Childhood Cancer Research Results and Study Updates

Giving the drug blinatumomab (Blincyto) after standard chemotherapy substantially increased survival for infants with an aggressive form of acute lymphoblastic leukemia (ALL), a recent study showed. If confirmed in larger studies, the treatment may become standard therapy for infants with ALL caused by KMT2A rearrangements.

Results from a new study highlight the progress being made toward developing liquid biopsies specifically for use in children with solid cancers like Ewing sarcoma and Wilms tumor. The tests can help detect and diagnose cancer and monitor for response to treatment and recurrence.

Doxorubicin is used to treat many types of childhood cancer, but it can damage the heart. Giving dexrazoxane (Zinecard) before each dose substantially decreases a child’s risk of treatment-related heart problems in adulthood, new study results show.

The protein ETV6 appears to promote tumor growth by affecting the behavior of the EWS-FLI1 fusion protein that drives most Ewing sarcomas. The research groups that made the discovery hope it leads to a targeted therapy for the aggressive childhood cancer.

Based on an NCI-sponsored clinical trial conducted by the Children’s Oncology Group, FDA has approved the drug brentuximab vedotin (Adcetris) in combination with chemotherapy for some children and adolescents with Hodgkin lymphoma.

An NCI study in mice has identified a drug combination that may help treat children with rhabdomyosarcoma. But one of the drugs, ganitumab, is no longer being made. Based on the study's promising results, the NCI researchers who led the study want to test the combination in humans.

The chemotherapy cisplatin often causes permanent hearing loss. Sodium thiosulfate (Pedmark) is the first treatment approved by FDA that can reduce the risk of hearing loss and the severity of damage to the inner ear in children treated with cisplatin.

Dr. Doug Hawkins, chair of the NCI-funded Children’s Oncology Group, discusses advances in treating children with cancer, COG’s role in conducting clinical trials, and efforts like the Childhood Cancer Data Initiative and Molecular Characterization Initiative.

Researchers have confirmed that the immunotherapy drug dinutuximab (Unituxin) can help children with high-risk neuroblastoma live longer. The finding is based on a trial of nearly 1,200 children with the disease.

The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) shrank more brain tumors, kept the tumors at bay for longer, and caused fewer side effects than chemotherapy, trial results showed. The children all had glioma with a BRAF V600 mutation that could not be surgically removed or came back after surgery.

The Molecular Characterization Initiative will offer state-of-the-art diagnoses to children, adolescents, and young adults with central nervous system tumors.

As adults, survivors of childhood cancer aren’t any less likely to have healthy babies than those without a history of cancer, a new study shows. However, they may have more health risks during pregnancy, warranting more intensive obstetric care.

A new test could potentially be used to identify children treated for medulloblastoma who are at high risk of their cancer returning. The test detects evidence of remaining cancer in DNA shed from medulloblastoma tumor cells into cerebrospinal fluid.

A Children’s Oncology Group trial shows that the combination of all-trans retinoic acid and arsenic trioxide is highly effective in children with acute promyelocytic leukemia. The therapy avoids or minimizes the use of conventional chemotherapy.

NCI Director Dr. Ned Sharpless discusses progress against childhood cancers, like CAR T-cell therapy and collecting more comprehensive data on children and adolescents with cancer, and the need to better address disparities in childhood cancer.

FDA has approved a new form of asparaginase called Rylaze. The drug was developed to help alleviate shortages of Erwinia asparaginase, a key part of treatment for children and adults with acute lymphoblastic leukemia.

Standard radiation for medulloblastoma can cause long-term damage to a child’s developing brain. A new clinical trial suggests that the volume and dose of radiation could be safely tailored based on genetic features in the patient’s tumor.

A team of international researchers has identified mutations in several genes, including TP53, MYOD1, and CDKN2A, that appear to be associated with an aggressive form of rhabdomyosarcoma in children. The findings could lead to more targeted treatments for the disease.

In a recent study, a treatment regimen using brentuximab vedotin (Adcetris) instead of the chemotherapy drug vincristine allowed some children and teens with advanced Hodgkin lymphoma to avoid radiation therapy—and the long-term health problems that can come with it.

The results of two trials establish blinatumomab (Blincyto) as a new standard treatment for children and young adults with high-risk relapsed B-cell acute lymphoblastic leukemia after remission has been achieved and before a stem cell transplant.

For children with the eye cancer retinoblastoma, researchers are studying a CAR T-cell therapy in which the engineered immune cells are packaged in a biodegradable material called a hydrogel and then injected directly into tumors.

For children and adults with advanced soft tissue sarcoma, adding pazopanib (Votrient) to chemotherapy and radiation before surgery may be a promising treatment option, early results from a clinical trial suggest.

Fusion proteins drive the development of many cancers in children, yet little is known about their biology. NCI’s Fusion Oncoproteins in Childhood Cancers Consortium brings together experts from varied disciplines to investigate these cancers.

Since launching the Childhood Cancer Data Initiative, NCI has undertaken a range of research activities to support this important effort. In this Cancer Currents post, NCI Director Dr. Norman Sharpless provides an update on these efforts.

For children with aggressive Burkitt lymphoma and other B-cell non-Hodgkin lymphomas, adding rituximab (Rituxan, Truxima) to chemotherapy substantially increases the likelihood of the child being cured, results from a large clinical trial show.

The Food and Drug Administration (FDA) has approved selumetinib (Koselugo) to treat children with neurofibromatosis 1 (NF1), a genetic disorder that causes tumors, called plexiform neurofibromas, to form throughout the nervous system.

A new study offers insight into genetic alterations associated with osteosarcoma, the most common bone tumor of children and adolescents, and the findings have implications for genetic testing of children with osteosarcoma and their families.

An NCI clinical trial finds the drug selumetinib improves outcomes for children with neurofibromatosis type 1 (NF1), shrinking inoperable tumors called plexiform neurofibromas, reducing pain, and improving function and overall quality of life.

Children with retinoblastoma in low- and middle-income countries were, on average, diagnosed at an older age and with more advanced disease than those in high-income countries, an analysis shows. The data provide clues about global disparities in outcomes.

For children and young adults with certain relapsed B-cell acute lymphoblastic leukemia (B-ALL), the immunotherapy drug blinatumomab is superior to standard chemotherapy, an NCI-sponsored Children’s Oncology Group trial shows.

Only 1.5% of children with acute lymphoblastic leukemia who skipped radiation had a recurrence in the central nervous system, according to a recent trial. The therapy, which is intended to prevent such a recurrence, can have devastating side effects.

For many children with high-risk neuroblastoma, receiving two separate stem cell transplants is more beneficial than receiving one, according to the results of an NCI-supported clinical trial conducted by the Children’s Oncology Group.

FDA has approved entrectinib (Rozlytrek) for the treatment of children and adults with tumors bearing an NTRK gene fusion. The approval also covers adults with non-small cell lung cancer harboring a ROS1 gene fusion.

To prepare for the proposed Childhood Cancer Data Initiative, NCI sponsored a 3-day symposium that brought together pediatric cancer researchers, advocates, and other stakeholders.

An early report from the NCI–COG Pediatric MATCH trial shows that 24% of young patients with advanced cancer who had their tumors tested for genetic changes were eligible to receive one of the targeted therapies being tested.

Some children with liver cancer may need less chemotherapy than is typically used, new research suggests. The study included children and infants with hepatoblastoma whose tumors had been surgically removed when the disease was diagnosed.

NCI has created special clinics that bring together clinicians, patients, and advocates to promote more rapid progress against rare cancers. The effort includes both rare pediatric cancers and central nervous system tumors in adults.

An experimental CAR T-cell therapy may have potential as a treatment for several types of childhood cancer, results from a new study in mice suggest. The CAR T cells eradicated tumors in mouse models of several different childhood cancers, including two forms of sarcoma and medulloblastoma.

A liquid biopsy blood test can detect DNA from brain tumors called diffuse midline gliomas, researchers have found. This minimally invasive test could be used to identify and follow molecular changes in children with these highly lethal brain tumors.

Health problems that develop years later as a result of a cancer treatment are known as late effects. The Childhood Cancer Survivor Study (CCSS) was started in 1994 to better understand and address these late effects.

The drug sodium thiosulfate can protect the hearing of children with cancer undergoing treatment with the chemotherapy drug cisplatin, results from a new clinical trial show. The trial involved children with a form of liver cancer called hepatoblastoma.

This NCI-funded Children’s Oncology Group trial tested the addition of nelarabine (Arranon) to standard treatment for children and young adults with T-cell acute lymphoblastic leukemia (T-ALL).

In a phase 2 clinical trial, the investigational drug selumetinib shrank tumors in some children with the genetic syndrome neurofibromatosis type 1 (NF1). The tumors, called neurofibromas, can cause pain, difficulty breathing or walking, and disfigurement.

Results from an NCI-sponsored clinical trial may point to an important change in how some children with advanced Wilms tumor, a form of kidney cancer, are treated.

An interactive website designed to promote physical activity among children and adolescents who have completed treatment for cancer may indeed help encourage them to get regular exercise, according to preliminary results from a pilot study.

An NCI-funded study has found significant differences in the genetics of acute myeloid leukemia in younger and older patients. The findings could help guide the development of treatments tailored specifically for childhood AML.

On November 9, the FDA approved dasatinib (Sprycel®) for the treatment of children with chronic myelogenous leukemia (CML) whose cancer cells express the Philadelphia chromosome and whose disease is in a relatively early stage, known as the chronic phase.

Progress continues to be made with the Gabriella Miller Kids First Research Program, which is creating opportunities for investigators from different research communities to share resources and collaborate on research into childhood cancers and certain birth defects.

FDA has approved tisagenlecleucel (Kymriah™), a type of immunotherapy called CAR T-cell therapy, for some children and young adults with advanced acute lymphoblastic leukemia (ALL).

In a small clinical trial, the drug crizotinib shrank tumors in children with cancers that have alterations in the ALK gene.

Two studies have identified proteins that drive growth of diffuse intrinsic pontine glioma (DIPG) tumor cells. Blocking these targets with investigational drugs slowed tumor growth in animal models.