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Given the abundance of new research, it can be challenging to stay current on the latest advancements and findings. Oncology Times is here to help with summaries of the newest studies to ensure you are up-to-date on the latest innovations in oncology practice.



FGL2 promotes tumor progression in the CNS by suppressing CD103+ dendritic cell differentiation

Researchers have discovered an immune regulator that appears to dictate glioblastoma (GBM) progression by shutting down immune surveillance, according to a new study (Nat Commun 2019;25;10(1):448). Findings indicate FGL2 (fibrinogen-like protein 2), which is known for suppressing the immune system, is highly expressed in GBM. Investigators showed that inactivating FGL2 from the tumor cells can eliminate tumor progression in mice with intact immune systems. Understanding this type of expression is key to discovering causes of GBM progression. Findings suggest the FGL2 present in tumor cells controls a specialized group of dendritic cells which activates T cells. More specifically, FGL2 secreted from tumor cells prevents the differentiation of a special subpopulation of CD103 dendritic cells that are essential for triggering the activation of the tumor-killing T cells, according to findings. The study also demonstrated that these dendritic cells must find a way to the tumor microenvironment in the central nervous center in order to activate the T cells. When the team analyzed human GBM from The Cancer Genome Atlas, they found that lower levels of FGL2 protein expression coupled with high levels of GM-CSF or IFN, DC differentiation inducer or T-cell activator, are associated with longer survival. "These findings are relevant to GBM patients because a low level of FGL2 expression with concurrent high GM-CSF expression is associated with higher CD8B expression and longer survival," study authors wrote. "These data provide a rationale for therapeutic inhibition of FGL2 in brain tumors."



Durable tumor regression and overall survival in patients with advanced Merkel cell carcinoma receiving pembrolizumab as first-line therapy

A study of pembrolizumab as the initial treatment for patients with Merkel cell carcinoma (MCC) reports better responses and longer survival than expected with conventional chemotherapy (J Clin Oncol 2019; doi:10.1200/JCO.18.01896). This is the longest observation to date of Merkel cell carcinoma patients treated with any anti-PD-1 immunotherapy drug used in the first line. In this multicenter phase II trial, 50 adults naive to systemic therapy for advanced MCC received pembrolizumab (2 mg/kg every 3 weeks) for up to 2 years. More than half of the patients (28 patients, 56%) had long-lasting responses to the treatment, 12 of whom (24%) experienced a complete disappearance of their tumors, according to researchers. Nearly 70 percent of patients in this study were alive 2 years after starting treatment. Researchers found that treatment with pembrolizumab worked well against both virus-positive and virus-negative Merkel cell carcinomas, resulting in high response rates and durable progression-free survival in both subtypes. Additionally, the findings showed that tumors expressing PD-L1 tended to respond longer to treatment, although patients whose tumors did not express PD-L1 also responded. In terms of safety, grade 3 or greater treatment-related adverse events occurred in 14 (28%) of 50 patients and led to treatment discontinuation in seven (14%) of 50 patients, including one treatment-related death. "Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile, and favorable overall survival compared with historical data from patients treated with first-line chemotherapy," researchers concluded.



A system-based intervention to reduce Black-White disparities in the treatment of early stage lung cancer: A pragmatic trial at five cancer centers

Results from a recent study show that a pragmatic system-based intervention within cancer treatment centers can eliminate existing disparities in treatment and outcomes for black patients with early-stage lung cancer across the U.S. (Cancer Med 2019; doi:10.1002/cam4.2005). The intervention consisted of three parts: a real-time warning system derived from electronic health records, race-specific feedback to clinical teams on treatment completion rates, and a nurse navigator to engage with patients throughout treatment. Researchers performed a 5-year pragmatic trial at five cancer centers using the system-based intervention. Eligible patients included those diagnosed with early-stage lung cancer, aged 18-85. There were 2,841 early-stage lung cancer patients (16% black) in the retrospective group and 360 (32% black) in the intervention group, according to investigators. Prior to the intervention, the treatment rates were 78 percent for white patients versus 69 percent for black patients. With the intervention in place, treatment rates climbed to 95 percent for white patients and 96.5 percent for black patients, according to study findings. "A multifaceted intervention tested in five cancer centers using the transparency of race-specific data feedback, real-time warnings derived from EHRs, and patient-centered navigation improved care for both black and white patients while reducing racial differences," investigators concluded. "Application of this system-based, pragmatic approach to other cancer treatment disparities at a health system level could have positive effects on treatment completion, treatment equity, and overall outcomes."



The landscape of selection in 551 esophageal adenocarcinomas defines genomic biomarkers for the clinic

Mutations that cause esophageal adenocarcinoma (EAC) have been mapped in great detail in a new study (Nat Genet 2019; doi:10.1038/s41588-018-0331-5). This could help stratify esophageal cancer patients to give them more personalized therapies as well as provide options not currently available to patients beyond standard chemotherapy, radiotherapy, or surgery. Researchers used whole genome sequencing and whole exome sequencing to map mutations in EAC. "Using a cohort of 551 genomically characterized EACs with matched RNA sequencing data, we discovered 77 EAC driver genes and 21 noncoding driver elements," study authors reported. "We identified a mean of 4.4 driver events per tumor, which were derived more commonly from mutations than copy number alterations, and compared the prevalence of these mutations to the exome-wide mutational excess calculated using non-synonymous to synonymous mutation ratios." Researchers observed mutual exclusivity or co-occurrence of events within and between several dysregulated EAC pathways. The team verified indicators of poor prognosis (SMAD4 and GATA4) in independent cohorts. In the study, driver mutations for EAC were found in 99 percent of patients and more than 50 percent were sensitive to drugs (CDK4/6 inhibitors) already in clinical trials for breast cancer. Women were found to have more KRAS mutations than men, according to the data.


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