title: Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial.
abstract: OBJECTIVE
  Intensified preoperative treatments have been increasingly investigated in locally advanced rectal cancer (LARC), but limited data are available for the impact of these regimens on quality of life (QoL) and bowel function (BF). We assessed these outcome measures in EXPERT-C, a randomized phase 2 trial of neoadjuvant capecitabine combined with oxaliplatin (CAPOX), followed by chemoradiation therapy (CRT), total mesorectal excision, and adjuvant CAPOX with or without cetuximab in magnetic resonance imaging-defined, high-risk LARC.
  
  
  METHODS
  QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. Bowel incontinence was assessed using the modified Fecal Incontinence Severity Index questionnaire.
  
  
  RESULTS
  Compared to baseline, QoL scores during preoperative treatment were better for symptoms associated with the primary tumor in the rectum (blood and mucus in stool, constipation, diarrhea, stool frequency, buttock pain) but worse for global health status, role functioning, and symptoms related to the specific safety profile of each treatment modality. During follow-up, improved emotional functioning and lessened anxiety and insomnia were observed, but deterioration of body image, increased urinary incontinence, less sexual interest (men), and increased impotence and dyspareunia were observed. Cetuximab was associated with a deterioration of global health status during neoadjuvant chemotherapy but did not have any long-term detrimental effect. An improvement in bowel continence was observed after preoperative treatment and 3 years after sphincter-sparing surgery.
  
  
  CONCLUSIONS
  Intensifying neoadjuvant treatment by administering induction systemic chemotherapy before chemoradiation therapy improves tumor-related symptoms and does not appear to have a significantly detrimental effect on QoL and BF, in both the short and the long term.
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sclafani
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Clare
authors.initials: C
authors.lastname: Peckitt
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, United Kingdom. Electronic address: david.cunningham@rmh.nhs.uk.
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Diana
authors.initials: D
authors.lastname: Tait
authors.affiliation: Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Department of Medical Oncology, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Giralt
authors.affiliation: University of Uppsala, Uppsala, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
authors.affiliation: Biomedical Research Institute INCLIVA, Department of Hematology and Medical Oncology, University of Valencia, Spain.
authors.forename: Susana Roselló
authors.initials: SR
authors.lastname: Keränen
authors.affiliation: Southampton General Hospital, Cancer Sciences Unit, University of Southampton, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bateman
authors.affiliation: Poole Hospital NHS Foundation Trust, Department of Medical Oncology, Bournemouth University, United Kingdom.
authors.forename: Tamas
authors.initials: T
authors.lastname: Hickish
authors.affiliation: Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Department of Medical Oncology, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Janet
authors.initials: J
authors.lastname: Thomas
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Gina
authors.initials: G
authors.lastname: Brown
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Oates
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Chau
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069287:Capecitabine / Q000008:administration & dosage; D000068818:Cetuximab / Q000009:adverse effects; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D017024:Chemotherapy, Adjuvant; D005242:Fecal Incontinence / Q000175:diagnosis / Q000209:etiology*; D006304:Health Status; D006801:Humans; D008279:Magnetic Resonance Imaging; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011788:Quality of Life; D012004:Rectal Neoplasms / Q000150:complications / Q000473:pathology / Q000628:therapy*; D012007:Rectum / Q000601:surgery; D012720:Severity of Illness Index; D020018:Sexual Dysfunctions, Psychological / Q000209:etiology; D011795:Surveys and Questionnaires
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine; D000068818:Cetuximab