Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer

Eur J Surg Oncol. 2015 Mar;41(3):333-8. doi: 10.1016/j.ejso.2014.11.040. Epub 2014 Nov 26.

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.

Keywords: Body composition; Chemotherapy toxicity; Oesophago-gastric cancer; Sarcopenia.

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Body Composition
  • Capecitabine
  • Carcinoma, Squamous Cell / complications
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Epirubicin / administration & dosage
  • Esophageal Neoplasms / complications
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / pathology
  • Esophagogastric Junction / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Prognosis
  • Sarcopenia / complications*
  • Stomach Neoplasms / complications
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Tomography, X-Ray Computed

Substances

  • Deoxycytidine
  • Epirubicin
  • Capecitabine
  • Cisplatin
  • Fluorouracil