title: Factors affecting risk of symptomatic temporal lobe necrosis: significance of fractional dose and treatment time.
abstract: OBJECTIVE
  To study the factors affecting the risk of symptomatic temporal lobe necrosis after different fractionation schedules.
  
  
  METHODS
  One thousand thirty-two patients with T1-2 nasopharyngeal carcinoma treated with radical radiotherapy in Hong Kong during 1990-1995 were studied. They were treated at four different centers with similar techniques but different fractionation schedules: 984 patients were given 1 fraction daily throughout (q.d.), and 48 patients were irradiated twice daily (b.i.d.) for part of the course. The median total dose was 62.5 Gy (range 50.4-71.2), dose per fraction was 2.5 Gy (range 1.6-4.2), and overall treatment time (OTT) was 44 days (range 29-70). In addition, 500 patients received supplementary doses for parapharyngeal extension, 113 received booster doses by brachytherapy, and 114 received sequential chemotherapy using cisplatin-based regimes.
  
  
  RESULTS
  Altogether, 24 patients developed symptomatic temporal lobe necrosis: 18 from the q.d. group and 6 from the b.i.d. group. The 5-year actuarial incidence ranged from 0% (after 66 Gy in 33 fractions within 44 days) to 14% (after 71.2 Gy in 40 fractions within 35 days). Multivariate analyses showed that the risk was significantly affected by the fractional effect of the product of total dose and dose per fraction (hazard ratio [HR] = 1.04, 95% confidence interval [CI] 1.02-1.05), OTT (HR 0.88, 95% CI 0.80-0.97), and b.i.d. scheduling (HR 13, 95% CI 3-54). Repeating the analyses for patients treated with the q.d. schedules confirmed the independent significance of OTT in addition to the product of total dose and dose per fraction.
  
  
  CONCLUSIONS
  The tentative results suggest that in addition to fractional dose, the OTT also had significant impact on the risk of temporal lobe necrosis, and b.i.d. scheduling increased the hazard further.
authors: Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, 3 Lok Man Road, Chai Wan, Hong Kong, SAR, China. awmlee@ha.org.hk
authors: Anne W M
authors: AW
authors: Lee
authors: Dora L W
authors: DL
authors: Kwong
authors: Sing Fai
authors: SF
authors: Leung
authors: Stewart Y
authors: SY
authors: Tung
authors: Wai Man
authors: WM
authors: Sze
authors: Jonathan S T
authors: JS
authors: Sham
authors: Peter M L
authors: PM
authors: Teo
authors: To Wai
authors: TW
authors: Leung
authors: Po Man
authors: PM
authors: Wu
authors: Rick
authors: R
authors: Chappell
authors: Lester J
authors: LJ
authors: Peters
authors: John F
authors: JF
authors: Fowler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002277:Carcinoma / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000473:pathology*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D012306:Risk; D013702:Temporal Lobe / Q000473:pathology / Q000528:radiation effects*