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Updated: Aug 29, 2025
A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma DIPG
Published on: March 7, 2017
Targeted therapy for pediatric diffuse intrinsic pontine glioma: a single-center experience
Giada Del Baldo1, Andrea Carai2, Rachid Abbas3
1Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Background:
Diffuse intrinsic pontine glioma (DIPG) is a fatal disease with a median overall survival (OS) of less than 12 months after diagnosis. Radiotherapy (RT) still remains the mainstay treatment. Several other therapeutic strategies have been attempted in the last years without a significant effect on OS. Although radiological imaging is the gold standard for DIPG diagnosis, the urgent need to improve the survival has led to the reconsideration of biopsy with the aim to better understand the molecular profile of DIPG and support personalized treatment.
Methods:
In this study, we present a single-center experience in treating DIPG patients at disease progression combining targeted therapies with standard of care. Biopsy was proposed to all patients at diagnosis or disease progression. First-line treatment included RT and nimotuzumab/vinorelbine or temozolomide. Immunohistochemistry-targeted research included study of mTOR/p-mTOR pathway and BRAFv600E. Molecular analyses included polymerase chain reaction, followed by Sanger sequences and/or next-generation sequencing.
Results:
Based on the molecular profile, targeted therapy was administered in 9 out of 25 patients, while the remaining 16 patients were treated with standard of care. Personalized treatment included inhibition of the PI3K/AKT/mTOR pathway (5/9), PI3K/AKT/mTOR pathway and BRAFv600E (1/9), ACVR1 (2/9) and PDGFRA (1/9); no severe side effects were reported during treatment. Response to treatment was evaluated according to Response Assessment in Pediatric Neuro-Oncology criteria, and the overall response rate within the cohort was 66%. Patients treated with targeted therapies were compared with the control cohort of 16 patients. Clinical and pathological characteristics of the two cohorts were homogeneous. Median OS in the personalized treatment and control cohort was 20.26 and 14.18 months, respectively (p = 0.032). In our experience, the treatment associated with the best OS was everolimus.
Conclusion:
Despite the small simple size of our study, our data suggest a prognostic advantage and a safe profile of targeted therapies in DIPG patients, and we strongly advocate to reconsider the role of biopsy for these patients.
Insights
Targeted therapies show promise for diffuse intrinsic pontine glioma (DIPG), a fatal brain tumor. Personalized treatment based on molecular profiling improved overall survival compared to standard care, suggesting biopsy reconsideration for DIPG patients.
Area of Science:
- Pediatric neuro-oncology
- Molecular profiling of brain tumors
- Targeted cancer therapies
Background:
- Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brain tumor with a median overall survival (OS) of less than 12 months.
- Radiotherapy (RT) remains the primary treatment, but novel therapeutic strategies are urgently needed to improve outcomes.
- Biopsy is being reconsidered to understand DIPG's molecular profile and enable personalized treatment approaches.
Purpose of the Study:
- To evaluate the efficacy and safety of combining targeted therapies with standard care in DIPG patients at disease progression.
- To investigate the role of molecular profiling and biopsy in guiding personalized treatment strategies for DIPG.
- To compare overall survival (OS) between DIPG patients receiving personalized targeted therapy and those receiving standard care.
Main Methods:
- A single-center study involving 25 DIPG patients treated at disease progression.
- Biopsy was proposed to all patients for molecular analysis, including immunohistochemistry for mTOR/p-mTOR and BRAFv600E, and molecular analyses (PCR, Sanger sequencing, NGS).
- Targeted therapy was administered based on molecular profile in 9 patients; 16 received standard of care. Treatment response was assessed using RANO criteria.
Main Results:
- Personalized treatment targeted pathways like PI3K/AKT/mTOR, BRAFv600E, ACVR1, and PDGFRA. No severe side effects were reported.
- The overall response rate was 66%. Median OS was significantly longer in the personalized treatment cohort (20.26 months) compared to the control cohort (14.18 months, p=0.032).
- Everolimus was identified as a particularly effective treatment in this cohort.
Conclusions:
- Targeted therapies demonstrate a prognostic advantage and a favorable safety profile in DIPG patients, despite the study's small sample size.
- The findings strongly advocate for reconsidering the role of biopsy in the management of DIPG to facilitate personalized treatment.
- Personalized, molecularly-guided therapy offers a promising avenue for improving survival in DIPG.
