title: Reirradiation of large-volume recurrent glioma with pulsed reduced-dose-rate radiotherapy.
abstract: OBJECTIVE
  Pulsed reduced-dose-rate radiotherapy (PRDR) is a reirradiation technique that reduces the effective dose rate and increases the treatment time, allowing sublethal damage repair during irradiation.
  
  
  METHODS
  A total of 103 patients with recurrent glioma underwent reirradiation using PRDR (86 considered to have Grade 4 at PRDR). PRDR was delivered using a series of 0.2-Gy pulses at 3-min intervals, creating an apparent dose rate of 0.0667 Gy/min to a median dose of 50 Gy (range, 20-60) delivered in 1.8-2.0-Gy fractions. The mean treatment volume was 403.5±189.4 cm3 according to T2-weighted magnetic resonance imaging and a 2-cm margin.
  
  
  RESULTS
  For the initial or upgraded Grade 4 cohort (n=86), the median interval from the first irradiation to PRDR was 14 months. Patients undergoing PRDR within 14 months of the first irradiation (n=43) had a median survival of 21 weeks. Those treated ≥14 months after radiotherapy had a median survival of 28 weeks (n=43; p=0.004 and HR=1.82 with a 95% CI ranging from 1.25 to 3.10). These data compared favorably to historical data sets, because only 16% of the patients were treated at first relapse (with 46% treated at the second relapse, 32% at the third or fourth relapse, and 4% at the fourth or fifth relapse). The median survival since diagnosis and retreatment was 6.3 years and 11.4 months for low-grade, 4.1 years and 5.6 months for Grade 3, and 1.6 years and 5.1 months for Grade 4 tumors, respectively, according to the initial histologic findings. Multivariate analysis revealed age at the initial diagnosis, initial low-grade disease, and Karnofsky performance score of ≥80 to be significant predictors of survival after initiation of PRDR.
  
  
  CONCLUSIONS
  PRDR allowed for safe retreatment of larger volumes to high doses with palliative benefit.
authors.affiliation: Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Jarrod B
authors.initials: JB
authors.lastname: Adkison
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Tomé
authors.forename: Songwon
authors.initials: S
authors.lastname: Seo
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Richards
authors.forename: H Ian
authors.initials: HI
authors.lastname: Robins
authors.forename: Karl
authors.initials: K
authors.lastname: Rassmussen
authors.forename: James S
authors.initials: JS
authors.lastname: Welsh
authors.forename: Peter A
authors.initials: PA
authors.lastname: Mahler
authors.forename: Steven P
authors.initials: SP
authors.lastname: Howard
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002648:Child; D019583:Dose Fractionation, Radiation; D005260:Female; D005910:Glioma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011878:Radiotherapy / Q000379:methods; D019233:Retreatment; D016019:Survival Analysis; D013997:Time Factors; D047368:Tumor Burden; D055815:Young Adult