Organoid technology for personalized pancreatic cancer therapy.

BACKGROUND: Pancreatic ductal adenocarcinoma has the lowest survival rate among all major cancers and is the third leading cause of cancer-related mortality. The stagnant survival statistics and dismal response rates to current therapeutics highlight the need for more efficient preclinical models. Patient-derived organoids (PDOs) offer new possibilities as powerful preclinical models able to account for interpatient variability. Organoid development can be divided into four different key phases: establishment, propagation, drug screening and response prediction. Establishment entails tailored tissue extraction and growth protocols, propagation requires consistent multiplication and passaging, while drug screening and response prediction will benefit from shorter and more precise assays, and clear decision-making tools. CONCLUSIONS: This review attempts to outline the most important challenges that remain in exploiting organoid platforms for drug discovery and clinical applications. Some of these challenges may be overcome by novel methods that are under investigation, such as 3D bioprinting systems, microfluidic systems, optical metabolic imaging and liquid handling robotics. We also propose an optimized organoid workflow inspired by all technical solutions we have presented.

The actual 5-year survivors of pancreatic ductal adenocarcinoma based on real-world data.

Survival data for pancreatic cancer are usually based on actuarial calculations and actual long-term survival rates are rarely reported. Here we use population-level data from the Surveillance, Epidemiology, and End Results program for patients with microscopically confirmed pancreatic ductal adenocarcinoma diagnosed from 1975 to 2011. A total of 84,275 patients with at least 5 years of follow-up were evaluated (follow-up cutoff date: December 31, 2016). Actual 5-year survival for pancreatic cancer increased from 0.9% in 1975 to 4.2% in 2011 in patients of all stages (p < 0.001), while in surgically resected patients, it rose from 1.5% to 17.4% (p < 0.001). In non-resected patients, the actual 5-year survival remained unchanged over the same time period (0.8% vs 0.9%; p = 0.121). Multivariable analysis of surgically resected patients diagnosed in the recent time era (2004-2011) showed that age, gender, grade, tumour size, TNM-stage and chemotherapy were significant independent predictors of actual 5-year survival, while age, grade and TNM-stage were significant independent predictors in non-resected patients. However, unfavourable clinicopathological factors did not preclude long-term survival. Collectively, our findings indicate that actual 5-year survival for pancreatic cancer is still below 5% despite improvement of survival for the subset of patients undergoing surgical resection.

Intraductal papillary mucinous carcinoma versus pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Previous studies have indicated that there may be a difference in tumor biology between intraductal papillary mucinous carcinoma (IPMC) and pancreatic ductal adenocarcinoma (PDAC). However, the data are still controversial. The aim of this systematic review and meta-analysis was to summarize and compare the outcome of IPMC and PDAC after surgical resection. METHODS: Studies comparing IPMC and PDAC were identified using Medline and Embase search engines. Primary outcomes of interest were survival and recurrence. Secondary outcomes were clinicopathological characteristics. Meta-analysis of data was conducted using a random-effects model. RESULTS: A total of 14 studies were included. Pooled analysis revealed an improved 5-year overall survival (OS) for IPMC compared to PDAC (OR 0.23, 95% CI 0.09-0.56). Both colloid and tubular IPMC showed improved 5-year OS compared to PDAC (OR 0.12, 95% CI 0.05-0.25 and OR 0.38, 95% CI 0.26-0.54, respectively). Median survival time ranged from 21 to 58 months in the IPMC group compared to 12-23 months in the PDAC group. No meta-analysis could be performed on recurrence or on time-to-event data. Descriptive data showed no survival difference for higher TNM stages. IPMC was more often found at a TNM-stage of 1 (OR 4.40, 95% CI 2.71-7.15) and had lower rates of lymph node spread (OR 0.43, 95% CI 0.32-0.57). CONCLUSION: Available data suggest that IPMC has a more indolent course with a better 5-year OS compared to PDAC. The histopathological features are less aggressive in IPMC. The reason may be earlier detection. However, for IPMC with higher TNM stages the survival seems to be similar to that of PDAC.