title: Differentiated Thyroid Cancer lymph-node relapse. Role of adjuvant radioactive iodine therapy after lymphadenectomy.
abstract: OBJECTIVE
  Our purpose as to evaluate the impact of adjuvant radioactive iodine therapy (RAI) on prognosis, as assessed by progression-free survival (PFS) and overall survival (OS), in patients affected by differentiated thyroid carcinoma (DTC) lymph-node relapse and previously treated with lymphadenectomy.
  
  
  METHODS
  We retrospectively evaluated DTC patients treated with lymph-node dissection for disease relapse. All patients had previously undergone total thyroidectomy and radioiodine remnant ablation (RRA). We used clinical and histological data obtained during follow-up to assess response and outcome. By means of univariate and multivariate time-to-event analyses, we assessed the impact of RAI on outcome (PFS and OS) and the prognostic role of thyroglobulin (Tg) levels under suppression with levothyroxine (Tg-on) measured 1-3 months after lymphadenectomy and of other risk factors.
  
  
  RESULTS
  We evaluated 113 patients (age at diagnosis: median 41 years, interquartile range: 31-59), 64 of whom were treated with RAI. Over a median follow-up time of 5.7 years, 27 patients showed disease progression and 13 died. Kaplan-Meier PFS and OS curves showed that age on diagnosis, tumor histology, tumor size, DTC aggressive variant, and Tg-on were associated with prognosis. Patients with Tg-on ≥1 ng/ml treated with RAI showed a better PFS (Log-rank pp 0.001) and OS (p = 0.005) than untreated patients, while no effect of RAI was observed in patients with Tg-on <1 ng/ml. Multivariate models showed that age, Tg-on (≥1 vs. < 1 ng/ml, HR: 18.2, 95% CI: 5.09-64.8, p = 0.001) and RAI (Yes vs. No, HR: 0.36,95%CI: 0.15-0. 9, p = 0.02) remained the only independent factors associated with PFS, but only age and Tg-on remained significantly associated with OS (HR: 8.31, 95%CI:1.56-44.3, p = 0.01). Nonetheless, patients treated with RAI showed a lower risk of mortality (HR: 0.34, 95%CI: 0.1-1.15 p = 0.08) than untreated patients.
  
  
  CONCLUSIONS
  RAI after lymphadenectomy for DTC relapse is significantly associated with better PFS only in patients with Tg-on ≥1 ng/ml.
authors.affiliation: Department of Nuclear Medicine, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy. arnoldo.piccardo@galliera.it.
authors.forename: Arnoldo
authors.identifier: http://orcid.org/0000-0002-6779-1471
authors.initials: A
authors.lastname: Piccardo
authors.affiliation: Clinical Trial Unit, Office of the Scientific Director, Galliera Hospital, Genoa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Puntoni
authors.affiliation: Department of Nuclear Medicine, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Bottoni
authors.affiliation: Department of Nuclear Medicine and PET/CT Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Treglia
authors.affiliation: Internal Medicine, Galliera Hospital, Genoa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Foppiani
authors.affiliation: Department of Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Bertoli
authors.affiliation: Department of Surgery, Thyroid Centre, Galliera Hospital, Genoa, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Catrambone
authors.affiliation: Department of Surgery, Thyroid Centre, Galliera Hospital, Genoa, Italy.
authors.forename: Anselmo
authors.initials: A
authors.lastname: Arlandini
authors.affiliation: Department of Nuclear Medicine, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy.
authors.forename: Bassam
authors.initials: B
authors.lastname: Dib
authors.affiliation: Department of Nuclear Medicine, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy.
authors.forename: Vania
authors.initials: V
authors.lastname: Altrinetti
authors.affiliation: Department of Nuclear Medicine, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Massollo
authors.affiliation: Department of Nuclear Medicine, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Bossert
authors.affiliation: Department of Nuclear Medicine, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy.
authors.forename: Manlio
authors.initials: M
authors.lastname: Cabria
authors.affiliation: Department of Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertagna
authors.affiliation: Department of Nuclear Medicine and PET/CT Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Giovanella
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant; D012008:Recurrence; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000473:pathology* / Q000532:radiotherapy* / Q000601:surgery; D013965:Thyroidectomy; D055815:Young Adult
chemical_list: D007457:Iodine Radioisotopes
keywords: Adjuvant RAI; Differentiated thyroid cancer; Lymphadenectomy; Prognosis