Gastric cancer is a leading cause of cancer death and is associated with poor prognosis. The treatment of advanced gastric cancer is changing with the development of novel agents. Until recently, no standard treatment was available for patients with advanced gastric cancer in the second-line setting. Single-agent chemotherapy with docetaxel or irinotecan has been shown to improve survival and quality of life in patients whose disease has progressed while on prior chemotherapy. Combination chemotherapy is associated with a modest benefit at the expense of increased toxicity. Recently, ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF) receptor-2, has been approved for the treatment of refractory advanced gastric cancer as a single agent or in combination with paclitaxel. Apatinib, a small molecule tyrosine kinase inhibitor targeting VEGF, has demonstrated activity in Asian populations whose disease has progressed on 2 lines of therapy. However, much work is still needed, including the development of biomarkers that could predict response to therapy.
Amit Mahipal, Minsig Choi and Richard Kim
Siddhartha Yadav, Sri Harsha Tella, Anuhya Kommalapati, Kristin Mara, Kritika Prasai, Mohamed Hamdy Mady, Mohamed Hassan, Rory L. Smoot, Sean P. Cleary, Mark J. Truty, Lewis R. Roberts and Amit Mahipal
Background: Current staging systems for gallbladder cancer (GBC) are primarily based on surgical pathology and therefore are not relevant for unresectable patients and those undergoing neoadjuvant chemotherapy. Methods: Patients with a confirmed diagnosis of GBC managed at a tertiary referral center (2000–2016) were included. Independent predictors of overall survival (OS) were identified using multivariable analysis (MVA). A combination of these variables was then assessed to identify a set of factors that provided maximal accuracy in predicting OS, and a nomogram and a new staging system were created based on these factors. Harrell’s C-statistic was calculated to evaluate the predictive accuracy of the nomogram and staging system. Results: A total of 528 patients were included in the final analysis. On MVA, factors predictive of poor OS were older age, ECOG performance status, hemoglobin level <9 g/dL, presence of metastases, and alkaline phosphatase (ALP) level >200 U/L. A nomogram and a 4-tier staging system predictive of OS were created using age at diagnosis, ECOG status, tumor size, presence or absence of metastasis, and ALP level. The C-statistic for this novel staging system was 0.71 compared with 0.69 for the TNM staging system (P=.08). In patients who did not undergo surgery, the C-statistics of the novel and TNM staging systems were 0.60 and 0.51, respectively (P<.001). Conclusions: We created a novel, clinically based staging system for GBC based on nonoperative information at the time of diagnosis that was superior to the TNM staging system in predicting OS in patients who did not undergo surgery, and that performed on par with TNM staging in surgical patients.