The purpose of this study was to compare the clinical usefulness of the seventh Union Internationale Contre le Cancer/American Joint Committee on Cancer (AJCC/UICC) staging system vs the sixth AJCC/UICC staging system in patients with gastric cancer. Included were 1,799 patients who underwent surgery for gastric cancer between January 2001 and June 2005 at the National Cancer Center (South Korea). For the sixth and seventh AJCC/UICC staging systems, survival outcomes stratified by stage, by T classification, and by N classification were summarized using Kaplan-Meier curves and compared statistically using a log rank test; survival differences were quantified using hazard ratios estimated from a Cox regression model. The 2 systems were compared in terms of prognostic performances using the linear trend chi-square test, likelihood ratio chi-square test, and Akaike information criterion (AIC) in the Cox regression analysis. Significant survival differences between each stage were not found using the seventh staging system, especially for stages IB, IIA, and IIB (p = 0.14 and p = 0.11). The sixth staging system had higher linear trend chi-square score and likelihood ratio chi-square score, which means better discriminatory ability, monotonicity, and homogeneity, and had smaller AIC, which indicates better optimistic prognostic stratification, especially in the N classification. The modified staging system combining the T classification of the seventh AJCC/UICC system and the N classification of the sixth system showed better prognostic performance compared with each separate version (sixth or seventh) of the staging system. The seventh AJCC/UICC staging system is not more clinically useful than the sixth system in surgically treated patients with gastric cancer because of an inappropriate N classification. A new TNM system is required with a different N classification.

Although sorafenib is the global standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC), it does not have reliable predictive or prognostic biomarkers. Circulating cell-free DNA (cfDNA) has shown promise as a biomarker for various cancers. We investigated the use of cfDNA to predict clinical outcomes in HCC patients treated with sorafenib. This prospective biomarker study analyzed plasma cfDNA from 151 HCC patients who received first-line sorafenib and 14 healthy controls. The concentration and VEGFA-to-EIF2C1 ratios (the VEGFA ratio) of cfDNA were measured. Low depth whole-genome sequencing of cfDNA was used to identify genome-wide copy number alteration (CNA), and the I-score was developed to express genomic instability. The I-score was defined as the sum of absolute Z-scores of sequenced reads on each chromosome. The primary aim of this study was to develop cfDNA biomarkers predicting treatment outcomes of sorafenib, and the primary study outcome was the association between biomarkers with treatment efficacy including disease control rate (DCR), time to progression (TTP) and overall survival (OS) in these patients. The cfDNA concentrations were significantly higher in HCC patients than in healthy controls (0.71 vs. 0.34 ng/μL; P < 0.0001). Patients who did not achieve disease control with sorafenib had significantly higher cfDNA levels (0.82 vs. 0.63 ng/μL; P = 0.006) and I-scores (3405 vs. 1024; P = 0.0017) than those achieving disease control. The cfDNA-high group had significantly worse TTP (2.2 vs. 4.1 months; HR = 1.71; P = 0.002) and OS (4.1 vs. 14.8 months; HR = 3.50; P < 0.0001) than the cfDNA-low group. The I-score-high group had poorer TTP (2.2 vs. 4.1 months; HR = 2.09; P < 0.0001) and OS (4.6 vs. 14.8 months; HR = 3.35; P < 0.0001). In the multivariable analyses, the cfDNA remained an independent prognostic factor for OS (P < 0.0001), and the I-score for both TTP (P = 0.011) and OS (P = 0.010). The VEGFA ratio was not significantly associated with treatment outcomes. Pretreatment cfDNA concentration and genome-wide CNA in cfDNA are potential biomarkers predicting outcomes in advanced HCC patients receiving first-line sorafenib.

Nivolumab has shown durable response and safety in patients with hepatocellular carcinoma (HCC) in previous trials. However, real-world data of nivolumab in HCC patients, especially those with Child–Pugh class B, are limited. To investigate the effectiveness and safety of nivolumab in a real-world cohort of patients with advanced HCC, we retrospectively evaluated 203 patients with HCC who were treated with nivolumab between July 2017 and February 2019. Of 203 patients, 132 patients were classified as Child–Pugh class A and 71 patients were Child–Pugh class B. Objective response rate was lower in patients with Child–Pugh class B than A (2.8% vs. 15.9%; p = 0.010). Child–Pugh class B was an independent negative predictor for objective response. Median overall survival was shorter in Child–Pugh B patients (11.3 vs. 42.9 weeks; adjusted hazard ratio [AHR], 2.10; p < 0.001). In Child–Pugh B patients, overall survival of patients with Child–Pugh score of 8 or 9 was worse than patients with Child–Pugh score of 7 (7.4 vs. 15.3 weeks; AHR, 1.93; p < 0.020). In conclusion, considering the unsatisfactory response in Child–Pugh B patients, nivolumab may not be used in unselected Child–Pugh B patients. Further studies are needed in this patient population.