8.3 Neuro-Oncology Therapies: Surgery, Radiation, Chemo & Immunotherapy

The treatment of central nervous system tumors requires a highly coordinated, multimodal approach. Depending on the tumor type, grade, and location, the treatment plan typically involves a combination of surgery, radiation, systemic therapies (chemotherapy, targeted therapy, immunotherapy), and device-based treatments. The neuroscience nurse must understand the mechanisms, goals, and toxicities of each modality to effectively monitor and support the patient.

Surgical Management

Surgery remains the cornerstone of treatment for most primary brain tumors and accessible solitary metastases.

Goals of Surgery

1. Tissue Diagnosis: Obtaining a tissue sample is critical for precise histological grading and molecular profiling, which dictate downstream therapies.
2. Maximal Safe Resection: The primary goal is to remove as much tumor as possible without causing new neurological deficits. Extensive resection correlates strongly with improved survival, particularly in high-grade gliomas.
3. Relief of Mass Effect: Removing the tumor bulk immediately reduces intracranial pressure, alleviating symptoms like headaches, nausea, and focal deficits.

Surgical Techniques

Advances in neurosurgical techniques have improved safety and outcomes. These include stereotactic navigation, intraoperative MRI, and awake craniotomy. Awake craniotomies are utilized when tumors are located near or within eloquent cortex (e.g., language or motor areas). The patient is awakened during the resection phase to perform specific tasks (like speaking or moving a limb), allowing the surgeon to map the cortex in real-time and avoid damaging critical pathways.

Radiation Therapy (RT)

Radiation therapy utilizes high-energy x-rays or protons to damage the DNA of rapidly dividing cancer cells, leading to cell death. It is standard for high-grade gliomas, many low-grade gliomas, and brain metastases.

Modalities

• Fractionated External Beam Radiation Therapy (EBRT): The total radiation dose is divided into smaller daily fractions delivered over several weeks. This allows normal brain tissue to repair itself between sessions while tumor cells accumulate lethal damage.
• Stereotactic Radiosurgery (SRS): (e.g., Gamma Knife, CyberKnife) Delivers a single, highly conformal, massive dose of radiation to a precisely defined target, sparing surrounding healthy tissue. It is primarily used for smaller metastases, acoustic neuromas, and meningiomas, rather than diffuse infiltrative gliomas.
• Whole-Brain Radiation Therapy (WBRT): Used when there are numerous brain metastases or leptomeningeal spread. It is associated with significant long-term cognitive toxicity.

Radiation Complications: Necrosis vs. Recurrence

Radiation causes inflammation and vascular damage in the brain.

• Acute/Subacute Toxicity: Fatigue, scalp erythema, alopecia, and worsening of baseline neurological symptoms due to transient edema (often treated with brief courses of corticosteroids).
• Radiation Necrosis: A critical late complication (occurring months to years after RT). It is an irreversible area of dead, necrotic brain tissue caused by radiation-induced vascular injury. On standard MRI, radiation necrosis shows ring enhancement and edema, making it indistinguishable from true tumor recurrence. Advanced imaging (like MR Perfusion or PET scans) or sometimes biopsy is required to differentiate the two. Radiation necrosis is often treated with high-dose steroids, hyperbaric oxygen, or bevacizumab (Avastin) to reduce edema and vascular permeability.

Chemotherapy and Systemic Therapies

The blood-brain barrier (BBB) significantly limits the efficacy of many systemic chemotherapies, as large or hydrophilic molecules cannot penetrate the CNS.

Temozolomide (TMZ)

Temozolomide (Temodar) is an oral alkylating chemotherapeutic agent and the standard of care for high-grade gliomas (often given concurrently with radiation, followed by adjuvant maintenance cycles). It is lipophilic and crosses the BBB effectively. Its efficacy is heavily dependent on the tumor's MGMT promoter methylation status. Side effects include myelosuppression (thrombocytopenia, neutropenia), nausea, vomiting, and fatigue. Patients require strict monitoring of complete blood counts.

Targeted Therapy and Immunotherapy

• Bevacizumab (Avastin): A monoclonal antibody that inhibits Vascular Endothelial Growth Factor (VEGF). Glioblastomas are highly vascular tumors that secrete VEGF to promote new blood vessel growth (angiogenesis). Bevacizumab starves the tumor of its blood supply and dramatically reduces surrounding vasogenic edema. It is often used for recurrent GBM or to manage severe radiation necrosis.
• Immunotherapy: While highly successful in cancers like melanoma and lung cancer, immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab) have shown limited efficacy in unselected glioblastoma populations, likely due to the highly immunosuppressive microenvironment of the brain. However, they are highly effective for melanoma or non-small cell lung cancer brain metastases.

Tumor Treating Fields (TTFields)

Tumor Treating Fields (Optune) is a novel, FDA-approved device for newly diagnosed and recurrent glioblastoma. The patient wears a portable array of transducer arrays on their shaved scalp. The device delivers continuous, low-intensity, intermediate-frequency alternating electrical fields to the brain. These electrical fields physically disrupt the formation of the mitotic spindle during cell division, leading to cancer cell apoptosis. The therapy must be worn almost continuously (ideally >18 hours/day) to be effective. The primary side effect is scalp irritation (contact dermatitis).

Differentiating Treatment Effects