It's not only about weight loss: Tackling pancreatic cancer-associated cachexia

Abstract Background Cachexia affects 70-80% patients with pancreatic adenocarcinoma (PA). Systemic inflammation is a key feature of this multifactorial syndrome of unintended weight loss (WL). Despite being often described, cancer-associated cachexia (CAC) remains poorly understood and rarely recognized in clinical settings, therefore an unmet need. This study aims to acknowledge the effect of CAC in PA patients and to study the impact of WL, body mass index (BMI) and other available biomarkers (BM) on survival. Methods Retrospective analysis of PA patients treated in our institution between 2013 - 2018. Patients were categorized at baseline as having CAC if 1 of 2 criteria were met: WL > 5% from previous stable weight; BMI  2%. Serum hemoglobin, c-reactive protein (CRP), albumin, inflammation-based score (Glasgow Prognostic Score mGPS), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and cancer specific antigen CA 19-9 were assessed at baseline and at 3-month. Data analysis with descriptive statistics, t-test, chi-square test, cox regression and log-rank test were performed with StataIC. Results 95 eligible patients (median age 72 [46;98], 60% female) were reviewed. At baseline, cachectic patients (CP) (74%), when compared to non-CP, had higher CA 19-9 (p = 0,047), more advanced disease (p = 0,001) lower BMI (p = 0,016), worse performance status (p = 0,016) and mean WL of 13,8 ± 6,7 (%) (p = 0,001). Also, NLR>3,5 (p = 0,001), PLR>150 (p = 0,018) and hypoalbuminemia (p = 0,004) were all statistically associated to CP. Median overall survival (OS) of non-CP was 19,13 months versus 5,03 months in CP (HR 2,69 95% CI 1,58-4,59, p = 0,001). In the latter, at baseline, higher CA 19.9 (HR 1,0 95% CI 1,01-1,021, p = 0,015), higher CRP (HR 1,21 95% CI 1,06-1,39, p = 0,006) and PLR>150 (HR 2,45; 95% CI 1,09-5,54, p = 0,031) were independent predictors of worst OS. In non-CP, normal baseline albumin (HR 0,04 95 CI 0,02-0,72, p = 0,029) was an independent predictor of better OS. Conclusions A better understanding of CAC in PA might improve outcomes for PA patients. Our study suggests that a prompt identification of prognostic BM may lead to a better standardized management of CAC and that nutritional parameters can be optimized, with impact on prognosis. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.