ATRT Publications

While radiation therapy (RT) is an important tool in treatment for ATRT, it comes with risks for severe cognitive impacts among young patients. Given that most ATRT patients are diagnosed before the age of three, it is especially important to understand how these impacts can be minimized while still obtaining the increased survival benefits that RT can provide. The aim of this study was to see if RT dose and delivery fields (focal versus craniospinal) impacted patient outcomes.

This article provides a thorough overview of the latest published information on ATRT research – summaries of results in recently completed clinical trials for newly diagnosed as well as relapsed ATRT, information about ongoing clinical trials, and a look at novel agents being tested in animal models of ATRT before possible inclusion in human clinical trials.

Because of the rarity of ATRT, there are few large-scale studies looking at variables that may impact clinical outcomes for patients – which makes it more difficult to choose the best treatment strategies for these children. This study used data from the National Cancer Database (NCDB), one of only two patient registries that track patient outcome data for ATRT. The researchers looked at NCDB data from 189 patients diagnosed with ATRT between 2004 and 2016. The majority of patients were white males, with a median age at diagnosis of 1 year. All these patients underwent surgery. The majority were further treated with combinations of chemotherapy, radiation and/or bone marrow/stem cell transplantation.

Researchers found that patients diagnosed at age 1 year or later had better prognoses overall. They also confirmed earlier study findings that chemo in addition to surgery significantly increased overall survival rates. Patients who underwent bone marrow/stem cell transplantation in addition to chemo and radiation saw an even greater increase in progression-free survival. However, more research is needed to confirm that transplantation is the cause for this increase.

An article published online in Clinical Cancer Research offers some insight into differing outcomes associated with the three molecular subtypes of ATRT. The study included 74 newly diagnosed ATRT patients, from infants to adolescents, who were treated in two clinical trials at multiple institutions using protocols established through St. Jude Children’s Research Hospital. Infants with ATRT-TYR had the best overall survival. ATRT-SHH was associated with metastatic disease and poorer outcomes regardless of age.  Among children – regardless of molecular subtype – those whose ATRT had not spread beyond the tumor site benefited from post-surgical chemotherapy and radiation therapy of the brain and spine.

Atypical Teratoid Rhabdoid Tumor can occur in some children who have rare genetic conditions known as rhabdoid tumor predisposition syndrome making young children vulnerable to an increased risk of developing Rhabdoid tumors. Tumor surveillance protocols for these rare families have not been established. The European Society for Pediatric Oncology (SIOPe) Host Genome working group invited pediatric oncologists and geneticists to contribute to an expert meeting that culminated in a consensus statement to guide clinicians and patient families.

A December 2020 article in the journal EMBO Molecular Medicine examines the potential of a long-known antibiotic for use against rhabdoid tumors like ATRT.

To date, the only common genetic feature identified in ATRT has been the inactivation of a gene called SMARCB1, one of several genes that serve as master regulators of gene expression. It’s believed that these genes, when functioning properly, also act to suppress tumor formation. Mutations in this group of genes are present in approximately 20% of human cancers.

Mithramycin is an antibiotic first identified as an anti-cancer agent in the 1950’s for its ability to bind to DNA and prevent cells from making RNA and proteins. It never gained broad clinical use because of its toxicity. An analogue of mithramycin, a drug known as EC8042, is much less toxic yet just as effective at targeting tumor cells. Both are used for treatment of advanced testicular cancer.

The researchers behind this study previously found these drugs could inhibit a mutated gene that drives the development of Ewing sarcoma. As part of that investigation, they looked at cell lines from a variety of solid tumors to see which were most sensitive to mithramycin/EC8042.  They found cell lines from rhabdoid tumors (including ATRT) were hypersensitive to both drugs.

In this study, the researchers used rhabdoid tumor cell lines and mice grafted with rhabdoid tumor tissue to establish an optimized dose and schedule of administration that may aid in the translation of this compound to the clinic for rhabdoid/ATRT tumors.

Checkpoint inhibitor drugs offer new hope for many types of cancer by unleashing the body’s immune system to attack cancer cells. To date, however, these drugs have not shown much success against pediatric cancers. A new study from researchers at the Dana Farber Institute and Boston Children’s Hospital may challenge that finding when it comes to patients with ATRT. A clinical trial based on this study’s results is already underway.

In a recently published letter to the journal Nature Medicine, researchers proposed that it might be possible to interrupt that lethal relationship through an immunotherapy approach called CAR-T. Normal immune system defenders called t-cells are gathered from a patient’s blood and reprogrammed in the laboratory to seek out and neutralize a target, in this case B7-H3. The researchers theorize that neutralizing B7-H3 would unmask ATRT cells so that the body’s normal defenses could attack them.

A treatment protocol involving surgery followed by high-dose chemotherapy and radiation therapy yielded dramatically improved survival compared to previously reported therapies.  Among 65 patients evaluated on the regimen called ACNS0333, 35% survived without relapse or new malignancies for four years after enrollment.  Patients over three years of age fared even better, with 48% event-free survival (EFS) at four years.  By comparison, two earlier studies of children with a spectrum of brain tumors who were treated with dose-intensified chemo showed 6.4% of the AT/RT patients survived without such events for a period of two years.

To date, the only common genetic feature identified in ATRT has been the inactivation of a gene called SMARCB1, usually through the complete or partial deletion of chromosome 22. The authors of this study looked at all ATRT research findings to date, searching for other commonalities. Their goal was to identify and describe subgroups of ATRT for further study to hopefully uncover targets for new treatments, and to allow a more thorough understanding of how patients in each subgroup respond to existing therapies.