A O03 Host phenotypic adversity independently predicts progression to resection in neoadjuvantly-treated pancreatic cancer

Abstract

Abstract Background Neoadjuvant treatment (NAT) offers a modest survival benefit to the otherwise dismal outcomes of pancreatic ductal adenocarcinoma (PDAC), however methods for assessing treatment response and disease trajectory during NAT are limited. Cachexia and sarcopenia are hallmark features of PDAC and defining host phenotypic adversity is crucial in understanding the tumour-host relationship and its influence on clinical outcomes. We sought to determine the relationship between body composition, systemic inflammation, and outcomes in NAT PDAC to lay foundations for improving assessment of treatment response. Methods This is a retrospective, observational study with an intention-to-treat design, analysing resected (n = 109) and non-resected (n = 117) NAT PDAC (total n = 226) from the tertiary West of Scotland Pancreatic Unit, Glasgow Royal Infirmary. Patients were included if they had resectable or borderline resectable disease and received NAT. Patients were excluded if they had locally advanced or metastatic disease. Body composition was determined by single-slice L3 cross-sectional measurements. Results Patients with an adverse phenotype defined by change in body composition were less likely to progress to resection (40.9% vs 68.8%, p < 0.001). Logistic regression confirms the independence of this effect (OR 3.79, 95% CI 1.99-7.22, p < 0.001). There was a trend towards systemic inflammation in the non-resected group (CRP rise 51.4% vs 29.9%, p = 0.008). Patients treated with Folfirinox who required dose reduction received higher doses of irinotecan, 5-fluorouracil (bolus) and 5-fluorouracil (infusion) per unit muscle mass (7.3 vs 6.9mg/cm2⋅m-2, p = 0.010; 16.2 vs 14.7mg/cm2⋅m-2, p = 0.002; 96.5 vs 91.1mg/cm2⋅m-2, p = 0.026). Conclusions Host phenotypic adversity during NAT presents a potentially valuable addition to a limited arsenal of tools to aid decision making in resectable and borderline resectable PDAC. Early assessment of body composition trend during chemotherapy may present an opportunity to switch the host phenotype from adverse to favourable in some patients, or highlight the futility of continuing aggressive treatment in others. Chemotherapeutic prescribing by body surface area overlooks crucial differences in lean body mass and may be exposing patients to avoidable and burdensome toxicities.