title: Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer.
abstract: BACKGROUND
  Patients with potentially curative oesophago-gastric cancer typically undergo neo-adjuvant chemotherapy prior to surgery. The majority of anti-cancer drugs have a narrow therapeutic index. The aim of this study was to determine if features of body composition, assessed using computed tomography (CT) scans, may be predictive of dose-limiting toxicity (DLT) in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer. The influence of sarcopenia and DLT on overall survival was also evaluated.
  
  
  METHODS
  89 Patients having potentially curative oesophago-gastric cancer surgery were studied. Patients studied had histologically confirmed oesophago-gastric cancer with no evidence of distant metastasis on pre-operative staging. CT scan was performed in all cases at diagnosis. DLT was defined as toxicity leading to postponement of treatment, a drug dose reduction or definitive interruption of drug administration.
  
  
  RESULTS
  DLT occurred in 37 out of 89 patients (41.6%) undergoing chemotherapy. Sarcopenia (odds ratio, 2.95; 95% confidence interval, 1.23-7.09; p = 0.015) was associated with DLT on multivariate analysis. Median overall survival for patients who were sarcopenic was 569 days (IQ range: 357-1230 days) vs. 1013 days (IQ range: 496-1318 days) for patients who were not sarcopenic (p = 0.04). There was no significant difference in overall survival in patients who experienced DLT compared with those that did not (p = 0.665).
  
  
  CONCLUSIONS
  Sarcopenia is a significant predictor of DLT in oesophago-gastric cancer patients undergoing neo-adjuvant chemotherapy. These results raise the potential for use of assessment of skeletal muscle mass using CT scans to predict toxicity and individualize chemotherapy dosing.
authors.affiliation: Department of Surgery, City Hospital Campus, Nottingham University Hospitals, Nottingham NG5 1PB, UK. Electronic address: benjamintan@hotmail.co.uk.
authors.forename: B H L
authors.initials: BH
authors.lastname: Tan
authors.affiliation: Department of Surgery, City Hospital Campus, Nottingham University Hospitals, Nottingham NG5 1PB, UK.
authors.forename: K
authors.initials: K
authors.lastname: Brammer
authors.affiliation: Department of Surgery, City Hospital Campus, Nottingham University Hospitals, Nottingham NG5 1PB, UK.
authors.forename: N
authors.initials: N
authors.lastname: Randhawa
authors.affiliation: Department of Surgery, City Hospital Campus, Nottingham University Hospitals, Nottingham NG5 1PB, UK.
authors.forename: N T
authors.initials: NT
authors.lastname: Welch
authors.affiliation: Department of Surgery, City Hospital Campus, Nottingham University Hospitals, Nottingham NG5 1PB, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Parsons
authors.affiliation: Department of Oncology, City Hospital Campus, Nottingham University Hospitals, Nottingham NG5 1PB, UK.
authors.forename: E J
authors.initials: EJ
authors.lastname: James
authors.affiliation: Department of Surgery, City Hospital Campus, Nottingham University Hospitals, Nottingham NG5 1PB, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Catton
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001823:Body Composition; D000069287:Capecitabine; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015251:Epirubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D055948:Sarcopenia / Q000150:complications*; D013274:Stomach Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: D003841:Deoxycytidine; D015251:Epirubicin; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil
keywords: Body composition; Chemotherapy toxicity; Oesophago-gastric cancer; Sarcopenia