title: Final report of a randomized trial on altered-fractionated radiotherapy in nasopharyngeal carcinoma prematurely terminated by significant increase in neurologic complications.
abstract: OBJECTIVE
  The aim of the present study was to compare the survival, local control and complications of conventional/accelerated-hyperfractionated radiotherapy and conventional radiotherapy in nonmetastatic nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  From February 1993 to October 1995, 159 patients with newly diagnosed nonmetastatic (M0) NPC with N0 or 4 cm or less N1 disease (Ho's N-stage classification, 1978) were randomized to receive either conventional radiotherapy (Arm I, n = 82) or conventional/accelerated-hyperfractionated radiotherapy (Arm II, n = 77). Stratification was according to the T stage. The biologic effective dose (10 Grays) to the primary and the upper cervical lymphatics were 75.0 and 73.1 for Arm I and 84.4 and 77.2 for Arm II, respectively.
  
  
  RESULTS
  With comparable distribution among the T stages between the two arms, the free from local failure rate at 5 years after radiotherapy was not significantly different between the two arms (85.3%; 95% confidence interval, 77.2-93.4% for Arm I; and 88.9%; 95% confidence interval, 81.7-96.2% for Arm II). The two arms were also comparable in overall survival, relapse-free survival, and rates of distant metastasis and regional relapse. Conventional/accelerated-hyperfractionated radiotherapy was associated with significantly increased radiation-induced damage to the central nervous system (including temporal lobe, cranial nerves, optic nerve/chiasma, and brainstem/spinal cord) in Arm II. Although insignificant, radiation-induced cranial nerve(s) palsy (typically involving VIII-XII), trismus, neck soft tissue fibrosis, and hypopituiturism and hypothyroidism occurred more often in Arm II. In addition, the complications occurred at significantly shorter intervals after radiotherapy in Arm II.
  
  
  CONCLUSIONS
  Accelerated hyperfractionation when used in conjunction with a two-dimensional radiotherapy planning technique, in this case the Ho's technique, resulted in increased radiation damage to the central nervous system without significant improvement in efficacy.
authors: Department of Clinical Oncology, Prince of Wales Hospital, Shatin, Hong Kong, People's Republic of China. teoml@ha.org.hk
authors: P M
authors: PM
authors: Teo
authors: S F
authors: SF
authors: Leung
authors: A T
authors: AT
authors: Chan
authors: T W
authors: TW
authors: Leung
authors: P H
authors: PH
authors: Choi
authors: W H
authors: WH
authors: Kwan
authors: W Y
authors: WY
authors: Lee
authors: R M
authors: RM
authors: Chau
authors: P K
authors: PK
authors: Yu
authors: P J
authors: PJ
authors: Johnson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001927:Brain Diseases / Q000209:etiology*; D016001:Confidence Intervals; D003389:Cranial Nerve Diseases / Q000209:etiology; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology*; D012062:Relative Biological Effectiveness; D016019:Survival Analysis; D013702:Temporal Lobe / Q000473:pathology / Q000528:radiation effects; D017211:Treatment Failure