title: Real-time pretreatment review limits unacceptable deviations on a cooperative group radiation therapy technique trial: quality assurance results of RTOG 0933.
abstract: OBJECTIVE
  RTOG 0933 was a phase II trial of hippocampal avoidance during whole brain radiation therapy for patients with brain metastases. The results demonstrated improvement in short-term memory decline, as compared with historical control individuals, and preservation of quality of life. Integral to the conduct of this trial were quality assurance processes inclusive of pre-enrollment credentialing and pretreatment centralized review of enrolled patients.
  
  
  METHODS
  Before enrolling patients, all treating physicians and sites were required to successfully complete a "dry-run" credentialing test. The treating physicians were credentialed based on accuracy of magnetic resonance imaging-computed tomography image fusion and hippocampal and normal tissue contouring, and the sites were credentialed based on protocol-specified dosimetric criteria. Using the same criteria, pretreatment centralized review of enrolled patients was conducted. Physicians enrolling 3 consecutive patients without unacceptable deviations were permitted to enroll further patients without pretreatment review, although their cases were reviewed after treatment.
  
  
  RESULTS
  In all, 113 physicians and 84 sites were credentialed. Eight physicians (6.8%) failed hippocampal contouring on the first attempt; 3 were approved on the second attempt. Eight sites (9.5%) failed intensity modulated radiation therapy planning on the first attempt; all were approved on the second attempt. One hundred thirteen patients were enrolled in RTOG 0933; 100 were analyzable. Eighty-seven cases were reviewed before treatment; 5 (5.7%) violated the eligibility criteria, and 21 (24%) had unacceptable deviations. With feedback, 18 cases were approved on the second attempt and 2 cases on the third attempt. One patient was treated off protocol. Twenty-two cases were reviewed after treatment; 1 (4.5%) violated the eligibility criteria, and 5 (23%) had unacceptable deviations.
  
  
  CONCLUSIONS
  Although >95% of the cases passed the pre-enrollment credentialing, the pretreatment centralized review disqualified 5.7% of reviewed cases, prevented unacceptable deviations in 24% of reviewed cases, and limited the final unacceptable deviation rate to 5%. Thus, pretreatment review is deemed necessary in future hippocampal avoidance trials and is potentially useful in other similarly challenging radiation therapy technique trials.
authors.affiliation: Cadence Brain Tumor Center and CDH Proton Center, Warrenville, Illinois; University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin. Electronic address: vgondi@chicagocancer.org.
authors.forename: Vinai
authors.initials: V
authors.lastname: Gondi
authors.affiliation: Duke University School of Medicine, Durham, North Carolina.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Cui
authors.affiliation: University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
authors.affiliation: Radiation Therapy Oncology Group-RTQA, Philadelphia, Pennsylvania.
authors.forename: Denise
authors.initials: D
authors.lastname: Manfredi
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: James M
authors.initials: JM
authors.lastname: Galvin
authors.affiliation: University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin.
authors.forename: Howard
authors.initials: H
authors.lastname: Rowley
authors.affiliation: Montefiore Medical Center and Institute for Onco-Physics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Tome
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis / Q000532:radiotherapy* / Q000556:secondary*; D016371:Cranial Irradiation / Q000592:standards* / Q000706:statistics & numerical data; D003406:Credentialing / Q000592:standards* / Q000706:statistics & numerical data; D006624:Hippocampus / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000592:standards*; D064847:Multimodal Imaging / Q000379:methods / Q000592:standards*; D059351:Organ Sparing Treatments / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data; D011785:Quality Assurance, Health Care; D011788:Quality of Life; D011880:Radiotherapy Planning, Computer-Assisted / Q000592:standards*; D050397:Radiotherapy, Intensity-Modulated / Q000592:standards; D014057:Tomography, X-Ray Computed / Q000592:standards*