Diffuse intrinsic pontine glioma (DIPG)

DIPG (diffuse intrinsic pontine glioma) belongs to the group of diffuse midline gliomas. In the current classification, a large proportion of these tumors fall under the category “diffuse midline glioma, altered H3 K27.” 

The pons connects different parts of the brain to the spinal cord. It contains nerve pathways involved in movement, balance, sensation, vision, swallowing, speech, and several vital functions. DIPG cells infiltrate between normal cells. This diffuse and infiltrating nature makes it impossible to remove the tumor without damaging essential structures.

In France, approximately 40 to 50 children and young adults are diagnosed with DIPG each year. The disease primarily occurs during childhood, but it can also affect adolescents and, more rarely, young adults. Median survival remains less than one year according to data published in 2026, despite highly variable individual outcomes.

These figures describe a population and do not allow for a precise prediction of a child’s course of the disease. The molecular profile, radiological characteristics, clinical status, and response to radiation therapy may be associated with different disease trajectories.

Symptoms often develop over a few weeks and reflect damage to the pons and the nerve pathways that pass through it. Their combination and rapid progression should prompt a neurological evaluation and a brain MRI.

Brain MRI

MRI is the gold standard test. It shows a diffuse lesion centered on the pons and specifies its extent. The appearance may be highly suggestive of a DIPG, but imaging alone does not provide all the biological information necessary for current classification.

Stereotactic Biopsy

A biopsy involves removing a small amount of tumor tissue through a highly precise neurosurgical procedure. It is not intended to remove the tumor. Its feasibility and benefits are evaluated on a case-by-case basis by an expert team, taking into account the child’s condition, imaging findings, the risks of the procedure, and the expected impact of the results on management.

The tissue sample allows for histopathological and molecular analysis. In particular, it looks for alterations in H3 K27 and other abnormalities that may clarify the diagnosis, provide prognostic information, or guide the patient toward a clinical trial. If a biopsy is not feasible or is not deemed appropriate, treatment may be initiated based on the clinical and radiological findings.

To date, there is no standard treatment that can cure the majority of children with GITC. The goal is to temporarily control the disease, relieve symptoms, preserve quality of life as much as possible, and, when feasible, provide safe access to clinical research.

Radiation Therapy

Focal radiation therapy is the standard of care. It targets the tumor in the pons and most often provides temporary symptom relief, along with temporary stabilization or reduction of the tumor as seen on imaging. However, it generally does not provide long-term control of the disease.

In the event of disease progression, a second course of radiation therapy may sometimes be considered if the patient’s clinical condition, the time elapsed since the first radiation therapy, and the doses already received permit it. This decision is made on a case-by-case basis. Radiation to the entire brain and spinal cord is not a routine treatment for GITC and is considered only in specific cases of dissemination.

Medications and Clinical Trials

No conventional chemotherapy has demonstrated a curative benefit in GITC. Targeted therapies, combinations with radiation therapy, treatments that act on epigenetics, cell signaling, or the tumor microenvironment, as well as new administration modalities, are being studied in clinical trials.

The choice of a protocol is not based solely on the presence of a molecular abnormality. It also depends on the available data regarding the drug, the patient’s age, clinical status, prior treatments, and the trial criteria. A sequencing result therefore does not automatically imply that a targeted therapy will be effective or available.

The care pathway is coordinated by the Department of Pediatric and Adolescent Oncology. Depending on the patient’s needs, it brings together pediatric oncologists, neuroradiologists, partner neurosurgeons, neuropathologists, molecular biologists, radiation oncologists, neurologists, pain specialists, rehabilitation professionals, and supportive care teams.

After the MRI and, if performed, the biopsy, the case is discussed in a multidisciplinary team meeting. The team presents the proposed treatment strategy to the family, along with the expected benefits, the limitations of the treatment, any available clinical trials, and support options.

Gustave Roussy is deeply committed to research on infiltrating brainstem gliomas through its BIOMEDE program. 

The results of the international randomized Phase II BIOMEDE 1.0 trial were published in April 2026 in *Nature Medicine*. Sponsored and coordinated by Gustave Roussy, the trial evaluated, in combination with radiation therapy, three targeted therapies selected based on the tumor’s biological characteristics: everolimus, erlotinib, and dasatinib.

The trial did not meet its primary endpoint of improving overall survival. The publication therefore does not demonstrate the overall superiority of this biomarker-guided targeted treatment strategy. Nevertheless, it provides a major biological and clinical resource, identifies characteristics associated with response, and documents the prolonged survival of four children.

BIOMEDE also has methodological significance. The program demonstrated that a biopsy, centralized molecular characterization, and an international trial could be organized immediately upon diagnosis of this rare disease. These data now make it possible to better stratify patients, interpret responses, and design new trials based on a more solid biological foundation.

Armed with this new biological knowledge, the teams at Gustave Roussy have already launched BIOMEDE 2.0, the only international comparative clinical trial dedicated to malignant midline and brainstem gliomas, a group of malignant brain tumors that includes GITCs but extends beyond them, affecting other deep structures of the brain and spinal cord in both children and adults. Conducted in ten European countries, the trial is recruiting 368 patients over four years and comparing everolimus—now established as the new standard of care thanks to BIOMEDE 1.0—with ONC201, the first representative of a new class of anticancer drugs.

At the same time, Gustave Roussy is leading BIOMEDE IA, a groundbreaking research program that uses artificial intelligence to analyze the biological, genomic, and imaging data collected throughout the trial, in order to identify insights that are inaccessible to human analysis. 

This work has received support from an INCa Hospital Clinical Research Program and from the organizations Imagine For Margo, l’Etoile de Martin, les Amis d’Antoine, La Ligue contre le cancer du 74 et du 94, La marche de l’écureuil, the Lisa Forever association, and all donors to the Gustave Roussy Foundation’s “Curing Childhood Cancer in the 21st Century” campaign. BIOMEDE 1.0, BIOMEDE 2.0, and BIOMEDE IA were all made possible thanks to the support of the Imagine for Margo association.

The teams at Gustave Roussy are working on the genomics and oncogenesis of pediatric brain tumors. Their work combines biopsy analysis, the study of transformation and resistance mechanisms, the development of experimental models, and clinical trials. Cells, organoids, and tumor-derived models can be used in research to replicate certain characteristics of the disease and test potential treatments.

The journal BIOMEDE brings together teams from Gustave Roussy, Inserm, the University of Evry Paris-Saclay, Paris-Saclay University, and international partners. This collaboration highlights the need for collaborative research on rare tumors.