Pediatric low‑grade gliomas (pLGGs) have distinct biology and treatment strategies compared to adult gliomas. These Chinese consensus guidelines, developed by a multidisciplinary panel, integrate evidence levels, expert consensus, and clinical practicality. They cover imaging, pathology, surgery, radiotherapy, and systemic therapy (chemotherapy and targeted therapy), emphasizing molecular diagnosis and age‑appropriate treatment to maximize tumor control while protecting neurodevelopment.
Introduction
pLGGs account for 25–40% of pediatric CNS tumors. The annual incidence in China is estimated at 0.53–0.65 per 100,000 children. The 2021 WHO classification defines pediatric‑type diffuse low‑grade gliomas, circumscribed gliomas, and glioneuronal tumors. Recommendations are graded using the GRADE system (High/Moderate/Low evidence; Strong/Weak strength).
I. Imaging Assessment
MRI is essential. pLGGs typically show low signal on T1WI, high signal on T2WI/FLAIR, with absent or mild edema. Some subtypes (e.g., pilocytic astrocytoma) may show marked enhancement.
Recommendation 1 : Routine T1WI, T2WI, FLAIR, and contrast‑enhanced T1WI are recommended. Multimodal sequences (DWI, DTI, SWI, MRS, PWI) are suggested when available (Moderate/Strong).
Response assessment : Use the RAPNO 2020 criteria. For non‑cystic tumors, ≥25% increase in solid component indicates progression. For cystic tumors, progression is defined by solid growth or progressive cyst wall enhancement.
Recommendations 2–4 : Postoperative MRI within 72 hours (or 2–3 weeks if obscured), and follow‑up every 3 months (High/Strong). Distinguish true cystic degeneration from mixed cystic‑solid tumors (High/Strong).
II. Pathological Diagnosis
Diagnosis requires integration of histology and molecular genetics. pLGGs are typically driven by RAS/MAPK pathway alterations. Key entities include: diffuse astrocytoma (MYB/MYBL1‑altered), angiocentric glioma, polymorphous low‑grade neuroepithelial tumor of the young, and diffuse low‑grade glioma (MAPK pathway‑altered).
Recommendations 5–7 : All tumors should undergo histology and immunohistochemistry (High/Strong). Comprehensive molecular profiling is recommended when possible (High/Strong). DNA methylation profiling may aid diagnosis when histology and molecular features are inconclusive (High/Weak).
Standardized terminology : Use integrated diagnosis with CNS WHO grade. Append “NOS” (molecular testing not performed/unsuccessful) or “NEC” (testing done but no match to known entity).
Recommendations 8–9 : Thoroughly interpret morphological and molecular features to achieve precise diagnosis (High/Strong). For “NOS/NEC” diagnoses, grade may be described as “equivalent to histological grade” (Moderate/Strong).
III. Surgical Management
Gross total resection (GTR) yields 10‑year overall survival up to 90% and is the primary predictor of progression‑free survival. For tumors in difficult locations (optic pathways, brainstem, deep midline), goals include debulking, symptom relief, and obtaining tissue.
Recommendation 10 : Surgical objectives should be determined by multidisciplinary discussion (High/Strong).
Recommendation 11 : Laser interstitial thermal therapy may be an option for surgically inaccessible tumors (Moderate/Weak).
Recommendation 12 : Biopsy is recommended for tumors that cannot be safely resected (Moderate/Strong).
IV. Radiotherapy
Radiotherapy is effective but carries long‑term risks (cognitive decline, endocrinopathy, vasculopathy, secondary malignancies), especially in young children. For unresectable pLGGs, chemotherapy or targeted therapy is preferred first‑line; radiotherapy is reserved for progression.
Recommendation 13 : Radiotherapy is indicated for children >3 years with incompletely resected symptomatic tumors, progressive disease, or failure of multiple therapies (Moderate/Strong). For children ≤3 years, delay or avoid radiotherapy using chemotherapy (Moderate/Strong).
Recommendation 14 : NF1‑associated optic pathway gliomas should not receive radiotherapy as initial treatment; it is salvage only (Low/Strong).
Recommendation 15 : Early radiotherapy may benefit children with diffuse astrocytoma or midbrain/thalamic tumors (Moderate/Weak).
Techniques (Recommendations 16–18) : Use IMRT (preferred) or proton therapy (Moderate/Strong). Immobilization with thermoplastic mask; sedation/anesthesia for uncooperative children (Moderate/Strong).
Target volumes and dosing (Recommendations 19–20) : CTV is typically GTV + 10 mm (Moderate/Strong). Prescribed dose: 45–54 Gy in 1.8–2.0 Gy fractions (Moderate/Strong).
V. Systemic Therapy
After GTR, no adjuvant therapy is needed (recurrence <20%). Chemotherapy is indicated for clinical deterioration or radiological progression. Infants/toddlers should start chemotherapy immediately; observation is not appropriate.
Recommendation 21 : Immediate chemotherapy for infants/toddlers with incomplete resection; for children >3 years with partial resection and symptoms or progression (High/Strong).
First‑line conventional chemotherapy :
CV (carboplatin + vincristine) or TPCV (thioguanine, procarbazine, lomustine, vincristine) – objective response rate ~50%. TPCV is not recommended for NF1 due to secondary malignancy risk.
Vinblastine monotherapy (response ~26%) is an option.
Recommendation 22 : CV or TPCV are recommended (High/Strong). Vinblastine is optional (Moderate/Weak). Adding etoposide to CV is not recommended (High/Strong).
Targeted therapy (pLGGs are driven by RAS/MAPK pathway alterations):
BRAF V600E mutation → dabrafenib + trametinib (FDA‑approved)
BRAF fusions → first‑generation BRAF inhibitors are NOT suitable; use MEK inhibitors or second‑generation BRAF inhibitor tovorafenib
TSC1/2 mutations (SEGA) → everolimus (mTOR inhibitor)
NTRK fusions → larotrectinib or entrectinib
Recommendations 23–25 : BRAF/MEK inhibitors for BRAF‑mutated pLGGs; avoid first‑generation BRAF inhibitors for BRAF fusions (High/Strong). mTOR inhibitors for TSC1/2‑mutant SEGA (High/Strong). TRK inhibitors for TRK fusion‑positive pLGGs (High/Strong).
Relapsed or progressive disease : About 50% relapse after first‑line treatment. No standard regimen; individualize based on prior therapy and genetics. Options include re‑treatment with CV, temozolomide (second‑line), bevacizumab (rapid but short‑lived), cisplatin+etoposide, vinblastine, or continued targeted therapy.
Recommendations 26–27 : For relapsed/progressive pLGGs with BRAF alterations, TRK fusions, or TSC1/2 mutations, molecularly targeted agents are recommended (High/Strong). Other chemotherapy options are available (Moderate/Weak).
Discussion and Conclusions
These guidelines provide a robust, evidence‑based multidisciplinary framework integrating molecular diagnostics to guide precision therapy. Key priorities: multimodal imaging and molecular profiling (BRAF, TRK) to select targeted inhibitors; age‑appropriate de‑escalation of radiotherapy to minimize long‑term morbidity. Limitations remain: advanced local therapies and salvage chemotherapy lack high‑level evidence. Future molecularly enriched randomized controlled trials and improved preclinical models are needed. Overall, these guidelines aim to maximize tumor control while safeguarding children’s developmental potential.
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The study was recently published in the Neurosurgical Subspecialties .
Neurosurgical Subspecialties (NSSS) is the official scientific journal of the Department of Neurosurgery at Union Hospital of Tongji Medical College, Huazhong University of Science and Technology. NSSS aims to provide a forum for clinicians and scientists in the field, dedicated to publishing high-quality and peer-reviewed original research, reviews, opinions, commentaries, case reports, and letters across all neurosurgical subspecialties. These include but are not limited to traumatic brain injury, spinal and spinal cord neurosurgery, cerebrovascular disease, stereotactic radiosurgery, neuro-oncology, neurocritical care, neurosurgical nursing, neuroendoscopy, pediatric neurosurgery, peripheral neuropathy, and functional neurosurgery.
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Neurosurgical Subspecialties
Guidelines for the Diagnosis and Treatment of Pediatric Low-Grade Gliomas in China (2024)
28-Mar-2026