title: Does radiation dose matter in thyroid cancer?: Patterns of local-regional failure in recurrent and metastatic well-differentiated thyroid cancers treated with dose-painted intensity-modulated radiation therapy.
abstract: BACKGROUND
  Due to complex multimodal treatments and a lengthy natural history of disease, the impact of radiation therapy for well-differentiated thyroid cancer (WDTC) is challenging to evaluate. We analysed the effect of dose escalation, as enabled by intensity-modulated radiation therapy (IMRT), on preventing local-regional failure (LRF) of microscopic and macroscopic WDTC.
  
  
  METHODS
  We performed a retrospective review of WDTC patients treated with IMRT from 1998-2011. Diagnostic imaging demonstrating first LRF was registered to the simulation CT containing the treated radiation isodose volumes. Areas of disease progression were contoured and the relationships of LRFs with isodose volumes were recorded.
  
  
  RESULTS
  Thirty patients had a median follow-up of 56 months (range = 1-139). Seventeen (57%) had gross residual, five (17%) had microscopic residual and eight (27%) had clear margins at the time of IMRT. Nine patients (30%) developed LRF, at a median time of 44 months (range = 0-116). Of these, six (67%) had been radiated to gross disease and one (11%) had microscopic residual. In the seven analysable cases, only one (14%) LRF occurred within the 70 Gy isodose volume. Marginal LRFs were: four (57%) outside 70 Gy, one (14%) outside 60 Gy and one (14%) outside 50 Gy. All but one recurrence (86%) occurred in the perioesophageal region.
  
  
  CONCLUSIONS
  Local-regional failure was seen most in patients who had gross disease at the time of IMRT, almost always occurred outside of the 70 Gy volume and was frequently in the area of oesophageal sparing. Meticulous surgical dissection, especially in the perioesophageal region, should be prioritised to prevent long-term LRF.
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California, USA.
authors.forename: Erin
authors.identifier: http://orcid.org/0000-0001-7688-8999
authors.initials: E
authors.lastname: Shugard
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California, USA.
authors.forename: Josephine
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California, USA.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Quivey
authors.affiliation: Department of Radiology, University of California, San Francisco, California, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Glastonbury
authors.affiliation: Department of Pathology, University of California, San Francisco, California, USA.
authors.forename: Elham
authors.initials: E
authors.lastname: Khanafshar
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California, USA.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Garsa
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, University of California, San Francisco, California, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: George
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, California, USA.
authors.forename: Sue S
authors.identifier: http://orcid.org/0000-0002-0779-7476
authors.initials: SS
authors.lastname: Yom
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000453:epidemiology*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012189:Retrospective Studies; D013961:Thyroid Gland / Q000000981:diagnostic imaging; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000532:radiotherapy*; D014057:Tomography, X-Ray Computed; D017211:Treatment Failure; D055815:Young Adult
keywords: follicular thyroid cancer; papillary; well differentiated