The differential clinical impacts of cachexia and sarcopenia on the prognosis of advanced pancreatic cancer

[[abstract]]Simple Summary Pancreatic cancer (PC) is one of the most lethal malignancies across the world. More than 80% patients are diagnosed at an advanced stage with limited treatment options. PC has the highest frequency of developing cancer cachexia (CC)-sarcopenia (SC) syndrome, but there is no optimal efficient intervention for CC or SC targeting their complicated biological and irreversible processes. As a result, identifying the clinicopathological features and patient characteristics in each advanced PC patient with CC and/or SC is urgently needed to distinguish different wasting phenotypes or body composition and thus support precision medicine and achieve optimal outcomes. We performed a retrospective cohort study of 232 advanced PC patients to determine the differential clinical characteristics of CC and SC and the overlap of CC- or SC-related factors in each patient. The impacts of CC, SC, and their relevant factors on the outcomes of PC patients were also evaluated. Pancreatic cancer (PC) has the highest frequency of developing cancer cachexia (CC)-sarcopenia (SC) syndrome, which negatively influences patients' outcome, quality of life, and tolerance/response to treatments. However, the clinical impacts of CC, SC, and their associated factors on outcomes for advanced PC has yet to be fully investigated. A total of 232 patients were enrolled in this study for the retrospective review of their clinical information and the measurement of skeletal muscle areas at the third lumber vertebra by computed tomography scan to identify CC or SC. The association and concurrent occurrence of clinicopathological features in each patient, prevalence rates, and prognosis with the CC or SC were calculated. CC and SC were observed in 83.6% (n = 194) and 49.1% (n = 114) of PC patients, respectively. Low hemoglobin levels more often occurred in CC patients than in non-CC patients (p = 0.014). Older age (p = 0.000), female gender (p = 0.024), low body mass index (BMI) values (p = 0.004), low hemoglobin levels (p = 0.036), and low albumin levels (p = 0.001) were more often found in SC patients than in non-SC patients. Univariate and multivariate analyses showed that CC was an independent poor prognostic factor of overall survival (OS) and progression-free survival for all patients, the chemotherapy (C/T) subgroup, and the high BMI subgroup. Meanwhile, SC was an independent predictor of poor OS for the subgroups of C/T or high BMI but not for all patients. These findings reveal the clinical differences for CC and SC and provide useful information for predicting the prognosis of advanced PC patients and conducting personalized medicine