World First: A 13-Year-Old Has Been Cured of DIPG, the Deadliest Childhood Brain Cancer

For the first time in medical history, a child has been completely cured of diffuse intrinsic pontine glioma (DIPG), one of the most aggressive and uniformly fatal forms of brain cancer that occurs almost exclusively in children. The patient, Lucas Jemeljanova from Belgium, was diagnosed with DIPG at age six. Today, at 13, he is considered officially cured, with no trace of tumour remaining on imaging scans after participating in a French clinical trial called BIOMEDE.

DIPG is a cancer that has defied treatment for decades. It arises in the brainstem, in the pons, a region that controls critical autonomic functions including breathing and heart rate. Because of its location deep within the brain's most essential structure, surgical removal is not possible. Radiation therapy can offer temporary symptomatic relief but cannot cure the disease. Fewer than 10 percent of children with DIPG survive beyond two years after diagnosis, and the median survival is nine to ten months. Until Lucas, no child had ever been reported to have been completely cured.

Lucas's family travelled from Belgium to France to enrol him in the BIOMEDE study, which began in 2014 and compared three drug candidates: erlotinib, everolimus, and dasatinib. A critical feature of the trial was that each patient underwent a molecular biopsy, extracting a small tissue sample from the tumour using a needle, allowing the researchers to profile the genetic characteristics of each patient's individual cancer before assigning treatment. Lucas was randomly assigned to receive everolimus, a drug that works by blocking a protein called mTOR, which drives cancer cell division and tumour angiogenesis.

Lucas responded to everolimus from the start. Lead BIOMEDE researcher Dr Jacques Grill told AFP: over a series of MRI scans, I watched as the tumour completely disappeared. A total of 233 DIPG patients were included in the study. Seven of them survived longer than statistics predicted, but only Lucas's tumour vanished entirely. After seeing no tumour activity for an extended period, Lucas eventually revealed to his treating team that he had stopped taking the medication on his own, yet the cancer has not returned.

The scientific teams at Gustave Roussy cancer centre in France are now working intensively to understand what made his response possible. Their current hypothesis centres on what Dr Grill described as an extremely rare mutation in Lucas's tumour cells that made them unusually sensitive to everolimus by creating a dependency on the mTOR pathway. Researchers have begun creating tumour organoids, three-dimensional laboratory-grown models that mirror each patient's tumour's genetic characteristics, to test whether Lucas's specific cellular profile can be replicated.

A subsequent BIOMEDE 2.0 study, which began in September 2022, has focused on everolimus as the candidate drug based on the first trial's results. A more recent immunotherapy-focused clinical trial for young DIPG patients has also shown promise, with tumour shrinkage in multiple participants. One further patient, identified only as Drew, has been tumour-free for over four years after receiving immunotherapy.

For clinical trial professionals, Lucas's case is significant for what it demonstrates about the value of molecular biopsy-driven trial design. Rather than treating all DIPG as a single entity, BIOMEDE's biopsy-first design allowed tumour biology to direct treatment assignment. This personalised approach to a previously homogenous-seeming diagnosis is consistent with advances in oncology more broadly, where molecular stratification has repeatedly unlocked treatment responses that population-level studies would never have identified.

Sources: ScienceAlert February 2024 | IFLScience February 2024 | MedScriptum | End Brain Cancer Foundation | AFP (Grill interview, cited multiple outlets)