Whole brain radiation therapy (WBRT) is a medical intervention used for widespread brain metastases, where cancer has spread extensively to the brain. This diagnosis signifies that the primary cancer (often lung, breast, or melanoma) has progressed to a serious stage. WBRT manages neurological symptoms and prevents rapid functional decline. The treatment addresses cancer cells too numerous or too small to be treated individually, making it common when the disease burden is high.
Defining Whole Brain Radiation
WBRT is a non-surgical treatment using external beam radiation to deliver a uniform dose across the entire cranial vault. The intent is primarily palliative: to relieve symptoms like headaches, seizures, or weakness, and to control the disease rather than offer a cure. The radiation targets both visible tumors and microscopic cancer cells too small for imaging technology to detect, sometimes called the “dandelion effect.”
A typical course of WBRT involves daily treatments, known as fractions, administered over one to three weeks. Common regimens include a total dose of 30 Gray delivered in 10 fractions or a shorter course of 20 Gray in five fractions, particularly for patients with a shorter expected life span. Each treatment session is quick, lasting only a few minutes, though the overall process involves careful patient positioning and setup. Irradiating the entire brain stabilizes neurological function and reduces the risk of new metastases developing.
Primary Factors Influencing Prognosis
The life expectancy following WBRT is highly varied and depends on several established clinical factors, often measured in months rather than years. Historically, the median survival time for patients receiving WBRT for brain metastases has ranged from three to six months. Oncologists use prognostic scales to estimate survival by assessing specific patient and disease characteristics.
The Recursive Partitioning Analysis (RPA) is a classic system that divides patients into three main classes based on key factors. Patients in RPA Class I generally have the best outcomes, typically being under age 65, having a high functional status, a controlled primary cancer site, and no systemic spread outside of the brain. This favorable group has a median survival that can range from six to over seven months.
Conversely, RPA Class III patients, who represent the poorest prognostic group, are defined by a low performance status, specifically a Karnofsky Performance Status (KPS) score below 70. These individuals often have a median survival of less than three months. RPA Class II includes all other patients, such as those with a good functional status but an uncontrolled primary tumor or extracranial metastases, with a median survival typically falling into the range of four to five months.
The Graded Prognostic Assessment (GPA) scale is a modern tool that assigns points based on age, KPS, the presence of other body metastases, and the number of brain lesions. This system also includes the specific type and molecular characteristics of the primary cancer, such as lung or breast cancer. Survival estimates based on the GPA range dramatically, from a median of a few months for the lowest scores (GPA 0-1.0) to over 16 months for the highest scores (GPA 3.5-4.0). Patients with breast cancer metastases often demonstrate a better median survival after WBRT compared to those with non-small cell lung cancer.
Common Side Effects and Quality of Life
The side effects of whole brain radiation therapy are categorized by their timing of onset: acute, early-delayed, and late-delayed. Acute side effects occur during or shortly after treatment and commonly include fatigue, temporary hair loss, skin irritation, nausea, and headaches. These effects are managed with supportive care and typically resolve within a few weeks of completing therapy.
An early-delayed reaction, known as somnolence syndrome, can manifest weeks to a few months after treatment, characterized by excessive sleepiness and a temporary worsening of neurological symptoms. The most significant long-term side effects are the late-delayed cognitive impairments, which can emerge six months to years after treatment and are often irreversible. These neurocognitive deficits include problems with memory, executive function, and processing speed, significantly impacting a patient’s quality of life.
The primary mechanism for this cognitive decline is damage inflicted by the radiation on the hippocampus, a brain region highly sensitive to radiation and responsible for learning and memory formation. To minimize this risk, two preventative strategies are often employed. The drug memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to delay the onset of cognitive decline when taken during and for several months after WBRT.
Another technique is hippocampal avoidance WBRT, which uses advanced radiation planning to spare the hippocampus from the full dose of radiation. Clinical trials have demonstrated that this targeted approach helps preserve memory and other cognitive functions without compromising the treatment’s effectiveness. These measures are important for patients with a better prognostic score who are expected to survive long enough to experience the late-delayed side effects.