title: Distant metastases in head-and-neck squamous cell carcinoma treated with intensity-modulated radiotherapy.
abstract: OBJECTIVE
  To determine the pattern and risk factors for distant metastases in head-and-neck squamous cell carcinoma (HNSCC) after curative treatment with intensity-modulated radiotherapy (IMRT).
  
  
  METHODS
  This was a retrospective study of 284 HNSCC patients treated in a single institution with IMRT. Sites included were oropharynx (125), oral cavity (70), larynx (55), hypopharynx (17), and unknown primary (17). American Joint Committee on Cancer stage distribution includes I (3), II (19), III (42), and IV (203). There were 224 males and 60 females with a median age of 57. One hundred eighty-six patients were treated with definitive IMRT and 98 postoperative IMRT. One hundred forty-nine patients also received concurrent cisplatin-based chemotherapy.
  
  
  RESULTS
  The median follow-up for all patients was 22.8 months (range, 0.07-77.3 months) and 29.5 months (4.23-77.3 months) for living patients. The 3-year local recurrence-free survival, regional recurrence-free survival, locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 94.6%, 96.4%, 92.5%, 84.1%, and 68.95%, respectively. There were 45 patients with distant metastasis. In multivariate analysis, distant metastasis was strongly associated with N stage (p = 0.046), T stage (p < 0.0001), and pretreatment maximum standardized uptake value of the lymph node (p = 0.006), but not associated with age, gender, disease sites, pretreatment standardized uptake value of the primary tumor, or locoregional control. The freedom from distant metastasis at 3 years was 98.1% for no factors, 88.6% for one factor, 68.3% for two factors, and 41.7% for three factors (p < 0.0001 by log-rank test).
  
  
  CONCLUSIONS
  With advanced radiation techniques and concurrent chemotherapy, the failure pattern has changed with more patients failing distantly. The majority of patients with distant metastases had no local or regional failures, indicating that these patients might have microscopic distant disease before treatment. The clinical factors identified here should be incorporated in future clinical trials.
authors.affiliation: Department of Radiation Oncology, University Hospitals Case Medical Center, Cleveland, OH 44106, USA. min.yao@uhhospitals.org
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Minggen
authors.initials: M
authors.lastname: Lu
authors.forename: Panayiotis S
authors.initials: PS
authors.lastname: Savvides
authors.forename: Rod
authors.initials: R
authors.lastname: Rezaee
authors.forename: Chad A
authors.initials: CA
authors.lastname: Zender
authors.forename: Pierre
authors.initials: P
authors.lastname: Lavertu
authors.forename: John M
authors.initials: JM
authors.lastname: Buatti
authors.forename: Mitchell
authors.initials: M
authors.lastname: Machtay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012189:Retrospective Studies