ATRT Publications

Recent Publications

Published May 2020

Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors. 

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. READ MORE

Published 27 February 2020

Efficacy of High-Dose Chemotherapy and Three-Dimensional Conformal Radiation for Atypical Teratoid/Rhabdoid Tumor: A Report From the Children's Oncology Group Trial ACNS0333

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. READ MORE

Published 31 December 2019

Molecular subgrouping of Atypical Teratoid / Rhabdoid Tumors (ATRT) – a reinvestigation and current consensus

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.. READ MORE

Older Publications

2019 Apr 13. Role of early and aggressive post-operative radiation therapy in improving outcome for pediatric central nervous system atypical teratoid/rhabdoid tumor.

Researchers followed 28 pediatric AT/RT patients through surgery and subsequent radiation therapy for an average of four years. The patients’ data showed that early and aggressive radiation therapy after surgery is critical for successful disease control. Delaying radiation therapy until the AT/RT progressed led to unfavorable outcomes in the group.

2019 Mar 5. Human Pluripotent Stem Cell-Derived Tumor Model Uncovers the Embryonic Stem Cell Signature as a Key Driver in Atypical Teratoid/Rhabdoid Tumor.

In their successful efforts to develop a better model of human AT/RT in mice, researchers also identified a promising therapeutic target for AT/RT as well as other pediatric cancers. This potential target merits further study.

2019 Feb 19. Safety and feasibility of outpatient autologous stem cell transplantation in pediatric patients with primary central nervous system tumors.

This study from Children’s Hospital Colorado looked at pediatric patients with central nervous system (CNS) tumors who received stem cell transplants using their own cells. Some were transplanted as hospital inpatients; others received preparatory, high-dose chemotherapy and stem cell transfusions on an outpatient basis. Through more than two years of follow-up, outcomes were similar for both groups. This shows that outpatient autologous stem cell transplants are safe and effective for properly selected children with CNS tumors.

2019 Feb 18. A Phase 2 Study of Alisertib in Children with Recurrent/Refractory Solid Tumors or Leukemia: Children’s Oncology Group Phase 1 and Pilot Consortium (ADVL0921).

A targeted therapy drug called alisertib was tested among 137 children with acute leukemias or relapsed/refractory solid tumors including AT/RT with certain mutations. Previously, the drug showed significant ability to trigger cell death in tumor samples in the laboratory. It also showed modest activity in a phase 2 trial among adults with ovarian cancer, certain lymphomas and acute myeloid leukemia. The 137 children in this trial could only tolerate a smaller dose of the drug, which generated responses in less than 5% of the cases.

2018 Dec 27. Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation.

For over 20 years, scientists have known that AT/RT is characterized by the inactivation of a gene called SMARCB1, usually through the complete or partial deletion of chromosome 22. But little is known as to how this leads to tumor development. Understanding the molecular mechanisms behind this is urgently needed in order to develop effective treatment strategies for AT/RT patients. In this study, investigators used a sophisticated method called ChIP sequencing to compare eleven AT/RT samples from all three recently identified molecular subgroups to existing data on a variety of brain tumors, normal brain tissue and the embryonic stem cells that eventually develop into brain. The results provide a better understanding of AT/RT’s basic biology and pointed out regulatory mechanisms disrupted in AT/RT. With further study, these may lead to potential targets for therapy.

2018 Dec 8. Overall Survival of Primary Intracranial Atypical Teratoid Rhabdoid Tumor Following Multimodal Treatment: A Pooled Analysis of Individual Patient Data.

This 2018 paper involved 18 patients with AT/RT treated at a center in Beijing, China, as well as published data on another 483 such patients worldwide. The authors evaluated the relative effectiveness of treatments including surgical tumor resection, radiotherapy, conventional chemotherapy, intensified chemotherapy or some combination thereof. Their findings suggest the best overall survival rates (88% at five years) were among patients whose masses could be removed surgically without any visual residual tumor and who subsequently received radiotherapy as well as conventional and intensified chemotherapy.

2017 Sep 15. Oncolytic Herpes Virus rRp450 Shows Efficacy in Orthotopic Xenograft Group 3/4 Medulloblastomas and Atypical Teratoid/Rhabdoid Tumors.

Pediatric brain tumors like AT/RT or medulloblastomas may or may not be totally removed through surgery. And subsequent treatments like radiotherapy and intensive chemotherapy can have debilitating side effects and limited effectiveness. This study looks at the possible use of a weakened herpes virus to infect and kill these brain cancer cells, much like a viral approach already FDA approved for use in melanoma patients. The researchers delivered a cancer-fighting but weakened form of herpes virus to AT/RT or medulloblastoma cancer cells in the laboratory as well as in mouse models. Their promising findings warrant further study.

2016 Jan 10. Atypical teratoid/rhabdoid tumors-current concepts, advances in biology, and potential future therapies.

Recent advances in technologies for cancer research have led to identification of subgroups within the diagnosis of AT/RT and corresponding potential molecular targets for treatment.  Further study may help physicians identify whether these subgroups of patients respond differently to existing therapies. Meanwhile, there is still no agreement on a standard of therapy for AT/RT. This 2016 article by an international group of physicians provides a thorough overview of published data on state-of-the-art approaches for clinical management of children with AT/RT.  It also outlines the current thinking on potential new targets for treatments within identified subgroups of AT/RT patients, and summarizes results of both laboratory research and early-stage clinical trials of these targeted therapy models.

Survival Benefit with Gross Total Resection and Adjuvant Radiotherapy in Childhood Atypical Teratoid/Rhabdoid Tumors: Results of a Single-Center Cohort of 27 Cases.

This study from a group of neurosurgery clinics in Turkey looked at 27 patients diagnosed with AT/RT between January 2000 and December 2017.  Total resection of the tumor was possible in nearly half (13) of the patients, though three died of postoperative complications. The remaining patients received chemotherapy and/or radiation therapy. Among the many variables compared in this group (sex, age at diagnosis, location of tumor, gross total resection, chemotherapy, radiotherapy), only the administration of radiotherapy was consistently associated with longer overall survival.

Additional Publications

 

2020 Mar 2. Genomic and Immunologic Characterization of INI1-Deficient Pediatric Cancers

2020 Jan 11. MEK/MELK inhibition and blood-brain barrier-deficiencies in atypical teratoid/rhabdoid tumors

2019 June 01. Atypical Teratoid Rhabdoid Tumors

2016 Jul 12. Immunotherapy in atypical teratoid-rhabdoid tumors: Data from a survey of the HGG-Immuno Group.

2015 Feb 20. Disrupting LIN28 in atypical teratoid rhabdoid tumors reveals the importance of the mitogen activated protein kinase pathway as a therapeutic target.

2013 Dec 11. Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy.

 

2013 Aug 11. Intensive induction chemotherapy followed by myeloablative chemotherapy with autologous hematopoietic progenitor cell rescue for young children newly-diagnosed with central nervous system atypical teratoid/rhabdoid tumors: the Head Start III experience.

2012 Sep 12. Atypical teratoid rhabdoid tumor: current therapy and future directions.

2008 Dec 8Intensive Multimodality Treatment for Children With Newly Diagnosed CNS Atypical Teratoid Rhabdoid Tumor.

 

2004 Jul 15. Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry.

Hope4ATRT Foundation

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