title: First interim analysis of a randomised trial of whole brain radiotherapy in melanoma brain metastases confirms high data quality.
abstract: BACKGROUND
  Brain metastases are a common cause of death in patients with melanoma. The role of adjuvant whole brain radiotherapy (WBRT) following local treatment of intracranial melanoma metastases is controversial. The Australian and New Zealand Melanoma Trials Group (ANZMTG) and the Trans-Tasman Radiation Oncology Group (TROG) are leading the first ever single histology randomised trial investigating this question. The primary endpoint is distant intracranial failure on magnetic resonance imaging (MRI) within twelve months of randomisation. The first planned interim analysis was performed twelve months after randomisation of the 100(th) patient. The analysis was an opportunity to review completeness of the trial data to date.
  
  
  METHODS
  All data received up to the end of twelve months after randomisation of the 100th patient was reviewed.
  
  
  RESULTS
  Review of pathology reports confirmed that all 100 patients had stage IV melanoma and were appropriately entered into the study. Of the 47 distant intracranial events, 34 occurred in isolation (i.e. only distant failure was identified), whilst 13 were accompanied by local failure. Data review showed compliance with the protocol mandated MRI schedule and accuracy of intracranial failure reporting was very high. The Quality of Life (QoL) component of the study achieved a 91% completion rate. For the neurocognitive function (NCF) assessments, a high completion rate was maintained throughout the 12 month period. Where assessments were not performed at expected time points, valid reasons were noted. Radiotherapy quality was high. Of 50 patients who received WBRT, 32 were reviewed as per protocol design and there was only one major variation out of 308 data points reviewed (0.3%). There were minimal trial related adverse events (AEs) and no serious adverse events (SAEs). Pre-specified protocol stopping rules were not met.
  
  
  CONCLUSIONS
  The Data Safety Monitoring Committee (DSMC) recommended the trial continue recruitment after reviewing the unblinded data. The data provision and quality to date indicates that a reliable outcome will be obtained when the final analysis is performed. Accrual is ongoing with 156 out of 200 patients randomised to date (26(th) November 2014).
authors.affiliation: Melanoma Institute Australia, Sydney, Australia. gerald.fogarty@cancer.com.au.|Department of Radiation Oncology, St Vincent's General Hospital, Sydney, Australia. gerald.fogarty@cancer.com.au.|Genesis Cancer Care, Department of Radiation Oncology, Mater Hospital, Sydney, Australia. gerald.fogarty@cancer.com.au.|Trans-Tasman Radiation Oncology Group (TROG), Newcastle, Australia. gerald.fogarty@cancer.com.au.|Australia and New Zealand Melanoma Trials Group (ANZMTG), North Sydney, Australia. gerald.fogarty@cancer.com.au.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Fogarty
authors.affiliation: Melanoma Institute Australia, Sydney, Australia. Angela.Hong@melanoma.org.au.|Trans-Tasman Radiation Oncology Group (TROG), Newcastle, Australia. Angela.Hong@melanoma.org.au.|Sydney Medical School, |The University of Sydney, Sydney, Australia. Angela.Hong@melanoma.org.au.
authors.forename: Angela
authors.initials: A
authors.lastname: Hong
authors.affiliation: Oslo University Hospital HF, The Norwegian Radium Hospital, Oslo, Norway. KDJ@ous-hf.no.
authors.forename: Kari
authors.initials: K
authors.lastname: Dolven-Jacobsen
authors.affiliation: Oslo University Hospital HF, The Norwegian Radium Hospital, Oslo, Norway. clarei@ous-hf.no.
authors.forename: Claudius H
authors.initials: CH
authors.lastname: Reisse
authors.affiliation: Trans-Tasman Radiation Oncology Group (TROG), Newcastle, Australia. Bryan.Burmeister@health.qld.gov.au.|Princess Alexandra Hospital, Brisbane, Australia. Bryan.Burmeister@health.qld.gov.au.|Australia and New Zealand Melanoma Trials Group (ANZMTG), North Sydney, Australia. Bryan.Burmeister@health.qld.gov.au.
authors.forename: Bryan
authors.initials: B
authors.lastname: Burmeister
authors.affiliation: Melanoma Institute Australia, Sydney, Australia. LEHaydu@mdanderson.org.
authors.forename: Lauren H
authors.initials: LH
authors.lastname: Haydu
authors.affiliation: Centre for Medical Psychology & Evidence-based Decision-making, Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia. haryana.dhillon@sydney.edu.au.|Psycho-Oncology Co-Operative Research Group (PoCoG), School of Psychology, Faculty of Science, University of Sydney, Sydney, Australia. haryana.dhillon@sydney.edu.au.
authors.forename: Haryana
authors.initials: H
authors.lastname: Dhillon
authors.affiliation: Australia and New Zealand Melanoma Trials Group (ANZMTG), North Sydney, Australia. Victoria.Steel@melanoma.org.au.
authors.forename: Victoria
authors.initials: V
authors.lastname: Steel
authors.affiliation: Royal Prince Alfred Hospital, Sydney, Australia. brindha@brain-surgeon.com.au.
authors.forename: Brindha
authors.initials: B
authors.lastname: Shivalingam
authors.affiliation: The Royal Melbourne Hospital & University of Melbourne, Parkville, Australia. Kate.Drummond@mh.org.au.
authors.forename: Kate
authors.initials: K
authors.lastname: Drummond
authors.affiliation: Sydney Medical School, |The University of Sydney, Sydney, Australia. janette.vardy@sydney.edu.au.|Centre for Medical Psychology & Evidence-based Decision-making, Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia. janette.vardy@sydney.edu.au.|Psycho-Oncology Co-Operative Research Group (PoCoG), School of Psychology, Faculty of Science, University of Sydney, Sydney, Australia. janette.vardy@sydney.edu.au.|Concord Repatriation and General Hospital, Concord, Australia. janette.vardy@sydney.edu.au.
authors.forename: Janette
authors.initials: J
authors.lastname: Vardy
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia. anna.nowak@uwa.edu.au.|Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia. anna.nowak@uwa.edu.au.
authors.forename: Anna
authors.initials: A
authors.lastname: Nowak
authors.affiliation: Sydney Medical School, |The University of Sydney, Sydney, Australia. ghruby@email.cs.nsw.gov.au.|Royal Prince Alfred Hospital, Sydney, Australia. ghruby@email.cs.nsw.gov.au.|Australia and New Zealand Melanoma Trials Group (ANZMTG), North Sydney, Australia. ghruby@email.cs.nsw.gov.au.
authors.forename: George
authors.initials: G
authors.lastname: Hruby
authors.affiliation: Melanoma Institute Australia, Sydney, Australia. richard.scolyer@sswahs.nsw.gov.au.|Sydney Medical School, |The University of Sydney, Sydney, Australia. richard.scolyer@sswahs.nsw.gov.au.|Royal Prince Alfred Hospital, Sydney, Australia. richard.scolyer@sswahs.nsw.gov.au.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.affiliation: Peter MacCallum Cancer Centre East Melbourne & University of Melbourne, Parkville, Australia. mandel@ausdoctors.net.
authors.forename: Catherine
authors.initials: C
authors.lastname: Mandel
authors.affiliation: Melanoma Institute Australia, Sydney, Australia. John.Thompson@melanoma.org.au.|Sydney Medical School, |The University of Sydney, Sydney, Australia. John.Thompson@melanoma.org.au.|Royal Prince Alfred Hospital, Sydney, Australia. John.Thompson@melanoma.org.au.|Australia and New Zealand Melanoma Trials Group (ANZMTG), North Sydney, Australia. John.Thompson@melanoma.org.au.
authors.forename: John F
authors.initials: JF
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D000068598:Data Accuracy; D003710:Demography; D018450:Disease Progression; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects