Molecular Targets and Emerging Therapies for Advanced Gallbladder Cancer

Biliary tract cancers (BTCs), for their low incidence, have been often considered together. Gallbladder cancer (GBC) is the most common biliary tract malignancy, characterized by late diagnosis and poor prognosis, and although it is considered a rare tumor in western countries, other areas of the world show considerable incidence rates. In 2010, results from the large phase III ABC-02 clinical trial on GBC identified the gemcitabine and cisplatin combination as the most effective first-line regimen for both GBC and other BTCs. Since then, various systemic therapies have proven active in BTCs in both first- and second-line settings. Molecular profiling has highlighted important genetic differences between GBC and other BTCs, opening new ways for targeted therapy in advanced disease where standard chemotherapies show marginal benefit. Genome-wide data analysis have shown that GBC molecular landscape offer possible strategies for precision medicine approaches, and a better molecular understanding of the GBC is needed to better stratify patients for treatment. In this review, we discuss the molecular targetable agents for GBC, including the results that emerged by clinical trials exploring new treatment strategies.

Nomogram Based on Log Odds of Positive Lymph Nodes Predicting Cancer-Specific Survival in Patients With T3 and T4 Gallbladder Cancer After Radical Resection

Background: The aim of this study based on log odds of positive lymph nodes (LODDS) is to develop and validate an effective prognostic nomogram for patients with T3 and T4 gallbladder cancer (GBC) after resection.Patients and Methods: A total of 728 T3 and T4 gallbladder cancer patients after resection from the Surveillance, Epidemiology, and End Results (SEER) database, randomly divided into training cohort and validation cohort according to 7:3. Another 128 patients from The Second Affiliated Hospital of Nanchang University for external validation. The nomograms were built by the Cox regression model and the Fine and Grey's model. Concordance index (C-index), calibration curve and the area under receiver operating characteristic (ROC) curve (AUC) were used to evaluate the nomogram and internal verification. The decision curve analysis (DCA) was used to measure clinical applicability.Result: LODDS was independent prognostic predictor for overall survival (OS) and cancer-specific survival (CSS), and established the nomograms on this basis. The nomogram we have established has a good evaluation effect, with a C-index of 0.719 (95%CI, 0.707–0.731) for OS and 0.747 (95%CI, 0.733–0.760) for CSS. The calibration curves of OS and CSS both showed good calibration capability, and the AUC for predicting 1-, 2-, and 3-year 0.858, 0.848 were and 0.811 for OS, and 0.794, 0.793, and 0.750 for CSS. The DCA of nomograms both showed good clinical applicability.Conclusion: The nomogram can provide effective OS and CSS prediction for patients with advanced gallbladder cancer after surgery.

The Multidisciplinary Treatment of Advanced Gallbladder Cancer to Disease-Free Survival: A Case Report

Background: Gallbladder cancer is the most common malignant tumor in the biliary system and is characterized by strong aggressiveness and an extremely poor prognosis. Current treatment for advanced gallbladder cancer remains unsatisfactory. Here we reported a patient with stage IV gallbladder cancer who achieved disease-free survival by multidisciplinary treatment.Case presentation: A 73-year-old man presented to our hospital with right abdominal pain for 3 days and was diagnosed with advanced gallbladder cancer with multiple intrahepatic metastases and distant lymph node metastases. The patient initially received chemotherapy, targeted therapy, radioactive seed implantation, and immunotherapy as there was no specific indications for radical surgery. With the progression of these adjuvant therapies, the patient’s tumor makers gradually decreased but remained higher than normal, lymph node metastases gradually disappeared, and intrahepatic metastases were gradually limited to the left liver. Finally, the patient received a radical surgery of left hepatectomy with partial diaphragmatic resection and radical lymphadenectomy. To date, the patient has survived for more than six years post-treatment, and the level of tumor markers is normal and the imaging examination shows no signs of disease recurrence.Conclusion: The treatment of advanced gallbladder cancer remains pessimistic in the current medical arena. This successful case is an inspiration and we believe that multidisciplinary treatment can benefit patients with advanced gallbladder cancer and help them achieve long-term survival or even disease-free survival.

Palliative chemotherapy for advanced gallbladder cancer

INTRODUCTION Gallbladder cancer is the most common malignancy of the biliary tract. Given the lack of therapeutic alternatives for advanced stage patients studies have suggested that palliative chemotherapy could benefit these patients. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis, and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified two systematic reviews including two studies overall, of which one was a randomized trial. We concluded that palliative chemotherapy may increase survival in advanced gallbladder cancer patients. However, palliative chemotherapy probably increases adverse effects. In addition, it is essential to carry out a new systematic review, since methodological errors were identified in the analysis and there is new evidence that has not been included in the previous reviews