title: Pretreatment screening on distant metastases and head and neck cancer patients: Validation of risk factors and influence on survival.
abstract: OBJECTIVE
  Previously identified high risk factors for development of distant metastases are: three or more lymph node metastases, bilateral lymph node metastases, lymph nodes larger than 6cm, low jugular lymph node metastases, locoregional tumor recurrence and second primary tumors. The aims of this study were to validate these specific risk factors and to investigate the impact of time (i.e. during screening or follow-up) of detection of distant metastases on survival.
  
  
  METHODS
  From a total of 301 HNSCC patients with high risk factors who were scheduled for extensive treatment and underwent pretreatment screening on distant metastases using chest CT and/or whole body PET(-CT) (in some patients combined with whole body MRI), the high risk factors, the development and time point of distant metastases and survival were analyzed.
  
  
  RESULTS
  Forty-four percent developed distant metastases. Multivariate analysis revealed that bilateral lymph node metastases is the strongest predictive factor. Locoregional recurrence and second primary tumor were the risk factors associated with the lowest cumulative incidence. However, if the risk factor locoregional recurrence was split into local and regional recurrences, regional recurrence became a high risk factor. The more high risk factors a patient had the lower the 5-year distant metastases free survival was. Patients with distant metastases detected pretreatment has a significant worse survival (corrected for lead time bias) compared to patients with distant metastases diagnosed during follow-up.
  
  
  CONCLUSIONS
  The validity of three or more lymph node metastases, bilateral lymph node metastases, lymph nodes larger than 6cm, low jugular lymph node metastases and regional recurrence as high risk factors for the development of distant metastases was confirmed. If more high risk factors are present the cumulative incidence of distant metastases increases significantly. The detection of distant metastases by pretreatment screening worsens the overall survival as compared to distant metastases detected during follow-up.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Peters
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Asaf
authors.initials: A
authors.lastname: Senft
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Castelijns
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Birgit I
authors.initials: BI
authors.lastname: Witte
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: C René
authors.initials: CR
authors.lastname: Leemans
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: r.bree@vumc.nl.
authors.forename: Remco
authors.initials: R
authors.lastname: de Bree
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000628:therapy; D006801:Humans; D008207:Lymphatic Metastasis; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D019275:Radiopharmaceuticals; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: Distant metastases; Risk factors; Screening; Survival