Immune Checkpoint Inhibitors versus VEGF Targeted Therapy as Second Line Regimen in Advanced Hepatocellular Carcinoma (HCC): A Retrospective Study.

Several targeted agents including multi-tyrosine kinase inhibitors (mTKIs) and immunotherapy (IO) agents have been approved for use beyond the frontline setting in patients with advanced hepatocellular carcinoma (HCC). Due to lack of prospective head-to-head comparative trials, there is no standardized way for alternating those agents beyond frontline. Therefore, we performed a retrospective review of the Kansas University (KU) cancer registry to determine whether IO may be superior to non-IO therapy. Patients with advanced HCC were divided into two groups based on the second-line systemic regimen received (IO vs. non-IO). Progression-free survival (PFS) and overall survival (OS) were calculated under the Kaplan-Meier and Cox proportional hazards models. No statistically significant differences in PFS and OS were found, although a non-significant delayed separation in the survival curve favoring IO was identified (median PFS 3.9 months vs. 3 months; median OS 10 months vs. 10 months respectively for IO vs. non-IO). This retrospective analysis is one of the earliest and largest studies comparing second-line IO and non-IO therapies thus far reported. Future studies should aim to define specific biomarkers for response prediction and treatment optimization based on individual patient and tumor characteristics. Furthermore, combinatorial therapeutic strategies is an evolving approach showing early promising signal.

Comparison of postoperative venous thromboembolism incidence in gastrointestinal and gynecologic solid tumors.

INTRODUCTION: Studies have shown the benefit of 28days of extended postoperative venous thromboembolism (VTE) prophylaxis for patients undergoing major cancer surgery in the abdomen or pelvis. We retrospectively evaluated the VTE incidence at the University of Kansas Hospital between gynecologic (GYN) cancer patients, who receive extended prophylaxis, and gastrointestinal (GI) cancer patients, who do not. METHODS: Patients were evaluated between January of 2010 and December of 2013, and VTE data for eligible patients were collected for 30 and 90days postoperatively. RESULTS: The study population composed of 190 GYN and 204 GI patients. Colon and endometrial cancers were the most common diagnoses. For GYN and GI patients respectively, VTE occurred in 4.2% and 5.4% at 30days (p=0.584) and 7.4% and 7.8% at 90days (p=0.514). One VTE-related death occurred in the GI group. GI patients underwent more open surgeries, 77.9% versus 66.3% (p=0.010) and had longer postoperative hospital stay, median of 7 versus 4days (p<0.0001). Out of all cancer patients combined, 40% versus 17.9% had stage IV disease and 10.2% versus 0.9% had open surgery in the VTE and non-VTE groups, respectively. CONCLUSIONS: There were no significant differences in overall VTE incidence between the two patient groups at 30 and 90days postoperatively. A majority of VTEs occurred in stage IV patients and patients who underwent open surgeries regardless of diagnosis.

Olive secoiridoids and semisynthetic bioisostere analogues for the control of metastatic breast cancer.

(-)-Oleocanthal (1) and ligstroside aglycone (2) are common bioactive olive oil secoiridoids. Secoiridoid 1 has been previously reported as a c-MET inhibitor. Chemically, (-)-oleocanthal is the elenolic acid ester of the common olive phenolic alcohol tyrosol. Therefore, several analogues (4-13) were synthesized by esterification and carbamoylation of tyrosol using diverse phenolic naturally occurring in olive and heterocyclic acids as elenolic acid bioisosteres to assess the effect of replacing the acid moiety of (-)-oleocanthal. Their c-MET inhibitory activity as well as their antiproliferative, antimigratory, and anti-invasive activities against the highly metastatic human breast cancer cell line MDA-MB231 has been assessed. Ligstroside aglycone (2) showed the best antimigratory activity. Generally, tyrosol esters showed better activities versus carbamate analogues. Tyrosol sinapate (5) showed the best c-MET phosphorylation inhibitory activity in Z'-LYTE kinase assay. Both 1 and 5 competitively inhibited the ATP binding into its pocket in the c-MET catalytic domain. Compound 5 showed selective activities against tumor cells without toxicity to the non-tumorigenic human breast MCF10A epithelial cell line. Tyrosol esters with a phenolic acid containing hydrogen bond donor and/or acceptor groups at the para-position have better anticancer and c-MET inhibitory activities. Olive oil secoiridoids are excellent scaffolds for the design of novel c-MET inhibitors.