Clinical trials conducted by investigators from The Jikei University School of Medicine, Kashiwa Hospital, Japan reveal potential biomarkers that can be used to predict overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDA) who are also receiving Wilms’ tumor 1 (WT1)-targeting immunochemotherapy.
What is pancreatic ductal adenocarcinoma or PDA?
PDA is a type of exocrine pancreatic cancer. It is the most common type of pancreatic cancer—95 out of 100 (95%) of all pancreatic cancers are PDA, according to Pancreatic Cancer UK. PDA develops from cells lining small tubes in the pancreas called ducts. According to investigators from Memorial Sloan Kettering, this is one of the most lethal cancers worldwide. The highest incidence rates occur in North America and Western Europe with an incidence rate in these parts of the world at about 7.2 per 100,000 population. Upon diagnosis, the situation is often dire with surgery only an option for about 20%.
The Japanese research team found that low cytoplasmic Wilms’ tumor 1 (WT1) expression in PDA cells and sustained low levels of a granulocyte-related systemic inflammatory response following the early period of therapy may be used to predict OS in those PDA patients receiving WT1-targeting immunotherapy, reported Hina Porcelli of the Oncology Learning Network.
The commenced their study to assess predictive markers of OS in patients with PDA given multiple major histocompatibility complex class I/II-restricted, WT1 peptide-pulsed DC vaccinations (DC/WTI/I/II) plus chemotherapy.
The investigators assessed cytoplasmic WT1 expression and systemic inflammatory response markers (I.e. neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and granulocyte-to-lymphocyte ratio (GLR). Moreover they evaluated plasma levels of soluble factors derived from granulocytes of 7 patients with PDA during this study.
The principal investigator, Dr. Zensho Ito with The Jikei University School of Medicine, reports that “Compared to the 4 non-super responders (OS< 1 year), the remaining 3 super-responders (OS ≥ 1 year) showed significantly decreased low plasma matrix metalloproteinase-9 levels throughout long-term therapy.” It was reported after 5 DC/WT1-I/II vaccinations and 3 gemcitabine therapy cycles, the NLR, MLR and GLR were significantly lower among super-responders versus non-super responders. The team noted that super-responders had overall weal cytoplasmic WT1 expression in their PDA compared with non-super responders, reports the Oncology Learning Network.
Dr. Ito noted, “Prolonged low levels of a granulocyte-related systemic inflammatory response after the early period of therapy and low cytoplasmic WT1 expression in PDA cells may be markers predictive of OS in PD.”
About The Jikei University School of Medicine
The Jikei University School of Medicine has its origins in a older medical training school founded in 1881. Based in Tokyo, the center employs 2,151 members on its teaching and research staff. There are an additional 4,157 staff, including nurses, clerks, and technicians. The university administers the faculty of medicine, the graduate school for medical research, the three training schools for nurses, and the four attached hospitals. The faculty of medicine has two schools: the school of medicine and the school of nursing. All of their institutions are engaged in education, research and clinical service.
Zensho Ito, MD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Japan