title: Patient reported outcome measures (PROMs) following forward planned field-in field IMRT: results from the Cambridge Breast IMRT trial.
abstract: BACKGROUND
  The use of intensity-modulated radiotherapy (IMRT) in breast cancer reduces clinician-assessed breast tissue toxicity including fibrosis, telangectasia and sub-optimal cosmesis. Patient reported outcome measures (PROMs) are also important as they provide the patient's perspective. This longitudinal study reports on (a) the effect of forward planned field-in-field IMRT (∼simple IMRT) on PROMs compared to standard RT at 5 years after RT, (b) factors affecting PROMs at 5years after RT and (c) the trend of PROMs over 5 years of follow up.
  
  
  METHODS
  PROMs were assessed at baseline (pre-RT), 6, 24 and 60 months after completion of RT using global health (EORTC QLQ C30) and 4 breast symptom questions (BR23). Also, 4 breast RT-specific questions were included at 6, 24 and 60 months: change in skin appearance, firmness to touch, reduction in breast size and overall change in breast appearance since RT. The benefits of simple IMRT over standard RT at 5 years after RT were assessed using standard t-test for global health and logistic regression analysis for breast symptom questions and breast RT-specific questions. Clinical factors affecting PROMs at 5 years were investigated using a multivariate analysis. A repeated mixed model was applied to explore the trend over time for each of PROMs.
  
  
  RESULTS
  (89%) 727/815, 84%, 81% and 61% patients completed questionnaires at baseline, 6, 24 and 60 months respectively. Patients reported worse toxicity for all four BR23 breast symptoms at 6 months, which then improved over time (p<0.0001). They also reported improvement in skin appearance and breast hardness over time (p<0.0001), with no significant change for breast shrinkage (p=0.47) and overall breast appearance (p=0.13). At 5years, PROMs assessments did not demonstrate a benefit for simple IMRT over standard radiotherapy. Large breast volume, young age, baseline surgical cosmesis and post-operative infection were the most important variables to affect PROMs.
  
  
  CONCLUSIONS
  This study was unable to demonstrate the benefits of IMRT on PROMs at 5years. PROMs are influenced by non-radiotherapy factors and surgical factors should be optimised to improve patients' outcome. Only a small proportion of patients report moderate-severe breast changes post radiotherapy, with most PROMs improving over time. The difference in clinician assessment and PROMs outcome requires further investigation.
authors.affiliation: Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, UK; Department of Oncology, Colchester Hospital University NHS Foundation Trust, Essex, UK. Electronic address: drmukesh1980@doctors.net.uk.
authors.forename: Mukesh B
authors.initials: MB
authors.lastname: Mukesh
authors.affiliation: Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Cambridge University Hospitals NHS Foundation Trust, Medical Research Council, Biostatistics Unit Hub for Trials Methodology, UK.
authors.forename: Wendi
authors.initials: W
authors.lastname: Qian
authors.affiliation: Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, UK.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Wilkinson
authors.affiliation: Cancer Research-UK Centre for Genetic Epidemiology & Dept of Oncology, University of Cambridge, Strangeways Research Laboratory, UK.
authors.forename: Leila
authors.initials: L
authors.lastname: Dorling
authors.affiliation: Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, UK; Cancer Research-UK Centre for Genetic Epidemiology & Dept of Oncology, University of Cambridge, Strangeways Research Laboratory, UK.
authors.forename: Gillian C
authors.initials: GC
authors.lastname: Barnett
authors.affiliation: Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, UK.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Moody
authors.affiliation: Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Twyman
authors.affiliation: University of Cambridge, Department of Oncology, Oncology Centre, Addenbrooke's Hospital, UK.
authors.forename: Neil G
authors.initials: NG
authors.lastname: Burnet
authors.affiliation: Faculty of Health, Social Care & Education, Anglia Ruskin University, Cambridge, UK.
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Wishart
authors.affiliation: Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, UK.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Coles
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000532:radiotherapy*; D002277:Carcinoma / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011880:Radiotherapy Planning, Computer-Assisted; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013997:Time Factors; D055815:Young Adult
keywords: Breast cancer; IMRT; Patient reported outcome measures