title: Multiparametric MRI as an outcome predictor for anal canal cancer managed with chemoradiotherapy.
abstract: BACKGROUND
  Organ-preserving chemo-radiotherapy (CRT) is the standard of care for non-metastatic anal squamous cell carcinoma (SCC). The optimal dosing schedules are yet to be determined. To improve local control rates, dose escalation has been investigated but found to not increase efficacy at the expense of increased toxicity for an unselected patient population. Diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) Magnetic Resonance Imaging (MRI) performed during CRT have early data suggesting it to be an effective tool in predicting later tumour response for SCC in related body sites. By performing multi-parametric MRI (mpmMRI) incorporating standard morphological, DWI and DCE sequences, we aim to determine whether the early changes in multi-parametric parameters during CRT can predict for later response in anal SCC. This may create opportunities to investigate treatment adaptation, either intensification or de-escalation, during CRT.
  
  
  METHODS
  This protocol describes a prospective non-interventional multi-centre single-arm clinical trial. Twenty eligible patients with histologically confirmed non-metastatic anal SCC will receive standard definitive CRT and undergo multi-parametric MRI's at the following 4 time points; prior to treatment, during the second and fourth weeks of treatment and 6-8 weeks following treatment. Complete response will be defined by the absence of tumour persistence or recurrence as determined by clinical examination at 6 months. Images will be retrospectively analysed to determine the apparent diffusion coefficient and tumour perfusion coefficients (Ktrans and Kep) at each time point. The Mann-Whitney-Wilcoxon Test will be utilised to compare the change in these parameters for responder's verses non-responders.
  
  
  CONCLUSIONS
  If validated, mpmMRI, along with other risk factors, can be used to stratify patients and guide radiation dosing in a prospective trial. Informed individualisation of treatment intensity should help us achieve our goals of improved efficacy and reduced toxicity.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001219673 (19/11/2014).
authors.affiliation: Radiation Oncology, Royal Prince Alfred Hospital, Salisbury Road, Camperdown, NSW, 2050, Australia. mpjones85@gmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Jones
authors.affiliation: Radiation Oncology, Chris O'brien Lifehouse, Missenden Road, Camperdown, NSW, 2050, Australia. George.Hruby@lh.org.au.
authors.forename: George
authors.initials: G
authors.lastname: Hruby
authors.affiliation: Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia. peter.stanwell@newcastle.edu.au.
authors.forename: Peter
authors.initials: P
authors.lastname: Stanwell
authors.affiliation: Calvary Mater Newcastle, Edith Street, Waratah, NSW, 2298, Australia. Sarah.Gallagher@calvarymater.org.au.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gallagher
authors.affiliation: Radiation Oncology, Liverpool Hospital, Corner of Elizabeth and Goulburn Streets, Liverpool, NSW, 2170, Australia. Karen.Wong@sswahs.nsw.gov.au.
authors.forename: Karen
authors.initials: K
authors.lastname: Wong
authors.affiliation: Radiation Oncology, Calvary Mater Newcastle, Edith Street, Waratah, NSW, 2298, Australia. jameen.arm@hnehealth.nsw.gov.au.
authors.forename: Jameen
authors.initials: J
authors.lastname: Arm
authors.affiliation: Radiation Oncology, Calvary Mater Newcastle, Edith Street, Waratah, NSW, 2298, Australia. jarad.martin@calvarymater.org.au.
authors.forename: Jarad
authors.initials: J
authors.lastname: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D001003:Anal Canal / Q000000981:diagnostic imaging / Q000473:pathology; D001005:Anus Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D001315:Australia; D059248:Chemoradiotherapy; D038524:Diffusion Magnetic Resonance Imaging; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009520:New Zealand; D011379:Prognosis; D011859:Radiography