title: Major late toxicities after conformal radiotherapy for nasopharyngeal carcinoma-patient- and treatment-related risk factors.
abstract: OBJECTIVE
  To retrospectively analyze the factors affecting late toxicity for nasopharyngeal carcinoma.
  
  
  METHODS
  Between 1998 and 2003, 422 patients were treated with a conformal technique with 2-Gy daily fractions to a total dose of 70 Gy. Conventional fractionation (5 fractions weekly) was used in 232 patients and accelerated fractionation (6 fractions weekly) in 190 patients. One hundred seventy-one patients were treated with the basic radiotherapy course alone (Group 1), 55 patients had an additional boost of 5 Gy in 2 fractions (Group 2), and 196 patients underwent concurrent cisplatin-based chemotherapy (Group 3).
  
  
  RESULTS
  The 5-year overall toxicity rate was significantly greater in Group 3 than in Group 1 (37% vs. 27%, p = 0.009). Although the overall rate in Group 2 was not elevated (28% vs. 27%, p = 0.697), a significant increase in temporal lobe necrosis was observed (4.8% vs. 0%, p = 0.015). Multivariate analyses showed that age and concurrent chemotherapy were significant factors. The hazard ratio of overall toxicity attributed to chemotherapy was 1.99 (95% confidence interval, 1.32-2.99, p = 0.001). The mean radiation dose to the cochlea was another significant factor affecting deafness, with a hazard ratio of 1.03 (95% confidence interval, 1.01-1.05, p = 0.005) per 1-Gy increase. The cochlea that received >50 Gy had a significantly greater deaf rate (Group 1, 18% vs. 7%; and Group 3, 22% vs. 14%).
  
  
  CONCLUSIONS
  The therapeutic margin for nasopharyngeal carcinoma is extremely narrow, and a significant increase in brain necrosis could result from dose escalation. The significant factors affecting the risk of deafness included age, concurrent chemoradiotherapy, and greater radiation dose to the cochlea.
authors: Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong. awmlee@ha.org.hk
authors: Anne W M
authors: AW
authors: Lee
authors: W T
authors: WT
authors: Ng
authors: W M
authors: WM
authors: Hung
authors: C W
authors: CW
authors: Choi
authors: Raymond
authors: R
authors: Tung
authors: Y H
authors: YH
authors: Ling
authors: Peter T C
authors: PT
authors: Cheng
authors: T K
authors: TK
authors: Yau
authors: Amy T Y
authors: AT
authors: Chang
authors: Samuel K C
authors: SK
authors: Leung
authors: Michael C H
authors: MC
authors: Lee
authors: Soren M
authors: SM
authors: Bentzen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000473:pathology; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D012189:Retrospective Studies; D012307:Risk Factors; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D002945:Cisplatin; D005472:Fluorouracil