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  • Updated 12.15.2023
  • Released 11.18.1998
  • Expires For CME 12.15.2026

Brain metastases: considerations for surgical and radiosurgical treatment



Each year, 200,000 to 400,000 people are diagnosed with brain metastases. Patients with brain metastases suffer worse quality of life and have poorer survival and increased costs associated with their health care. Multidisciplinary care, including neurosurgery, radiation oncology, medical oncology, and neuro-oncology, has improved functional survival for these patients.

Key points

• Brain metastases are the most common brain tumors in adults and are a common source of morbidity and mortality for cancer patients.

• The selection of optimal therapy requires multidisciplinary input, including neuroradiology, neurosurgery, radiation oncology, neuro-oncology, and medical oncology.

• Surgical resection is indicated for larger, symptomatic lesions with mass effect or to establish a histologic diagnosis and, increasingly, a molecular diagnosis as well.

• Radiation therapy options include whole-brain radiation therapy for more diffuse metastatic disease or stereotactic radiosurgery for more limited disease.

Historical note and terminology

Tumors that have metastasized to the brain have been identified on autopsies for centuries. Grant's report of Harvey Cushing's series in 1926 was the first regarding patients who underwent surgical excision of brain metastases (20). During the mid-twentieth century, whole-brain radiotherapy significantly increased survival; thus, WBRT soon became a primary treatment modality for patients with brain metastases (10). With the technological advancement of delivering focused high-dose radiation to defined small metastases, stereotactic radiosurgery became the standard of care for managing limited brain metastases and was associated with fewer side effects than WBRT. Systemic therapies that can cross the blood-brain barrier have added another option for treating patients with brain metastases (24).

The most common sources of brain metastases are lung cancer (50% to 60%), breast cancer (10% to 20%), and melanoma (5% to 10%) (22). Patients with brain metastases most commonly present with neurologic symptoms that can be related to tumor location, peritumoral edema, or mass effect (49). Although CT imaging is commonly used as the initial diagnosis, MRI has become the mainstay of intracranial imaging due to its superior ability to detect small lesions (12).

Surgical management of brain metastases is recommended for immediate decompression of critical structures and relief of mass effect, and it provides an opportunity to obtain tissue for pathologic and molecular diagnosis. Thus, resection is indicated for large tumors causing mass effect and, in some cases, for smaller, isolated metastases in the setting of oligometastatic disease. It can also be recommended for radiation-resistant tumors or those that are refractory to other treatments, especially when it is believed that the overall prognosis will be driven by CNS disease. When the radiographic appearance of a lesion is diagnostically equivocal, less invasive approaches, such as stereotactic biopsy, may also be performed to obtain tissue for pathology.

Radiation therapy involves delivering high-energy radiation to regions of cancer involvement. Radiation is typically delivered with a linear accelerator, which uses electrons to generate high-energy photons that can be focused within the patient. Alternative photon radiation devices, such as the Gamma Knife, use radioactive cobalt sources to generate gamma rays that are then directed at targets within the patient. Photon radiation deposits energy that decreases with distance within the patient. Multiple convergent beams enable the sparing of nontarget tissue from high doses of radiation therapy. The use of intensity-modulated radiation therapy, which delivers different doses to various parts of the radiation field, can further shape the radiation dose. Newer approaches using accelerated protons and other particles have been used to further reduce the radiation dose to nontarget tissue. Protons take advantage of a unique property of particles called the Bragg peak, which results in the deposition of the beam’s dose at a fixed depth in tissue. This results in a substantially reduced dose (downstream) beyond the target, allowing better sparing of distal tissue.

The sensitivity of cancer and normal tissue to radiation relates to the dose of radiation, measured in Gray (Gy), as well as the size of the dose delivered in a given treatment, termed a fraction. The term fractionated radiation refers to radiation delivered over multiple treatments. Normal tissues are generally more sensitive to larger fractional doses, whereas tumors are relatively less so. However, certain tumor types, such as melanoma and renal cell carcinoma, are generally more resistant to smaller doses of radiation therapy. The delivery of larger fractional doses of radiation is termed hypofractionation, often involving a limited number of large fractional doses delivered over 1 to 5 days.

Whole-brain radiotherapy consists of irradiating the entire brain, typically with 30 Gy in 3 Gy fractions, although other dose and fractionation schemes can also be used. This radiation technique appears to be most effective for controlling many small (less than 0.5 cm), radiosensitive metastases, as well as metastases that are too small to be detected on standard contrast (gadolinium)-enhanced MR imaging (ie, micrometastases).

However, as patients with brain metastases survive longer, the delayed cognitive impairment that often results from whole-brain radiotherapy is becoming a more important consideration in treatment planning (38). Impairment typically occurs in a biphasic pattern, consisting of a transient subacute decline that peaks at 4 months post-irradiation, followed by a delayed irreversible impairment.

Techniques to mitigate neurocognitive decline due to WBRT include hippocampal-avoidance WBRT and prophylactic use of memantine, an NMDA antagonist. The hippocampus is known to play a vital role in memory formation, learning, and spatial processing, and the neurons in this region of the brain are particularly vulnerable to radiation damage. NMDA-rich neurons in the hippocampus are susceptible to radiation-induced overexcitation and toxicity. The phase 3 RTOG 0614 study showed that patients randomized to receive memantine during WBRT had fewer neurocognitive toxicities (03). This was followed by the phase 3 NRG CC001 trial evaluating the efficacy of memantine and hippocampal-avoidance WBRT versus memantine and traditional WBRT, which demonstrated a reduction in the severity of neurocognitive dysfunction with the use of this combined approach (05).

Stereotactic radiosurgery is an alternative approach to fractionated radiation therapy. Convergent small radiation beams that overlap at the target are used to precisely deliver a high dose of radiation to a small tumor. The major benefit of this technique is that the radiation dose rapidly falls off at the tumor margins, thereby sparing surrounding normal tissues from the effects of high-dose radiation. This can be achieved using many different radiation devices. The most common technique is the linear accelerator, which delivers multiple convergent arcs of radiation directed at the target. Other common techniques include CyberKnife, which uses a small linear accelerator mounted on a robotic arm, and the Gamma Knife, which employs fixed Cobalt-60 radiation sources focused on a central point by a helmet that allows passage of multiple select radiation beams. Additional technologies are continuously developed that allow for equivalently focused high doses of radiation to small targets.

A variation of stereotactic radiosurgery for larger lesions or those near vital radiation-sensitive structures (eg, optic nerves, chiasm, or brainstem) is fractionated stereotactic radiosurgery and hypofractionated stereotactic radiosurgery, the latter often referred to as stereotactic body radiotherapy). In these cases, the treatment is delivered using a stereotactic setup with similarly rapid dose fall off, but it is given using standard fraction sizes in fractionated stereotactic radiosurgery or few fractions of intermediate to large doses of radiation (hypofractionated stereotactic radiosurgery or stereotactic body radiotherapy) to limit the impact on sensitive, normal tissues while still providing a shorter course of therapy compared to standard fractionation.

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