Surgical Goals in Neuro-Oncology

• Maximal safe resection: primary surgical goal for most gliomas — remove as much tumor as possible without causing new neurological deficits
• Cytoreduction benefits: tissue diagnosis, molecular profiling (IDH, 1p/19q, MGMT), relief of mass effect, reduced tumor burden for adjuvant therapy
• Extent of resection (EOR) is an independent prognostic factor in both low-grade gliomas (LGG) and high-grade gliomas (HGG)

Resection vs. Biopsy: Decision Factors

Types of Biopsy

• Stereotactic needle biopsy: frame-based or frameless neuronavigation; targets deep or eloquent lesions; diagnostic yield ~90–95%; complication rate ~2–5% (hemorrhage)
• Open biopsy: small craniotomy for tissue sampling; used when stereotactic approach is not feasible (e.g., posterior fossa, highly vascular lesion)
• Diagnostic pitfall: sampling error — biopsy may not capture the highest-grade region of a heterogeneous tumor

Extent of Resection and Outcomes

• Postop MRI: obtain within 24–72 hours to assess EOR and distinguish residual tumor from surgical changes
• Supramarginal resection: in LGG, resection beyond the FLAIR abnormality (into normal-appearing brain) may improve survival — requires intraoperative mapping

Indications

• Tumors in or adjacent to eloquent cortex: primary motor cortex, supplementary motor area (SMA), Broca area (dominant inferior frontal gyrus), Wernicke area (dominant posterior superior temporal gyrus)
• Goal: maximize resection while preserving neurological function through real-time cortical and subcortical mapping
• Most commonly used for low-grade gliomas in young patients where preserving function is paramount

Technique: Asleep-Awake-Asleep

• Phase 1 (Asleep): general anesthesia or deep sedation for craniotomy opening, dural opening, exposure
• Phase 2 (Awake): patient awakened for cortical mapping — direct electrical stimulation (DES) of cortex and subcortical white matter while patient performs tasks (naming, counting, motor movements)
• Phase 3 (Asleep): resedation for hemostasis, closure

Cortical Mapping

• Motor mapping: low-frequency stimulation of precentral gyrus → observe contralateral muscle contractions (EMG monitoring)
• Language mapping: stimulation during object naming, counting, reading → speech arrest or paraphasic errors indicate eloquent site
• Positive site: stimulation produces a response (motor movement, speech arrest) → cortex is functional → must be preserved
• Safety margin: resection should maintain ≥1 cm from positive motor/language sites when possible
• Subcortical mapping: identifies white matter tracts (arcuate fasciculus, corticospinal tract, IFOF) during deep resection

Patient Selection

• Cooperative, able to follow commands and perform language/motor tasks for 45–90 minutes
• No severe anxiety, claustrophobia, or cognitive impairment that would prevent task performance
• Contraindications: severe dysphasia (cannot perform language tasks), morbid obesity (airway concern), uncontrollable cough

Eloquent Brain Regions

Preoperative Functional Mapping

• Functional MRI (fMRI): BOLD signal identifies activated cortex during motor, language, and visual tasks — used for preoperative planning to localize eloquent cortex relative to tumor
• Diffusion tensor imaging (DTI) / tractography: maps white matter tracts (corticospinal tract, arcuate fasciculus, optic radiations) — identifies tract displacement or infiltration by tumor
• Wada test (intracarotid amobarbital): largely replaced by fMRI for language lateralization; Wada (or alternatives — methohexital/etomidate) is still used for memory lateralization in temporal lobe epilepsy surgery
• Navigated transcranial magnetic stimulation (nTMS): noninvasive preoperative motor and language mapping; can guide intraoperative mapping
• Magnetoencephalography (MEG): localizes somatosensory, auditory, visual, and language cortex; useful adjunct for presurgical planning

Language Lateralization

• >95% of right-handed individuals are left-hemisphere dominant for language
• ~70% of left-handed individuals are also left-hemisphere dominant; ~15% bilateral; ~15% right-dominant
• fMRI laterality index can determine dominance noninvasively in most cases

Platforms

Indications for SRS

SRS vs. Fractionated Stereotactic Radiotherapy (SRT)

• SRS: single fraction, high dose (e.g., 15–24 Gy); best for small, well-defined targets <3 cm
• SRT (fractionated): 3–5 fractions; preferred for lesions >3 cm, near optic apparatus (<3 mm), or brainstem — reduces radiation necrosis risk
• Optic apparatus constraint: single-fraction Dmax to optic nerve/chiasm should be <8 Gy (risk of radiation-induced optic neuropathy rises significantly above 10 Gy)

Contraindications to SRS

• Lesion >3–4 cm (high risk of radiation necrosis and edema)
• Need for tissue diagnosis (SRS does not provide histology)
• Significant mass effect requiring decompression
• Radiosensitive tumors better treated with chemotherapy (e.g., CNS lymphoma, germinoma)

WHO 2021 CNS5 Classification

• IDH-mutant astrocytoma: grades 2–4 (grading now integrates molecular features — CDKN2A/B homozygous deletion upgrades to grade 4 even without necrosis/microvascular proliferation)
• Glioblastoma (GBM): defined as IDH-wildtype only (grade 4); requires TERT promoter mutation, EGFR amplification, or +7/−10 chromosomal signature for diagnosis in the absence of histologic criteria
• Oligodendroglioma: defined by IDH mutation + 1p/19q codeletion (grades 2–3)
• Diffuse midline glioma, H3 K27–altered: grade 4 (thalamus, brainstem, spinal cord); pediatric and young adult
• Other key markers: ATRX loss (astrocytic lineage), TERT promoter mutations (GBM, oligodendroglioma), H3 G34–mutant diffuse hemispheric glioma
• MGMT promoter methylation: predicts response to temozolomide and improved survival in GBM

Stupp Protocol — Newly Diagnosed GBM

• Landmark trial: Stupp et al., NEJM 2005 — established standard of care for newly diagnosed GBM
• Concurrent phase: external beam RT 60 Gy (30 fractions over 6 weeks) + concurrent temozolomide (TMZ) 75 mg/m²/day daily during RT
• Adjuvant phase: TMZ 150–200 mg/m² days 1–5 every 28 days × 6 cycles
• PJP prophylaxis (e.g., TMP-SMX) during concurrent TMZ + RT phase due to lymphopenia

Additional GBM-Directed Therapies

• TTFields / Optune: FDA-approved for newly diagnosed GBM (EF-14 trial); 200 kHz alternating electric fields delivered via scalp transducer arrays; added to adjuvant TMZ improves OS
• Bevacizumab (anti-VEGF): FDA-approved for recurrent GBM; improves PFS but not OS; also useful for symptomatic radiation necrosis and steroid-sparing

IDH-Mutant Low-Grade Glioma

• Vorasidenib (Voranigo): FDA-approved 2024 for residual/recurrent IDH-mutant grade 2 glioma (astrocytoma or oligodendroglioma) after resection; oral IDH1/IDH2 inhibitor
• INDIGO trial: showed significantly improved PFS vs placebo in patients with non-enhancing IDH-mutant grade 2 glioma after surgery
• Allows deferral of RT/chemotherapy in selected patients with residual/recurrent disease

Meningioma: Simpson Grading

• Simpson Grade I is the goal for convexity meningiomas but may not be achievable for skull base tumors
• Skull base meningiomas (cavernous sinus, petroclival): prioritize cranial nerve preservation over GTR — subtotal resection + SRS is often preferred
• WHO Grade II (atypical) and Grade III (anaplastic) meningiomas: higher recurrence → adjuvant radiation recommended after resection

Pituitary Adenoma

• Transsphenoidal surgery (TSS): first-line for most pituitary adenomas — endoscopic endonasal approach is now standard
• Microadenoma (<10 mm): cure rates 80–90% for functioning tumors (biochemical remission rates for functioning adenomas)
• Macroadenoma (≥10 mm): cure rates lower (50–70%) due to cavernous sinus invasion (biochemical remission rates for functioning adenomas); non-functioning macroadenomas are assessed by extent of resection and visual outcome rather than biochemical cure
• Transcranial approach: reserved for giant adenomas with significant suprasellar/lateral extension not accessible transsphenoidally
• Exception — prolactinoma: medical therapy (cabergoline) is first-line, NOT surgery; surgery only if medication intolerant/resistant or pituitary apoplexy
• Complications of TSS: CSF leak (most common), diabetes insipidus (transient in 10–20%, permanent in 1–2%), hypopituitarism, carotid injury (rare), SIADH (delayed hyponatremia at 5–10 days post-op; peak incidence POD 7; check serum sodium at one-week follow-up)

Vestibular Schwannoma

• Intraoperative CN VII monitoring: mandatory during microsurgery; continuous EMG of orbicularis oculi/oris
• NF2: bilateral vestibular schwannomas are pathognomonic; management is more complex — hearing preservation is prioritized

Posterior Fossa Tumors

• Surgical approach: suboccipital (retrosigmoid) or midline posterior fossa craniotomy depending on tumor location
• Hydrocephalus: common complication due to fourth ventricle obstruction — may require preop EVD or endoscopic third ventriculostomy (ETV)
• Cerebellar mutism (posterior fossa syndrome): mutism, emotional lability, hypotonia — seen in children after midline cerebellar tumor resection (medulloblastoma); mutism typically resolves over weeks to months, but residual dysarthria, ataxia, and neurocognitive deficits persist long-term in a substantial subset
• Key tumors: medulloblastoma (children, midline), hemangioblastoma (VHL association, cystic + mural nodule), ependymoma (floor of 4th ventricle), pilocytic astrocytoma (cerebellar hemisphere, children)

Spinal Tumors

Perioperative Steroids

• Dexamethasone: standard preoperative treatment for vasogenic edema surrounding brain tumors
• Typical dose: 4–10 mg IV/PO q6h; begin taper as soon as clinically feasible to minimize steroid side effects
• Mechanism: reduces BBB permeability and vasogenic edema; does NOT treat cytotoxic edema
• Caution with suspected lymphoma: dexamethasone can cause rapid tumor regression (“vanishing lymphoma”) → biopsy BEFORE steroids when possible

Seizure Prophylaxis

• AAN Guideline: routine prophylactic antiseizure medications (ASMs) are NOT recommended for brain tumor patients who have never had a seizure
• Patients with cortical tumors, especially low-grade gliomas (70–90% seizure incidence), often present with seizures and should be treated
• If prophylaxis is used perioperatively, taper off within 1–2 weeks after surgery in seizure-free patients
• Preferred agents: levetiracetam (no enzyme induction, no drug interactions with chemotherapy); avoid phenytoin/carbamazepine (CYP inducers that reduce chemotherapy efficacy)

VTE Prophylaxis

• Brain tumor patients have among the highest VTE risk of any surgical population (~20–30% incidence without prophylaxis)
• Mechanical prophylaxis: pneumatic compression devices from admission; no bleeding risk
• Pharmacologic prophylaxis: low-molecular-weight heparin (LMWH) typically started 24–48 hours post-craniotomy once hemostasis is confirmed on postop imaging
• Balance: intracranial hemorrhage risk vs. high DVT/PE risk — delay pharmacologic prophylaxis only if active hemorrhage or concern

Intraoperative Adjuncts

Central Sulcus Identification

• Phase reversal technique: cortical SSEPs recorded from a strip electrode placed across the suspected central sulcus — N20/P20 waveform polarity inverts at the central sulcus (N20 from postcentral/sensory; P20 from precentral/motor)
• Essential when anatomy is distorted by tumor