What is the management approach for a patient with a brain mass?

Management of Brain Mass

The management of a brain mass requires immediate multidisciplinary evaluation to determine whether it represents a primary brain tumor or metastatic disease, followed by tissue diagnosis (via biopsy or resection) and individualized treatment based on histology, molecular characteristics, number of lesions, and patient performance status. 1, 2

Initial Diagnostic Approach

All patients with suspected brain masses should be transferred immediately to a specialized neurosurgical center for evaluation by neurosurgeons, radiation oncologists, medical oncologists, neurologists, and neuroradiologists. 2

Imaging Requirements

• MRI with gadolinium enhancement is mandatory for both initial diagnosis and follow-up, as it provides superior resolution and sensitivity compared to CT scanning 3, 2
• Obtain postoperative MRI within 24-72 hours after any surgical intervention to document extent of residual disease and establish baseline for monitoring 1, 2

Establishing Diagnosis

• Histological confirmation is mandatory before initiating adjuvant therapy unless the patient has prohibitive surgical risk 2
• For patients with known cancer and probable brain metastases on imaging, proceed with biopsy or resection followed by early postoperative imaging 1
• For brain mass of unknown primary (BM-CUP), extensive diagnostic work-up including PET scanning is required 1

Immediate Symptomatic Management

Cerebral Edema

• Dexamethasone is first-line treatment: 4-8 mg/day for moderate symptoms, escalating to 16 mg/day for severe symptoms with marked mass effect 3, 4, 2
• Consider gastric protection in patients receiving high-dose corticosteroids or those with risk factors for ulcers 2

Seizure Management

• Anticonvulsants should only be given to patients who have experienced seizures, not as prophylaxis 3, 4, 2
• Prefer agents that don't impact hepatic metabolizing enzymes to avoid drug interactions with chemotherapy 3, 2

Treatment Algorithm Based on Clinical Scenario

For Brain Metastases (Confirmed or Suspected)

Treatment decisions should be discussed at a dedicated brain metastasis board or disease-specific tumor board with CNS tumor expertise. 1

Favorable Prognosis Patients (≤10 metastases, controlled extra-CNS disease, expected survival >3 months):

Single Brain Metastasis:

• If >3-4 cm or symptomatic mass effect: Neurosurgical evaluation for resection is mandatory, followed by stereotactic radiosurgery (SRS) to the resection bed 1, 3, 4
• If <3-4 cm without symptomatic mass effect: Offer either SRS or surgical resection based on location, surgical accessibility, need for tissue diagnosis, and patient preference 1
• If <2 cm without symptomatic mass effect and HER2-directed therapy with CNS activity available: Discuss options including SRS or deferring local therapy with multidisciplinary team 1

Multiple Brain Metastases (1-4 lesions):

• SRS alone is preferred over whole-brain radiotherapy (WBRT) for patients with good performance status to avoid neurocognitive decline 3, 4, 5
• Surgery followed by SRS/stereotactic radiotherapy (SRT) for accessible lesions requiring resection 1
• Systemic pharmacotherapy based on primary tumor histology and molecular characteristics 1

Multiple Brain Metastases (>4 lesions):

• SRS/SRT remains an option with modern technology 5
• Systemic pharmacotherapy as first-line consideration for asymptomatic patients with certain tumor types (NSCLC with targetable mutations, HER2+ breast cancer, melanoma with BRAF mutations) 1, 3, 4
• WBRT reserved for patients with extensive disease burden 1

Unfavorable Prognosis Patients (>10 metastases, uncontrolled extra-CNS disease, expected survival <3 months):

• WBRT with hippocampal avoidance and memantine if no hippocampal lesions and ≥4 months expected survival 3
• Palliative surgery only if large metastases causing significant mass effect, particularly in posterior fossa 1
• Palliative care consultation 1

For Primary Malignant Gliomas (Glioblastoma, Anaplastic Astrocytoma)

Maximal safe surgical resection is recommended when technically feasible with low risk of permanent functional deterioration. 2

Proceed with optimal resection EXCEPT in:

• Patients with high physiological age, multiple comorbidities, or poor performance status 2
• Tumors in eloquent/functional brain regions where resection would cause permanent deficit 2
• Multifocal or centrally located lesions 2

Postoperative Treatment for Glioblastoma:

• Standard regimen: Concurrent radiotherapy (60 Gy/30 fractions) and temozolomide 75 mg/m² daily for 42 days (maximum 49 days), starting first day of RT 2, 6
• Followed by adjuvant temozolomide 150-200 mg/m² on Days 1-5 of every 28-day cycle for 6 cycles, starting 4 weeks after RT completion 2, 6
• Treatment must begin within one month of surgery 2
• Pneumocystis pneumonia prophylaxis is required during temozolomide + RT regardless of lymphocyte count 6

For Low-Grade Gliomas (Grade 2 Astrocytoma, Oligodendroglioma)

Risk stratification determines treatment approach. 2

Poor Prognostic Factors:

• Age >35-40 years, low Karnofsky score, intracranial hypertension, uncontrolled epilepsy, large tumor volume, localization in functional zones, involvement of deep structures, contrast enhancement on MRI 2

Treatment Selection:

• Patients with ≥1 poor prognostic factor: Surgical resection recommended 2
• Patients without poor prognostic factors: Options include surgical resection, surveillance, or biopsy 2

Tumor-Specific Systemic Therapy Considerations

Non-Small Cell Lung Cancer (NSCLC):

• For EGFR mutations or ALK translocations: Upfront brain-penetrant TKIs (osimertinib for EGFR, alectinib/brigatinib for ALK) combined with early SRS may provide optimal outcomes 1
• For patients without driver mutations: Early combination of immune checkpoint inhibitors and SRS may improve overall survival compared to sequential approach 1
• Avoid upfront WBRT in patients with EGFR mutation or ALK translocation 1

Small Cell Lung Cancer (SCLC):

• Decision to add SRS or WBRT depends on symptoms and disease burden 1
• Consider prophylactic cranial irradiation (PCI) in appropriate candidates 1

Melanoma:

• For asymptomatic patients (both BRAF wild-type and BRAF-mutated): Combination ipilimumab and nivolumab should be preferred first-line treatment 1
• For multiple symptomatic BRAF-mutated metastases or patients requiring ≥4 mg dexamethasone: Dabrafenib plus trametinib 1

HER2-Positive Breast Cancer:

• Systemic HER2-directed therapy with CNS activity should be integrated with local therapy decisions 1
• Multidisciplinary discussion required for optimal sequencing 1

Management of Treatment Complications

Radiation Necrosis:

• First-line treatment: Glucocorticoids 3, 4, 2
• If unsuccessful: Consider neurosurgical resection, laser interstitial thermal therapy (LITT), or bevacizumab 3, 4, 2

Neurocognitive Decline:

• Consider acetylcholinesterase-inhibiting medication and cognitive rehabilitation 3, 2

Thromboembolism:

• Prophylactic low-molecular weight heparin and compression stockings perioperatively 2
• Therapeutic anticoagulation after 4-5 days post-surgery for thromboembolic complications without undue hemorrhagic risk 2

Follow-Up Protocol

All patients with brain masses should undergo neurological assessment and neuroimaging (MRI) every 3 months. 1, 2

Management of Progression or Recurrence

Options determined by performance status, neurological function, type of CNS progression, and prior treatment: 1

• Surgery followed by SRS/SRT 1
• SRS/SRT alone 1
• Change of systemic pharmacotherapy 1
• WBRT if not previously administered 1
• Palliative care 1

Critical Pitfalls to Avoid

• Never delay tissue diagnosis when histology is uncertain, as treatment algorithms differ dramatically between primary tumors and metastases 2
• Avoid prophylactic anticonvulsants in patients without seizure history, as they provide no benefit and cause drug interactions 3, 4, 2
• Do not use WBRT as first-line treatment for limited brain metastases (1-4 lesions) with good performance status, as SRS preserves neurocognition 3, 4, 5
• Never combine BRAF inhibitors with WBRT due to severe dermatitis risk; avoid concomitant treatment 1
• Do not initiate adjuvant therapy without histological confirmation except in prohibitive surgical risk 2