Clinical Significance of Preoperative 18F-FDG

PET Non-Avidity in Papillary Thyroid Carcinoma

Do Hoon Koo1, Ho-Young Lee2, Kyu Eun Lee3,4, So Won Oh2, Hyung Ju 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, Korea2Department of Nuclear medicine, Seoul National University College of Medicine, Seoul, Korea3Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea4Division of Surgery, Thyroid Center, Seoul National University Cancer Hospital, Seoul, Ko-rea5Department of Surgery, Seoul National University Bundang Hospital and College of Medicine, Seongnam, Korea

- 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 associ-ated with dedifferentiated tumors and a grave prognosis.

[Rivera 2008 Cancer; Chung 1999 J Nucl Med]

However, preoperative FDG PET in papillary thyroid carci-noma (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 de-spite their well-differentiated histology.

[Kim 2010 Annals Nucl Med; Kang 2003 JCEM]

- 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 cen-tral 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 Laryn-goscope; Choi 2010 ASO]

Whether PET non-avid group, as is regarded as better dif-ferentiated characteristics, would truly show less aggres-sive nature needed to be evaluated.

We aimed to evaluate the rate of preoperative FDG non-avidity and assess clinical significance in PTC.

- Patients and Methods -

Between 2011 Jan and 2012 Apr, from 201 patients who underwent thyroidectomy d/t thyroid cancer in Seoul Na-tional 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 de-partment of nuclear medicine and the clinicopathologic fac-tors were analyzed.

- Patients Characteristics -

Variables Value (n=81)

Age (years) 50.0 ± 12.1 (25-79)

Sex, M : F 1:4.1 (16:65)

Size of tumor (cm) 1.06 ± 0.64 (0.3-3.3)

PTMC rate 50 (61.7%)

Preop. PET non-avidity 20 (24.7%)

Multifocality 30 (37.0%)

Extrathyroid extension 51 (62.9%)

LN meta 37 (45.7%)

Retrieved LN number 8.7 ± 8.8 (0-36)

Positive LN number 4.1 ± 3.4 (1-15)

Variables PET non-avid (n=20) PET avid (n=61) p value

Age (years) 48.1 ± 11.1 (29-73) 50.6 ± 12.4 (25-79) 0.198

Sex, M / F 8 (40.0%) / 12 8 (13.1%) / 53 0.009

Size of tumor (cm) 0.76 ± 0.34 (0.3-1.5) 1.20 ± 0.69 (0.3-3.3) 0.001

PTMC rate 16 (80.0%) 34 (55.7%) 0.053

Multifocality 4 (20.0%) 26 (42.6%) 0.069

Extrathyroid extension 6 (30.0%) 45 (73.8%) 0.001

LN meta 4 (20.0%) 33 (54.1%) 0.008

Retrieved LN number 4.3 ± 4.4 (0-17) 10.2 ± 9.3 (0-36) < 0.001

Positive LN number 3.5 ± 3.0 (1-7) 4.1 ± 3.5 (1-15) 0.721

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

Patient†TSUVmax

nlTSUVmean

TSUVmax/nlTSU-Vmean

LiverSUVmean

TSUVmax/LiverSU-Vmean

1 3.1 1.7 1.82 2.6 1.19

2 1.5 1.4 1.07 1.9 0.79

3 6.4 1.5 4.27 2.3 2.78

⁞

79 15.8 1.1 14.36 1.9 8.32

80 1.6 1.3 1.23 2.1 0.76

81 1.5 1.1 1.36 2.5 0.60

Median (range)

2.4 (1.1-25.8)

1.4 (0.9-2.8)

1.8 (0.52-23.0)

2.1 (1.2-3.0)

1.2 (0.48-9.58)

† 2 cases un-known

Definition of TSUVmax/nlTSUVmean and TSUVmax/LiverSUVmean

Nilsson et al 2011 World J Surg

TSUVmax: maximum SUVs of focally increased thyroid FDG up-take at the anatomic location of the tumornlTSUVmean: mean SUV from the surrounding normal thyroidLiverSUVmean : for normal organ reference

Variables (median) PET non-avid (n=20)† PET avid (n=61)† p value

TSUVmax1.74 (1.1-4.4) 5.19 (1.3-25.8) < 0.001

TSUVmax/nlTSUVmean1.27 (0.52-1.5) 3.89 (0.64-23) < 0.001

TSUVmax/LiverSUVmean0.84 (0.48-2.0) 2.44 (0.52-9.58) < 0.001

† 1 case un-known

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)

▷ TSUVmax/nlTSUVmean

Cut-off value 1.5) Sensitivity 0.717, Specificity 0.895

# ROC curve by TSUVmax, TSUVmax/nlTSUVmean and

TSUVmax/LiverSU-

Vmean

▷ 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

Area = 0.797 Area = 0.845Area = 0.857

Variables PET non-avid (n=31)

: TSUVmax <2PET avid (n=48)

: TSUVmax ≥2 p value

Age (years) 47.5 ± 9.9 (26-67) 52.1 ± 13.0 (25-79) 0.093

Sex, M / F 9 (29.0%) / 22 6 (12.5%) / 42 0.067

PTMC rate 27 (87.1%) 22 (45.8%) < 0.001

Multifocality 13 (41.9%) 17 (35.4%) 0.560

ETE 16 (51.6%) 34 (70.8%) 0.084

LN meta 9 (29.0%) 27 (56.2%) 0.018

Retrieved LNs 5.8 ± 5.7 (1-20) 10.2 ± 9.7 (0-36) 0.001

Positive LNs 2.8 ± 2.0 (1-7) 4.3 ± 3.7 (1-15) 0.243

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

† 2 cases un-known

Variables PET non-avid (n=34)

: TSUVmax/nlTSUVmean <1.5PET avid (n=45)

: TSUVmax/nlTSUVmean ≥1.5 p value

Age (years) 50.1 ± 8.6 (29-67) 50.5 ± 14.2 (25-79) 0.861

Sex, M / F 8 (23.5%) / 26 7 (15.6%) / 38 0.371

PTMC rate 31 (91.2%) 18 (40.0%) <0.001

Multifocality 14 (41.2%) 16 (35.6%) 0.610

ETE 17 (50.0%) 33 (73.3%) 0.033

LN meta 9 (26.5%) 27 (60.0%) 0.003

Retrieved LNs 5.5 ± 5.3 (1-24) 11.2 ± 10.1 (0-36) 0.002

Positive LNs 2.2 ± 1.9 (1-7) 4.5 ± 3.6 (1-15) 0.023

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

† 2 cases un-known

Variables

PET non-avid (n=35): TSUVmax/LiverSUVmean

<1.13

PET avid (n=44): TSUVmax/LiverSUVmean

≥1.13p value

Age (years) 48.6 ± 10.2 (25-67) 51.7 ± 13.3 (25-79) 0.253

Sex, M / F 10 (28.6%) / 25 5 (11.4%) / 39 0.053

PTMC rate 30 (85.7%) 19 (43.2%) <0.001

Multifocality 13 (37.1%) 17 (38.6%) 0.892

ETE 19 (54.3%) 31 (70.5%) 0.139

LN meta 11 (31.4%) 25 (56.8%) 0.024

Retrieved LNs 6.3 ± 5.8 (1-24) 10.7 ± 10.3 (0-36) 0.041

Positive LNs 2.7 ± 1.8 (1-7) 4.5 ± 3.8 (1-15) 0.073

Result 3-3) Comparison of PET non-avid vs PET–avid groups: classified by cut-off value 1.13 of TSUVmax/LiverSUVmean

† 2 cases un-known

- 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).

- Summary & Conclusion (II) -

• In terms of quantitative analysis (TSUVmax/nlTSUVmean <1.5 vs TSUVmax/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 <1.13 vs TSUVmax/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 dis-cernible uptake and quantitative analysis could be evalu-able.

• Further large-cohort prospective trial would be needed.

Thank you for your atten-tion