Using PET in Thyroid Cancer Place your logo here

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

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.

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.

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

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.

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

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.

Accuracy of PET in characterizing adrenal masses Differentiation of Benign from Malignant Adrenal Masses Sensitivity Specificity 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 3

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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; 27:490-496

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;84:2291-2302

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

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

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

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

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

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

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

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