Molecular profiling and patient selection for the multimodal approaches for patients with resectable colorectal liver metastases.

Colorectal cancer represents the third most common cancer and about 20% are diagnosed with synchronous metastatic disease. From a historical point of view, surgery remains the mainstream treatment for resectable colorectal liver metastases (CRLM). Furthermore, disease outcomes are improving due significant advances in systemic treatments and diagnostic methods. However, the optimal timing for neoadjuvant chemotherapy or upfront surgery for CRLM has not yet been established and remains an open question. Thus, patient selection combining image workouts, time of recurrence, positive lymph nodes, and molecular biomarkers can improve the decision-making process. Nevertheless, molecular profiling is rising as a promising field to be incorporated in the multimodal approach and guide patient selection and sequencing of treatment. Tumor biomakers, genetic profiling, and circulating tumor DNA have been used to offer as much personalized treatment as possible, based on the precision oncology concept of tailored care rather than a guideline-based therapy. This review article discusses the role of molecular pathology and biomarkers as prognostic and predictor factors in the diagnosis and treatment of resectable CRLM.

Advances in the treatment of biliary tract cancers.

PURPOSE OF REVIEW: To review new treatment and advances in biliary tract cancer (BTC). RECENT FINDINGS: In the prespecified per-protocol analysis of the randomized phase III trial BILCAP, adjuvant capecitabine offers overall survival (OS) benefit when compared with observation with statistical significance. In the first-line setting in metastatic BTC, gemcitabine and S-1 had noninferior OS compared with gemcitabine and cisplatin. In a separate phase III study, the triplet of gemcitabine, cisplatin and S-1 (GCS) had superior OS compared with standard gemcitabine and cisplatin. The regimen of modified FOLFOX (fluorouracil, leucovorin and oxaliplatin) regimen can be considered a potential standard option in the second-line setting for patients who failed first-line therapy with gemcitabine-based regimens. Trials in genomically selected patients indicate activity of fibroblast growth factor receptor inhibitors, mutant isocitrate dehydrogenase inhibitors and immune checkpoint inhibitors. SUMMARY: Capecitabine is a new option for adjuvant treatment in resected BTC. In the metastatic setting, gemcitabine and S-1 or GCS are new options for first-line therapy and modified FOLFOX regimen should be considered as a potential new empirical standard of care in genomically agnostic patients requiring second-line therapy. Future randomized trials will evaluate the role of targeted agents and immunotherapy in advanced BTC, both in monotherapy and in combination.

Predictive Value of Serum Carbohydrate Antigen 19-9 (CA19-9) for Early Mortality in Advanced Pancreatic Cancer.

INTRODUCTION: Levels of carbohydrate antigen 19-9 (CA19-9) in metastatic pancreatic cancer are used in daily practice as a marker of response to chemotherapy. The association between CA19-9 levels and mortality remains uncertain. This study sought to determine the most accurate level of CA19-9 associated with early mortality, both at diagnosis and during the course of metastatic disease. METHODS: This research is a retrospective analysis of 64 patients with metastatic adenocarcinoma of the pancreas evaluated from January 2010 to December 2015. A receiver-operating characteristic (ROC) curve analysis was performed to evaluate the CA19-9 value and the association with early death (death within 2 months after diagnosis of advanced disease). The survival analysis was estimated by the Kaplan-Meier method, and variables of interest were assessed by proportional hazards regression Cox models. RESULTS: The mortality rate was 92.2%, and the estimated median survival was 11.0 months. For the ROC curve analysis of initial CA19-9, an area under the curve of 0.868 (95% confidence interval 0.782 to 0.954) was obtained; the cutoff of 2504 U/ml had a sensitivity of 100% and specificity of 82.8% for early death. The effect of initial CA19-9 and chemotherapy contributed independently to the survival time, and every increase of 1000 CA19-9 units increased the risk of death by 9% (p = 0.0003). CONCLUSION: CA19-9 levels in advanced pancreatic adenocarcinoma are associated independently with worse prognosis and early death. CA19-9 levels could be considered as a stratification factor for future clinical trials.