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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.



Contribution of solid organ transplant recipients to the pediatric non-Hodgkin lymphoma burden in the United States

Recently published data confirms a significant and growing portion of children and adolescents with non-Hodgkin lymphoma are solid organ transplant recipients (Cancer 2017; doi:10.1002/cncr.30923). A cohort study was performed using data linked from the U.S. transplant registry to 16 different cancer registries. Researchers calculated incidence rates for patients 20 years and younger in the general population, as well as among those who had received solid organ transplants. According to study findings from 1990 to 2012, an estimated 22,270 cases of non-Hodgkin lymphoma occurred in children and adolescents; this included 628 cases diagnosed in transplant recipients, which accounted for 2.82 percent of non-Hodgkin lymphoma cases (95% CI, 2.45-3.19). Among transplant recipients, the most common subtypes were diffuse large B-cell lymphoma (64.5% of cases) and Burkitt lymphoma (8.6%), according to researchers. The number of solid organ transplant recipients who contribute to non-Hodgkin lymphoma diagnoses continues to increase. "Prevention efforts targeted toward this group could reduce the overall pediatric non-Hodgkin lymphoma burden," researchers concluded.



Constitutive IDO1 expression in human tumors is driven by cyclooxygenase-2 and mediates intrinsic immune resistance

Preclinical studies have shown that tumors expressing the protein indoleamine 2,3-dioxygenase (IDO1) responded to the cyclooxygenase-2 (COX-2) inhibitor celecoxib and had improved infiltration of certain subsets of T cells, making them more likely to respond to anti-PD1 therapies (Cancer Immunol Res 2017; doi:10.1158/2326-6066.CIR-16-0400). Researchers used two human melanoma cell lines and found that COX-2 and its product, prostaglandin E2 (PGE2), caused the constitutive expression of IDO1 by utilizing the MAPK, PKC, and PI3K cell-signaling pathways. These results were confirmed in other human tumor cell lines, including lung, ovarian, and head and neck cancer. Additionally, findings showed that immunodeficient mice reconstituted with human lymphocytes and bearing human ovarian tumor xenografts with constitutive IDO1 expression responded to celecoxib as well as the IDO1 inhibitor, epacadostat. By utilizing data of 1,041 different human tumor cell lines, the investigators confirmed a correlation between IDO1 expression and activation of the COX-2/PGE2 axis in several different cancers, including stomach, pancreatic, liver, lung, and sarcoma. "Our results highlight the role of COX-2 in constitutive IDO1 expression by human tumors and substantiate the use of COX-2 inhibitors to improve the efficacy of cancer immunotherapy, by reducing constitutive IDO1 expression, which contributes to the lack of T-cell infiltration in 'cold' tumors, which fail to respond to immunotherapy," authors concluded.



Lenalidomide maintenance after autologous stem-cell transplantation in newly-diagnosed multiple myeloma: a meta-analysis

According to a recent meta-analysis, mortality rates were reduced by 25 percent among patients with newly-diagnosed multiple myeloma who were treated with lenalidomide maintenance therapy following autologous hematopoietic stem cell transplantation compared to those who received placebo or observation (J Clin Oncol 2017; doi:10.1200/JCO.2017.72.6679). Researchers collected and analyzed patient-level data from three randomized clinical trials from the U.S., France, and Italy. The primary endpoint was overall survival (OS); additional analyses included progression-free survival (PFS) and safety. Improved PFS was seen among patients treated with lenalidomide compared to those who received placebo or observation (52.8 months vs. 23.5 months; HR = 0.48; 95% CI, 0.41-0.55). Median OS was not reached in the lenalidomide cohort, while the placebo/observation group had a median OS of 86 months (HR = 0.75; 95% CI, 0.63-0.9), which indicates a significant OS benefit. Additionally, a higher 7-year OS rate was observed in the lenalidomide group compared to placebo (62% vs. 50%).



Identification of essential genes for cancer immunotherapy

Researchers have identified genes in cancer cells that are necessary for immunotherapy to work, which could address the problem of why some tumors don't respond to immunotherapy or respond initially, but then stop as tumor cells develop resistance to immunotherapy (Nature 2017; doi:10.1038/nature23477).


Researchers utilized a genome-scale CRISPR-Cas9 library that consisted of around 123,000 single-guide RNAs, and profiled genes whose loss in tumor cells impaired the effector function of CD8+ T cells. More than 100 genes were identified that could play a role in facilitating tumor destruction by T cells. Investigators then examined data on cytolytic activity in more than 11,000 patient tumors from The Cancer Genome Atlas. Among the genes validated, "[researchers] identified multiple loss-of-function mutations in APLNR, encoding the apelin receptor, in patient tumors that were refractory to immunotherapy." According to study authors, "Our results link the loss of essential genes for the effector function of CD8+ T cells with the resistance or non-responsiveness of cancer to immunotherapies."



Therapeutic radiation for childhood cancer drives structural aberrations of NF2 in meningiomas

A genetic basis for why many childhood cancer survivors develop meningiomas has been uncovered in a recently published study (Nat Commun 2017; doi:10.1038/s41467-017-00174-7). The findings show that radiation causes genetic rearrangements in DNA that lead to meningiomas. Investigators compared radiation-induced meningiomas (RIMs) to sporadic meningioma (SM) in the general population. The research team analyzed RIMs from patients who had received cranial-spinal radiation as children; the majority of whom (74%) had survived either leukemia or pediatric brain cancer. Thirty-one RIMs were characterized with exome/NF2 intronic sequencing, RNA sequencing, and methylation profiling, and researchers found NF2 gene rearrangements in 12 of 31 RIMs, an observation previously unreported in SM, researchers noted. "The findings indicate that the mutational landscape of RIMs is distinct from SMs, and [they] have significant therapeutic implications for survivors of childhood cranial radiation and the elucidation of the molecular pathogenesis of meningiomas," study authors concluded.


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