title: Is outcome of differentiated thyroid carcinoma influenced by tumor stage at diagnosis?
abstract: BACKGROUND
  There is no international consensus on surveillance strategies for differentiated thyroid carcinoma (DTC) after radiotherapy for childhood cancer. Ultrasonography could allow for early detection of DTC, however, its value is yet unclear since the prognosis of DTC is excellent. We addressed the evidence for the question: 'is outcome of DTC influenced by tumor stage at diagnosis?'.
  
  
  METHODS
  A multidisciplinary working group answered the sub-questions: 'is recurrence or mortality influenced by DTC stage at diagnosis? Does detection of DTC at an early stage contribute to a decline in adverse events of treatment?' The literature was systematically reviewed, and conclusions were drawn based on the level of evidence (A: high, B: moderate to low, C: very low).
  
  
  RESULTS
  In children, level C evidence was found that detection of DTC at an early stage is associated with lower recurrence and mortality rates. No evidence was found that it influences morbidity rates. In adults, clear evidence was found that less advanced staged DTC is a favorable prognostic factor for recurrence (level B) and mortality (level A). Additionally, it was found that more extensive surgery increases the risk to develop transient hypoparathyroidism (level A) and that higher doses of radioiodine increases the risk to develop second primary malignancies (level B).
  
  
  CONCLUSIONS
  Identification of DTC at an early stage is beneficial for children (very low level evidence) and adults (moderate to high level evidence), even considering that the overall outcome is excellent. These results are an important cornerstone for the development of guidelines for childhood cancer survivors at risk for DTC.
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands. Electronic address: s.c.clement@amc.uva.nl.
authors.forename: S C
authors.initials: SC
authors.lastname: Clement
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands; Dutch Childhood Oncology Group (DCOG-LATER), PO Box 43515, 2504 AM The Hague, The Netherlands.
authors.forename: L C M
authors.initials: LC
authors.lastname: Kremer
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: T P
authors.initials: TP
authors.lastname: Links
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: R L
authors.initials: RL
authors.lastname: Mulder
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands; Dutch Childhood Oncology Group (DCOG-LATER), PO Box 43515, 2504 AM The Hague, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Ronckers
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: B L F
authors.initials: BL
authors.lastname: van Eck-Smit
authors.affiliation: Department of Radiology, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: R R
authors.initials: RR
authors.lastname: van Rijn
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands; Dutch Childhood Oncology Group (DCOG-LATER), PO Box 43515, 2504 AM The Hague, The Netherlands; Department of Oncology, Academic Medical Center, Amsterdam, University of Amsterdam, PO Box 22660 1100 DD Amsterdam, The Netherlands.
authors.forename: H J H
authors.initials: HJ
authors.lastname: van der Pal
authors.affiliation: Dutch Childhood Oncology Group (DCOG-LATER), PO Box 43515, 2504 AM The Hague, The Netherlands; Department of Pediatric Oncology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: W J E
authors.initials: WJ
authors.lastname: Tissing
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: G O
authors.initials: GO
authors.lastname: Janssens
authors.affiliation: Dutch Childhood Oncology Group (DCOG-LATER), PO Box 43515, 2504 AM The Hague, The Netherlands; Department of Pediatric Hematology and Oncology, Erasmus MC/Sophia Children's Hospital, PO Box 2060, 3000 CB Rotterdam, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
authors.affiliation: Dutch Childhood Oncology Group (DCOG-LATER), PO Box 43515, 2504 AM The Hague, The Netherlands; Department of Internal Medicine/Endocrinology, Erasmus MC-University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: S J C M M
authors.initials: SJ
authors.lastname: Neggers
authors.affiliation: Department of Pediatric Surgery, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: E J M Nieveen
authors.initials: EJ
authors.lastname: van Dijkum
authors.affiliation: Department of Internal Medicine/Endocrinology, Erasmus MC-University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands; Rotterdam Thyroid Center, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: R P
authors.initials: RP
authors.lastname: Peeters
authors.affiliation: Department of Pediatric Endocrinology, Wilhelmina Children's Hospital/University Medical Center Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: van Santen
mesh_terms: D000328:Adult; D002648:Child; D055088:Early Detection of Cancer; D006801:Humans; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy
keywords: Childhood Cancer Survivors; Differentiated thyroid carcinoma; External radiotherapy; Radiation damage; Thyroid ultrasonography