Impact of an individual pre-habilitation program on body composition, physical fitness and perioperative outcome in patients with pancreatic ductal adenocarcinoma undergoing neoadjuvant treatment

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with cachexia and reduced physical activity that is deteriorating further during neoadjuvant treatment. Systemic inflammation plays an important role in the host to cancer interactions associated with these conditions. The aim of this study is to assess the impact of an individual pre-habilitation program, comprising of physical training and nutritional support on cachexia, physical fitness, quality of life (QoL) and inflammatory activity in patients with PDAC undergoing neoadjuvant treatment and to compare it with standard care. We hypothesize that pre-habilitation has the potential to preserve body composition, physical fitness and QoL during neoadjuvant treatment and improves perioperative outcome. Methods: Patients with borderline resectable or locally advanced PDAC scheduled for neoadjuvant treatment were assessed for participation and randomized to either a pre-habilitation program or standard care. The level of fitness, body composition and indicators of cachexia were assessed together with QoL and daily nutrient intake before and during neoadjuvant treatment as well as 1 month after surgery and compared between groups. Various modules of physical training and nutritional support were selected individually for each patient in the pre-habilitation group aiming to preserve physical fitness and body components as much as possible. Patients in the control group receive standard, symptom-based care without any specific pre-habilitation. Blood inflammatory activity was determined by C-reactive protein, IL-6, IL-1ra,IL-10, TNF-a and albumin together with neutrophil lymphocyte ratio, platelet lymphocyte ratio and Glasgow Prognostic Score. Perioperative outcome was determined by R0 resection rate, frequency of surgical complications according to Clavien-Dindo and length of hospital stay. Primary endpoint analysis between groups were conducted by paired samples t-test and Wilcoxon test for metric variables depending on the underlying distribution and McNemar test for categorical variables. For subgroup analysis Friedman test and analysis of variance were undertaken.