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The Role of PET/CT in Differentiated Thyroid Cancer Managment

The Role of PET/CT in Differentiated Thyroid Cancer Managment. Presented By:B.Rezvankhah MD Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences June 2017. Agenda. Case presentation Introduction(Principles of PET/CT)

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The Role of PET/CT in Differentiated Thyroid Cancer Managment

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  1. The Role of PET/CT in Differentiated Thyroid Cancer Managment Presented By:B.RezvankhahMD Research Institute for Endocrine Sciences ShahidBeheshti University of Medical Sciences June 2017

  2. Agenda • Case presentation • Introduction(Principles of PET/CT) • What is the diagnostic value of PET/CT? • How much does PET/CT influence therapeutic management? • What is the prognostic significance of PET/CT? • Conclusion

  3. Case presentation

  4. Agenda • Case presentation • Introduction(Principles of PET/CT) • What is the diagnostic value of PET/CT? • How much does PET/CT influence therapeutic management? • What is the prognostic significance of PET/CT? • Conclusion

  5. Principles ofPET/CT Positron is Beta (+) particle, Annihilates with electron Two gamma rays 511 keV in opposite directions Better resolution 4-5 mm (SPECT 8-10mm) Positron emitters are often isotopes of elements naturally present in the body Basics and principles of radiopharmaceuticals for PET/CTEur J Radiol 2010 Mar;73(3):461-9

  6. F-18Fluorodeoxyglucose(18F -FDG) • Malignant cells typically have glycolytic rates up to 200 times higher than those of their normal tissues of origin. • F18-FDG • FDG is Phosphorylated in the cells, but not metabolized further; • Not re-absorbed in kidneys (good for imaging) • Accumulates in inflammation.

  7. Brain - intense uptake • Thyroid - low uptake • Heart - variable uptake • Urinary tract - intense uptake • GI tract- • (Stomach,Liver –SUV->3) • Skeletalmuscle • Larynx • Salivarygland • Brownfat FDG Normal Distribution SUV (Standard Uptake Value): activity concentration(MBq/g) x body weight(kg) administered activity (MBq)

  8. PatientPreparation • Fasting for 4 - 6hours • No insulin for 4hours (Insulin will cause diffuse muscle uptake) • Glucose level < 150mg/dl(Glucose competes with labelledglucose) • Goodhydration (to help clear the tracer from the background) • No vigorous exercise for 24hours (to avoid muscularuptake)

  9. FDG-PET/CT Malignant transformed cells :An accelerated rate of glucose metabolism mediated by the overexpression of key regulatory glycolytic enzymes and transporters Thyroid tumors: increased uptake of FDG in more aggressive and high-grade tumors In 1996, Feine et al. :inverse relationship between RAI and FDG uptake in thyroid carcinoma (the so-called ‘flip-flop phenomenon’) loss in RAI concentration capacity during dedifferentiation combined with an increased demand of tumor cells for glucose. Salvatori M. 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in differentiated thyroid carcinoma: clinical indications and controversies in diagnosis and follow-up .European Journal of Endocrinology ;2015:173, R115–R130

  10. Agenda • Case presentation • Introduction(Principles of PET/CT) • What is the diagnostic value of PET/CT? • How much does PET/CT influence therapeutic management? • What is the prognostic significance of PET/CT? • Conclusion

  11. Background: To evaluate the diagnostic accuracy of 18F-FDG PET/CT in detection of recurrent differentiated thyroid cancer (DTC) in patients with elevated stimulated thyroglobulin (Tg) or anti-Tg antibody (Ab) levels, and negative 131I whole body scan according to the Tg level. Methods: a total of 68 PET/CT images from 60 patients who had total thyroidectomy and radioiodine ablation were included. Patients showing elevated Tg titer (≥2.0 ng/ml after TSH stimulation) or elevated anti-Tg titer (≥ 70.0 IU/ml) while diagnostic radioiodine scan was negative were enrolled. The PET/CT findings were compared with histological or clinical follow-up results based on other imaging modalities and serum Tg/anti-Tg Ab titers.

  12. Overall sensitivity, specificity,accuracy, positive predictive value and negative predictive value of 18F-FDG PET/CT for detection of papillary thyroid cancer local recurrence or metastasis were computed as 69.4, 66.7, 69.1, 95.6, and 17.4% in patients with elevated Tg but negative radioiodine WBS (TP) (FP) (FN) (TN)

  13. The sensitivity of 18F-FDG PET/CT and SUVmax according to the groups of Tg levels by patients based SUVmax ranged widely from 1.3 to 29.7 (mean 4.7 ± 5.7) in lesions suspicious for recurrence on PET/CT.SUVmax of cervical LNs in the 2 FP PET/ CT cases was relatively low, 1.6 and 1.7.

  14. Key message • Diagnostic accuracy of FDG PET in radioiodine negative thyroid cancer may vary depending on serum Tg levels at imaging. • 18F-FDG PET/CT is useful for detection and localization of recurrence or metastasis in DTC patients with negative radioiodine scan but elevated stimulated Tg greater than 20 ng/ml or high anti-Tg Ab titers. • PET/ CT can also be helpful in patients with relatively low Tg level between 5 and 10 ng/ml • FDG PET/CT was not very beneficial in patients with Tg titer below 5 ng/ml.

  15. Purpose: 1- the usefulness of F-18 FDGPET/CT for PTC patients with negative diagnostic radioiodine scan and elevated serum Tg level or positive anti-thyroglobulin antibody 2-the effect of endogenous TSH stimulation (ETS) on detecting recurrence 3-cut-off value of serum Tg for recurrence in PTC patients Patients and Method: 84 patients( 75 patients who had Tg levels>2 ng/mL and normal TgAb levels were included in the Tg-positive group:57 under TSH stimulation (TSH>30 IU/ mL). 9patients who had increased TgAb levels and negative Tg were categorized as the TgAb-positive group: 7 under TSH stimulation medical records were retrospectively reviewed.

  16. The sensitivity, specificity, PPV, NPV, and accuracy of F-18 FDG PET/CT for detecting recurrence were: 64 %, 94 %, 86 %, 81 %, and 83 %, respectively in 75 patients with Tg values higher than 2 ng/mL.

  17. In 21 patients with positive F-18 FDG PET/CT, cut-off Tg level for prediction recurrence was 21.5 ng/mL using the ROC curve analysis. The AUC for a Tg cut-off level of 21.5 ng/mL was 0.926 (P<0.001) with 83 % sensitivity and 100 % specificity for predicting the recurrence. • The mean SUVmax was 5.0±3.1 in 18 patients with TP findings and the mean was 2.4±0.7 in three patients with FP lesions. The difference between SUVmax values for TP and FP lesions were statistically significant (P=0.007).

  18. Key message • Despite low sensitivity,F-18 FDG PET/CT showed high specificity, PPV, NPV and accuracy and can be useful for those patients with negative diagnostic radioiodine scan and elevated serum Tg level or positive anti-Tg Ab

  19. Hell J Nucl Med 2016; 19(3): 208-217

  20. Purpose:To investigate the clinicopathologicfeatures and other related risk factors of patients with DTC having elevated Tg levels and negative WBS in which metastasis/recurrence was detected by F-FDG PET/CT during the follow-up after ablation therapy. • We tried to stratify 18 patients who could benefit from F-FDG PET/CT for the detection of metastasis/recurrence according to predefined risk factors.

  21. Method: Nearly 3500 patients with DTC were treated with RAI and followed up by our Nuclear Medicine Department of the Training and Research Hospital of Medical School between 1991-2016; During the follow-up we performed restaging by F-FDG PET/CT for the 165 patients with elevated Tg levels and/or any doubtful lesions detected by any conventional imaging modalities (US, CT, MRI, bone scintigraphy) and also a negative DxWBS. The mean time interval between Dx WBS and F-FDG PET/CT was 20 days • The patients were divided in 2 groups; those in which F-FDG PET/CT found metastasis/recurrence (81/165 (49%) patients) (Group A ) and those with negative findings (84/165 (51%) patients) (Group B)

  22. The evaluated risk factors were sex, age,histopathology(variants), TS, CI, ETE, initial metastatic LN(neck) dissection, stage, cumulative I dose, count of I therapy,local cervical surgery for LN metastasis/recurrence during the follow-up period, the time from initial diagnosis to restaging F-FDG PET/CT, Tg and SUVmax. • These factors were evaluated in true positive (TP) and false negative (FN) patient population and compared between groups A and B

  23. Results: • Those in which F-FDG PET/CT found metastasis/recurrence (74/165(45%) patients) which formed Group A and those with negative findings (91/165(51%) patients) which formed Group B. Recurrence/Metastasis PET/CT

  24. A cut off value of 4.5 for SUVmax to detect metastasis/recurrence had a sensitivity and specificity of 74% and 100%. • The Pearson correlation test between serum Tg levels and SUVmax correlated significantly (r=0.229, P=0.03) in the study group. • Neverthless, it was not meaningful in groups A and B

  25. Clinical consequence: • The PET findings led to a change in the management of all the metastatic/recurrent patients. 50 patients underwent surgery for removal of cervical LN and a residual tumor,and those with distant organ metastases were given additional higher repetitive doses of I131.

  26. Key massage: • PET/CT should be performed routinely in DTC patients with elevated Tg levels and a negative Dx WBS especially in the existence of risk factors to show metastasis/recurrence. Themost important factors effecting a true positive FDG PET/CT are ETE, total iodine dose and SUVmax. No apparentpredefined risk factor exists for false negative F-FDG PET/CT scan. • There was statistically no difference for follicular carcinoma, Hürtle cell carcinoma and papillary carcinoma with regard to F-FDG PET/CT results. • The variants of papillary carcinoma had also no statistical difference either.

  27. Agenda • Case presentation • Introduction(Principles of PET/CT) • What is the diagnostic value of PET/CT? • How much does PET/CT influence therapeutic management? • What is the prognostic significance of PET/CT? • Conclusion

  28. Purpose:to evaluate the role of FDGPET/ CT in radioiodine whole body scan negative patients with elevated serum Tg levels with special regard to the impact on further patient management. • Methods and materials :After total thyroidectomy followed by radioiodine ablation, 30 consecutive patients with differentiated thyroid cancer, elevated serum thyroglobulin levels and negative whole body radioiodine scan underwent 8F-FDG-PET/CT. Results were verified by histology, ultrasound, or clinical follow-up. Diagnostic accuracy was determined for the whole study population and for subgroups with serum thyroglobulin below and above 10 ng/ml, respectively. Impact of PET/CT on clinical management was assessed.

  29. The fact that no false-positive findings occurred in the group of patients with Tg levels above 10 ng/ml resulted in both a specificity and PPV of 100% in this subgroup as compared to 50.0 and 60.0%, respectively, in patients with Tg levels below 10 ng/ml. • The overall sensitivity, specificity, and accuracy were 68.0, 60.0,and 66.7%, respectively.

  30. !18F-FDG-PET/CT and neck ultrasonography; • 11 of the 17 patients had loco-regional recurrence or cervical lymph node metastasis, 3 presented distant metastases only and 3 suffered from both.Ultrasonography detected loco-regional recurrence in only 5 of the 14 patients (35.7%).

  31. Clinical consequences: • In 17 of the 30 patients (57%), FDG-PET/CT resulted in treatment changes. • Surgery was performed in 9 patients with local recurrence, with results from FDG-PET/CT guiding the surgical strategy. In the remaining 8 patients, FDG-PET/CT detected multiple non-resectable metastases and the initial therapeutic strategy was altered. 7 patients were held under TSH suppression and 1 patient was treated with chemotherapy. 2 of the 8 patients had recurrent disease in the neck only, 3 patients had additional pulmonary metastases and 3 patients had pulmonary metastases only. Progressive disease was documented in all patients on follow-up.

  32. Key massage • Our results show that in patients with suspected recurrent thyroid cancer and negative radioiodine whole body scan sensitivity of neck ultrasonography is too low for reliable detection of local recurrent disease. CT alone has a high accuracy for pulmonary metastases, but it is suboptimal in the post-operative neck. • FDG-PET/CT optimally combines the strengths of morphologic and functional images and can be recommended as a routine diagnostic tool with high impact on subsequent patient management.

  33. Purpose: • Performing 18F-FDG PET/CT in addition to the first radioiodine treatment to detect iodinenegative metastases, which might be more frequent in highrisk patients and elude standard therapy. • To determine whether the results led to a deviation from the established procedure • Material & Method:We analysed the data of 90 patients who presented at our hospital with high-risk DTC, All patients underwent 18F-FDG -PET/CT for assessment of iodine-negative tumour lesions about 1week after the first radioiodine treatment

  34. Results:18F-FDG PET-positive lesions were seen in 26 patients (29%) and negative lesions in 64 patients (71%).

  35. … • Of the 26 patients with FDG PET-positive lesions, 8 had only distant metastases, 12 had only cervical lymph-node lesions and 6 had both cervical and distant metastases. • FDG PET-positive cervical lymph-node lesions were seen in 18 patients. Ultrasonography revealed all of these lesions in 5 patients, only some of the lesions in 4 patients, and none of the lesions in 9 patients.

  36. Clinical consequence: • Patient management was changed from the standard therapy, consisting of RIT only, to individual procedures in all but those patients with lesions showing FDG as well as iodine accumulation (19 of 90, 21%). In the 19 patients, RIT was amended by surgery in 6, by external beam therapy in 2 and by an additional imaging modality during follow-up in 8, and was replaced by therapy with a multikinase inhibitor in 3.

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