1. Using PET in Thyroid Cancer
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2. Oncology Imaging Computed Tomography (CT) Photon attenuation Anatomy
Magnetic Resonance (MR) Spin flip time Anatomy (blood flow)
Ultrasound (US) Sound attenuation Anatomy
Conventional Nuclear Radioactive tracer Function
Medicine (NM) uptake
Positron Emission Radioactive tracer Function
Tomography (PET) uptake
Function

3. 18F-FDG Pharmacokinetics
Plasma Cell
Glucose
FDG
Glucose-6-P
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.

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 3

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

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
Sensitivity Specificity
Yun % (18/18) 94% (30/32)
J Nucl Med 2001;42:1795
Erasmus % (23/23) 80% (8/10)
Am J Roentgenol 1997;168:1361
Maurea % (7/7) 100% (6/6)
Radiol Med 1996;92:782
Boland % (14/14) 100% (10/10)
Radiology 1995;194:131 3

10. Detection of a radiographically occult lesion
61 yr old man s/p partial colectomy for sigmoid cancer, rising CEA level to 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
Restaging a Known Recurrence
In this case, a patient with a history of Rt. Breast cancer, post wedge resection, chemo and radiation therapy, presented with elevated tumor markers and a new right breast mass. The excisional breast biopsy was positive for metastatic breast cancer. Restaging by conventional imaging was negative and she was scheduled for a mastectomy. Tumor markers remained elevated after the excisional biopsy (should have returned to zero if that were the sole metastatic lesion). PET was performed to confirm extent of disease prior to surgery. PET demonstrated widespread liver metastases, a 7 cm abdominal mass, unsuspected Lt breast tumor, and a bone lesion on the left acetabulum. Her mastectomy was cancelled and she received high dose chemotherapy.
Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

14. Restaging a known recurrence
Restaging at completion of therapy
The post treatment scan demonstrated complete resolution of her metastatic disease and confirmed the effectiveness of the chemotherapy.
Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

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

16. Thyroid Carcinomas Problem: 37,340 new cases in 2008; 1,590 deaths
Yearly incidence is low, 3-5 cases per 100,000
Incidence & prevalence increase with age and in women, 3-5 times more frequently than men
Major risk factor: external exposure of the neck to large amounts of ionizing radiation
Therapeutic radiation therapy - treatment for HD, acne
Radiation accidents (down wind Hanford, Chernobyl)
Cancers may take over 20 yrs to occur
Source: American Cancer Society. Cancer Facts and Figures 2008

17. Thyroid Carcinomas Prognosis
Aggressiveness of cell type
Stage of disease at presentation
Contained to thyroid gland
Spread to regional lymph nodes
Distant metastasis
Patient age & overall health
Differentiated tumors – papillary & follicular – highly treatable, curable if discovered early
Poorly differentiated tumors – medullary & anaplastic, are aggressive, metastasize early, worse prognosis
Gambhir, JNM 2001; 42:160S

18. Thyroid Carcinomas Diagnosis
Physical exam & histology after biopsy
Most common presentation - palpable neck mass
Less common – lymphadenopathy, hoarseness
Evaluation:
Ultrasound – localize mass, cystic vs solid
Nuclear medicine if hyperthyroidism is suspected
FNA biopsy – determine histology, cytology of mass
CT or MRI to confirm equivocal findings & confirm anatomic relationships before surgery

19. Thyroid Carcinomas Treatment
Differentiated cancers (follicular & papillary)
Surgical resection of primary tumor
Near total thyroidectomy
Subsequent radioiodine ablation therapy
Sterilize remnant thyroid tissue in surgical bed
Treat any occult microscopic disease
External beam radiation – anaplastic tumors that do not concentrate radioiodine
Thyroid hormone replacement

20. Thyroid Carcinomas Recurrence
Differentiated cancers (follicular & papillary)
Monitor serum thyroglobulin levels
Serum glycoprotein secreted by cancer cells
Rising serum Thyroglobulin (Tg) levels > 10 ng/ml ~ 85% of patients found to have metastases
Survey with whole body I-131 imaging
Majority of thyroid cancers concentrate I-131
Highly specific technique ~ 99%
Sensitivity relatively low ~ 50-70%
High dose I-131 therapy cures most metastatic disease
Source: Alibazoglu H, Discussions in PET Imaging, PET and Thyroid Cancer

21. Thyroid Carcinomas Role for PET
Patients with elevated Tg levels, negative I-131 WB scan
Some recurrent thyroid cancer patients have true metastases that do not concentrate iodine
Metastases that have lost ability to concentrate iodine (dedifferentiated) are more aggressive
Most physicians are unwilling to treat without identification of an index lesion
Accurate identification of metastatic focus allows appropriate treatment selection – surgery, external beam radiation

22. Thyroid Carcinomas Role for PET
Patients with elevated Tg levels, negative I-131 WB scan
Anatomic imaging (CT, MRI, US) – inferior specificity
Not practical for whole body survey, challenged by post surgical patients with altered neck anatomy
Unable to distinguish active disease from post surgical fibrosis
Source: Alibazoglu H, Discussions in PET Imaging, PET and Thyroid Cancer

23. Thyroid Cancer Staging
Patient 207
Data Courtesy of University of Tennessee, Knoxville, Tennessee, U.S.A.
71 y/o female with primary thyroid carcinoma for initial staging. The exam showed a large hypermetabolic neck mass with multiple necrotic areas along with extensive tracer avid metastases in the skeletal system.
Images courtesy of Dr. David Townsend, Univ of TN Medical Center

24. Recurrent papillary thyroid cancer 131I / FDG flip-flop
As thyroid cancer cells dedifferentiate, they lose the ability to concentrate iodine, become more aggressive and metabolically active, concentrating FDG
Images courtesy of Northern California PET Imaging Center

25. Papillary Thyroid Cancer Restaging
56 year old s/p thyroidectomy with rising Tg and negative 131I scan. PET demonstrates focal area of increased uptake of FDG in the left neck inferiorly, localized on PETCT to a small left level 4 lymph node.
This small, normal sized jugulodigastric lymph node was resected and found to be positive for recurrent papillary carcinoma.
Images courtesy of Dr. Todd Blodgett, UPMC

26. Thyroid Carcinomas Role for PET
PET demonstrates high degree of sensitivity ~ 80-90% in detection of recurrent differentiated thyroid cancer facilitating early & more aggressive therapy.
Improved ability to localize metastases accessible to surgery or external beam radiation therapy
FDG avid lesions are often resistant to I-131 therapy
53% change in patient management – review of 21 studies involving > 600 patients (Gambhir)
Rising Thyroglobulin level, -I131 scan, aggressive features ---is a PET population
Small study of 20 pts medullary carcinoma
Rising calcitonin levels, negative conventional imaging
PET sensitivity of 76% for localization of metastases
Source: Gambhir et al. JNM 2001; 42:1S-93S
Brandt-Mainz Eur JNM 2000; 27:

27. Thyroid Carcinomas Prognosis
Memorial Sloan Kettering (Wang, Larson, et al)
125 patients, 41-month follow-up
Total volume of FDG avid disease was the single strongest predictor of survival (higher the volume, shorter the survival)
FDG avid volumes > 125 ml; more prognostic than age, gender, histologic type, tumor grade, presence of iodine uptake or AJCC stage
PET may be useful in determining which patients would benefit from more aggressive therapy
Source: Wang et al. J Clin Endocrinol Metab 1999;84:

28. Thyroid Carcinomas Role for PET
Evaluate extent of disease
Assess prognosis (- PET)
Determine which patients would benefit from more aggressive therapy

29. Thyroid Carcinomas Role for PET - Summary
Evaluation of recurrence in less well differentiated thyroid cancers
Elevated Tg, negative I-131 whole body scan
Hurthle cell cancer—little to no I131 or I123 uptake but 90% + on FDG(rare subset, usually Tg positive, iodine negative)
Anaplastic cancer (often Tg and iodine negative)
Medullary cancer (calcitonin positive)
Medicare coverage, October 2003 – evaluation of recurrence in patients with follicular thyroid cancer, s/p thyroidectomy, I-131 ablation, elevated Tg > 10 ng/ml & negative I-131 whole body scan

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
Inflammation pneumonitis, wounds, arthritis, reactive nodes
Uncertain sarcoid
Benign tumors thyroid, parathyroid, carcinoid, colon
Autoimmune rheumatoid nodules, thyroiditis
Miscellaneous fractures, Paget’s disease

32. PET in Oncology Summary
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

33. PET in Oncology Conclusions
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 Oncology Conclusions
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

35. Questions?
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