The significance of relative dose intensity in adjuvant chemotherapy of pancreatic ductal adenocarcinoma-including the analysis of clinicopathological factors influencing relative dose intensity

Abstract

Recently, it has been reported that the relative dose intensity (RDI) of adjuvant chemotherapy (AC) influences survival in various cancers, but there are very few reports about RDI in pancreatic ductal adenocarcinoma (PDAC). The optimal timing for initiation of AC for PDAC also remains unknown. The aim of this study was to identify the significance of RDI and the time interval between surgery and initiation of AC on survival of patients with PDAC. Clinicopathological factors that affect RDI were also investigated. A total of 311 consecutive PDAC patients who underwent curative resection between May 2005 and January 2015 were enrolled. Patients who underwent neoadjuvant chemoradiation, had UICC stage IV disease, or had early recurrences within 6 months were excluded, and the remaining 168 cases were analyzed. Patients with RDIs ≥80% (n=79) showed significantly better overall survival (OS) compared to patients with RDIs <80% (n=55) (median survival time (MST): 45.6 months, 26.0 months, P<0.001). Patients with no AC (n=34) showed the worst OS (MST: 20.8 months). Whether the AC was initiated earlier or later than 8 weeks after surgery did not influence survival, either in patients with RDIs ≥80% (P=0.79) or in those with<80% (P=0.73). Patients in the S-1 monotherapy group (n=49) showed significantly better OS than patients in the gemcitabine monotherapy group (n=51) (MST: 95.0 months, 26.0 months, respectively; P=0.001). Univariate analysis conducted after adjusting for the chemotherapeutic drug used identified several prognostic factors; male gender (P=0.01), intraoperative blood transfusion (P=0.005), lymph node metastasis (P=0.03), and postoperative WBC count (P=0.03). Multivariate analysis identified intra-plus postoperative blood transfusion (P=0.002) and high postoperative platelet-to-lymphocyte ratios (PLR) (P=0.04) as independent predictors of poor RDI. Efforts to maintain RDI had a greater impact on survival than the struggle to start AC early after surgery. Intra-plus postoperative blood transfusion and a high postoperative PLR could be predictive markers of reduced RDI in AC of PDAC patients. Avoidance of perioperative blood transfusions where possible and nutritional support during the perioperative period could maintain adequate RDI and may lead to improved long-term outcome.