title: Methodology for analysis and reporting patterns of failure in the Era of IMRT: head and neck cancer applications.
abstract: BACKGROUND
  The aim of this study is to develop a methodology to standardize the analysis and reporting of the patterns of loco-regional failure after IMRT of head and neck cancer.
  
  
  METHODS
  Twenty-one patients with evidence of local and/or regional failure following IMRT for head-and-neck cancer were retrospectively reviewed under approved IRB protocol. Manually delineated recurrent gross disease (rGTV) on the diagnostic CT documenting recurrence (rCT) was co-registered with the original planning CT (pCT) using both deformable (DIR) and rigid (RIR) image registration software. Subsequently, mapped rGTVs were compared relative to original planning target volumes (TVs) and dose using a centroid-based approaches. Failures were then classified into five types based on combined spatial and dosimetric criteria; A (central high dose), B (peripheral high dose), C (central elective dose), D (peripheral elective dose), and E (extraneous dose).
  
  
  RESULTS
  A total of 26 recurrences were identified. Using DIR, recurrences were assigned to more central TVs compared to RIR as detected using the spatial centroid-based method (p = 0.0002). rGTVs mapped using DIR had statistically significant higher mean doses when compared to rGTVs mapped rigidly (mean dose 70 vs. 69 Gy, p = 0.03). According to the proposed classification 22 out of 26 failures were of type A (central high dose) as assessed by DIR method compared to 18 out of 26 for the RIR because of the tendencey of RIR to assign failures more peripherally.
  
  
  CONCLUSIONS
  RIR tends to assigns failures more peripherally. DIR-based methods showed that the vast majority of failures originated in the high dose target volumes and received full prescribed doses suggesting biological rather than technology-related causes of failure. Validated DIR-based registration is recommended for accurate failure characterization and a novel typology-indicative taxonomy is recommended for failure reporting in the IMRT era.
authors.affiliation: Head and Neck Section, Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Box 0097, 1515 Holcombe Blvd, Houston, TX, 77030, USA. asmohamed@mdanderson.org.|Department of Clinical Oncology and nuclear medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt. asmohamed@mdanderson.org.
authors.forename: Abdallah S R
authors.initials: AS
authors.lastname: Mohamed
authors.affiliation: Head and Neck Section, Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Box 0097, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
authors.forename: David I
authors.initials: DI
authors.lastname: Rosenthal
authors.affiliation: Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Musaddiq J
authors.initials: MJ
authors.lastname: Awan
authors.affiliation: Head and Neck Section, Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Box 0097, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Garden
authors.affiliation: Head and Neck Section, Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Box 0097, 1515 Holcombe Blvd, Houston, TX, 77030, USA.|Department of Radiation Oncology, Beykent University, Istanbul, Turkey.
authors.forename: Esengul
authors.initials: E
authors.lastname: Kocak-Uzel
authors.affiliation: Department of Clinical Oncology and nuclear medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: Abdelaziz M
authors.initials: AM
authors.lastname: Belal
authors.affiliation: Department of Clinical Oncology and nuclear medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: Ahmed G
authors.initials: AG
authors.lastname: El-Gowily
authors.affiliation: Head and Neck Section, Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Box 0097, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Phan
authors.affiliation: Head and Neck Section, Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Box 0097, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
authors.forename: Beth M
authors.initials: BM
authors.lastname: Beadle
authors.affiliation: Head and Neck Section, Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Box 0097, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
authors.forename: G Brandon
authors.initials: GB
authors.lastname: Gunn
authors.affiliation: Head and Neck Section, Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Box 0097, 1515 Holcombe Blvd, Houston, TX, 77030, USA. cdfuller@mdanderson.org.|Graduate School of Biomedical Science, University of Texas Health Science Center, Houston, TX, USA. cdfuller@mdanderson.org.
authors.forename: Clifton D
authors.initials: CD
authors.lastname: Fuller
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods* / Q000592:standards*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D018787:Radiation Oncology / Q000379:methods* / Q000592:standards*; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated; D012107:Research Design / Q000592:standards; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D017211:Treatment Failure
keywords: Deformable image registration; Head-and-neck cancer; IMRT; Patterns of failure