Blanc, Jean‐Frédéric

NAPOLI-1 (NCT01494506) was a phase III study of liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This post hoc analysis of NAPOLI-1 aimed to develop a predictive nomogram for overall survival (OS) at 6 and 12 months. Analyses were derived from all patients in NAPOLI-1 randomized to receive nal-IRI+5-FU/LV, nal-IRI monotherapy, or 5-FU/LV combination therapy. OS was associated with baseline factors using univariate and multivariable Cox analyses. A predictive nomogram was derived and validated using a concordance index and calibration plots. The univariate analyses identified 21 independent factors that contributed to OS, with eight factors significantly associated with OS. The Karnofsky Performance Score contributed the largest number of points (100), followed by presence of liver metastasis (98) and randomization to nal-IRI+5-FU/LV (96). The other baseline factors showing effects were albumin (g/dL), neutrophil/lymphocyte ratio, carbohydrate antigen 19-9 (U/mL), disease stage at diagnosis, and body mass index (kg/m2). The nomogram was used to predict the 6- and 12-month survival probability. The mean absolute errors between the observed and predicted probabilities for OS at 3, 6, and 9 months were 0.07, 0.08, and 0.07, respectively. This nomogram, based on NAPOLI-1, provides additional insight to aid decision-making for patients with mPDAC after previous gemcitabine-based therapy.

Current guidelines recommend surgical resection as the primary treatment for a single hepatocellular cancer (HCC) with Child's A cirrhosis, normal serum bilirubin, and no clinically significant portal hypertension. We determined how frequently guidelines were followed and whether straying from them impacted survival. BRIDGE is a multiregional cohort study including HCC patients diagnosed between January 1, 2005 and June 30, 2011. A total of 8,656 patients from 20 sites were classified into four groups: (A) 718 ideal resection candidates who were resected; (B) 144 ideal resection candidates who were not resected; (C) 1,624 nonideal resection candidates who were resected; and (D) 6,170 nonideal resection candidates who were not resected. Median follow‐up was 27 months. Log‐rank and Cox's regression analyses were conducted to determine differences between groups and variables associated with survival. Multivariate analysis of all ideal candidates for resection (A+B) revealed a higher risk of mortality with treatments other than resection. For all resected patients (A+C), portal hypertension and bilirubin >1 mg/dL were not associated with mortality. For all patients who were not ideal candidates for resection (C+D), resection was associated with better survival, compared to embolization and “other” treatments, but was inferior to ablation and transplantation. Conclusions : The majority of patients undergoing resection would not be considered ideal candidates based on current guidelines. Not resecting ideal candidates was associated with higher mortality. The study suggests that selection criteria for resection may be modestly expanded without compromising outcomes, and that some nonideal candidates may still potentially benefit from resection over other treatment modalities. (H epatology 2015;62:440–451