title: Critical impact of radiotherapy protocol compliance and quality in the treatment of advanced head and neck cancer: results from TROG 02.02.
abstract: OBJECTIVE
  To report the impact of radiotherapy quality on outcome in a large international phase III trial evaluating radiotherapy with concurrent cisplatin plus tirapazamine for advanced head and neck cancer.
  
  
  METHODS
  The protocol required interventional review of radiotherapy plans by the Quality Assurance Review Center (QARC). All plans and radiotherapy documentation underwent post-treatment review by the Trial Management Committee (TMC) for protocol compliance. Secondary review of noncompliant plans for predicted impact on tumor control was performed. Factors associated with poor protocol compliance were studied, and outcome data were analyzed in relation to protocol compliance and radiotherapy quality.
  
  
  RESULTS
  At TMC review, 25.4% of the patients had noncompliant plans but none in which QARC-recommended changes had been made. At secondary review, 47% of noncompliant plans (12% overall) had deficiencies with a predicted major adverse impact on tumor control. Major deficiencies were unrelated to tumor subsite or to T or N stage (if N+), but were highly correlated with number of patients enrolled at the treatment center (< five patients, 29.8%; > or = 20 patients, 5.4%; P < .001). In patients who received at least 60 Gy, those with major deficiencies in their treatment plans (n = 87) had a markedly inferior outcome compared with those whose treatment was initially protocol compliant (n = 502): -2 years overall survival, 50% v 70%; hazard ratio (HR), 1.99; P < .001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; P < .001, respectively.
  
  
  CONCLUSIONS
  These results demonstrate the critical importance of radiotherapy quality on outcome of chemoradiotherapy in head and neck cancer. Centers treating only a few patients are the major source of quality problems.
authors.affiliation: Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. Lester.Peters@petermac.org
authors.forename: Lester J
authors.initials: LJ
authors.lastname: Peters
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: Jordi
authors.initials: J
authors.lastname: Giralt
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Fitzgerald
authors.forename: Andy
authors.initials: A
authors.lastname: Trotti
authors.forename: Jacques
authors.initials: J
authors.lastname: Bernier
authors.forename: Jean
authors.initials: J
authors.lastname: Bourhis
authors.forename: Kally
authors.initials: K
authors.lastname: Yuen
authors.forename: Richard
authors.initials: R
authors.lastname: Fisher
authors.forename: Danny
authors.initials: D
authors.lastname: Rischin
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D019983:Guideline Adherence; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007390:International Agencies; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D011785:Quality Assurance, Health Care; D011879:Radiotherapy Dosage; D015996:Survival Rate; D000077704:Tirapazamine; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage
chemical_list: D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin