Prognostic impact of incomplete surgical clearance of radioiodine sensitive local lymph node metastases diagnosed by post-operative (124)I-NaI-PET/CT in patients with papillary thyroid cancer.
OBJECTIVE
Nodal involvement is an independent risk factor of recurrence in papillary thyroid cancer (PTC). Neither the international guidelines nor the recently introduced ongoing risk adaptation concept consider the extent of initial surgical clearance of radioiodine sensitive lymph node metastases in their stratification systems. We investigated the prognostic relevance of incomplete initial surgical clearance in patients with purely lymphogeneous metastatic PTC (pN1 M0) despite successful radioiodine therapy. Accurate assessment of pre-ablative nodal status was attempted using PET/CT studies with both (124)I-NaI and (18)F-FDG along with high-resolution cervical ultrasound.


METHODS
Sixty-five patients with histologically diagnosed lymph node metastases (pN1 M0) were retrospectively analyzed. Patients with iodine-negative lymph node metastases diagnosed by (18)F-FDG PET/CT or distant metastases were excluded from the analysis. The association of disease recurrence with the pre-ablative nodal status, as well as other baseline characteristics, were examined applying nonparametric tests for independent samples and multiple regression analysis. Patients with persistent lymph node metastases in (124)I-NaI PET/CT were further divided according to the additional presence or absence of FDG-uptake in (18)F-FDG PET/CT. Survival analyses were performed using Kaplan-Meier curves and the Cox proportional hazards model for uni- and multivariate analyses to assess the influence of prognostic factors on progression free survival (PFS).


RESULTS
Incomplete metastatic lymph node resection captured by (124)I-NaI PET/CT (n = 33) was an independent risk factor for recurrence (61 % vs 25 %, p = 0.006) and shorter PFS (46 months vs not reached, HR 4.0 [95 %-CI, 1.7-9.2], p = 0.001). Ultrasound could detect lymph node metastases only in 19/33 patients (58 %). Among patients with positive nodal status, FDG-avidity of metastatic iodine positive lymph nodes worsened the outcome (16 vs 69 months, p = 0.047). From all other investigated factors including age, N-stage (N1a vs N1b), and T-Stage (T4 vs T1-3), only large tumor size (pT4) had a significant impact on PFS (HR 2.9 [95 %-CI, 1.3-6.4], p = 0.007).


CONCLUSIONS
Incomplete initial surgical clearance of lymph node metastases even after successful radioiodine therapy may increase the chances of recurrence and is an independent risk factor for impaired survival of patients with PTC. Pre-ablative (dual tracer PET/CT) imaging with (124)I-Na and (18)F provides a prognostic tool for these patients and may considerably complement the current risk stratification systems.
Department of Nuclear Medicine, University Duisburg-Essen, Hufelandstr. 55, D-45147, Essen, Germany. amir.sabet@ukessen.de.
Amir
A
Sabet
Department of Nuclear Medicine, University Duisburg-Essen, Hufelandstr. 55, D-45147, Essen, Germany.
Ina
I
Binse
Department of Nuclear Medicine, University Duisburg-Essen, Hufelandstr. 55, D-45147, Essen, Germany.
Hong
H
Grafe
Department of Nuclear Medicine, Saarland University, Homburg, Germany.
Samer
S
Ezziddin
Department of Nuclear Medicine, University Duisburg-Essen, Hufelandstr. 55, D-45147, Essen, Germany.
Rainer
R
Görges
Department of Nuclear Medicine, University Duisburg-Essen, Hufelandstr. 55, D-45147, Essen, Germany.
Thorsten D
TD
Poeppel
Department of Nuclear Medicine, University Duisburg-Essen, Hufelandstr. 55, D-45147, Essen, Germany.
Andreas
A
Bockisch
Department of Nuclear Medicine, University Duisburg-Essen, Hufelandstr. 55, D-45147, Essen, Germany.
Sandra J
SJ
Rosenbaum-Krumme
D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000000981:diagnostic imaging / Q000401:mortality* / Q000601:surgery*; D002291:Carcinoma, Papillary; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D000072078:Positron Emission Tomography Computed Tomography / Q000706:statistics & numerical data*; D015995:Prevalence; D011379:Prognosis; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D000071036:Sentinel Lymph Node / Q000000981:diagnostic imaging* / Q000601:surgery; D012974:Sodium Iodide; D015996:Survival Rate; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality* / Q000601:surgery*; D016896:Treatment Outcome; D055815:Young Adult
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D012974:Sodium Iodide
Lymph node; PTC; Radioiodine therapy; Risk factor; Surgical clearance