Patients and procedures
Objective(s)
A single-center study was performed at the Centre Henri Becquerel (Rouen, France). The population included all new LAOC patients referred to the Radiotherapy and Medical Physics department between October 5, 2005 and June 5, 2012. The inclusion criteria were: histologically confirmed oesophageal cancer, pre-therapeutic 18FDG-PET/CT with available images, and curative-intent chemo-radiotherapy. Surgical resection of residual tumour after chemo-radiotherapy was allowed.
The following baseline clinical data were collected: age, sex, WHO performance status, histological subtypes, TNM stage, and cancer location. The baseline nutritional parameters were: weight, size, Body Mass Index (BMI), weight loss history, serum albumin level, and the Buzby Nutritional Risk Index (NRI) [24]. We also collected treatment characteristics including the chemotherapy protocol and radiotherapy data (total dose, treatment duration). Finally, we collected imaging data from 18FDG-PET/CT, such as the Standardized Uptake Value Maximum (SUV Max), Total Volume of 40% of SUVmax segmentation (Tvol40), SUVmean, and Total Lesion Glycolysis (TLG).
Sarcopenia was assessed by a homemade plugin running on our institutional Picture Archiving and Communication System (PACS, Telemis version 4.7, Telemis SA, Louvain la Neuve, Belgium). The skeletal muscles were automatically delineated by fixed thresholds (-29 to +150 Hounsfield Unit) [25] on two adjacent cross-sectional CT images acquired at the third lumbar vertebra (L3) and extracted from the staging 18FDG-PET/CT. The L3 skeletal muscles were the psoas, quadratus lumborum, paraspinal and abdominal wall muscles. The mean of the delineated surfaces on both images was defined as skeletal muscle L3 area (cm²). All delineations were visually checked and, if necessary, corrected by a single observer (RM). The Skeletal Muscle Index was calculated by dividing the skeletal muscle area by the squared height (SMI, cm²/m²) [25]. Sarcopenia was defined as SMI <52.4cm²/m² for men and <38.5 cm²/m² for women [26]. We also measured were the Mean Muscular Density (MMDL3, HU), the Visceral Fat Mass (VFML3, cm²) and the Subcutaneous Fat Mass (SCFML3, cm²) (Figure 1). The cut-off values for SUVmax and Tvol40 by univariate analysis were based on Palie et al [27].
The primary endpoint was overall survival, defined as the time from the start of the radiotherapy to death or last follow-up. Secondary endpoints were to define optimal cut-off values to predict the overall survival for SCFML3, VFML3 and mean muscular density.
All patients were irradiated at the Centre Henri Becquerel. Concomitant chemotherapy was delivered in the referring hospitals (CHU Rouen, CH Dieppe, CHI Elbeuf).
Statistical Analysis
Sarcopenic and non-sarcopenic patients were compared by Fisher’s exact and Pearson’s chi-square tests for categorical data, and by independent samples t tests or Mann-Whitney tests as appropriate for quantitative data. Survival probabilities were estimated by the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analyses of variables associated to variations in survival were performed using the Cox model. In order to respect the TRIPOD criteria, the performance of the retained model was validated internally by a bootstrap method (1b statement). The Concordance index (C-index) was computed to assess discrimination between observed and predictive data. Predictive accuracydeath by SMI, SCFM, or VFM was assessed by Receiver Operating Characteristics ROC analysis. Optimal cut-off values were computed by maximizing predictive performance criteria (sensitivity Se, specificity Sp, Positive and Negative Predictive Values PPV and NPV). Two-sided tests and confidence intervals were reported at the 5% level of significance. All statistical analyses were performed using R software version 3.3.3 using the “survival” package for survival analysis, “boot” package for bootstrap analysis, and “ROCR” and “OptimalCutpoints” packages for ROC analysis.
Ethics and deontology
The study protocol RTEP3 has been approved by the Centre Henri Becquerel Cancer ethics committee (www.becquerel.fr).