title: Non-metastatic stage IV nasopharyngeal carcinoma patients: analysis of the pattern of relapse and survival.
abstract: OBJECTIVE
  The objective of this study is to analyze the mode of recurrence patterns and survival of our 96 non-metastatic stage IVA and IVB nasopharyngeal carcinoma (NPC) patients.
  
  
  METHODS
  A total of 234 previously untreated, histologically confirmed non-metastatic NPC patients were treated in our department between 1993 and 2001. Among them 96 patients (41%) were staged as IVA or B disease. All patients were uniformly staged using the fifth edition of AJCC/UICC staging system. There were 76 male and 20 female patients. Their ages ranged from 9 to 72 years (median age: 43.5). Histopathological diagnosis was WHO 2 and 3 in 89 (93%) patients. All patients were treated with external radiotherapy and 77 out of 96 patients (80%) with stage IV disease received either concomitant or neoadjuvant cisplatin based combined chemotherapy regimens. Median follow-up time was 30 months (range: 4-101 months).
  
  
  RESULTS
  At the time of this analysis, 60 (62%) patients were alive and 48 of them were free of disease. Local recurrence rate was found to be significantly higher in stage IVA patients (28 vs. 11%, P=0.02) and distant metastasis rate was significantly higher in stage IVB patients (40 vs. %8, P=0.0001). The 3 year overall (OS), disease free (DFS), loco regional relapse free (LRRFS) and distant metastasis free survival (DMFS) rates were 71, 74, 77 and 94% for stage IVA and 60, 46, 77 and 58% for stage IVB patients, respectively. Three year LRFS rates for stage IVA and IVB were 77 and 89%, respectively (P=0.1). Age older than 40 years was found to be statistically significant adverse prognostic factor both for OS (P=0.01) and LRRFS (P=0.005) in univariate analysis. Advanced N status was an unfavorable prognostic factor both for OS (P=0.03), DFS (P=0.0004) and DMFS (P=0.0003). DMFS was adversely affected by the presence of cranial nerve palsy at diagnosis (P=0.01), advanced T status (P=0.03) and advanced N status (P=0.0003). In univariate analysis treatment with chemotherapy was found to be an unfavorable prognostic factor for DMFS (P=0.02). According to the multivariate analysis, older age (>40 year of age) was a significant independent prognostic factor for OS (P=0.02), DFS (P=0.05) and LRRFS (P=0.01). Patients with advanced N status had worse OS (P=0.03), DFS (P<0.0001) and DMFS (P=0.07). Patients treated with chemotherapy as an adjuvant to radiotherapy had tended to have a better DFS (P=0.04).
  
  
  CONCLUSIONS
  The local relapse was the major cause of failure in patients with stage IVA disease, and distant metastasis was the predominant treatment failure in stage IVB patients. While stage IVA patients may benefit more intensive local treatment strategies, stage IVB patients definitely need more systemic treatment.
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
authors.forename: Enis
authors.initials: E
authors.lastname: Ozyar
authors.forename: Murat
authors.initials: M
authors.lastname: Gurkaynak
authors.forename: Ferah
authors.initials: F
authors.lastname: Yildiz
authors.forename: I Lale
authors.initials: IL
authors.lastname: Atahan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D002945:Cisplatin