 2008

17. Esophageal Cancer Diagnosis • CT and physical examination through esophagoscopy and biopsy • Standard staging modalities include: • CT – chest & abdomen for evaluation of local tumor extension & detection of distant metastases (may miss distant mets) • Endoscopic ultrasound (EUS) for evaluation of tumor depth and locoregional lymph node staging

18. Esophageal Cancer Treatment options include: • Radical surgery in early disease (curative esophagectomy with 2 or 3 field lymphadenectomy) • Multi-modality treatments combining neoadjuvant chemotherapy and radiation therapy followed by surgery in locoregional advanced disease • Palliative courses in cases of distant metastatic disease

19. Esophageal Cancer • Tumor stage is the major determinant of prognosis • Provides the basis for selection of therapeutic course • Pivotal staging points are: • Depth of wall penetration of primary tumor • Presence of locoregional lymph node metastases • Distant lymph node or organ metastases

20. Esophageal Cancer Role for PET: • More accurate preoperative staging – reduced surgeries for nonresectable disease • Identify distant lymph node or organ metastases • Evaluation of response to adjuvant therapies prior to surgical resection • Evaluation of suspected or known recurrence

21. Esophageal CancerStaging Primary esophageal tumors are well visualized by PET with an accuracy of > 95% • Sensitivity of PET for surgically proven positive locoregional lymph nodes is only between 33-50% • Sensitivity of CT for nodal involvement is 25% • Primary tumors have intense FDG uptake; locoregional lymph nodes are adjacent to the tumor • Scanner is unable to resolve the discrete lymph nodes immediately surrounding the tumor • EUS is the preferred method for assessing local lymph node involvement with sensitivity of 81% • Source: Flamen, et al, JCO 18:2302-3210, 2000

22. Esophageal Cancer Staging Block, et al reported: • 30% of newly diagnosed esophageal cancer patients, thought to be surgical candidates with limited Stage I disease, had unsuspected distant metastases identified by PET • CT was able to accurately detect distant metastases in only 1/3 of these patients • Source: Block, et al, Ann Thor Surg 64:770-777. 1997

23. Esophageal Cancer Staging Flamen, et al have reported that for the diagnosis of Stage IV disease in 74 patients: • PET had higher accuracy – 82% • CT and EUS compare with accuracy – 64% • PET resulted in a 22% change in patient management (15% up staged, 7% down staged) For assessment of regional and distant lymph node involvement: • PET had higher specificity – 98% • Compared with combination of CT & EUS – 90% • Source: Flamen, el al. JCO 18:3202-3210. 2000

24. Esophageal Cancer Staging 52 year old man with dysphagia and obstructing esophageal mass. S/P neoadjuvant chemo/radiation therapy CT did not show any adenopathy or distant metastases. He was referred for a PET scan for staging 2 days prior to esophagectomy.

25. Esophageal Cancer Staging 72 year old man with recently diagnosed esophageal cancer for staging. There is very intense uptake of the radiotracer in the mid-esophagus extending to the lower esophagus consistent with the recent diagnosis of esophageal cancer. In addition PET/CT scan revealed moderate uptake of radiotracer by the soft tissue mass in the medial aspect of the left kidney, suspicious for primary renal cell carcinoma. Images courtesy of Todd Blodgett, MD, UPMC

26. Esophageal Cancer Restaging • 60 y/o female w/ history of esophageal CA, s/p chemo & radiation therapy, severe esophagitis, biopsies during endoscopy – negative for recurrent CA. S/p chemo • CT – enlarged mediastinal mass = paraesophageal lymphadenopathy • PET – hypermetabolic mediastinal mass = metastatic lymph nodes; diffuse uptake is esophagus = esophagitis Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

27. Esophageal Cancer Response to Therapy • 40 patients with locally advanced GE junction tumors • PET studies performed at baseline and 14 days post cisplatin based polychemotherapy • Clinical response was evaluated after 90 days using endoscopy & standard imaging techniques • Reduction of tumor length and wall thickness by >50% • Patients with potentially resectable tumors underwent surgery, tumor regression was assessed with histopathology Source: Weber, et al. JCO 19:12. 2001 pp 3058-3065

28. Esophageal Cancer Early Response to Therapy Results: • Reduction of tumor FDG uptake after 14 days was significantly different between responding and non-responding tumors • Optimal differentiation was achieved with a cutoff value of 35% reduction of initial FDG uptake • PET predicted clinical response: • Sensitivity = 93% (14/15 pts) • Specificity = 95% (21/22 pts) • Early identification of tumor response avoids ineffective and toxic preoperative therapy Source: Weber, et al. JCO 19:12. 2001 pp 3058-3065

29. Esophageal Cancer Summary • PET significantly improves the detection of Stage IV disease compared with conventional staging • PET is more accurate than CT or EUS for evaluating metastasis to individual lymph node groups • PET improves diagnostic specificity for lymph node staging • PET shows promise in early identification of non-responding tumors allowing patients to proceed to immediate surgery (for patients w/ resectable tumors) or definitive chemoradiotherapy (for patients with unresectable tumors)

30. Problems and Pitfalls False negative: Size less than 10 mm Diabetes fasting blood glucose level >150 mg/dl Histology low grade glioma low grade lymphoma bronchoalveolar carcinoma mucinous adenocarcinoma thyroid, liver, kidney, prostate CA

31. Problems and Pitfalls Non-Malignant (false) positives: Infection granuloma, abscess, pneumonia Inflammationpneumonitis, wounds, arthritis, reactive nodes Uncertainsarcoid Benign tumors thyroid, parathyroid, carcinoid, colon Autoimmunerheumatoid nodules, thyroiditis Miscellaneous fractures, Paget’s disease

32. Clinical Applications of PET Characterization of radiographic abnormalities Detection of radiographically occult lesions Staging – initial evaluation of the extent of disease Restaging - evaluation of the extent of recurrent disease (resectability) Evaluation of response to therapy Benefits of PET Imaging Impact on patient mgmt (identifies most appropriate course of treatment for a specific patient) Avoid unnecessary biopsies or surgeries Reduce patient risk, improves patient outcome Determine patient response to therapy PET in OncologySummary

33. PET in OncologyConclusions • Every patient does not need PET, but many will benefit from the addition of PET into their staging/restaging work up • The information provided by PET and CT is complementary • PET is not perfect - there are false negative and false positive results • PET often changes the treatment plan, usually by avoiding futile surgery

34. PET in OncologyConclusions • A negative PET scan usually eliminates the need for biopsy or surgery – avoid complications associated with unnecessary invasive procedures • A negative PET scan rules out cancer with a high degree of confidence • A positive PET scan usually indicates malignancy, but should be confirmed with biopsy • PET should be used to determine the extent of malignancy any time surgery or local radiation therapy is considered as the definitive treatment • The predictive or prognositic power of PET following therapy is greater than CT

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