title: Unknown primary head and neck squamous cell carcinoma in the era of fluorodeoxyglucose-positron emission tomography/CT and intensity-modulated radiotherapy.
abstract: The diagnosis and treatment of head and neck carcinoma of unknown primary (CUP) have changed with the introduction of fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT and intensity-modulated radiotherapy (IMRT), with potential implications for outcome.
  
  
  
  We conducted a retrospective analysis of 80 patients with head and neck CUP who were PET-staged and treated with curative intention using IMRT between 2006 and 2016 in the Netherlands Cancer Institute. Patient, tumor, and treatment demographics were recorded and oncologic outcomes were analyzed.
  
  
  
  Local control was 100% in mucosal irradiated patients. Regional control was 90%. Ten patients developed distant metastases, which were associated with N3, extracapsular extension (ECE) and lower neck positive lymph nodes. Overall survival (OS) at 5 years was 62% and disease-specific survival was 78%. ECE, N3 neck, multiple levels of positive lymph nodes, and positive lymph nodes in the lower neck were associated with worse prognosis.
  
  
  
  Locoregional outcome of head and neck CUP managed with modern techniques is good. Future research needs to focus on reducing toxicity and patients prone for distant metastasis.
authors.affiliation: Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Mischa
authors.identifier: 0000-0002-8467-0006
authors.initials: M
authors.lastname: de Ridder
authors.affiliation: Department of Head and Neck Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Klop
authors.affiliation: Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Olga
authors.initials: O
authors.lastname: Hamming-Vrieze
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: JanPaul
authors.initials: J
authors.lastname: de Boer
authors.affiliation: Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Jasperse
authors.affiliation: Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: Smit
authors.affiliation: Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Vogel
authors.affiliation: Department of Head and Neck Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands.|Department of Oral and Maxillofacial Surgery, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: van den Brekel
authors.affiliation: Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Abrahim
authors.initials: A
authors.lastname: Al-Mamgani
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D006801:Humans; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000000981:diagnostic imaging / Q000532:radiotherapy; D009426:Netherlands; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods; D011379:Prognosis; D016016:Proportional Hazards Models; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: head and neck cancer; intensity-modulated radiotherapy (IMRT); metastasis; radiotherapy; survival; unknown primary