Which locations of Central Nervous System (CNS) tumors are not suitable for Radiation Therapy (RT)?

CNS Tumor Locations Not Suitable for Radiation Therapy

No specific CNS tumor location is absolutely contraindicated for radiation therapy; however, conventional photon-based craniospinal irradiation (CSI) targeting the entire neuroaxis is too toxic in adult patients with leptomeningeal metastases due to off-target damage to internal organs and myelosuppression of the vertebral bodies. 1

Location-Based RT Considerations

Leptomeningeal Disease (Entire Neuroaxis)

• Conventional photon-based CSI is not suitable for adult patients with leptomeningeal metastases because it causes excessive toxicity from off-target organ damage and vertebral body myelosuppression 1
• While employed successfully in childhood leptomeningeal cancers, this approach cannot be safely applied to adults 1
• Proton-beam CSI has emerged as a safer alternative that can treat the entire neuroaxis with limited exit dose and comparable toxicity profile 1

Eloquent/Functional Brain Regions

• Tumors located in eloquent or functional brain regions present challenges where maximal safe resection should be prioritized over aggressive RT to avoid permanent functional deterioration 2
• The radiosensitivity of certain brain structures limits the ability to apply higher radiation doses to tumors affecting or located near these sensitive tissues 3

Brainstem and Optic Chiasm

• These locations are difficult to access for histological verification due to high complication risk, which complicates treatment planning including RT 3
• The radiosensitivity of these structures makes them particularly vulnerable to radiation-induced toxicity 3

Clinical Context Where RT Should Be Avoided or Modified

Reirradiation Scenarios

• Reirradiation carries significant toxicity concerns with overt necrosis occurring in 9% of patients and actuarial risk of necrosis reaching 22% at 1 year following retreatment 4
• Cumulative maximum overlap doses within the CNS ranging from 43.2-111 Gy (median 79.7 Gy) were associated with only modest palliative and survival benefits 4

High-Dose Per Fraction Concerns

• Higher dose per fraction schedules (such as 20 Gy in 5 fractions) should only be used for patients with poor performance status or short predicted survival due to neurocognitive toxicity concerns 1
• WBRT doses exceeding 30 Gy in 10 fractions (or biologically equivalent doses) are not recommended except in poor performance status patients 1

Specific Clinical Situations

• Focal rather than craniospinal irradiation is preferred for patients with isolated cranial neuropathies or spinal cord dysfunction to avoid prolonged myelosuppression 1
• RT to sites of CSF flow obstruction should be delivered as involved-field radiotherapy rather than whole neuroaxis treatment 1

Key Toxicity Considerations

Neurotoxicity Risk Factors

• Leukoencephalopathy is especially prominent when RT is administered before or concurrently with intrathecal or systemic chemotherapy, particularly methotrexate 1
• Major adverse effects include myelosuppression, mucositis, esophagitis, and leukoencephalopathy 1
• Delayed symptomatic leukoencephalopathy occurred in 20% of patients in one series 1

Treatment Sequencing

• RT should be delivered to sites of CSF flow block before administration of intrathecal therapy 1
• Treatment must begin within one month of surgery for optimal outcomes 2

Common Pitfalls

• Avoid treating the entire neuroaxis with conventional photon CSI in adults - this is the most critical location-based contraindication 1
• Do not exceed standard WBRT doses (30 Gy in 10 fractions) except in patients with limited life expectancy 1
• Recognize that isolated radiation to one region of leptomeninges fails to control disseminated disease throughout the compartment 1
• Consider proton-beam therapy when neuroaxis treatment is necessary to minimize toxicity 1