Comparison of Age-Appropriate Therapies for Children with Rhabdoid Brain Tumors (ATRT)

Rhabdoid tumors are highly aggressive cancers that can develop in the central nervous system, among other locations, and are then referred to as atypical teratoid/rhabdoid tumors (ATRT). The disease primarily affects infants and toddlers during their first two years of life. The exact causes of rhabdoid tumors are not yet fully understood. However, nearly all patients have a specific genetic mutation. The gene involved is the so-called SMARCB1 gene, also known as INI1. This gene contains the blueprint for a protein that is responsible for important processes within the cell—such as ensuring that cells divide and grow properly. If the gene is altered, this protein can no longer be produced. As a result, cell growth becomes unbalanced and cells can multiply uncontrollably, which can lead to the development of a tumor.

When treating ATRT, special care is taken to tailor the therapy to the individual child’s risk and condition. An important factor here is the child’s age, as it determines how intensive the treatment can be. For example, radiation therapy carries significantly higher risks for children under 3 years of age or under 12 months than for adults, because their bodies are still developing. Consequently, radiation therapy can only be used to a limited extent, if at all. Other treatments, such as surgery or chemotherapy, must also be administered with greater caution in very young children. Age therefore has a major influence on treatment options and, consequently, on the chances of recovery.

The goal of the SIOPE ATRT01 study is to investigate age-specific treatment strategies for children with an atypical teratoid/rhabdoid tumor. The aim is to determine which therapy is most effective at which age and what side effects occur. This should make future treatments more effective and better tolerated. The SIOPE ATRT-01 study is being conducted as a so-called umbrella study because it simultaneously investigates several different treatment approaches tailored to the individual needs and circumstances of the patients. This study design is particularly well-suited for rare and complex diseases such as ATRT. Under the “umbrella” of this single diagnosis, various subgroups are then formed—in this case, based on the children’s age—with each group receiving a specific treatment.

At the start of treatment, all patients receive introductory chemotherapy (induction chemotherapy) according to the EU-RHAB protocol to initially shrink the tumor. Subsequently, depending on age, tumor stage, and suitability for specific therapies (e.g., physical condition), a decision is made as to which study group the child will be assigned to for further treatment. Children between the ages of 12 and 35 months are randomly assigned to one of two treatment groups. Group 1 receives three cycles of high-dose chemotherapy (HDCT) with carboplatin and thiotepa, followed by a transplant of their own stem cells, which are collected beforehand. Group 2 receives the current standard therapy, a combination of radiation and chemotherapy (radiochemotherapy). In this age group, a direct comparison is being made to determine whether HDCT is just as effective as the currently standard radiochemotherapy.

The goal is to find out whether radiation therapy can be omitted without compromising treatment success. Children under 12 months of age or those who are not eligible for radiation therapy will also receive three cycles of HDCT followed by stem cell transplantation after induction chemotherapy. Since they are not suitable for comparison with other study groups, their treatment outcomes are compared with data from patients treated earlier. Children older than 36 months or those who are not suitable for HDCT—for example, due to another medical condition—receive radiation therapy in combination with standard chemotherapy following induction chemotherapy; here, too, a comparison is made with previous treatment data.

Children and adolescents under 18 years of age with newly diagnosed ATRT and a confirmed deletion of the SMARCB1 or SMARCA4 gene are eligible to participate. Good physical condition—particularly adequate organ function—is a prerequisite. Patients are excluded if the tumor has spread to other parts of the body (metastases), if they have previously undergone tumor therapy, or if they have a history of severe pre-existing conditions.