Clinical Significance of Preoperative 18F-FDG PET Non-Avidity in Papillary Thyroid Carcinoma

1. Clinical Significance of Preoperative 18F-FDG PET Non-Avidity in Papillary Thyroid Carcinoma Do Hoon Koo1, Ho-Young Lee2, KyuEun Lee3,4, So Won Oh2, HyungJu Kwon3,4, Sehyun Pack3,4, Youngpeck Song5, June Key Chung2, Yeo-Kyu Youn3,4 1Department of Surgery, Seoul National University Boramae Medical Center, and College of Medicine, Seoul, Korea 2Department of Nuclear medicine, Seoul National University College of Medicine, Seoul, Korea 3Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea 4Division of Surgery, Thyroid Center, Seoul National University Cancer Hospital, Seoul, Korea 5Department of Surgery, Seoul National University Bundang Hospital and College of Medicine, Seongnam, Korea

2. - Introduction (I) - • [18F] FDG-PET positivity is known to be associated with a tumor aggressiveness and poor prognosis in various types of malignancy. • In post-thyroidectomy thyroid cancer patients, RAI negative /FDG-positive recurrences are known to be associated with dedifferentiated tumors and a grave prognosis. [Rivera 2008 Cancer; Chung 1999 J Nucl Med] • However, preoperative FDG PET in papillary thyroid carcinoma (PTC) patients had shown limited sensitivity, because majority of them are well differentiated. • Nevertheless, a large number of thyroid cancers, including incidentalomas and PTCs, exhibit increased FDG uptake despite their well-differentiated histology. [Kim 2010 Annals Nucl Med; Kang 2003 JCEM]

3. - Introduction (II) - • PET avidity could be utilized as a potential risk factor for tumor aggressiveness like extrathyroid extension or lymph node metastasis [Yun 2010 JCEM] • SUV max higher than cutoff value was associated with central compartment LN metastasis. [Byun 2012 Annals Nucl Med] • Some limitations since ETE or LN metastasis would not be predicted in all PET avid cases[Jeong 2006 Laryngoscope; Choi 2010 ASO] • Whether PET non-avid group, as is regarded as better differentiated characteristics, would truly show less aggressive nature needed to be evaluated. • We aimed to evaluate the rate of preoperative FDG non-avidity and assess clinical significance in PTC.

4. - Patients and Methods - • Between 2011 Jan and 2012 Apr, from 201 patients who underwent thyroidectomy d/t thyroid cancer in Seoul National University Boramae Medical Center, 81 patients who performed preoperative FDG PET examination and revealed final diagnosis of PTC were included in this study. • 12 cases (MTC 1, FTC 2, PTC+SCC 1, recurred 2, diffuse sclerosing variant 1 and fvPTC 5) was excluded. • Preoperative FDG PET results were re-evaluated by the department of nuclear medicine and the clinicopathologic factors were analyzed.

5. - Patients Characteristics -

6. Result 1) Comparison of PET non-avid vs PET–avid groups : classified by visually discernible uptake

7. Definition of TSUVmax/nlTSUVmean and TSUVmax/LiverSUVmean †2 cases unknown TSUVmax: maximum SUVs of focally increased thyroid FDG uptake at the anatomic location of the tumor nlTSUVmean: mean SUV from the surrounding normal thyroid LiverSUVmean: for normal organ reference Nilsson et al 2011 World J Surg

8. Result 2) Comparison of visual PET avidity by using quantitative analysis of SUV TSUVmax correlated to tumor size (r=0.686, p<0.001) TSUVmax/nlTSUVmean correlated to tumor size (r=0.664, p<0.001) TSUVmax/LiverSUVmean correlated to tumor size (r=0.667, p<0.001) †1 case unknown

9. # ROC curve by TSUVmax,TSUVmax/nlTSUVmean and TSUVmax/LiverSUVmean Area = 0.857 Area = 0.797 Area = 0.845 ▷TSUVmax/nlTSUVmean Cut-off value 1.5) Sensitivity 0.717, Specificity 0.895 ▷TSUVmax/LiverSUVmean Cut-off value 1.13) Sensitivity 0.700, Specificity 0.895 ▷TSUVmax Cut-off value 2.0) Sensitivity 0.750, Specificity 0.842

10. Result 3-1) Comparison of PET non-avid vs avid groups : classified by cut-off value 2 of TSUVmax †2 cases unknown

11. Result 3-2) Comparison of PET non-avid vs PET–avid groups : classified by cut-off value 1.5 of TSUVmax/nlTSUVmean †2 cases unknown

12. Result 3-3) Comparison of PET non-avid vs PET–avid groups : classified by cut-off value 1.13 of TSUVmax/LiverSUVmean †2 cases unknown

13. - Summary & Conclusion (I) - • Preoperative FDG PET was non-avid in 20 out of 81 cases (24.7%) and mean tumor size was 1.06 ± 0.64 cm (0.3-3.3). • When classified by visually discernible uptake, Preoperative PET non-avid cases showed lower significant ETE (30.0% vs 73.8%, p=0.001) and LN metastasis rate (20.0% vs 54.1%, p=0.008) than PET avid cases with less number of retrieved LNs (4.3 vs 10.2, p<0.001) and greater proportion of male (40.0% vs 13.1%, p=0.009). • There was significant difference in TSUVmax (1.74 vs 5.19, p<0.001), TSUVmax/nlTSUVmean(1.27 vs 3.89, p=0.001) and TSUVmax/LiverSUVmean(0.84 vs 2.44, p<0.001) between PET avid and non-avid groups, which of all showed correlation with tumor size (p<0.001).

14. - Summary & Conclusion (II) - • In terms of quantitative analysis (TSUVmax/nlTSUVmean<1.5vsTSUVmax/nlTSUVmean≥1.5) , TSUVmax/nlTSUVmean<1.5 (PET non-avid) group showed lower ETE (50.0% vs 73.3%, p=0.033) and LN meta. (26.5% vs 60.0%, p=0.003) rate with less number of retrieved (5.5 vs 11.2, p=0.002) and positive LN (2.2 vs 4.5, p=0.023). • In terms of quantitative analysis (TSUVmax/liverSUVmean<1.13vsTSUVmax/LiverSUVmean≥ 1.13) , TSUVmax/LiverSUVmean<1.13 (PET non-avid) group showed lower LN meta. rate (31.4% vs 56.8%, p=0.024) with less number of retrieved LNs (6.3 vs 10.7, p=0.041). • Preoperative PET avidity in PTC in terms of visual discernible uptake and quantitative analysis could be evaluable. • Further large-cohort prospective trial would be needed.

15. Thank you for your attention