Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.

Introduction Racial disparities in outcomes have been documented among patients with esophageal cancer. The purpose of this study is to identify mechanisms for ethnicity/race-related differences in the use of cancer-directed surgery and mortality. Methods Data from the Surveillance, Epidemiology and End Results (SEER) program were used to evaluate non-hispanic black, non-hispanic white and hispanic patients diagnosed with non-metastatic esophageal cancer (squamous cell carcinoma (SCC) or adenocarcinoma) from 2003–2008. Age, marital status, stage, histology and location were examined as predictors of receipt of surgery and mortality in multivariate analyses. Results 6,737 patient files (84% white, 10% black, 6% hispanic) were analyzed. Black and hispanic patients were more likely than whites to have SCC (86% vs. 41% vs. 26%, respectively; p<0.001) and lesions in the mid-esophagus (58% vs. 38% vs. 26%, respectively; p<0.001). Blacks and hispanics were less likely to undergo esophagectomy (adjusted OR 0.49, 95%CI=0.39–0.60 and 0.72, 95%CI=0.57–0.90). We noted significant variations in esophagectomy rates among patients with mid-esophageal cancers; 15% of blacks underwent esophagectomy compared to 22% of hispanics and 29% of whites (p<0.001). Black and hispanic patients had a higher unadjusted risk of mortality (HR 1.38, 95%CI=1.25–1.52 and 1.20, 95%CI=1.05–1.37). However, differences in mortality were no longer significant after adjusting for receipt of surgery. Conclusion Disparities in esophageal cancer outcomes are associated with the lower use of cancer-directed surgery. To decrease disparities in mortality it will be necessary to understand and target underlying causes of lower surgery rates in non-white patients and develop interventions, especially for mid-esophageal cancers.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy and is increasing in incidence. Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy. Unfortunately, a significant proportion of patients present with locally advanced, unresectable disease. Furthermore, recurrence rates are high even among patients who undergo surgical resection. The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer. Nevertheless, the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies, chemotherapy regimens, and targeted therapies have generated increasing interest its role. In this article, we review the rationale for, current evidence for, and ongoing research efforts in the use of neoadjuvant therapy for ICC.

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