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    E-mail addresses: [email protected], [email protected] (O.M. Griffin).
    classification, and the advent of neo-adjuvant therapy for patients with borderline resectable disease [3].
    Malnutrition and cachexia affect up to 80% of patients at diag-nosis [4], and remain limiting factors to successful treatment de-livery and tolerance [5,6]. Increasing pre-morbid obesity levels increase the risk of developing pancreatic cancer, as well as delaying diagnosis. Initial unintentional weight loss experienced by overweight and obese patients may be overlooked as a symptom of the disease, or misperceived as advantageous. Furthermore, excess adiposity and obesity may mask underlying sarcopenia, an estab-lished adverse prognostic factor for patients with advanced pancreatic cancer [6].
    The prevalence and prognostic significance of cachexia,
    Please cite this Fer-1 article as: Griffin OM et al., Characterising the impact of body composition change during neoadjuvant chemotherapy for pancreatic cancer, Pancreatology,
    sarcopenia and sarcopenic obesity in cancer have gained recogni-tion in recent years [7,8]. There has, however, been considerable disparity in the methods used in various studies regarding muscle measurement as well as in the definition of sarcopenia used [9]. This precludes adequate comparison of studies and presents a de-gree of uncertainty around the true prevalence of sarcopenia and its impact on clinical outcomes in pancreatic cancer [10]. Recent at-tempts to evaluate the impact of sarcopenia on survival in pancreatic cancer concluded that future studies evaluating body composition in pancreatic cancer utilise the international consensus definition for cachexia [9,11] and include a direct mea-surement of muscle mass (dual-energy X-ray absorptiometry, Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)).
    Given the uncertainty to date, we designed a study to evaluate the impact of body composition in pancreatic cancer patients un-dergoing neoadjuvant chemotherapy. Specifically, we had three aims. Firstly, we sought to determine the prevalence and degree of cachexia, sarcopenia and low muscle attenuation at baseline for patients with BRPC. Secondly, we sought to investigate changes in body composition between baseline (diagnosis) and post-chemotherapy. Finally, we evaluated the impact of both baseline body composition characteristics, and changes endured during treatment, on survival.
    Patient selection and management
    Consecutive patients with pancreatic adenocarcinoma who were referred for neoadjuvant chemotherapy between 2012 and 2015 were identified from a prospectively maintained database, and comprised the study population. Additional inclusion criteria included the availability of the digital CT images required for body composition analysis, along with necessary anthropometric data for interpretation.
    Patients were referred to the National Surgical Centre for Pancreatic Cancer (NSCPC), at diagnosis for specialist multidisci-plinary discussion. The NSCPC was established at St Vincent's University Hospital (SVUH) in Dublin, following the centralisation of pancreatic cancer surgery in Ireland. Following discussion and team consensus patients underwent neo-adjuvant chemotherapy either at SVUH or their local cancer centre. Tumour staging was defined as per current National Comprehensive Cancer Network criteria [3]. Chemotherapy agent selection was decided by the local treating oncologist, and individual patient private health insurance policy cover. Upon completion of chemotherapy patients under-went a restaging CT scan which was submitted to the NSCPC to assess their response to treatment and potential for resectability before potentially proceeding to radiotherapy.
    Body composition assessment
    Existing CT scans, acquired for cancer diagnosis and restaging, were analysed for body composition by a single, trained investi-gator (OMG) using a validated programme, Slice-O-Matic version 5.0 (Tomovision, Montreal, Canada). The relevant, sequential, axial CT images which clearly visualised the L3 vertebrae were land-marked, anonymised and downloaded in DICOM format. The sur-face area of skeletal muscle tissue (psoas, erector spinae, quadratus lumborum, transversus abdominus, external and internal obliques and rectus abdominus structures) and adipose tissue (visceral, intra-muscular and subcutaneous) were measured using estab-lished radio-density cut-offs [7]. Lumbar Skeletal Muscle Index (LSMI) was calculated by normalising skeletal muscle area for
    height, and subsequently compared values to gender- and body mass index (BMI)-specific references [8]. Muscle attenuation (MA) was quantified by measuring average skeletal muscle radio-density, and defined as per BMIespecific values (<33 Hounsfield Units in patients with BMI 25 Kg/M2, and <41 Hounsfield Units in patients whose BMI < 25 Kg/M2) [8]. Validated regression equations [12] were then applied to estimate whole body fat and fat-free mass: