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Pediatric Low Grade Glioma:

Therapeutic Training

Diana S. Osorio, MD, MPH

April 8, 2022
Pediatric brain tumors

– Second most common cancer in childhood after leukemia

– Approximately 4,500 new diagnoses per year in USA (SEER data)
– Leading cause of cancer related death in pediatrics

– Pediatric brain tumors ≠ Adult brain tumors

– Different behavior
– Different biology
– Majority are primary brain tumors
– Adults: majority are metastasis of another primary
– Variety of tumor subtypes, very heterogeneous
– Treatment approaches vary
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Pediatric Low Grade Gliomas: are not benign tumors

– Most common central nervous system tumor of childhood

(30-50%)
– Encompass WHO Grade 1 and 2 (primarily glial) tumors
– GRADE 1: Pilocytic Astrocytoma and Ganglioglioma
– GRADE 2: Pediatric type Diffuse Low Grade Astrocytomas,
Pleomorphic Xanthoastrocytomas (among others)
– Overall survival is very good – 10-year OS for many can
exceed 90%.
– PFS approx 50%, thus, half of patients will require adjuvant
therapy
– Children can suffer from multiple progressions and functional
morbidities

Ryall et al., 2020, Cancer Cell 3

Distribution of Pediatric Low Grade Gliomas

• Can occur anywhere

in the CNS, including
spine.

Ryall et al., 2020, Cancer Cell 4

Survival (PFS) curve depending on tumor location

Ryall et al., 2020, Cancer Cell 5

Genetic Predisposition Syndromes- Neurocutaneous syndromes

– Neurofibromatosis Type 1
– 15-30% of patients develop a
LGG in the first two decades of
life – majority of which are in the
optic pathway majority of which
are pilocytic astrocytomas
– Treated if symptomatic

– Tuberous Sclerosis
– SEGA- subependymal giant cell
astrocytomas
– Respond well to mTOR inhibitors
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Treatment options

1) SURGERY:
– Mainstay of therapy is a complete surgical resection = curative, when safely possible.
– LOCATION of the tumor is key in this objective. Not always feasible could otherwise
lead to irreversible damage/morbidity.
2) CHEMOTHERAPY (examples):
-Vincristine/Carboplatin
-Vinblastine weekly
3) TARGETED THERAPY (examples):
-MEK inhibitors
-BRAF inhibitors
4) RADIATION THERAPY: least favored, “last resort”, associated with long-term morbidity
and mortality (ie: can induce malignant transformation).
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Low grade gliomas – pilocytic astrocytoma

• Classic example
• Imaging: solid tumor nodule with large
cystic component.
• Typical location: Cerebellum

• In experienced hands, curable with

surgery alone.

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 Low grade gliomas: MRI Examples

LGG of the
Spinal Cord
LGG of the Optic
Chiasm/Hypothalamus
(left) and optic nerve
glioma (right).

LGG of the
Brainstem 9
 Standard Chemotherapy Regimens

– CCG A9952 (COG, USA)

– Vincristine/Carboplatin (n=137)
– 5yr EFS 39% (OS 86%; all patients)
– ~30% stable disease
– Toxicity:
– Allergic reaction (20%)
– Myelosuppression
– Neuropathy
– SIOPe Vincristine/Carboplatin (Europe)
– Induction V/C first 24 weeks (first 7 cycles). During consolidation, V/C will repeat cycles until completion of 81
weeks of therapy. Each consolidation cycle is 6 weeks.
– Similar toxicity profile
JCO 2011 Ater et al 10
Standard Chemotherapy Regimens

– Vinblastine, weekly for 70 weeks (3-6 mg/m2/dose)

– Well-tolerated
– Myelosuppression
– EFS 53%, OS 94% (n=54)
– 87% of patients had disease stabilization (complete, stable, minor or stable disease)

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JCO 2016 Lassaletta et al
RAS/MAPK alterations in pediatric low-grade glioma

Acta NP Comm 2020 Ryall et al

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RAS/MAPK alterations in pediatric low-grade glioma

Kieran MW. Tareting BRAF, 2014 ASCO

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Side-effects of BRAF or MEK inhibitor therapy

• Rash (majority of patients)

• Acne
• Maculopapular
• Photosensitivity
• Hand-foot skin reaction
• Paronychia (nails)
• Edema of limbs
• Electrolyte abnormalities
• Mild myelosuppression
Distribution of Pediatric Low Grade Gliomas

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JCO 2017 Strum et al 15

Example of a favorable response on BRAF inhibitor

Cureus 2021 Howden et al 16