1. Understanding CNS Tumours
Primary CNS cancers originate within the brain or spinal cord and do not behave like systemic cancers that spread to the brain.
They are distinct entities defined by cell of origin (astrocyte, oligodendrocyte, ependymal cell, meningeal cell, lymphoid cell) and molecular signature.
The 2021 WHO classification re-organised brain tumours around molecular identity rather than microscope appearance—creating more than 100 precise subtypes.
At Coimbatore Cancer Clinic, every patient’s tumour undergoes histologic review and next-generation sequencing to assign both histologic and molecular grade, allowing therapy that is truly customised.
2. Key Histologic Families
3. Pathophysiology
The blood–brain barrier (BBB) protects the brain from toxins but also blocks many
anti-cancer drugs.
Modern treatment therefore relies on agents with high CNS penetration or on
disrupting the BBB safely through convection-enhanced delivery, nanoparticles, or
engineered antibodies.
CNS tumours also create an immunologically “cold” environment; hence
immunotherapies must overcome local immune suppression using advanced
checkpoint combinations or CAR-T cells capable of surviving in the CNS.
4. Symptoms and Red Flags
● Morning headaches with vomiting
● Seizures in adults without prior history
● Focal weakness, imbalance, speech or vision change
● Behavioral alteration, memory loss
● Endocrine changes (pituitary region)
● Persistent back pain or limb weakness (spinal tumours)
Any such symptoms lasting > 2 weeks should prompt MRI evaluation.
5. Diagnostic Pathway
1. MRI Brain + Spine with contrast – defines lesion and infiltration.
2. Functional MRI / Diffusion Tensor Imaging – maps eloquent tracts for safe
surgery.
3. Stereotactic or Open Biopsy – mandatory for grading and molecular
profiling.
4. Histopathology + IHC – GFAP, Olig2, EMA, Synaptophysin etc.
5. Molecular Testing (NGS) – IDH, 1p/19q, MGMT, TERT, BRAF, H3K27M,
EGFRvIII.
6. Post-operative MRI (within 48 h) – documents extent of resection.
6. Treatment Principles
Surgery
● Aim: maximal safe resection.
● Techniques: intra-op neuronavigation, 5-ALA fluorescence, awake mapping,
ultrasonic aspirators.
● Complete removal improves both symptom control and survival.
Radiotherapy
● Standard 60 Gy/30 fractions for high-grade glioma.
● IMRT, VMAT, or Proton therapy to minimise cognitive effects.
● Stereotactic radiosurgery (Gamma Knife/CyberKnife) for small, recurrent, or
deep lesions.
Systemic Therapy
7. Molecularly Targeted Therapies
8. Cellular & Gene Therapies
● CAR-T Cells:
o Targets EGFRvIII, IL13Rα2, HER2; early trials show partial and
complete responses lasting > 1 year.
o “Armoured” CAR-Ts with cytokine secretion designed to survive BBB
and tumour micro-environment.
● TCR-Engineered T cells for H3K27M mutant glioma.
● Oncolytic Viruses (DNX-2401, G47Δ) selectively replicate in tumour cells
and stimulate immunity.
● Viral vector gene therapy delivering suicide genes (HSV-TK) into tumour
bed.
These are still trial-based but accessible through collaborative referral networks.
9. Supportive & Integrative Care
● Dexamethasone for cerebral edema, tapered slowly.
● Antiepileptics (Levetiracetam) prophylactically.
● Rehabilitation: physiotherapy, speech, occupational therapy.
● Cognitive preservation: memantine and hippocampal sparing RT when
possible.
● Psychological support for patients and caregivers; early palliative
integration.
● Nutritional counselling: high-protein, anti-inflammatory diet.
10. Prognosis & Survival
11. Recent & Future Directions
● AI-driven radiomics predicting grade and recurrence from MRI.
● ctDNA liquid biopsy for non-invasive monitoring.
● Combination IO + TTF protocols.
● Vaccine therapy targeting tumour-specific neoantigens.
● MR-guided focused ultrasound to transiently open BBB for drug delivery.
● Integration of CAR-T and oncolytic virus approaches in adaptive trials.
12. Our Expertise @ Coimbatore Cancer Clinic
● Rapid MRI-guided stereotactic biopsy pathway.
● In-house NGS panels for IDH, 1p/19q, MGMT, TERT, BRAF, H3 mutations.
● Collaboration with neurosurgery and rehabilitation units.
● Access to Temozolomide, Bevacizumab, and emerging targeted agents.
● Referral link to national CAR-T and vaccine trials.
● Long-term follow-up and neuro-rehab support.
13. When to Seek Consultation
Any new persistent headache, seizure, or focal neurological deficit requires early
MRI and neuro-oncology review.
Early intervention improves surgery safety and survival.
Frequently Asked Questions
Disclaimer
Educational content only; not a substitute for personalised medical advice.
Pediatric Central Nervous System (CNS) Cancers
Overview
Brain and spinal tumours are the most common solid tumours in children and the
leading cause of cancer-related death in childhood.
Unlike adult brain tumours, pediatric CNS cancers have a unique biology — often
driven by developmental and genetic signaling pathways rather than
environmental exposures.
Thanks to modern neuroimaging, microsurgery, precision radiotherapy, and
advances in molecular genetics, survival rates have improved substantially.
At Coimbatore Cancer Clinic, our pediatric neuro-oncology program integrates
advanced molecular diagnostics, multidisciplinary therapy planning, and
compassionate long-term follow-up to optimise cure rates while preserving
neurological and cognitive function.
Major Pediatric CNS Tumour Types
Each type behaves differently and requires individualised therapy guided by
histologic grade, molecular subgroup, and age.
Symptoms and Early Warning Signs
Symptoms depend on tumour location and rate of growth:
● Headache, worse in the morning or with vomiting
● Nausea, projectile vomiting (raised intracranial pressure)
● Gait imbalance, clumsiness, frequent falls (cerebellar tumours)
● Vision loss or squint (optic pathway)
● Endocrine changes (pituitary or hypothalamic region)
● Seizures or limb weakness
● Failure to thrive, irritability (infants)
Diagnosis and Work-up
1. MRI Brain/Spine with contrast – primary diagnostic tool; defines tumour size, edema, cysts, and hydrocephalus.
2. MR Spectroscopy / Perfusion – distinguishes high- vs low-grade.
3. Surgical biopsy or excision – tissue diagnosis and molecular testing.
4. CSF cytology – for medulloblastoma and ependymoma to assess leptomeningeal spread.
5. Molecular profiling – IDH, H3K27M, BRAF, MYC, WNT/SHH, TP53, SMARCB1, NF1, depending on histology.
At our centre, each case is discussed in a pediatric neuro-oncology tumour board
including medical, surgical, radiation, and rehabilitation experts.
Diagnosis and Work-up
Treatment Principles
1️⃣ Surgery
Goal: maximal safe resection while preserving neurologic function.
Techniques include:
● Image-guided neuronavigation
● Intra-operative MRI / ultrasound
● Neurophysiologic monitoring
● Endoscopic approaches (e.g., third ventriculostomy for hydrocephalus)
Gross-total resection offers the best chance of cure, especially for low-grade
tumours.
2️⃣ Radiotherapy
● Used cautiously due to risk of developmental and cognitive impact.
● Craniospinal irradiation (CSI) for medulloblastoma and ependymoma with CSF spread.
● Conformal / Proton beam therapy preferred to reduce late toxicity.
● Typical schedules:
o 23.4 Gy CSI for average-risk medulloblastoma + posterior fossa boost.
o 54–59.4 Gy focal RT for ependymoma.
o Avoid RT < 3 years of age when possible (use chemo-first strategy).
3️⃣ Chemotherapy
● Essential for high-grade or disseminated tumours and to delay RT in young children.
● Regimens are tumour-specific:
4️⃣ Molecularly Guided & Targeted Therapy
The genomic revolution has transformed pediatric neuro-oncology. Treatment now
depends on molecular subgrouping rather than just histology.
Medulloblastoma Subgroups
Other Precision Strategies
● BRAF V600E → Dabrafenib + Trametinib (pilocytic astrocytoma, ganglioglioma)
● NF1-related OPG → MEK inhibitors (Selumetinib) under routine use.
● H3K27M-mutant DMG → ONC201 / DRD2 antagonist; panobinostat (HDAC inhibitor).
● SMARCB1-deficient ATRT → EZH2 inhibitors (Tazemetostat) in trials.
● CDK4/6 inhibitors → for high-grade gliomas with cell-cycle dysregulation.
● Immunotherapy: Pembrolizumab, Nivolumab, or CAR-T in MSI-high or PD-L1+ tumours.
5️⃣ Cellular & Gene Therapies (Frontier Approaches)
● CAR-T Cells targeting GD2, HER2, B7-H3, IL13Rα2 — showing safety and early efficacy in DMG and recurrent medulloblastoma.
● Oncolytic viral therapy (DNX-2401, G47Δ, HSV-TK) being trialled in gliomas and ATRT.
● Tumour vaccines for WNT and SHH subgroup medulloblastoma.
● Convection-enhanced drug delivery (CED) directly infusing agents into tumour tissue.
● Gene editing / RNA interference targeting H3K27M mutations — early research.
Coimbatore Cancer Clinic collaborates with tertiary centres offering trial access to
these advanced therapies.
6️⃣ Supportive & Long-Term Care
During Treatment
● Corticosteroids to reduce brain swelling.
● Anticonvulsants for seizure control.
● Endocrine support: monitor for hypothyroidism, growth delay, adrenal suppression.
● Nutritional and infection prophylaxis during chemotherapy.
After Treatment (Survivorship)
● Neurocognitive rehabilitation for learning or memory difficulties.
● Speech and physical therapy for motor deficits.
● Vision and hearing assessment post-RT.
● Endocrine and fertility preservation monitoring.
● Psychological and educational support to reintegrate children into normal schooling.
5-year survival for pediatric CNS tumours now exceeds 70 % overall, but lifelong
follow-up remains crucial.
7️⃣ Prognosis & Outcomes
8️⃣ Recent Advances (2024–2025)
● Selumetinib approved for NF1-associated low-grade glioma (FDA 2023).
● Vorasidenib / Ivosidenib expanding use in IDH-mutant adolescent glioma.
● GD2-CAR-T and B7-H3-CAR-T trials showing clinical responses in DMG.
● MR-guided focused ultrasound to enhance blood–brain barrier permeability.
● Long-term data from molecularly risk-adapted medulloblastoma therapy confirming 90%+ survival with reduced RT doses.
● AI-driven MRI analytics predicting relapse earlier than conventional scans.
9️⃣ Our Expertise @ Coimbatore Cancer Clinic
● Collaborative care with pediatric neurosurgeons and neuro-rehabilitation units.
● Access to molecular diagnostics including WNT/SHH, BRAF, and H3K27M panels.
● Multimodality treatment with MRI-guided surgery, conformal RT, and systemic therapy.
● Availability of targeted agents such as Dabrafenib, Trametinib, and Temozolomide.
● Connection with national and international CAR-T and medulloblastoma vaccine trials.
● Dedicated survivorship and neurocognitive rehabilitation programs.
🔔 When to Seek Medical Evaluation
Persistent morning headaches, repeated vomiting, clumsiness, or squint in a child
should never be ignored.
An MRI brain and a paediatric oncology consultation can make the difference
between complete recovery and delayed detection.
Frequently Asked Questions
Disclaimer
This information is for educational use only. Treatment should be tailored by pediatric
oncologists and neurosurgeons based on individual diagnosis, age, and tumour
genetics.
