Ovarian cancer typically arises from cells on the ovary or, more commonly, the fallopian tubes. It is characterized by the uncontrolled growth of these cells, which can spread throughout the body. Most cases are diagnosed at an advanced stage because early symptoms are often vague. The cancer most frequently spreads within the abdominal cavity, affecting the peritoneum, the surface of the liver, and regional lymph nodes. Distant spread outside the abdomen often involves the lungs, sometimes causing fluid buildup.
Central Nervous System Metastasis: A Rare Occurrence
While ovarian cancer is highly metastatic, its spread to the central nervous system (CNS) is uncommon. The incidence of brain metastasis is low, estimated to occur in only 1% to 3% of patients. This contrasts sharply with other solid tumors, such as lung cancer or melanoma, which metastasize far more frequently. The protective nature of the brain environment contributes to this low rate.
The reported incidence of CNS metastasis appears to be slowly increasing, likely due to extended patient survival from systemic therapies. This extended survival provides more time for cancer cells to overcome initial barriers and establish distant sites of disease. The risk is highest for high-grade serous carcinoma, the most common and aggressive subtype.
The spread to the brain is most often observed in patients with Stage III or Stage IV disease. Patients carrying BRCA1 or BRCA2 genetic mutations also face a higher risk of developing brain metastases. The median time from initial diagnosis to the detection of a brain lesion is often around two to three years.
Biological Mechanisms of Brain Spread
The primary defense against cancer cells entering the brain is the specialized blood-brain barrier (BBB). This barrier is composed of tightly packed endothelial cells lining the brain’s capillaries, which strictly control the passage of substances from the bloodstream into the brain tissue. While protecting the neural environment, it also inadvertently shields cancer cells from many chemotherapy drugs.
For ovarian cancer cells to colonize the brain, they must breach this formidable barrier, usually via the bloodstream in a process called hematogenous spread. Successful cells often undergo Epithelial-Mesenchymal Transition (EMT). This process transforms the cells into a more mobile and invasive type capable of navigating the circulatory system and invading new tissues.
Once a metastatic lesion grows, the local BBB alters, becoming a Blood-Tumor Barrier (BTB). This modified barrier can be leaky in some areas, facilitating tumor growth, yet often remains intact enough to exclude therapeutic agents. In rare cases, cancer cells may also spread into the cerebrospinal fluid, causing leptomeningeal carcinomatosis, where cancer infiltrates the membranes surrounding the brain and spinal cord.
Identifying Neurological Signs and Symptoms
Symptoms are directly related to the location and size of the metastatic lesion. Initial signs are often caused by the tumor’s mass effect, which increases pressure within the skull (increased intracranial pressure). Persistent headaches, often worse in the morning, that do not respond to typical pain relievers are common indicators of this pressure. Nausea and vomiting, particularly without a clear gastrointestinal cause, can also result from the growing pressure on brain structures.
Metastases in specific functional areas can produce focal neurological deficits. A tumor in the motor cortex may cause weakness or numbness on one side of the body, a condition termed hemiparesis. Lesions along the visual pathways can lead to vision changes, such as blurred or double vision. Problems with speech, including slurring words or difficulty finding the right words, may indicate involvement of the language centers.
A seizure, or sudden uncontrolled electrical disturbance, is another frequent symptom. Seizures can manifest as generalized convulsions or as more subtle focal events, such as a strange sensation or uncontrollable twitching. Cognitive changes, including confusion, memory problems, or shifts in personality, may also occur due to the tumor’s impact on higher-level brain functions.
Treatment Strategies for CNS Involvement
Management of CNS metastasis typically requires a multimodal approach, combining local therapies for brain lesions with systemic treatments for cancer elsewhere. Surgery is often considered for patients with a single, accessible lesion causing significant symptoms. The goal of surgery is to relieve pressure, obtain tissue for diagnosis, and potentially prolong survival.
Radiation therapy is a primary local treatment modality, utilizing two main techniques.
Stereotactic Radiosurgery (SRS)
SRS uses highly focused beams of radiation to deliver a high dose to a small, well-defined tumor or a small number of lesions in one session.
Whole-Brain Radiation Therapy (WBRT)
WBRT treats the entire brain with lower doses over several weeks. It is typically reserved for patients with multiple lesions or when the cancer has spread diffusely through the cerebrospinal fluid.
The blood-brain barrier significantly limits the effectiveness of many standard chemotherapies, as they cannot reach therapeutic concentrations in the brain. This challenge has led to the exploration of specialized systemic agents that can cross the barrier. Poly(ADP-ribose) polymerase (PARP) inhibitors, a class of targeted drugs often used for ovarian cancer, have shown an ability to penetrate the CNS in some cases. For example, the use of PARP inhibitors like niraparib, particularly in patients with BRCA mutations, is a promising area of research to control both systemic disease and brain lesions simultaneously.