title: Timing of surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer - A comparison of magnetic resonance imaging at two time points and histopathological responses.
abstract: OBJECTIVE
  There is wide inter-institutional variation in the interval between neoadjuvant chemoradiotherapy (NACRT) and surgery for locally advanced rectal cancer. We aimed to assess the association of magnetic resonance imaging (MRI) at 9 and 14 weeks post-NACRT; T-staging (ymrT) and post-NACRT tumour regression grading (ymrTRG) with histopathological outcomes; histopathological T-stage (ypT) and histopathological tumour regression grading (ypTRG) in order to inform decision-making about timing of surgery.
  
  
  METHODS
  We prospectively studied 35 consecutive patients (26 males) with MRI-defined resection margin threatened rectal cancer who had completed standardized NACRT. Patients underwent a MRI at Weeks 9 and 14 post-NACRT, and surgery at Week 15. Two readers independently assessed MRIs for ymrT, ymrTRG and volume change. ymrT and ymrTRG were analysed against histopathological ypT and ypTRG as predictors by logistic regression modelling and receiver operating characteristic (ROC) curve analyses.
  
  
  RESULTS
  Thirty-five patients were recruited. Inter-observer agreement was good for all MR variables (Kappa > 0.61). Considering ypT as an outcome variable, a stronger association of favourable ymrTRG and volume change at Week 14 compared to Week 9 was found (ymrTRG - p = 0.064 vs. p = 0.010; Volume change - p = 0.062 vs. p = 0.007). Similarly, considering ypTRG as an outcome variable, a greater association of favourable ymrTRG and volume change at Week 14 compared to Week 9 was found (ymrTRG - p = 0.005 vs. p = 0.042; Volume change - p = 0.004 vs. 0.055).
  
  
  CONCLUSIONS
  Following NACRT, greater tumour down-staging and volume reduction was observed at Week 14. Timing of surgery, in relation to NACRT, merits further investigation.
  
  
  BACKGROUND
  NCT01325909.
authors.affiliation: Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Road, Southampton, United Kingdom. Electronic address: m.west@soton.ac.uk.
authors.forename: M A
authors.initials: MA
authors.lastname: West
authors.affiliation: Primary Care and Population Sciences, University of Southampton, Southampton, United Kingdom. Electronic address: b.dimitrov@soton.ac.uk.
authors.forename: B D
authors.initials: BD
authors.lastname: Dimitrov
authors.affiliation: National Institute for Health Research, Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom; National Institute for Health Research, Southampton Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom. Electronic address: h.e.moyses@soton.ac.uk.
authors.forename: H E
authors.initials: HE
authors.lastname: Moyses
authors.affiliation: Department of Musculoskeletal Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom. Electronic address: g.j.kemp@liverpool.ac.uk.
authors.forename: G J
authors.initials: GJ
authors.lastname: Kemp
authors.affiliation: Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Road, Southampton, United Kingdom; Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. Electronic address: l.loughney@gmail.com.
authors.forename: L
authors.initials: L
authors.lastname: Loughney
authors.affiliation: Department of Radiology, Aintree University Hospital NHS Foundation Trust, Liverpool, United Kingdom. Electronic address: david.white@aintree.nhs.uk.
authors.forename: D
authors.initials: D
authors.lastname: White
authors.affiliation: Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Road, Southampton, United Kingdom; Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. Electronic address: mike.grocott@soton.ac.uk.
authors.forename: M P W
authors.initials: MP
authors.lastname: Grocott
authors.affiliation: Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Road, Southampton, United Kingdom; Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. Electronic address: s.jack@soton.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Jack
authors.affiliation: Department of Radiology, The Royal Marsden NHS Foundation Trust, London, United Kingdom. Electronic address: gina.brown@rmh.nhs.uk.
authors.forename: G
authors.initials: G
authors.lastname: Brown
mesh_terms: D000368:Aged; D059248:Chemoradiotherapy / Q000379:methods*; D013505:Digestive System Surgical Procedures / Q000379:methods*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010865:Pilot Projects; D011446:Prospective Studies; D012372:ROC Curve; D012004:Rectal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D012007:Rectum / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden
keywords: Magnetic resonance imaging; Neoadjuvant chemoradiotherapy; Rectal cancer; Surgery; Time for surgery; Tumour regression