Biphenotypic (hepatobiliary) primary liver carcinomas [B(H-B)PLCs] are rare tumors with features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). These tumors are associated with a poor overall prognosis and treatment is not well defined. Research over the past 20 years has identified aberrations in several molecular pathways, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in hepatocellular and biliary tract cancers. These discoveries led to the evaluation of targeted therapies, such as tyrosine kinase inhibitors, for the treatment of HCC and ICC. We report a case of a patient with metastatic B(H-B)PLC found to have a single nucleotide variant in the EGFR gene locus R521K who achieved a complete response on imaging after treatment with the combination of an EGFR inhibitor and a VEGF inhibitor. This case prompts consideration of further genomic analysis of these rare tumors and the potential use of targeted therapies in the treatment of patients with B(H-B)PLCs.
Amy Zhou, Manik Amin, Kathryn J. Fowler, Elizabeth M. Brunt, Jesse Keller and Benjamin Tan
Yvonne H. Sada, Brandon G. Smaglo, Joy C. Tan, Hop S. Tran Cao, Benjamin L. Musher and Nader N. Massarweh
Background: Pathologically positive lymph nodes (ypN+) after preoperative chemotherapy are associated with poor survival in patients with gastric cancer. Little is known about the association between response to preoperative therapy and the benefit of postoperative therapy. Methods: This retrospective cohort study of the National Cancer Database included patients with clinically node-positive (cN+) gastric cancer treated with preoperative therapy followed by surgery (2006–2014). Preoperative treatment modality was categorized as the inclusion of radiation therapy (RT) or chemotherapy alone. Pretreatment clinical and pathologic stages were used to determine pathologic treatment response rates. The association between overall risk of death and preoperative treatment, disease response, and adjuvant therapy use was evaluated using multivariable Cox regression. Results: Preoperative RT was used in 53.6% of 1,976 patients with cN+ gastric cancer, (74.3% cardia and 10.1% noncardia). The nodal response rate was 38.9% and was higher with RT than with chemotherapy alone (cardia, 46.0% vs 29.1%; P<.001; noncardia, 43.8% vs 31.9%; P=.06). Preoperative RT was associated with an approximate 2-fold increase in the odds of pathologic response compared with chemotherapy. Overall, use of adjuvant therapy was not associated with a decreased risk of death. A primary tumor response with residual nodal disease was not associated with survival (hazard ratio [HR], 1.03; 95% CI, 0.66–1.60). However, a nodal response with residual primary disease was significantly associated with survival (HR, 0.54; 95% CI, 0.44–0.65). Conclusions: More than one-third of node-positive gastric cancers showed pathologic nodal response with preoperative treatment. RT is associated with a higher response than chemotherapy. Patients with ypN+ disease have worse survival, regardless of whether they receive postoperative therapy. Future gastric cancer trials should evaluate the role of preoperative RT and individualize postoperative therapy use.
Nikolaos A. Trikalinos, Amy Zhou, Maria B. Majella Doyle, Kathryn J. Fowler, Ashley Morton, Neeta Vachharajani, Manik Amin, Jesse W. Keller, William C. Chapman, Elizabeth M. Brunt and Benjamin R. Tan
Background: Combined hepatocellular-cholangiocarcinoma tumors (cHCC-CCA) are a heterogeneous group of rare malignancies that have no established optimal treatment. Patients and Methods: We identified patients with cHCC-CCA treated at a tertiary center and retrospectively examined their histology, interventions, and outcomes. We calculated disease control rate (DCR), disease progression, overall survival, and progression-free survival (PFS) between treatment subgroups. Results: A total of 123 patients were evaluable. Interventions included resection, locoregional therapy, transplant, chemotherapy, and targeted agents. Ultimately, 68 patients received systemic treatment—57 with gemcitabine plus either 5-fluoropyrimidine (5-FU) or a platinum combination. Disease progression was more common in the gemcitabine/5-FU group versus gemcitabine/platinum (P=.028), whereas DCR favored gemcitabine/platinum (78.4% vs 38.5%; P=.0143). Median PFS from time of initial diagnosis favored the gemcitabine/platinum group, but the difference did not reach statistical significance. Targeted agents had minimal to no effect on survival metrics. Conclusions: Gemcitabine/platinum seems to be a superior regimen for patients with cHCC-CCA who require systemic treatment. Further studies are needed to clarify the regimen's efficacy and applicability in patient subgroups.