Management of Diffuse Intrinsic Pontine Glioma (DIPG)
Initial Treatment Approach
Radiation therapy is the standard and only proven treatment for DIPG, and should be initiated as soon as possible after diagnosis. 1, 2 The prognosis remains dismal with median survival of 8-12 months despite treatment. 2, 3
Diagnostic Confirmation
Biopsy is not mandatory when classic clinical and radiographic features are present on MRI. 4 Diagnosis can be made on clinical and imaging grounds alone in typical cases. 4
However, biopsy should be strongly considered when feasible to obtain molecular characterization that can guide treatment decisions and clinical trial enrollment. 4 Even 1 mm³ of tissue is sufficient for molecular analysis. 4
Do not delay radiation therapy to obtain biopsy in typical cases, as radiation should begin immediately after diagnosis for symptom control. 4
Radiation Therapy Protocol
The recommended radiation dose is 54-60 Gy delivered in fractions of 1.8-2.0 Gy. 5 This remains the standard approach based on decades of clinical experience. 3, 6
Conventionally fractionated RT achieves mean median overall survival of 12.0 months. 6
Hyperfractionated RT (mean median OS 7.9 months) and hypofractionated RT (mean median OS 10.2 months) have not demonstrated survival benefit over conventional fractionation. 3, 6
Radiation should be delivered using modern techniques such as volumetric arc therapy (VMAT) to minimize dose to surrounding critical structures. 7
Concurrent Chemotherapy
For patients ≥3 years of age, clinical trial enrollment is preferred, or standard brain radiation therapy with concurrent temozolomide. 1, 5
The addition of temozolomide to radiation therapy is a reasonable option, though survival benefit remains unproven. 7 Patients receiving radiosensitizing therapy had mean median OS of 11.5 months versus 9.4 months without concomitant therapy. 6
Bevacizumab added to radiation plus temozolomide has not demonstrated improved event-free survival and should not be used routinely. 5
Management for Children <3 Years
Systemic chemotherapy alone is recommended to delay the need for radiation in children <3 years due to risk of brain injury from RT. 1
Recommended chemotherapy regimens include: cyclophosphamide with vincristine; vincristine, cisplatin, and etoposide; or vincristine, carboplatin, and temozolomide. 1
Standard brain RT should only be used if other options are not feasible. 1
Molecular-Targeted Therapy Options
When molecular testing reveals actionable mutations, consider the following targeted therapies: 5
BRAF V600E mutations (10-15% of cases): Dabrafenib/trametinib combination or vemurafenib monotherapy. 1, 5
TRK fusion-positive tumors: Larotrectinib or entrectinib. 5
ALK rearrangements: Lorlatinib or alectinib. 5
Hypermutated tumors: Nivolumab or pembrolizumab. 5
Surveillance Protocol
Begin brain MRI surveillance 2-6 weeks after completion of radiation therapy. 1, 5
Be aware of pseudoprogression if changes appear on MRI within 6-9 months post-radiation, which can mimic true progression. 5
Management of Progressive Disease
Palliative re-irradiation can alleviate symptoms and improve quality of life in patients with disease progression after initial RT. 1 Patients receiving salvage RT had mean median OS from initial diagnosis of 16.3 months. 6
Critical Clinical Pitfalls
Do not perform surgical resection. DIPG location within the pons makes surgical resection not feasible and contraindicated due to proximity to critical brainstem structures. 1, 7, 8
Do not assume all pontine masses are DIPG without proper imaging evaluation, as missing alternative diagnoses has profound treatment implications. 4
Monitor for signs of increased intracranial pressure, including headaches, nausea, vomiting, and blurred vision, which are typically present in DIPG patients. 2
Expect multiple cranial nerve deficits including abducens nerve palsy, facial nerve weakness, dysphagia, and dysarthria. 2
Manage post-radiation edema symptoms (dizziness, nausea) with corticosteroids as needed. 7